diff --git a/CODE_OF_CONDUCT.md b/CODE_OF_CONDUCT.md
deleted file mode 100644
index 5b627cfa..00000000
--- a/CODE_OF_CONDUCT.md
+++ /dev/null
@@ -1,4 +0,0 @@
-## Code of Conduct
-This project has adopted the [Amazon Open Source Code of Conduct](https://aws.github.io/code-of-conduct).
-For more information see the [Code of Conduct FAQ](https://aws.github.io/code-of-conduct-faq) or contact
-opensource-codeofconduct@amazon.com with any additional questions or comments.
diff --git a/CONTRIBUTING.md b/CONTRIBUTING.md
deleted file mode 100644
index c4b6a1c5..00000000
--- a/CONTRIBUTING.md
+++ /dev/null
@@ -1,59 +0,0 @@
-# Contributing Guidelines
-
-Thank you for your interest in contributing to our project. Whether it's a bug report, new feature, correction, or additional
-documentation, we greatly value feedback and contributions from our community.
-
-Please read through this document before submitting any issues or pull requests to ensure we have all the necessary
-information to effectively respond to your bug report or contribution.
-
-
-## Reporting Bugs/Feature Requests
-
-We welcome you to use the GitHub issue tracker to report bugs or suggest features.
-
-When filing an issue, please check existing open, or recently closed, issues to make sure somebody else hasn't already
-reported the issue. Please try to include as much information as you can. Details like these are incredibly useful:
-
-* A reproducible test case or series of steps
-* The version of our code being used
-* Any modifications you've made relevant to the bug
-* Anything unusual about your environment or deployment
-
-
-## Contributing via Pull Requests
-Contributions via pull requests are much appreciated. Before sending us a pull request, please ensure that:
-
-1. You are working against the latest source on the *main* branch.
-2. You check existing open, and recently merged, pull requests to make sure someone else hasn't addressed the problem already.
-3. You open an issue to discuss any significant work - we would hate for your time to be wasted.
-
-To send us a pull request, please:
-
-1. Fork the repository.
-2. Modify the source; please focus on the specific change you are contributing. If you also reformat all the code, it will be hard for us to focus on your change.
-3. Ensure local tests pass.
-4. Commit to your fork using clear commit messages.
-5. Send us a pull request, answering any default questions in the pull request interface.
-6. Pay attention to any automated CI failures reported in the pull request, and stay involved in the conversation.
-
-GitHub provides additional document on [forking a repository](https://help.github.com/articles/fork-a-repo/) and
-[creating a pull request](https://help.github.com/articles/creating-a-pull-request/).
-
-
-## Finding contributions to work on
-Looking at the existing issues is a great way to find something to contribute on. As our projects, by default, use the default GitHub issue labels (enhancement/bug/duplicate/help wanted/invalid/question/wontfix), looking at any 'help wanted' issues is a great place to start.
-
-
-## Code of Conduct
-This project has adopted the [Amazon Open Source Code of Conduct](https://aws.github.io/code-of-conduct).
-For more information see the [Code of Conduct FAQ](https://aws.github.io/code-of-conduct-faq) or contact
-opensource-codeofconduct@amazon.com with any additional questions or comments.
-
-
-## Security issue notifications
-If you discover a potential security issue in this project we ask that you notify AWS/Amazon Security via our [vulnerability reporting page](http://aws.amazon.com/security/vulnerability-reporting/). Please do **not** create a public github issue.
-
-
-## Licensing
-
-See the [LICENSE](LICENSE) file for our project's licensing. We will ask you to confirm the licensing of your contribution.
diff --git a/LICENSE b/LICENSE
deleted file mode 100644
index 09951d9f..00000000
--- a/LICENSE
+++ /dev/null
@@ -1,17 +0,0 @@
-MIT No Attribution
-
-Copyright Amazon.com, Inc. or its affiliates. All Rights Reserved.
-
-Permission is hereby granted, free of charge, to any person obtaining a copy of
-this software and associated documentation files (the "Software"), to deal in
-the Software without restriction, including without limitation the rights to
-use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of
-the Software, and to permit persons to whom the Software is furnished to do so.
-
-THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR
-IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS
-FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR
-COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER
-IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN
-CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE.
-
diff --git a/Makefile b/Makefile
deleted file mode 100644
index e1a86140..00000000
--- a/Makefile
+++ /dev/null
@@ -1,473 +0,0 @@
-# Makefile for Cost Effective and Scalable Model Inference on AWS Graviton with EKS
-# This Makefile automates the deployment of the complete ML inference solution
-
-.PHONY: help install install-platform setup-base setup-models setup-gateway setup-observability setup-idp setup-rag setup-rag-strands setup-milvus clean clean-pvcs clean-safe verify-cluster
-
-# Default target
-help:
-	@echo "Available targets:"
-	@echo "  install           - Complete installation of all components including RAG Strands application"
-	@echo "  install-platform  - Install platform only (base, models, observability, gateway)"
-	@echo "  verify-cluster    - Verify EKS cluster access"
-	@echo "  setup-base        - Install base infrastructure components (includes GP3 with Immediate binding)"
-	@echo "  setup-models      - Deploy model hosting services"
-	@echo "  setup-gateway     - Deploy model gateway (LiteLLM)"
-	@echo "  setup-observability - Deploy monitoring and observability"
-	@echo "  setup-idp         - Setup Intelligent Document Processing"
-	@echo "  setup-rag         - Setup RAG with OpenSearch"
-	@echo "  setup-rag-strands - Setup RAG with Strands SDK and OpenSearch (Kubernetes deployment)"
-	@echo "  setup-milvus      - Install Milvus vector database"
-	@echo "  clean             - Complete cleanup including PVCs and persistent resources"
-	@echo "  clean-safe        - Safe cleanup (applications only, preserves data)"
-	@echo "  clean-pvcs        - Remove only persistent volume claims and volumes"
-	@echo "  status            - Check deployment status"
-	@echo ""
-	@echo "🚀 Quick Start:"
-	@echo "  Run 'make install' for complete setup including the multi-agent RAG system"
-	@echo ""
-	@echo "Storage Configuration:"
-	@echo "  - GP3 storage class uses Immediate binding mode to prevent timeout issues"
-	@echo "  - This ensures StatefulSets and complex workloads provision volumes correctly"
-	@echo ""
-	@echo "Prerequisites:"
-	@echo "  - EKS cluster must be set up following AWS Solutions Guidance"
-	@echo "  - kubectl configured to access the cluster"
-	@echo "  - Required environment variables configured"
-	@echo "  - TAVILY_API_KEY for web search functionality"
-
-# Complete installation including RAG Strands application
-install: verify-cluster setup-base setup-models setup-observability setup-gateway setup-rag-strands
-	@echo "✅ Complete installation finished!"
-	@echo ""
-	@echo "🎉 Your complete Agentic AI platform is now deployed with:"
-	@echo "   ✓ Base infrastructure (KubeRay, GPU operators, storage)"
-	@echo "   ✓ Model hosting services (Ray Serve, vLLM)"
-	@echo "   ✓ Observability tools (Langfuse)"
-	@echo "   ✓ Model gateway (LiteLLM proxy)"
-	@echo "   ✓ Multi-agent RAG system with Strands SDK"
-	@echo ""
-	@echo "🔧 Configuration completed during installation:"
-	@echo "   - LiteLLM proxy with unified API gateway"
-	@echo "   - Langfuse for LLM observability and tracing"
-	@echo "   - OpenSearch cluster for vector storage"
-	@echo "   - Multi-agent system with web search capabilities"
-	@echo ""
-	@echo "🚀 Your system is ready to use!"
-	@echo "   - Access the RAG application via the deployed ALB endpoint"
-	@echo "   - All agents include built-in OpenTelemetry tracing"
-	@echo "   - Web search integration with Tavily API"
-	@echo "   - Comprehensive observability through Langfuse"
-	@echo ""
-	@echo "📖 For detailed usage instructions, refer to the README documentation."
-
-# Platform-only installation (without RAG application)
-install-platform: verify-cluster setup-base setup-models setup-observability setup-gateway
-	@echo "✅ Platform installation finished!"
-	@echo ""
-	@echo "🎉 Your Agentic AI platform is now deployed with:"
-	@echo "   ✓ Base infrastructure (KubeRay, GPU operators, storage)"
-	@echo "   ✓ Model hosting services (Ray Serve, vLLM)"
-	@echo "   ✓ Observability tools (Langfuse)"
-	@echo "   ✓ Model gateway (LiteLLM proxy)"
-	@echo ""
-	@echo "Next steps:"
-	@echo "1. Configure LiteLLM:"
-	@echo "   - Export the LiteLLM ingress ALB address:"
-	@echo "     export LITELLM_ALB_URL=\$$(kubectl get ingress litellm-ingress -o jsonpath='{.status.loadBalancer.ingress[0].hostname}')"
-	@echo "   - Access LiteLLM web interface at http://\$$LITELLM_ALB_URL"
-	@echo "   - Login with username 'admin' and password 'sk-123456'"
-	@echo "   - Create a virtual key in 'Virtual Keys' section"
-	@echo "   - Mark 'All Team Models' for the models field"
-	@echo "   - Note down the key value for use in agentic applications"
-	@echo ""
-	@echo "2. Deploy agentic applications:"
-	@echo "   - Run 'make setup-rag-strands' for the multi-agent RAG system"
-	@echo "   - Or refer to the README for other agentic application options"
-
-# Verify cluster access
-verify-cluster:
-	@echo "🔍 Verifying EKS cluster access..."
-	kubectl cluster-info
-	kubectl get nodes
-	@echo "✅ Cluster verification complete"
-
-# Setup base infrastructure
-setup-base: verify-cluster
-	@echo "🚀 Installing base infrastructure components..."
-	@echo "   - KubeRay Operator for distributed model serving"
-	@echo "   - NVIDIA GPU Operator for GPU workloads"
-	@echo "   - GP3 storage class with Immediate binding (prevents timeout issues)"
-	@echo "   - Karpenter node pools for different workload types"
-	cd base_eks_setup && chmod +x install_operators.sh && ./install_operators.sh
-	@echo "✅ Base infrastructure setup complete"
-
-# Setup model hosting services
-setup-models: setup-base
-	@echo "🤖 Deploying model hosting services..."
-	cd model-hosting && chmod +x setup.sh && ./setup.sh
-	@echo "✅ Model hosting services deployed"
-
-# Setup observability
-setup-observability: setup-models
-	@echo "📊 Deploying observability tools..."
-	@echo "⏱️  Note: Langfuse deployment may take up to 10 minutes to complete"
-	cd model-observability && chmod +x setup.sh && ./setup.sh
-	@echo "✅ Observability tools deployed"
-	@echo ""
-	@echo "⚠️  IMPORTANT: Configure Langfuse after deployment:"
-	@echo "   1. Access Langfuse web interface"
-	@echo "   2. Create organization 'test' and project 'demo'"
-	@echo "   3. Go to 'Tracing' menu and set up tracing"
-	@echo "   4. Record Public Key (PK) and Secret Key (SK)"
-
-# Setup model gateway
-setup-gateway: setup-observability
-	@echo "🌐 Deploying model gateway..."
-	cd model-gateway && chmod +x setup.sh && ./setup.sh
-	@echo "✅ Model gateway deployed"
-	@echo ""
-	@echo "⚠️  IMPORTANT: Configure LiteLLM after deployment:"
-	@echo "   1. Export the LiteLLM ingress ALB address:"
-	@echo "     export LITELLM_ALB_URL=\$$(kubectl get ingress litellm-ingress -o jsonpath='{.status.loadBalancer.ingress[0].hostname}')"
-	@echo "   2. Access LiteLLM web interface"
-	@echo "   3. Login with username 'admin' and password 'sk-123456'"
-	@echo "   4. Go to 'Virtual Keys' and create a new key"
-	@echo "   5. Mark 'All Team Models' for the models field"
-	@echo "   6. Store the generated secret key for agentic applications"
-
-# Setup Intelligent Document Processing
-setup-idp:
-	@echo "📄 Setting up Intelligent Document Processing..."
-	@if [ ! -f agentic-apps/agentic-idp/.env ]; then \
-		echo "Creating .env file from template..."; \
-		cd agentic-apps/agentic-idp && cp .env.example .env; \
-		echo "⚠️  Please edit agentic-apps/agentic-idp/.env with your configuration"; \
-		echo "   - LLAMA_VISION_MODEL_KEY=your-litellm-virtual-key"; \
-		echo "   - API_GATEWAY_URL=your-litellm-gateway-url"; \
-		echo "   - LANGFUSE_HOST=your-langfuse-endpoint"; \
-		echo "   - LANGFUSE_PUBLIC_KEY=your-langfuse-public-key"; \
-		echo "   - LANGFUSE_SECRET_KEY=your-langfuse-secret-key"; \
-		echo ""; \
-		echo "After configuring .env, run: cd agentic-apps/agentic-idp && pip install -r requirements.txt && python agentic_idp.py"; \
-	else \
-		echo "Installing Python dependencies..."; \
-		cd agentic-apps/agentic-idp && pip install -r requirements.txt; \
-		echo "✅ IDP setup complete. Run: cd agentic-apps/agentic-idp && python agentic_idp.py"; \
-	fi
-
-# Setup RAG with OpenSearch
-setup-rag:
-	@echo "🔍 Setting up RAG with OpenSearch..."
-	cd agentic-apps/agentic_rag_opensearch && chmod +x setup-opensearch.sh && ./setup-opensearch.sh
-	@if [ ! -f agentic-apps/agentic_rag_opensearch/.env ]; then \
-		echo "Creating .env file from template..."; \
-		cd agentic-apps/agentic_rag_opensearch && cp .env.example .env; \
-		echo "⚠️  Please edit agentic-apps/agentic_rag_opensearch/.env with your configuration"; \
-		echo "   - OPENAI_API_KEY=your-litellm-virtual-key"; \
-		echo "   - OPENAI_BASE_URL=your-model-endpoint-url"; \
-		echo "   - LANGFUSE_HOST=your-langfuse-endpoint"; \
-		echo "   - LANGFUSE_PUBLIC_KEY=your-langfuse-public-key"; \
-		echo "   - LANGFUSE_SECRET_KEY=your-langfuse-secret-key"; \
-		echo ""; \
-		echo "After configuring .env, run the following commands:"; \
-		echo "   cd agentic-apps/agentic_rag_opensearch"; \
-		echo "   pnpm install"; \
-		echo "   pnpm embed-knowledge"; \
-		echo "   pnpm dev"; \
-	else \
-		echo "Installing Node.js dependencies..."; \
-		cd agentic-apps/agentic_rag_opensearch && pnpm install; \
-		echo "✅ RAG setup complete. Run the following commands:"; \
-		echo "   cd agentic-apps/agentic_rag_opensearch"; \
-		echo "   pnpm embed-knowledge"; \
-		echo "   pnpm dev"; \
-	fi
-
-# Setup RAG with Strands SDK and OpenSearch (Kubernetes deployment)
-setup-rag-strands:
-	@echo "🔍 Setting up RAG with Strands SDK and OpenSearch..."
-	@echo "📋 This will deploy a containerized multi-agent RAG system with:"
-	@echo "   - SupervisorAgent (Orchestrator) with built-in tracing"
-	@echo "   - KnowledgeAgent for managing knowledge base and embeddings"
-	@echo "   - MCPAgent for tool interactions via MCP protocol"
-	@echo "   - OpenSearch cluster for vector storage"
-	@echo "   - Tavily web search integration"
-	@echo "   - OpenTelemetry tracing with Langfuse integration"
-	@echo ""
-	@echo "⚠️  Prerequisites:"
-	@echo "   - Python 3.9+"
-	@echo "   - EKS cluster"
-	@echo "   - TAVILY_API_KEY (https://docs.tavily.com/documentation/quickstart#get-your-free-tavily-api-key)"
-	@echo "   - AWS credentials configured"
-	@echo "   - Docker daemon in running status"
-	@echo ""
-	@echo "🚀 Starting deployment..."
-	cd agentic-apps/strandsdk_agentic_rag_opensearch && chmod +x setup.sh && ./setup.sh
-	@echo "✅ RAG with Strands SDK deployment complete!"
-
-# Setup Milvus vector database
-setup-milvus:
-	@echo "🗄️  Installing Milvus vector database..."
-	@echo "Installing cert-manager..."
-	kubectl apply -f https://github.com/jetstack/cert-manager/releases/download/v1.5.3/cert-manager.yaml
-	@echo "Waiting for cert-manager to be ready..."
-	kubectl wait --for=condition=ready pod -l app=cert-manager -n cert-manager --timeout=300s
-	@echo "Installing Milvus operator..."
-	kubectl apply -f https://raw.githubusercontent.com/zilliztech/milvus-operator/main/deploy/manifests/deployment.yaml
-	kubectl wait --for=condition=ready pod -l control-plane=controller-manager -n milvus-operator --timeout=300s
-	@echo "Creating EBS storage class..."
-	kubectl apply -f milvus/ebs-storage-class.yaml
-	@echo "Deploying Milvus standalone..."
-	kubectl apply -f milvus/milvus-standalone.yaml
-	@echo "Creating Network Load Balancer service..."
-	kubectl apply -f milvus/milvus-nlb-service.yaml
-	@echo "✅ Milvus installation complete"
-
-# Function calling setup
-setup-function-calling:
-	@echo "🔧 Setting up function calling service..."
-	kubectl apply -f agent/kubernetes/combined.yaml
-	@echo "✅ Function calling service deployed"
-	@echo ""
-	@echo "Test function calling with:"
-	@echo "curl -X POST http://<YOUR-LOAD-BALANCER-URL>/chat \\"
-	@echo "  -H \"Content-Type: application/json\" \\"
-	@echo "  -d '{\"message\": \"What is the current weather in London?\"}'"
-
-# Performance benchmarking setup
-setup-benchmark:
-	@echo "📊 Setting up performance benchmarking..."
-	@echo "Please ensure you have:"
-	@echo "1. Launched a client EC2 instance in the same AZ as your Ray cluster"
-	@echo "2. Installed Golang on the client instance"
-	@echo "3. Set environment variables:"
-	@echo "   export URL=http://localhost:8000/v1/chat/completions"
-	@echo "   export REQUESTS_PER_PROMPT=<concurrent_calls>"
-	@echo "   export NUM_WARMUP_REQUESTS=<warmup_requests>"
-	@echo "4. Run: kubectl port-forward service/ray-service-llamacpp-serve-svc 8000:8000"
-	@echo "5. Execute: go run perf_benchmark.go"
-
-# Clean up all deployments including persistent volumes
-clean:
-	@echo "🧹 Cleaning up deployments and resources created by this Makefile..."
-	@echo ""
-	@echo "⚠️  WARNING: This will delete resources installed by this Makefile!"
-	@echo "📋 Resources that will be deleted:"
-	@echo "   - Application deployments and services in default, kuberay, gpu-operator, milvus, and langfuse namespaces"
-	@echo "   - Persistent volume claims and volumes created by this Makefile"
-	@echo "   - Custom storage classes"
-	@echo "   - Secrets and configmaps in managed namespaces (except system ones)"
-	@echo "   - Custom resource definitions related to Ray and Milvus"
-	@echo "   - Operators and components installed by this Makefile"
-	@echo "   - Custom namespaces created by this Makefile"
-	@echo ""
-	@echo "📋 Resources that will NOT be deleted:"
-	@echo "   - ArgoCD components"
-	@echo "   - AWS Load Balancer Controller"
-	@echo "   - CoreDNS"
-	@echo "   - EBS CSI Controller"
-	@echo "   - Karpenter"
-	@echo "   - Other system components"
-	@echo ""
-	@echo "Press Ctrl+C within 15 seconds to cancel..."
-	@sleep 15
-	@echo ""
-	@echo "🗑️  Step 1: Removing workloads installed by this Makefile..."
-	@echo "   Removing deployments (excluding system components)..."
-	-kubectl delete deployment --all -n default 2>/dev/null || true
-	-kubectl delete deployment -n kuberay --all 2>/dev/null || true
-	-kubectl delete deployment -n gpu-operator --all 2>/dev/null || true
-	-kubectl delete deployment -n milvus --all 2>/dev/null || true
-	-kubectl delete deployment -n langfuse --all 2>/dev/null || true
-	@echo "   Removing statefulsets (excluding system components)..."
-	-kubectl delete statefulset --all -n default 2>/dev/null || true
-	-kubectl delete statefulset -n kuberay --all 2>/dev/null || true
-	-kubectl delete statefulset -n milvus --all 2>/dev/null || true
-	-kubectl delete statefulset -n langfuse --all 2>/dev/null || true
-	@echo "   Removing daemonsets (excluding system ones)..."
-	-kubectl delete daemonset --all -n default 2>/dev/null || true
-	-kubectl delete daemonset -n gpu-operator --all 2>/dev/null || true
-	@echo "   Removing jobs and cronjobs (excluding system ones)..."
-	-kubectl delete job --all -n default 2>/dev/null || true
-	-kubectl delete cronjob --all -n default 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 2: Removing agentic applications..."
-	-kubectl delete -f agent/kubernetes/combined.yaml 2>/dev/null || true
-	@echo "🗑️  Removing Strands SDK RAG applications..."
-	-kubectl delete -f agentic-apps/strandsdk_agentic_rag_opensearch/k8s/ 2>/dev/null || true
-	-kubectl delete ingress strandsdk-rag-ingress-alb 2>/dev/null || true
-	-kubectl delete secret app-secrets 2>/dev/null || true
-	-kubectl delete configmap app-config 2>/dev/null || true
-	-kubectl delete serviceaccount strandsdk-rag-service-account 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 3: Removing Milvus and related resources..."
-	-kubectl delete -f milvus/milvus-nlb-service.yaml 2>/dev/null || true
-	-kubectl delete -f milvus/milvus-standalone.yaml 2>/dev/null || true
-	-kubectl delete -f milvus/ebs-storage-class.yaml 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 4: Removing observability components..."
-	@echo "   Uninstalling Langfuse Helm release..."
-	-helm uninstall langfuse 2>/dev/null || true
-	-cd model-observability && kubectl delete -f . 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 5: Removing model gateway..."
-	-cd model-gateway && kubectl delete -f . 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 6: Removing model hosting services..."
-	-cd model-hosting && kubectl delete -f . 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 7: Waiting for pods to terminate..."
-	@echo "   This may take a few minutes..."
-	-kubectl wait --for=delete pod --all --all-namespaces --timeout=300s 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 8: Force deleting any stuck pods..."
-	-kubectl delete pods --all --all-namespaces --grace-period=0 --force 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 9: Removing persistent volume claims..."
-	-kubectl delete pvc --all --all-namespaces --timeout=60s 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 10: Removing persistent volumes..."
-	-kubectl delete pv --all --timeout=60s 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 11: Removing NVIDIA GPU Operator..."
-	@echo "   Uninstalling NVIDIA GPU Operator Helm releases..."
-	-helm list -n gpu-operator --short | xargs -r -I {} helm uninstall {} -n gpu-operator 2>/dev/null || true
-	@echo "   Removing NVIDIA Device Plugin..."
-	-kubectl delete -f https://raw.githubusercontent.com/NVIDIA/k8s-device-plugin/v0.17.2/deployments/static/nvidia-device-plugin.yml 2>/dev/null || true
-	@echo "   Removing GPU operator namespace..."
-	-kubectl delete namespace gpu-operator 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 12: Removing KubeRay Operator..."
-	@echo "   Uninstalling KubeRay Operator Helm release..."
-	-helm uninstall kuberay-operator -n kuberay 2>/dev/null || true
-	@echo "   Removing KubeRay namespace..."
-	-kubectl delete namespace kuberay 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 13: NOW removing base infrastructure components..."
-	@echo "   Removing Karpenter nodepools..."
-	-kubectl delete -f base_eks_setup/karpenter_nodepool/ 2>/dev/null || true
-	@echo "   Removing GP3 storage class..."
-	-kubectl delete -f base_eks_setup/gp3.yaml 2>/dev/null || true
-	@echo "   Removing Prometheus monitoring..."
-	-kubectl delete -f base_eks_setup/prometheus-monitoring.yaml 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 14: Removing storage classes (custom ones)..."
-	-kubectl delete storageclass gp3 2>/dev/null || true
-	-kubectl delete storageclass gp3-csi 2>/dev/null || true
-	-kubectl delete storageclass ebs-sc 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 15: Removing secrets and configmaps created by this Makefile..."
-	-kubectl delete secret --all -n default --field-selector type!=kubernetes.io/service-account-token 2>/dev/null || true
-	-kubectl delete secret --all -n kuberay --field-selector type!=kubernetes.io/service-account-token 2>/dev/null || true
-	-kubectl delete secret --all -n langfuse --field-selector type!=kubernetes.io/service-account-token 2>/dev/null || true
-	-kubectl delete secret --all -n milvus --field-selector type!=kubernetes.io/service-account-token 2>/dev/null || true
-	-kubectl delete configmap --all -n default --field-selector metadata.name!=kube-root-ca.crt 2>/dev/null || true
-	-kubectl delete configmap --all -n kuberay --field-selector metadata.name!=kube-root-ca.crt 2>/dev/null || true
-	-kubectl delete configmap --all -n langfuse --field-selector metadata.name!=kube-root-ca.crt 2>/dev/null || true
-	-kubectl delete configmap --all -n milvus --field-selector metadata.name!=kube-root-ca.crt 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 16: Removing service accounts in default namespace..."
-	-kubectl delete serviceaccount --all -n default --field-selector metadata.name!=default 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 17: Removing custom resource definitions..."
-	-kubectl delete crd rayclusters.ray.io 2>/dev/null || true
-	-kubectl delete crd rayservices.ray.io 2>/dev/null || true
-	-kubectl delete crd rayjobs.ray.io 2>/dev/null || true
-	-kubectl delete crd milvuses.milvus.io 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 18: Removing operators and system components..."
-	-kubectl delete -f https://raw.githubusercontent.com/zilliztech/milvus-operator/main/deploy/manifests/deployment.yaml 2>/dev/null || true
-	-kubectl delete -f https://github.com/jetstack/cert-manager/releases/download/v1.5.3/cert-manager.yaml 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 19: Removing namespaces (non-system)..."
-	-kubectl delete namespace kuberay 2>/dev/null || true
-	-kubectl delete namespace milvus-operator 2>/dev/null || true
-	-kubectl delete namespace cert-manager 2>/dev/null || true
-	-kubectl delete namespace gpu-operator 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 20: Final check for any remaining resources..."
-	@echo "Checking for stuck resources..."
-	-kubectl get pods --all-namespaces --field-selector=status.phase!=Running,status.phase!=Succeeded 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Step 21: Removing Helm repositories..."
-	-helm repo remove kuberay 2>/dev/null || true
-	-helm repo remove nvidia 2>/dev/null || true
-	-helm repo remove langfuse 2>/dev/null || true
-	@echo ""
-	@echo "✅ Cleanup of Makefile-installed components complete!"
-	@echo ""
-	@echo "ℹ️  Note: Some AWS Load Balancers and EBS volumes may take additional time to be cleaned up by AWS."
-	@echo "ℹ️  Check your AWS console to verify all resources have been properly removed."
-	@echo "ℹ️  Karpenter-managed nodes will be automatically terminated when workloads are removed."
-	@echo "ℹ️  System components like ArgoCD, AWS Load Balancer Controller, CoreDNS, EBS CSI Controller, and Karpenter were preserved."
-
-# Safe cleanup - removes applications but preserves persistent data
-clean-safe:
-	@echo "🧹 Safe cleanup - removing applications but preserving data..."
-	@echo ""
-	@echo "🗑️  Removing agentic applications..."
-	-kubectl delete -f agent/kubernetes/combined.yaml 2>/dev/null || true
-	@echo "🗑️  Removing Strands SDK RAG applications..."
-	-kubectl delete -f agentic-apps/strandsdk_agentic_rag_opensearch/k8s/ 2>/dev/null || true
-	-kubectl delete ingress strandsdk-rag-ingress-alb 2>/dev/null || true
-	-kubectl delete secret app-secrets 2>/dev/null || true
-	-kubectl delete configmap app-config 2>/dev/null || true
-	-kubectl delete serviceaccount strandsdk-rag-service-account 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Removing Milvus services (keeping data)..."
-	-kubectl delete -f milvus/milvus-nlb-service.yaml 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Removing observability components..."
-	@echo "   Uninstalling Langfuse Helm release..."
-	-helm uninstall langfuse 2>/dev/null || true
-	-cd model-observability && kubectl delete -f . 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Removing model gateway..."
-	-cd model-gateway && kubectl delete -f . 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Removing model hosting services..."
-	-cd model-hosting && kubectl delete -f . 2>/dev/null || true
-	@echo ""
-	@echo "✅ Safe cleanup complete! Persistent data has been preserved."
-	@echo "ℹ️  To remove persistent data, run 'make clean-pvcs' or 'make clean'"
-
-# Clean only persistent volume claims and volumes
-clean-pvcs:
-	@echo "🗑️  Removing persistent volume claims and volumes..."
-	@echo ""
-	@echo "⚠️  WARNING: This will delete all persistent data!"
-	@echo "Press Ctrl+C within 10 seconds to cancel..."
-	@sleep 10
-	@echo ""
-	@echo "🗑️  Removing persistent volume claims..."
-	-kubectl delete pvc --all --all-namespaces --timeout=60s 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Removing persistent volumes..."
-	-kubectl delete pv --all --timeout=60s 2>/dev/null || true
-	@echo ""
-	@echo "🗑️  Removing custom storage classes..."
-	-kubectl delete storageclass gp3-csi 2>/dev/null || true
-	-kubectl delete storageclass ebs-sc 2>/dev/null || true
-	@echo ""
-	@echo "✅ Persistent volume cleanup complete!"
-
-# Status check
-status:
-	@echo "📋 Checking deployment status..."
-	@echo ""
-	@echo "Namespaces:"
-	kubectl get namespaces
-	@echo ""
-	@echo "Pods across all namespaces:"
-	kubectl get pods --all-namespaces
-	@echo ""
-	@echo "Services:"
-	kubectl get services --all-namespaces
-	@echo ""
-	@echo "Ingresses:"
-	kubectl get ingress --all-namespaces
-
-# Quick development setup (models + gateway only)
-dev-setup: verify-cluster setup-base setup-models setup-observability setup-gateway
-	@echo "✅ Development setup complete!"
-	@echo "Core components (base, models, observability, gateway) are ready for development."
diff --git a/README.md b/README.md
index dc1b69b9..8cc45389 100644
--- a/README.md
+++ b/README.md
@@ -1,777 +1,9 @@
-# Cost Effective and Scalable Model Inference and Agentic AI on AWS Graviton with EKS
+# clinical-assistant
 
-## Table of Contents
-
-- [Overview](#overview)
-- [Important Setup Instructions](#️-important-setup-instructions)
-- [Architecture](#architecture)
-- [Architecture Steps](#architecture-steps)
-- [Plan Your Deployment](#plan-your-deployment)
-  - [Cost](#cost)
-  - [Sample Cost Table](#sample-cost-table)
-- [Quick Start Guide](#quick-start-guide)
-  - [Option 1: Automated Setup with Makefile (Recommended)](#option-1-automated-setup-with-makefile-recommended)
-    - [Prerequisites](#prerequisites)
-    - [How to Create a Hugging Face Token](#how-to-create-a-hugging-face-token)
-    - [Complete Installation](#complete-installation)
-    - [Individual Components](#individual-components)
-    - [Utility Commands](#utility-commands)
-  - [Option 2: Manual Step-by-Step Setup](#option-2-manual-step-by-step-setup)
-    - [Step 1: Set Up EKS Cluster](#step-1-set-up-eks-cluster)
-    - [Step 2: Install Base Infrastructure Components](#step-2-install-base-infrastructure-components)
-    - [Step 3: Deploy Model Hosting Services](#step-3-deploy-model-hosting-services)
-    - [Step 4: Set Up Observability](#step-4-set-up-observability)
-    - [Step 5: Deploy Model Gateway](#step-5-deploy-model-gateway)
-- [Deploy Agentic Applications](#deploy-agentic-applications)
-  - [Multi-Agent RAG with Strands SDK and OpenSearch](#multi-agent-rag-with-strands-sdk-and-opensearch)
-  - [Key Features](#-key-features)
-  - [Usage](#️-usage)
-    - [Option 1: Container Deployment on Kubernetes (Recommended)](#option-1-container-deployment-on-kubernetesrecommended)
-    - [Option 2: Local Development](#option-2-local-development)
-  - [Observability & Tracing](#-observability--tracing)
-  - [Agent Workflows](#-agent-workflows)
-  - [Extending the System](#-extending-the-system)
-  - [Monitoring and Observability](#-monitoring-and-observability)
-  - [Example Use Cases](#-example-use-cases)
-  - [Architecture Benefits](#-architecture-benefits)
-  - [Key Improvements](#-key-improvements)
-
-## Overview
-This solution implements a comprehensive, scalable ML inference architecture using Amazon EKS, leveraging both Graviton processors for cost-effective CPU-based inference and GPU instances for accelerated inference. The system provides a complete end-to-end platform for deploying large language models with agentic AI capabilities, including RAG (Retrieval Augmented Generation) and intelligent document processing.
-
-## ⚠️ Important Setup Instructions
-
-**Before proceeding with this solution, ensure you have:**
-
-1. **AWS CLI configured** with appropriate permissions for EKS, ECR, CloudFormation, and other AWS services
-2. **kubectl installed** and configured to access your target AWS region
-3. **Docker installed** and running (required for building and pushing container images)
-4. **Sufficient AWS service quotas** - This solution requires multiple EC2 instances, EKS clusters, and other AWS resources
-5. **Valid Hugging Face token** - Required for accessing models (see instructions below)
-6. **Tavily API key** - Required for web search functionality in agentic applications
-
-**Recommended Setup Verification:**
-```bash
-# Verify AWS CLI access
-aws sts get-caller-identity
-
-# Verify kubectl installation
-kubectl version --client
-
-# Verify Docker is running
-docker ps
-
-# Check available AWS regions and quotas
-aws ec2 describe-regions
-aws service-quotas get-service-quota --service-code ec2 --quota-code L-1216C47A
-```
-
-**Cost Awareness:** This solution will incur AWS charges. Review the cost breakdown section below and set up billing alerts before deployment.
-
-## Architecture
-![Architecture Diagram](image/arch.png)
-
-The architecture diagram illustrates our scalable ML inference solution with the following components:
-
-1. **Amazon EKS Cluster**: The foundation of our architecture, providing a managed Kubernetes environment with automated provisioning and configuration.
-   
-2. **Karpenter Auto-scaling**: Dynamically provisions and scales compute resources based on workload demands across multiple node pools.
-   
-3. **Node Pools**:
-   - **Graviton-based nodes (ARM64)**: Cost-effective CPU inference using m8g/c8g instances
-   - **GPU-based nodes (x86_64)**: High-performance inference using NVIDIA GPU instances (g5, g6 families)
-   - **x86-based nodes**: General purpose compute for compatibility requirements
-   
-4. **Model Hosting Services**:
-   - **Ray Serve**: Distributed model serving with automatic scaling
-   - **Standalone Services**: Direct model deployment for specific use cases
-   - **Multi-modal Support**: Text, vision, and reasoning model capabilities
-   
-5. **Model Gateway**: 
-   - **LiteLLM Proxy**: Unified OpenAI-compatible API gateway with load balancing and routing
-   - **Ingress Controller**: External access management with SSL termination
-   
-6. **Agentic AI Applications**:
-   - **RAG with OpenSearch**: Intelligent document retrieval and question answering
-   - **Intelligent Document Processing (IDP)**: Automated document analysis and extraction
-   - **Multi-Agent Systems**: Coordinated AI workflows with specialized agents
-   
-7. **Observability & Monitoring**: 
-   - **Langfuse**: LLM observability and performance tracking
-   - **Prometheus & Grafana**: Infrastructure monitoring and alerting
-
-This architecture provides flexibility to choose between cost-optimized CPU inference on Graviton processors or high-throughput GPU inference based on your specific requirements, all while maintaining elastic scalability through Kubernetes and Karpenter.
-
-## Architecture Steps
-
-1. **Foundation Setup**: The foundation begins with an Amazon EKS cluster, configured for application readiness and with compute plane managed by Karpenter. This setup efficiently provisions both AWS Graviton and GPU based instances across multiple Availability Zones (AZs), ensuring robust infrastructure distribution and high availability of various Kubernetes services.
-
-2. **User Request Entry**: User interaction starts through HTTP requests directed to an exposed endpoint, managed by Elastic Load Balancing (ELB). This entry point serves as the gateway for all user queries and ensures balanced distribution of incoming traffic while maintaining consistent accessibility.
-
-3. **Orchestration and Analysis**: The orchestrator agent, powered by Strands Agent SDK, serves as the central coordination hub. It processes incoming queries by connecting with reasoning models supported by LiteLLM and vLLM services, analyzing the requests, and determining the appropriate workflow and tools needed for response generation. LiteLLM functions as a unified API gateway for model management, providing centralized security controls and standardized access to both embedding and reasoning models.
-
-4. **Knowledge Validation**: Knowledge validation begins as the orchestrator agent delegates to the RAG agent to verify knowledge base currency. When updates are needed, the RAG agent initiates the process of embedding new information into the Amazon Opensearch cluster, ensuring the knowledge base remains current and comprehensive.
-
-5. **Embedding Process**: The embedding process is handled within a KubeRay cluster, where the Ray header dynamically manages worker node scaling based on resource demands. These worker nodes execute the embedding process through the llamacpp framework, while the RAG agent simultaneously embeds user questions and searches for relevant information within the OpenSearch cluster.
-
-6. **Quality Assurance**: Quality assurance is performed by the Evaluation Agent, which leverages models hosted in Amazon Bedrock. This agent implements a feedback-based correction loop using RAGAS metrics to assess response quality and provides relevancy scores to the orchestrator agent for decision-making purposes.
-
-7. **Web Search Fallback**: When the RAG agent's responses receive low relevancy scores, the orchestrator agent initiates a web search process. It retrieves the Tavily web search API tool from the web search MCP server and performs dynamic queries to obtain supplementary or corrective information.
-
-8. **Final Response Generation**: The final response generation occurs on GPU instances running vLLM. The reasoning model processes the aggregated information, including both knowledge base data and web search results when applicable, refining and rephrasing the content to create a coherent and accurate response for the user.
-
-9. **Comprehensive Tracking**: Throughout this entire process, the Strands Agent SDK maintains comprehensive interaction tracking. All agent activities and communications are automatically traced, with the resulting data visualized through the Langfuse service, providing complete transparency and monitoring of the system's operations.
-
-
-## Plan your deployment
-
-### Cost
-
-You are responsible for the cost of the AWS services used while running this guidance. 
-As of August 2025, the cost for running this guidance with the default settings in the US East (N. Virginia) Region is approximately **$447.47/month**.
-
-We recommend creating a [budget](https://alpha-docs-aws.amazon.com/awsaccountbilling/latest/aboutv2/budgets-create.html) through [AWS Cost Explorer](http://aws.amazon.com/aws-cost-management/aws-cost-explorer/) to help manage costs. Prices are subject to change. For full details, refer to the pricing webpage for each AWS service used in this guidance.
-
-### Sample cost table
-
-The following table provides a sample cost breakdown for deploying this guidance with the default parameters in the `us-east-1` (N. Virginia) Region for one month. This estimate is based on the AWS Pricing Calculator output for the full deployment as per the guidance.
-
-| **AWS service** | Dimensions | Cost, month [USD] |
-|-----------------|------------|-------------------|
-| Amazon EKS | 1 cluster | $73.00 |
-| Amazon VPC | 3 NAT Gateways | $98.67 |
-| Amazon EC2 | 2 m6g.large instances | $112.42 |
-| Amazon Managed Service for Prometheus (AMP) | Metric samples, storage, and queries | $100.60 |
-| Amazon Managed Grafana (AMG) | Metrics visualization - Editor and Viewer users | $14.00 |
-| Amazon EBS | gp2 storage volumes and snapshots | $17.97 |
-| Application Load Balancer | 1 ALB for workloads | $16.66 |
-| Amazon VPC | Public IP addresses | $3.65 |
-| AWS Key Management Service (KMS) | Keys and requests | $7.00 |
-| Amazon CloudWatch | Metrics | $3.00 |
-| Amazon ECR | Data storage | $0.50 |
-| **TOTAL** |  | **$447.47/month** |
-
-For a more accurate estimate based on your specific configuration and usage patterns, we recommend using the [AWS Pricing Calculator](https://calculator.aws).
-
-## Quick Start Guide
-
-The whole solution is including two parts, Agentic AI platform and Agentic AI application, let us go through the Agentic AI platform firstly 
-
-We provide two approaches to set up the Agentic AI platform:
-
-### Option 1: Automated Setup with Makefile (Recommended)
-
-For the fastest and most reliable setup, use our automated Makefile:
-
-#### Prerequisites
-- EKS cluster set up following the [AWS Solutions Guidance: Automated Provisioning of Application-Ready Amazon EKS Clusters](https://aws.amazon.com/solutions/guidance/automated-provisioning-of-application-ready-amazon-eks-clusters/)
-- `kubectl` configured to access your cluster
-- Required CLI tools installed (`pnpm`, `pip`, etc.)
-- a Hugging Face Token
-
-#### How to create a Hugging Face Token
-
-To access Hugging Face models, you'll need to create an access token:
-
-1. **Sign up or log in** to [Hugging Face](https://huggingface.co/)
-2. **Navigate to Settings**: Click on your profile picture in the top right corner and select "Settings"
-3. **Access Tokens**: In the left sidebar, click on "Access Tokens"
-4. **Create New Token**: Click "New token" button
-5. **Configure Token**:
-   - **Name**: Give your token a descriptive name (e.g., "EKS-ML-Inference")
-   - **Type**: Select "Read" for most use cases (allows downloading models)
-   - **Repositories**: Leave empty to access all public repositories, or specify particular ones
-6. **Generate Token**: Click "Generate a token"
-7. **Copy and Store**: Copy the generated token immediately and store it securely
-
-**Important Notes**:
-- Keep your token secure and never share it publicly
-- You can revoke tokens at any time from the same settings page
-- For production environments, consider using organization tokens with appropriate permissions
-- Some models may require additional permissions or agreements before access
-
-
-#### Complete Installation
-```bash
-# Install all core components (base infrastructure, models, gateway, observability)
-make install
-
-# Install agent app
-make setup-rag-strands
-```
-
-#### Individual Components
-```bash
-# Install specific components as needed
-make setup-base           # Base infrastructure
-make setup-models         # Model hosting services
-make setup-observability  # Langfuse monitoring
-make setup-gateway        # LiteLLM proxy gateway
-```
-
-#### Utility Commands
-```bash
-make help                 # Show all available targets
-make status               # Check deployment status
-make verify-cluster       # Verify EKS cluster access
-make clean                # Remove all deployments
-```
-
-### Option 2: Manual Step-by-Step Setup
-
-If you prefer manual control or need to customize the installation:
-
-#### Step 1: Set Up EKS Cluster
-
-Set up your EKS cluster using the AWS Solutions Guidance for automated provisioning:
-
-**Follow the [AWS Solutions Guidance: Automated Provisioning of Application-Ready Amazon EKS Clusters](https://aws.amazon.com/solutions/guidance/automated-provisioning-of-application-ready-amazon-eks-clusters/)**
-
-This guidance provides:
-- Automated EKS cluster provisioning with best practices
-- Pre-configured add-ons and operators
-- Security and networking configurations
-- Monitoring and observability setup
-
-After completing the guidance, ensure your `kubectl` is configured to access the cluster:
-
-```bash
-# Verify cluster access
-kubectl cluster-info
-kubectl get nodes
-```
-
-#### Step 2: Install Base Infrastructure Components
-
-Navigate to the base setup directory and run the installation script:
-
-```bash
-cd base_eks_setup
-chmod +x install_operators.sh
-./install_operators.sh
-```
-
-This script installs:
-- KubeRay Operator for distributed model serving
-- NVIDIA GPU Operator for GPU workloads
-- GP3 storage class for optimized storage
-- All Karpenter node pools for different workload types
-
-#### Step 3: Deploy Model Hosting Services
-
-Set up the model hosting infrastructure:
-
-```bash
-cd model-hosting
-chmod +x setup.sh
-./setup.sh
-```
-
-This deploys:
-- Ray service with LlamaCPP and embedding capabilities
-- Standalone vLLM reasoning service
-- Standalone vLLM vision service
-- All necessary Kubernetes resources and configurations
-
-#### Step 4: Set Up Observability
-
-Deploy monitoring and observability tools:
-
-```bash
-cd model-observability
-chmod +x setup.sh
-./setup.sh
-```
-
-This installs:
-- Langfuse for LLM observability
-- Web ingress for external access
-- Service monitoring and logging
-
-**Important**: After deployment, configure Langfuse:
-1. Access Langfuse web interface
-2. Create an organization named "test"
-3. Create a project inside it named "demo"
-4. Go to "Tracing" menu and set up tracing
-5. Record the Public Key (PK) and Secret Key (SK) - you'll need these for the agentic applications
-
-
-#### Step 5: Deploy Model Gateway
-
-Set up the unified API gateway:
-
-```bash
-cd model-gateway
-chmod +x setup.sh
-./setup.sh
-```
-
-This deploys:
-- LiteLLM proxy deployment
-- Load balancer and ingress configuration
-- Waits for services to be ready before proceeding
-
-**Important**: After deployment, configure LiteLLM:
-1. Access the LiteLLM web interface
-2. Login with username "admin" and password "sk-123456"
-3. Go to "Virtual Keys" on the sidebar and create a new key
-4. Mark "All Team Models" for the models field
-5. Store the generated secret key - you'll need it for the agentic applications
-
-Right now, let us go through the deployment of an Agentic RAG application based on the Agentic AI platform
-
-### Deploy Agentic Applications
-
-#### Multi-Agent RAG with Strands SDK and OpenSearch
-
-This project implements a sophisticated multi-agent Large Language Model (LLM) system using the **Strands SDK** that combines Model Context Protocol (MCP) for tool usage and Retrieval Augmented Generation (RAG) for enhanced context awareness, using OpenSearch as the vector database.
-
-The system is built with a modular multi-agent architecture using Strands SDK patterns with built-in OpenTelemetry tracing:
-
-```
-SupervisorAgent (Orchestrator) [with built-in tracing]
-├── KnowledgeAgent → Manages knowledge base and embeddings [traced]
-├── MCPAgent → Manages tool interactions via MCP protocol [traced]
-└── Strands SDK → Provides agent framework, tool integration, and OpenTelemetry tracing
-```
-
-#### 🚀 Key Features
-
-##### Multi-Agent Orchestration
-- **SupervisorAgent**: Main orchestrator with integrated RAG capabilities using Strands SDK
-- **KnowledgeAgent**: Monitors and manages knowledge base changes
-- **MCPAgent**: Executes tasks using MCP tools and file operations
-- **Built-in Tracing**: All agents include OpenTelemetry tracing via Strands SDK
-
-##### Advanced RAG Capabilities
-- **OpenSearch Integration**: Vector storage and similarity search
-- **Embedding Generation**: Configurable embedding models and endpoints
-- **Multi-format Support**: Handles markdown, text, JSON, and CSV files
-- **Intelligent Search**: Vector similarity search with metadata and scoring
-- **Relevance Scoring**: Automatic relevance assessment for search results
-
-##### External Web Search Integration 🌐
-- **Tavily API Integration**: Real-time web search via MCP server
-- **Automatic Triggering**: Web search activated when RAG relevance < 0.3
-- **News Search**: Dedicated recent news and current events search
-- **Hybrid Responses**: Combines knowledge base and web search results
-- **Smart Fallback**: Graceful degradation when web search unavailable
-
-##### MCP Tool Integration
-- **Filesystem Operations**: Read, write, and manage files using Strands tools
-- **Web Search Tools**: Tavily-powered web and news search capabilities
-- **Extensible Architecture**: Easy to add new MCP servers
-- **Error Handling**: Robust tool execution with fallbacks
-- **Built-in Tools**: Integration with Strands built-in tools
-
-##### Observability & Tracing
-- **OpenTelemetry Integration**: Native tracing through Strands SDK
-- **Multiple Export Options**: Console, OTLP endpoints, Jaeger, Langfuse
-- **Automatic Instrumentation**: All agent interactions are automatically traced
-- **Performance Monitoring**: Track execution times, token usage, and tool calls
-
-#### 🏃‍♂️ Usage
-
-##### Option 1: Container Deployment on Kubernetes(Recommended)
-
-For production deployments, use the containerized solution with Kubernetes:
-
-###### Prerequisites
-
-- Python 3.9+
-- EKS cluster
-- TAVILY_API_KEY(https://docs.tavily.com/documentation/quickstart#get-your-free-tavily-api-key)
-- AWS credentials configured
-- Docker daemon in running status
-
-###### Installation
-
-**1. Build and Push Container Images**
-
-```bash
-# Navigate to the strandsdk agentic app directory
-cd agentic-apps/strandsdk_agentic_rag_opensearch
-
-# Build Docker images and push to ECR
-./build-images.sh
-
-# This script will:
-# - Create ECR repositories if they don't exist
-# - Build main application and MCP server images
-# - Push images to ECR
-# - Update Kubernetes deployment files with ECR image URLs
-```
-
-**2. Deploy OpenSearch Cluster**
-
-```bash
-# Deploy OpenSearch with CloudFormation and EKS Pod Identity
-./deploy-opensearch.sh [stack-name] [region] [namespace]
-
-# Example:
-./deploy-opensearch.sh strandsdk-rag-opensearch-stack us-east-1 default
-
-# This script will:
-# - Deploy OpenSearch cluster via CloudFormation
-# - Set up EKS Pod Identity for secure access
-# - Create the vector index automatically
-# - Configure IAM roles and policies
-```
-
-**3. Configure Kubernetes Secrets and ConfigMap**
-
-Update the ConfigMap with your actual service endpoints and configuration:
-
-```bash
-# Apply the ConfigMap and Secrets
-kubectl apply -f k8s/configmap.yaml
-# Edit the ConfigMap with your actual values
-kubectl edit configmap app-config
-
-# Key values to update:
-# - LITELLM_BASE_URL: Your LiteLLM service endpoint
-# - EMBEDDING_BASE_URL: Your embedding service endpoint  
-# - OPENSEARCH_ENDPOINT: From OpenSearch deployment output
-# - LANGFUSE_HOST: Your Langfuse instance (optional)
-```
-
-Update secrets with your API keys:
-
-```bash
-# Update secrets with base64 encoded values
-kubectl edit secret app-secrets
-
-# To encode your keys:
-echo -n "your-api-key" | base64
-
-# Keys to update:
-# - litellm-api-key: Your LiteLLM API key
-# - embedding-api-key: Your embedding service API key
-# - tavily-api-key: Your Tavily API key for web search
-# - langfuse-public-key: Langfuse public key (optional)
-# - langfuse-secret-key: Langfuse secret key (optional)
-```
-
-**4. Deploy Kubernetes Applications**
-
-```bash
-# Apply the service account (if not already created)
-kubectl apply -f k8s/service-account.yaml
-
-# Deploy the MCP server first
-kubectl apply -f k8s/tavily-mcp-deployment.yaml
-
-# Deploy the main application
-kubectl apply -f k8s/main-app-deployment.yaml
-
-# Check deployment status
-kubectl get pods -l app=tavily-mcp-server
-kubectl get pods -l app=strandsdk-rag-app
-
-# Check services and ingress
-kubectl get svc
-kubectl get ingress
-```
-
-**5. Test the Deployed System**
-
-```bash
-# Get the Application Load Balancer endpoint
-ALB_ENDPOINT=$(kubectl get ingress strandsdk-rag-ingress-alb -o jsonpath='{.status.loadBalancer.ingress[0].hostname}')
-
-# Test the health endpoint
-curl -X GET "http://${ALB_ENDPOINT}/health"
-
-# Test knowledge embedding
-curl -X POST "http://${ALB_ENDPOINT}/embed" \
-  -H "Content-Type: application/json" \
-  -d '{"force_refresh": false}'
-
-# Force refresh all embeddings
-curl -X POST "http://${ALB_ENDPOINT}/embed" \
-  -H "Content-Type: application/json" \
-  -d '{"force_refresh": true}'
-
-# Test with a more complex medical query
-curl -X POST "http://${ALB_ENDPOINT}/query" \
-  -H "Content-Type: application/json" \
-  -d '{
-    "question": "Find information about \"What was the purpose of the study on encainide and flecainide in patients with supraventricular arrhythmias\". Summarize this information and create a comprehensive story.Save the story and important information to a file named \"test1.md\" in the output directory as a beautiful markdown file.",
-    "top_k": 3
-  }' \
-  --max-time 600
-```
-
-##### Option 2: Local Development
-
-###### Prerequisites
-
-- Python 3.9+
-- EKS cluster
-- TAVILY_API_KEY
-- Public facing Opensearch cluster
-- AWS credentials configured
-
-###### Installation
-
-```bash
-# Navigate to the strandsdk agentic app directory
-cd agentic-apps/strandsdk_agentic_rag_opensearch
-
-# Create virtual environment
-python3 -m venv venv
-source venv/bin/activate  # On Windows: venv\Scripts\activate
-
-# Install dependencies
-pip install -r requirements.txt
-
-# Set up environment variables
-cp .env.example .env
-# Edit .env with your configuration
-```
-
-###### Configuration
-
-Create a `.env` file with the following variables:
-
-```env
-# OpenAI Configuration
-OPENAI_API_KEY=your-openai-api-key
-OPENAI_BASE_URL=https://api.openai.com/v1
-DEFAULT_MODEL=us.anthropic.claude-3-7-sonnet-20250219-v1:0
-
-# AWS Configuration  
-AWS_REGION=us-east-1
-OPENSEARCH_ENDPOINT=https://your-opensearch-domain.region.es.amazonaws.com
-
-# Tavily Web Search Configuration
-TAVILY_API_KEY=your-tavily-api-key
-
-# Tracing Configuration (Optional)
-OTEL_EXPORTER_OTLP_ENDPOINT=http://localhost:4318
-OTEL_EXPORTER_OTLP_HEADERS=key1=value1,key2=value2
-STRANDS_OTEL_ENABLE_CONSOLE_EXPORT=true
-
-# Optional: Langfuse for observability
-LANGFUSE_HOST=https://cloud.langfuse.com
-LANGFUSE_PUBLIC_KEY=your-public-key
-LANGFUSE_SECRET_KEY=your-secret-key
-
-# Application Settings
-KNOWLEDGE_DIR=knowledge
-OUTPUT_DIR=output
-VECTOR_INDEX_NAME=knowledge-embeddings
-TOP_K_RESULTS=5
-```
-
-###### Deploy
-
-**1. Start Tavily MCP Server (for Web Search)**
-
-```bash
-# Start the Tavily web search server
-python scripts/start_tavily_server.py
-
-# Or run directly
-python src/mcp_servers/tavily_search_server.py
-```
-
-**2. Embed Knowledge Documents**
-
-```bash
-# Process and embed all knowledge documents
-python -c "from src.agents.knowledge_agent import knowledge_agent; print(knowledge_agent('Please embed all knowledge files'))"
-```
-
-**3. Run the Multi-Agent System**
-
-```bash
-# Standard mode (with built-in tracing)
-source venv/bin/activate
-python -m src.main
-
-# Clean mode (async warnings suppressed)
-python run_main_clean.py
-
-# Single query - standard mode
-python -c "from src.main import run_single_query; print(run_single_query('What is Bell\'s palsy?'))"
-
-# Single query - clean mode
-python run_single_query_clean.py "What is Bell's palsy?"
-
-# Single query - ultra clean mode (completely suppressed stderr)
-python run_completely_clean.py "What is Bell's palsy?"
-```
-
-**4. Test the System**
-
-```bash
-# Run comprehensive tests including web search integration
-python -m src.test_agents
-
-# Test the enhanced RAG system with chunk relevance evaluation
-python test_enhanced_rag.py
-
-# Test web search integration specifically
-python src/test_web_search_integration.py
-
-# Run tests with clean output (async warnings filtered)
-python run_clean_test.py
-```
-
-**Note**: The enhanced system uses RAGAs for chunk relevance evaluation, which may generate harmless async cleanup warnings. Use `run_clean_test.py` for a cleaner testing experience.
-
-
-##### Container Features
-
-- **Auto-scaling**: Kubernetes HPA for dynamic scaling
-- **Health Checks**: Built-in health endpoints for monitoring
-- **Service Discovery**: Internal service communication via Kubernetes DNS
-- **Security**: EKS Pod Identity for secure AWS service access
-- **Observability**: OpenTelemetry tracing with multiple export options
-- **Load Balancing**: ALB for external traffic distribution
-- **Configuration Management**: ConfigMaps and Secrets for environment-specific settings
-
-#### 🔍 Observability & Tracing
-
-The system includes comprehensive observability through Strands SDK's built-in OpenTelemetry integration:
-
-##### Automatic Tracing
-- **All agents** are automatically traced using Strands SDK
-- **Tool calls**, **LLM interactions**, and **workflows** are captured
-- **Performance metrics** including token usage and execution times
-
-##### Trace Export Options
-- **Console Output**: Set `STRANDS_OTEL_ENABLE_CONSOLE_EXPORT=true` for development
-- **OTLP Endpoint**: Configure `OTEL_EXPORTER_OTLP_ENDPOINT` for production
-- **Langfuse**: Use Langfuse credentials for advanced observability
-- **Jaeger/Zipkin**: Compatible with standard OpenTelemetry collectors
-
-##### Local Development Setup
-```bash
-# Pull and run Jaeger all-in-one container
-docker run -d --name jaeger \
-  -e COLLECTOR_OTLP_ENABLED=true \
-  -p 16686:16686 \
-  -p 4317:4317 \
-  -p 4318:4318 \
-  jaegertracing/all-in-one:latest
-
-# Access Jaeger UI at http://localhost:16686
-```
-
-#### 🧠 Agent Workflows
-
-##### Knowledge Management Workflow
-1. **File Monitoring**: Scans knowledge directory for changes
-2. **Change Detection**: Uses file hashes and timestamps
-3. **Document Processing**: Handles multiple file formats
-4. **Embedding Generation**: Creates vector embeddings
-5. **Vector Storage**: Stores in OpenSearch with metadata
-
-##### RAG Retrieval Workflow  
-1. **Query Processing**: Analyzes user queries
-2. **Embedding Generation**: Converts queries to vectors
-3. **Similarity Search**: Finds relevant documents in OpenSearch
-4. **Context Formatting**: Structures results for LLM consumption
-5. **Relevance Ranking**: Orders results by similarity scores
-
-##### MCP Tool Execution Workflow
-1. **Tool Discovery**: Connects to available MCP servers
-2. **Context Integration**: Combines RAG context with user queries
-3. **Tool Selection**: Chooses appropriate tools for tasks
-4. **Execution Management**: Handles tool calls and responses
-5. **Result Processing**: Formats and returns final outputs
-
-#### 🔧 Extending the System
-
-##### Adding New Agents
-
-```python
-from strands import Agent, tool
-from src.utils.strands_langfuse_integration import create_traced_agent
-
-# Define tools for the agent
-@tool
-def my_custom_tool(param: str) -> str:
-    """Custom tool implementation."""
-    return f"Processed: {param}"
-
-# Create the agent with built-in tracing
-my_agent = create_traced_agent(
-    Agent,
-    model="us.anthropic.claude-3-7-sonnet-20250219-v1:0",
-    tools=[my_custom_tool],
-    system_prompt="Your specialized prompt here",
-    session_id="my-agent-session",
-    user_id="system"
-)
-```
-
-##### Adding New MCP Servers
-
-```python
-from fastmcp import FastMCP
-
-mcp = FastMCP("My Custom Server")
-
-@mcp.tool(description="Custom tool description")
-def my_custom_tool(param: str) -> str:
-    """Custom tool implementation."""
-    return f"Processed: {param}"
-
-if __name__ == "__main__":
-    mcp.run(transport="streamable-http", port=8002)
-```
-
-#### 📊 Monitoring and Observability
-
-The system includes comprehensive observability features:
-
-- **OpenTelemetry Integration**: Native tracing through Strands SDK
-- **Multiple Export Options**: Console, OTLP endpoints, Jaeger, Langfuse
-- **Workflow Summaries**: Detailed execution reports
-- **Performance Metrics**: Duration and success tracking
-- **Error Handling**: Comprehensive error reporting and recovery
-
-#### 🧪 Example Use Cases
-
-##### Medical Knowledge Query
-```python
-query = "What are the symptoms and treatment options for Bell's palsy?"
-result = supervisor_agent(query)
-print(result['response'])
-```
-
-##### Document Analysis and Report Generation
-```python
-query = "Analyze the medical documents and create a summary report saved to a file"
-result = supervisor_agent(query)
-# System will retrieve relevant docs, analyze them, and save results using MCP tools
-```
-
-#### 🔍 Architecture Benefits
-
-1. **Modularity**: Each agent has specific responsibilities
-2. **Scalability**: Agents can be scaled independently  
-3. **Reliability**: Isolated failures don't affect the entire system
-4. **Extensibility**: Easy to add new capabilities
-5. **Observability**: Comprehensive monitoring and tracing via Strands SDK
-6. **Standards Compliance**: Uses MCP for tool integration and OpenTelemetry for tracing
-
-#### 🔧 Key Improvements
-
-##### Unified Architecture
-- **Single Codebase**: No separate "enhanced" versions - all functionality is built into the standard agents
-- **Built-in Tracing**: OpenTelemetry tracing is automatically enabled through Strands SDK
-- **Simplified Deployment**: One main application with all features included
-- **Consistent API**: All agents use the same tracing and configuration patterns
-
-##### Enhanced Developer Experience
-- **Automatic Instrumentation**: No manual trace management required
-- **Multiple Export Options**: Console, OTLP, Jaeger, Langfuse support out of the box
-- **Environment-based Configuration**: Easy setup through environment variables
-- **Clean Code Structure**: Removed duplicate wrapper functions and complex manual tracing
-- **Async Warning Management**: Clean test runner filters harmless async cleanup warnings
-- **Robust Error Handling**: Fallback mechanisms ensure system reliability
+Healthcare professionals face increasing challenges in managing complex patient data and making timely, accurate decisions. This lab demonstrates how to build a clinical assistant using AWS technologies that can assist providers by integrating multiple data sources and AI capabilities.
+As a healthcare provider, we want an AI agent that analyzes a patient’s current symptoms, medical history, and existing documentation to recommend an accurate and personalized course of action. The agent shall help with the following:
 
+- Ingest and understand the patient’s current symptoms and complaints.
+- Retrieve relevant historical medical records and documentation through MCP servers.
+- Utilize AWS Strands SDK to orchestrate the AI agent’s reasoning, planning, and tool invocation, enabling dynamic and flexible decision-making workflows.
+- Run Agents, LiteLLM and MCP servers on EC2 instances powered by Amazon EKS, optimizing cost and performance.
diff --git a/agentic-apps/agentic-idp/.env.example b/agentic-apps/agentic-idp/.env.example
deleted file mode 100644
index b58dd69e..00000000
--- a/agentic-apps/agentic-idp/.env.example
+++ /dev/null
@@ -1,20 +0,0 @@
-# Model Configuration
-# API key for accessing the LLM vision model through the gateway
-LLAMA_VISION_MODEL_KEY=your-api-key-here
-
-# URL of the LiteLLM API gateway deployed in your EKS cluster
-# This should be the load balancer URL from your model-gateway deployment
-API_GATEWAY_URL=http://your-litellm-gateway-url
-
-# Langfuse Configuration for LLM Observability
-# URL of the Langfuse service deployed in your EKS cluster
-# This should be the load balancer URL from your model-observability deployment
-LANGFUSE_HOST=http://your-langfuse-host-url
-
-# Langfuse public key for authentication
-# Get this from your Langfuse dashboard after creating a project
-LANGFUSE_PUBLIC_KEY=pk-lf-your-public-key
-
-# Langfuse secret key for authentication
-# Get this from your Langfuse dashboard after creating a project
-LANGFUSE_SECRET_KEY=sk-lf-your-secret-key
diff --git a/agentic-apps/agentic-idp/__pycache__/decision.cpython-313.pyc b/agentic-apps/agentic-idp/__pycache__/decision.cpython-313.pyc
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diff --git a/agentic-apps/agentic-idp/agentic_idp.py b/agentic-apps/agentic-idp/agentic_idp.py
deleted file mode 100644
index d59df1da..00000000
--- a/agentic-apps/agentic-idp/agentic_idp.py
+++ /dev/null
@@ -1,412 +0,0 @@
-from langchain_openai import ChatOpenAI
-from langchain_core.prompts import ChatPromptTemplate, MessagesPlaceholder
-from langchain_core.messages import AIMessage, HumanMessage
-from langgraph.graph import StateGraph, START, END
-from langgraph.graph.message import add_messages
-from langgraph.checkpoint.memory import MemorySaver
-from langchain_core.messages import SystemMessage, HumanMessage
-
-from typing import Annotated, List
-from langchain.prompts.chat import HumanMessagePromptTemplate
-
-
-from typing_extensions import TypedDict
-
-import requests 
-import json
-import base64
-
-import logging
-
-from langfuse import Langfuse
-from datetime import datetime, timedelta
-import os
-import math
-import openai
-
-from PyPDF2 import PdfReader
-
-from pathlib import Path
-
-from langgraph.pregel import RetryPolicy
-
-from doc_reader import encode_image
-
-from exteral_service import external_service_node 
-from storage import external_storage_node
-from decision import external_automation_node, external_human_node, State
-
-# Load environment variables from .env file
-from dotenv import load_dotenv
-load_dotenv()
-
-
-
-local_public_key = os.getenv("LANGFUSE_PUBLIC_KEY")
-local_secret_key = os.getenv("LANGFUSE_SECRET_KEY")
-langfuse_host = os.getenv("LANGFUSE_HOST")
-if local_public_key is None or local_secret_key is None or langfuse_host is None:
-    raise ValueError("Please set the LANGFUSE_PUBLIC_KEY, LANGFUSE_SECRET_KEY, and LANGFUSE_HOST environment variables.")
-
-langfuse = Langfuse(
-    secret_key=local_secret_key,
-    public_key=local_public_key,
-    host=langfuse_host
-)
-
-
-generation_model_key_var = os.getenv("LLAMA_VISION_MODEL_KEY")
-api_gateway_url = os.getenv("API_GATEWAY_URL")
-if generation_model_key_var is None or api_gateway_url is None:
-    raise ValueError("Please set the LLAMA_VISION_MODEL_KEY and API_GATEWAY_URL environment variables.")
-generation_model_url = api_gateway_url
-generation_model_key = generation_model_key_var
-
-reflection_model_key_var = os.getenv("LLAMA_VISION_MODEL_KEY")
-if reflection_model_key_var is None:
-    raise ValueError("Please set the LLAMA_VISION_MODEL_KEY environment variable.")
-reflection_model_url = api_gateway_url
-reflection_model_key = reflection_model_key_var
-
-desired_iterations = 2
-
-reflection_model = "Qwen/QwQ-32B-AWQ"
-generation_model = "vllm-server-qwen-vision"
-
-
-
-
-
-    
-
-# Prompt for ocr Generation
-generation_llm = ChatOpenAI(model=generation_model, temperature=0.7, max_tokens=1500, api_key=generation_model_key, base_url=generation_model_url)
-
-client = openai.OpenAI(
-    api_key=generation_model_key,             # pass litellm proxy key, if you're using virtual keys
-    base_url=api_gateway_url # litellm-proxy-base url
-)
-
-
-
-# Path to your image
-image_path = "birth_cert.png"
-base64_image = encode_image(image_path)
-
-
-
-generation_prompt = ChatPromptTemplate.from_messages([
-    SystemMessage(content="You are an expert birth certificate document processor. Extract and structure information from birth certificates, focusing on key verification fields including name, date of birth, and place of birth. Ensure accurate extraction of hospital or medical facility names for subsequent verification."),
-    MessagesPlaceholder(variable_name="messages"),
-    ])
-
-
-# Bind the prompt to the LLM
-generate_report = generation_prompt | generation_llm
-
-async def generation_node(state: State) -> State:
-
-    # combined_content = f"{state['messages'][0].content}\n Birth Certificate Image Content:\n {base64_image}"
-    # state["messages"][0].content = combined_content    
-    response = client.chat.completions.create(
-        model="vllm-server-qwen-vision",
-        messages=[
-            {
-                "role": "user",
-                "content": [
-                    {
-                        "type": "text",
-                        "text": "This is my birth certificate. Extract all the fields from this image and provide the information in a structured json only format, no other text or wrapper around json. The json will be read by machine. The fields include name, date of birth, place of birth. Make sure the output only contains JSON and nothing else. Be strict about it."
-                    },
-                    {
-                        "type": "image_url",
-                        "image_url": {
-                            "url": f"data:image/png;base64,{base64_image}"
-                        }
-                    }
-                ]
-            }
-        ]
-    )    
-    
-    # Extract the JSON from the vision model response
-    vision_json = response.choices[0].message.content.strip()
-    
-    # Create a structured response that includes both the original request and the extracted JSON
-    structured_response = f"""Birth Certificate Analysis Request: {state['messages'][0].content}
-
-Extracted Birth Certificate Data (JSON):
-{vision_json}
-
-Analysis: Based on the extracted birth certificate information, I need to verify the authenticity of this document by validating the place of birth details. The extracted data shows the place of birth as specified in the JSON above, which will be verified against official hospital records and databases."""
-    
-    return {"messages": [AIMessage(content=structured_response)]}
-
-
-
-
-
-reflection_llm = ChatOpenAI(model=reflection_model, temperature=0, max_tokens=1000, api_key=reflection_model_key, base_url=reflection_model_url)
-
-# Prompt for Reflection
-reflection_prompt = ChatPromptTemplate.from_messages(
-    [
-        (
-            "system",
-            "You are an expert birth certificate verification assessor. Your task is to evaluate birth certificate legitimacy based on place of birth verification results.\n\n"
-            "ASSESSMENT CRITERIA:\n"
-            "1. PRIMARY FACTOR - Hospital/Place Verification:\n"
-            "   - If place_verified=true and confidence_score >= 0.90: High confidence (0.85-0.95)\n"
-            "   - If place_verified=true and confidence_score 0.80-0.89: Good confidence (0.75-0.84)\n"
-            "   - If place_verified=true and confidence_score 0.70-0.79: Moderate confidence (0.65-0.74)\n"
-            "   - If place_verified=false or confidence_score < 0.70: Low confidence (0.20-0.40)\n\n"
-            "2. SUPPORTING FACTORS (adjust +/- 0.05):\n"
-            "   - Hospital status (Active vs Inactive)\n"
-            "   - Verification sources quality\n"
-            "   - Contact information availability\n\n"
-            "CRITICAL: You must respond with ONLY a valid JSON object in this exact format:\n"
-            '{{\"confidence_score\": 0.XX, \"message\": \"explanation here\"}}\n\n'
-            "Do not include any other text, thinking, or formatting. Just the JSON object."
-        ),
-        MessagesPlaceholder(variable_name="messages"),
-    ]
-)
-
-# Bind the prompt to the LLM
-reflect_on_report = reflection_prompt | reflection_llm
-
-# Reflection Node
-async def reflection_node(state: State) -> State:
-    # Swap message roles for reflection
-    cls_map = {"ai": HumanMessage, "human": AIMessage}
-    print("***********************")
-    print(state["messages"])
-    
-    translated = [state["messages"][0]] + [
-        cls_map[msg.type](content=msg.content) for msg in state["messages"][1:]
-    ]
-    
-    # Try multiple times to get proper JSON response
-    max_attempts = 3
-    for attempt in range(max_attempts):
-        try:
-            # Create proper input for the prompt template
-            prompt_input = {"messages": translated}
-            res = await reflect_on_report.ainvoke(prompt_input)
-            response_content = res.content.strip()
-            
-            print(f"Reflection attempt {attempt + 1}: {response_content[:200]}...")
-            
-            # Check if response contains valid JSON structure
-            import re
-            if '"confidence_score"' in response_content and '"message"' in response_content:
-                # Try to extract and validate JSON
-                json_pattern = r'\{[^{}]*"confidence_score"[^{}]*"message"[^{}]*\}'
-                json_match = re.search(json_pattern, response_content, re.DOTALL)
-                
-                if json_match:
-                    try:
-                        json_str = json_match.group()
-                        json.loads(json_str)  # Validate JSON
-                        print(f"✓ Valid JSON found on attempt {attempt + 1}")
-                        return {"messages": [HumanMessage(content=response_content)]}
-                    except json.JSONDecodeError:
-                        pass
-            
-            # If no valid JSON, try with more explicit prompt
-            if attempt < max_attempts - 1:
-                print(f"⚠ Attempt {attempt + 1} failed, retrying with more explicit prompt...")
-                # Add more explicit instruction for next attempt
-                translated.append(HumanMessage(content="Please respond with ONLY a JSON object in this exact format: {\"confidence_score\": 0.XX, \"message\": \"your explanation\"}. No other text."))
-            
-        except Exception as e:
-            print(f"Error in reflection attempt {attempt + 1}: {e}")
-            if attempt == max_attempts - 1:
-                # Fallback response for final attempt
-                fallback_response = '{"confidence_score": 0.5, "message": "Unable to complete automated assessment due to processing error. Manual review recommended."}'
-                return {"messages": [HumanMessage(content=fallback_response)]}
-    
-    # If all attempts failed, return the last response anyway
-    return {"messages": [HumanMessage(content=response_content)]}
-
-# Build the graph
-builder = StateGraph(State)
-
-# Add all nodes
-builder.add_node("generate", generation_node)
-builder.add_node("store", external_storage_node, retry=RetryPolicy(max_attempts=3))
-builder.add_node("external_process", external_service_node, retry=RetryPolicy(max_attempts=3))
-builder.add_node("reflect", reflection_node)
-builder.add_node("automatic_approval", external_automation_node)
-builder.add_node("human_approval", external_human_node)
-
-
-# Define the edges
-builder.add_edge(START, "generate")
-builder.add_edge("generate", "store")
-builder.add_edge("store", "external_process")
-builder.add_edge("external_process", "reflect")
-# Add edges from approval nodes to END
-builder.add_edge("automatic_approval", END)
-builder.add_edge("human_approval", END)
-
-async def route_after_reflection(state: State) -> str:
-    """
-    Dynamic router to decide between automatic or human approval
-    based on reflection output focusing on hospital verification confidence
-    """
-    last_message = state["messages"][-1].content
-    
-    print("=== REFLECTION ROUTING ANALYSIS ===")
-    print(f"Raw reflection message: {last_message}")
-    print("=" * 50)
-    
-    try:
-        # Clean up the message to extract JSON
-        cleaned_message = last_message.strip()
-        
-        # Handle QwQ model thinking tags - extract content after </think>
-        if "<think>" in cleaned_message and "</think>" in cleaned_message:
-            # Extract content after the last </think>
-            parts = cleaned_message.split("</think>")
-            if len(parts) > 1:
-                cleaned_message = parts[-1].strip()
-        
-        # Remove markdown formatting
-        cleaned_message = cleaned_message.replace("```json", "").replace("```", "").strip()
-        
-        # Try multiple JSON extraction approaches
-        confidence_score = None
-        message_text = ""
-        
-        # Approach 1: Look for complete JSON object
-        import re
-        json_pattern = r'\{[^{}]*"confidence_score"[^{}]*"message"[^{}]*\}'
-        json_match = re.search(json_pattern, cleaned_message, re.DOTALL)
-        
-        if json_match:
-            try:
-                json_str = json_match.group()
-                reflection_result = json.loads(json_str)
-                confidence_score = reflection_result.get("confidence_score")
-                message_text = reflection_result.get("message", "")
-            except json.JSONDecodeError:
-                pass
-        
-        # Approach 2: Extract confidence_score value directly
-        if confidence_score is None:
-            score_pattern = r'"confidence_score":\s*([0-9]*\.?[0-9]+)'
-            score_match = re.search(score_pattern, cleaned_message)
-            if score_match:
-                confidence_score = float(score_match.group(1))
-                
-                # Try to extract message too
-                msg_pattern = r'"message":\s*"([^"]*)"'
-                msg_match = re.search(msg_pattern, cleaned_message)
-                if msg_match:
-                    message_text = msg_match.group(1)
-        
-        # Approach 3: Look for any decimal number that could be confidence score
-        if confidence_score is None:
-            # Look for numbers between 0 and 1 that could be confidence scores
-            number_pattern = r'\b(0\.[0-9]+|1\.0+|0)\b'
-            numbers = re.findall(number_pattern, cleaned_message)
-            if numbers:
-                # Take the first reasonable confidence score
-                for num_str in numbers:
-                    num = float(num_str)
-                    if 0.0 <= num <= 1.0:
-                        confidence_score = num
-                        break
-        
-        if confidence_score is not None:
-            print(f"✓ Successfully extracted confidence score: {confidence_score}")
-            print(f"✓ Message: {message_text}")
-            
-            # Hospital verification focused threshold
-            requires_human_review = confidence_score < 0.75
-            
-            if requires_human_review:
-                print(f"→ ROUTING TO HUMAN REVIEW (confidence {confidence_score} < 0.75)")
-                return "human_approval"
-            else:
-                print(f"→ ROUTING TO AUTOMATIC APPROVAL (confidence {confidence_score} >= 0.75)")
-                return "automatic_approval"
-        else:
-            print("✗ No confidence score found in reflection")
-            print("→ DEFAULTING TO HUMAN REVIEW")
-            return "human_approval"
-            
-    except Exception as e:
-        print(f"✗ Unexpected error in routing: {e}")
-        print("→ DEFAULTING TO HUMAN REVIEW")
-        return "human_approval"
-
-builder.add_conditional_edges(
-    "reflect",
-    route_after_reflection
-)
-
-
-# Compile the graph with memory checkpointing
-memory = MemorySaver()
-graph = builder.compile(checkpointer=memory)
-
-
-# from langgraph.visualize import visualize
-# # Generate the visualization
-# viz_graph = visualize(graph)
-
-
-
-
-
-
-
-# Use environment variables for Langfuse configuration
-os.environ["LANGFUSE_SECRET_KEY"] = local_secret_key
-os.environ["LANGFUSE_HOST"] = langfuse_host
-os.environ["LANGFUSE_PUBLIC_KEY"] = local_public_key
-
-from langfuse.langchain import CallbackHandler
- 
-# Initialize Langfuse CallbackHandler for Langchain (tracing)
-langfuse_handler = CallbackHandler()
-
-config = {"configurable": {"thread_id": "1"}, "callbacks": [langfuse_handler]}
-topic = "Verify the authenticity of this birth certificate by analyzing the document information and validating the place of birth details."
-
-
-async def run_agent():
-    
-    async for event in graph.astream(
-        {
-            "messages": [
-                HumanMessage(content=topic)
-            ],
-        },
-        config,
-    ):
-        if "generate" in event:
-            print("=== BIRTH CERTIFICATE EXTRACTION ===")
-            print(event["generate"]["messages"][-1].content)
-            print("\n")
-        elif "external_process" in event:
-            print("=== HOSPITAL VERIFICATION RESULTS ===")
-            print(event["external_process"]["messages"][-1].content)
-            print("\n")
-        elif "reflect" in event:
-            print("=== FINAL VERIFICATION ASSESSMENT ===")
-            print(event["reflect"]["messages"][-1].content)
-            print("\n")
-        elif "automatic_approval" in event:
-            print("=== ✅ AUTOMATIC APPROVAL ===")
-            print("Birth certificate verification passed automated checks")
-            print("\n")
-        elif "human_approval" in event:
-            print("=== 👤 HUMAN REVIEW REQUIRED ===")
-            print("Birth certificate requires manual verification")
-            print("\n")
-
-import asyncio
-asyncio.run(run_agent())
diff --git a/agentic-apps/agentic-idp/birth_cert.png b/agentic-apps/agentic-idp/birth_cert.png
deleted file mode 100644
index 35d29f38..00000000
Binary files a/agentic-apps/agentic-idp/birth_cert.png and /dev/null differ
diff --git a/agentic-apps/agentic-idp/decision.py b/agentic-apps/agentic-idp/decision.py
deleted file mode 100644
index ec32afa6..00000000
--- a/agentic-apps/agentic-idp/decision.py
+++ /dev/null
@@ -1,60 +0,0 @@
-
-from langchain_openai import ChatOpenAI
-from langchain_core.prompts import ChatPromptTemplate, MessagesPlaceholder
-from langchain_core.messages import AIMessage, HumanMessage
-from langgraph.graph import StateGraph, START, END
-from langgraph.graph.message import add_messages
-from langgraph.checkpoint.memory import MemorySaver
-from langchain_core.messages import SystemMessage, HumanMessage
-
-from typing import Annotated, List
-from langchain.prompts.chat import HumanMessagePromptTemplate
-
-
-from typing_extensions import TypedDict
-
-import requests 
-import json
-import base64
-
-import logging
-
-from langfuse import Langfuse
-from datetime import datetime, timedelta
-import os
-import math
-import openai
-
-from PyPDF2 import PdfReader
-
-from pathlib import Path
-
-from langgraph.pregel import RetryPolicy
-
-
-
-class State(TypedDict):
-    messages: Annotated[list, add_messages]
-    
-# Add new node for external processing
-async def external_automation_node(state: State) -> State:
-    """
-    Node that calls external processing service
-    """
-    # Get the last message content
-    last_message = state["messages"][-1].content
-    
-    # Call external auto approve service
-    
-    return {"messages": [last_message]}
-
-async def external_human_node(state: State) -> State:
-    """
-    Node that calls external processing service
-    """
-    # Get the last message content
-    last_message = state["messages"][-1].content
-    
-    # Call external auto approve service
-    
-    return {"messages": [last_message]}
\ No newline at end of file
diff --git a/agentic-apps/agentic-idp/doc_reader.py b/agentic-apps/agentic-idp/doc_reader.py
deleted file mode 100644
index 1a972055..00000000
--- a/agentic-apps/agentic-idp/doc_reader.py
+++ /dev/null
@@ -1,23 +0,0 @@
-from PyPDF2 import PdfReader
-
-from pathlib import Path
-import logging, base64
-
-
-def encode_image(image_path):
-    """Encode image to base64 string"""
-    with open(image_path, "rb") as image_file:
-        return base64.b64encode(image_file.read()).decode("utf-8")
-    
-# Add this function to handle PDF processing
-def process_pdf(pdf_path: str) -> str:
-    """Process PDF and return its content"""
-    try:
-        reader = PdfReader(pdf_path)
-        text = ""
-        for page in reader.pages:
-            text += page.extract_text()
-        return text
-    except Exception as e:
-        logging.error(f"PDF processing error: {str(e)}")
-        return ""
\ No newline at end of file
diff --git a/agentic-apps/agentic-idp/exteral_service.py b/agentic-apps/agentic-idp/exteral_service.py
deleted file mode 100644
index 1f9dbcee..00000000
--- a/agentic-apps/agentic-idp/exteral_service.py
+++ /dev/null
@@ -1,303 +0,0 @@
-from langchain_openai import ChatOpenAI
-from langchain_core.prompts import ChatPromptTemplate, MessagesPlaceholder
-from langchain_core.messages import AIMessage, HumanMessage
-from langgraph.graph import StateGraph, START, END
-from langgraph.graph.message import add_messages
-from langgraph.checkpoint.memory import MemorySaver
-from langchain_core.messages import SystemMessage, HumanMessage
-
-from typing import Annotated, List
-from langchain.prompts.chat import HumanMessagePromptTemplate
-
-
-from typing_extensions import TypedDict
-
-import requests 
-import json
-import base64
-
-import logging
-
-from langfuse import Langfuse
-from datetime import datetime, timedelta
-import os
-import math
-import openai
-
-from PyPDF2 import PdfReader
-
-from pathlib import Path
-
-from langgraph.pregel import RetryPolicy
-from decision import  State
-
-
-# External function to verify place of birth information
-async def verify_place_of_birth(place_name: str) -> dict:
-    """
-    Verify if a place of birth is a real location
-    """
-    try:
-        # Known hospitals and medical facilities database (simplified for demo)
-        known_hospitals = {
-            "armidale and new england hospital": {
-                "official_name": "Armidale and New England Hospital",
-                "location": "Armidale, New South Wales, Australia",
-                "type": "Public Hospital",
-                "established": "1950s",
-                "status": "Active",
-                "verification_sources": [
-                    "NSW Health Directory",
-                    "Australian Hospital Association",
-                    "Google Maps verification"
-                ],
-                "coordinates": {
-                    "latitude": -30.5136,
-                    "longitude": 151.6669
-                },
-                "postal_code": "2350",
-                "phone": "+61 2 6776 8888",
-                "website": "https://www.health.nsw.gov.au/",
-                "services": ["Emergency", "Maternity", "General Medicine", "Surgery"]
-            },
-            "royal north shore hospital": {
-                "official_name": "Royal North Shore Hospital",
-                "location": "St Leonards, New South Wales, Australia",
-                "type": "Public Hospital",
-                "status": "Active"
-            },
-            "westmead hospital": {
-                "official_name": "Westmead Hospital",
-                "location": "Westmead, New South Wales, Australia", 
-                "type": "Public Hospital",
-                "status": "Active"
-            }
-        }
-        
-        # Normalize the input for comparison
-        normalized_place = place_name.lower().strip()
-        
-        # Remove common location suffixes that might prevent exact matching
-        # Handle cases like "Hospital Name, City" -> "Hospital Name"
-        if ", armidale" in normalized_place:
-            normalized_place = normalized_place.replace(", armidale", "")
-        if ", new south wales" in normalized_place:
-            normalized_place = normalized_place.replace(", new south wales", "")
-        if ", nsw" in normalized_place:
-            normalized_place = normalized_place.replace(", nsw", "")
-        if ", australia" in normalized_place:
-            normalized_place = normalized_place.replace(", australia", "")
-        
-        # Check if the place exists in our database (exact match)
-        if normalized_place in known_hospitals:
-            hospital_info = known_hospitals[normalized_place]
-            return {
-                "place_verified": True,
-                "confidence_score": 0.95,
-                "verification_result": {
-                    "input_place": place_name,
-                    "verified_name": hospital_info["official_name"],
-                    "location": hospital_info["location"],
-                    "type": hospital_info["type"],
-                    "status": hospital_info["status"],
-                    "established": hospital_info.get("established", "Unknown"),
-                    "coordinates": hospital_info.get("coordinates", {}),
-                    "contact_info": {
-                        "phone": hospital_info.get("phone", "Not available"),
-                        "website": hospital_info.get("website", "Not available")
-                    },
-                    "services": hospital_info.get("services", []),
-                    "verification_sources": hospital_info.get("verification_sources", [])
-                },
-                "verification_notes": [
-                    f"Hospital '{hospital_info['official_name']}' is a verified medical facility",
-                    f"Located in {hospital_info['location']}",
-                    "Facility is currently active and operational",
-                    "Information cross-referenced with official health directories"
-                ]
-            }
-        else:
-            # Check for partial matches or similar names
-            partial_matches = []
-            exact_match_found = False
-            
-            # First, try to find a hospital name that's contained in the input
-            for key, hospital in known_hospitals.items():
-                if key in normalized_place or normalized_place in key:
-                    # Found a strong partial match - treat as verified
-                    return {
-                        "place_verified": True,
-                        "confidence_score": 0.90,  # Slightly lower than exact match
-                        "verification_result": {
-                            "input_place": place_name,
-                            "verified_name": hospital["official_name"],
-                            "location": hospital["location"],
-                            "type": hospital["type"],
-                            "status": hospital["status"],
-                            "established": hospital.get("established", "Unknown"),
-                            "coordinates": hospital.get("coordinates", {}),
-                            "contact_info": {
-                                "phone": hospital.get("phone", "Not available"),
-                                "website": hospital.get("website", "Not available")
-                            },
-                            "services": hospital.get("services", []),
-                            "verification_sources": hospital.get("verification_sources", [])
-                        },
-                        "verification_notes": [
-                            f"Hospital '{hospital['official_name']}' is a verified medical facility",
-                            f"Located in {hospital['location']}",
-                            "Facility is currently active and operational",
-                            "Information cross-referenced with official health directories",
-                            "Matched via partial name matching (input contained location suffix)"
-                        ]
-                    }
-            
-            # If no strong match found, collect weaker partial matches for reporting
-            for key, hospital in known_hospitals.items():
-                if any(word in normalized_place for word in key.split()) or any(word in key for word in normalized_place.split()):
-                    partial_matches.append({
-                        "name": hospital["official_name"],
-                        "location": hospital["location"]
-                    })
-            
-            return {
-                "place_verified": False,
-                "confidence_score": 0.2,
-                "verification_result": {
-                    "input_place": place_name,
-                    "status": "Not found in verified database",
-                    "partial_matches": partial_matches
-                },
-                "verification_notes": [
-                    f"Place '{place_name}' not found in verified hospital database",
-                    "This could indicate a non-existent location or outdated information",
-                    "Manual verification recommended for unknown locations"
-                ],
-                "risk_factors": [
-                    "Unverified birth location",
-                    "Potential fraudulent document if location doesn't exist",
-                    "Requires additional verification through official channels"
-                ]
-            }
-            
-    except Exception as e:
-        logging.error(f"Place verification error: {str(e)}")
-        return {
-            "place_verified": False,
-            "confidence_score": 0.0,
-            "error": str(e),
-            "verification_notes": ["Verification service temporarily unavailable"]
-        }
-
-
-
-# External function to call an API such as google search. it can be hard coded for the moment
-async def call_external_service(text: str) -> str:
-    """
-    External function to process text through a service
-    """
-    try:
-        # Example API call - replace with your actual service endpoint
-        # response = requests.post(
-        #     "http://your-service-endpoint/process",
-        #     json={"text": text}
-        # )
-        # return response.json()
-        print(f"Making external Call with data {text}")
-        
-        # Extract place of birth from the text/messages
-        place_of_birth = None
-        
-        # Parse the text to find place of birth information
-        if isinstance(text, list):
-            # If text is a list of messages, search through them
-            for item in text:
-                if hasattr(item, 'content'):
-                    content = item.content
-                else:
-                    content = str(item)
-                
-                # Look for place_of_birth in multiple formats
-                import re
-                
-                # Method 1: Look for JSON format
-                json_match = re.search(r'"place_of_birth":\s*"([^"]+)"', content)
-                if json_match:
-                    place_of_birth = json_match.group(1)
-                    break
-                
-                # Method 2: Look for text mentioning hospital/place names
-                # Look for "Armidale and New England Hospital" or similar patterns
-                hospital_patterns = [
-                    r'Armidale and New England Hospital[,\s]*Armidale',
-                    r'New England Hospital[,\s]*Armidale',
-                    r'place of birth[^:]*:\s*"?([^".\n]+(?:Hospital|Medical|Centre)[^".\n]*)"?',
-                    r'stated as\s*"([^"]+Hospital[^"]*)"',
-                    r'birth[^:]*:\s*"?([^".\n]*Hospital[^".\n]*)"?'
-                ]
-                
-                for pattern in hospital_patterns:
-                    match = re.search(pattern, content, re.IGNORECASE)
-                    if match:
-                        if match.groups():  # Check if there are capture groups
-                            place_of_birth = match.group(1).strip()
-                        else:
-                            place_of_birth = match.group(0).strip()  # Use full match if no groups
-                        # Clean up common suffixes
-                        place_of_birth = re.sub(r'[,\s]*$', '', place_of_birth)
-                        if place_of_birth:
-                            break
-                
-                if place_of_birth:
-                    break
-        
-        # If we found a place of birth, verify it
-        if place_of_birth:
-            print(f"Verifying place of birth: {place_of_birth}")
-            verification_result = await verify_place_of_birth(place_of_birth)
-            
-            return {
-                "verification_type": "place_of_birth",
-                "input_data": place_of_birth,
-                **verification_result
-            }
-        else:
-            # Debug: Print the content we're trying to parse
-            print("DEBUG: Content being parsed:")
-            if isinstance(text, list):
-                for i, item in enumerate(text):
-                    content = item.content if hasattr(item, 'content') else str(item)
-                    print(f"Item {i}: {content[:200]}...")
-            
-            return {
-                "verification_type": "place_of_birth",
-                "error": "No place of birth information found in the provided data",
-                "verification_notes": ["Unable to extract place of birth from document"]
-            }
-            
-    except Exception as e:
-        logging.error(f"External service error: {str(e)}")
-        return {"error": str(e)}
-
-# Add new node for external processing
-async def external_service_node(state: State) -> State:
-    """
-    Node that calls external processing service
-    """
-    # Get the last message content
-    # last_message = state["messages"][-1].content
-    # last_message = state["messages"]
-    ai_messages = [msg for msg in state["messages"] if isinstance(msg, AIMessage)]
-    print(f"AI Messages to Make external call: {json.dumps([msg.content for msg in ai_messages], indent=2)}")
-    
-    
-    # Call external service
-    result = await call_external_service(ai_messages)
-    
-    # Create new message with processed result
-    processed_message = HumanMessage(
-        content=f"External Processing Results: {json.dumps(result, indent=2)}"
-    )
-    
-    return {"messages": [processed_message]}
-
diff --git a/agentic-apps/agentic-idp/mcp.py b/agentic-apps/agentic-idp/mcp.py
deleted file mode 100644
index a0bed099..00000000
--- a/agentic-apps/agentic-idp/mcp.py
+++ /dev/null
@@ -1,27 +0,0 @@
-# # https://modelcontextprotocol.io/quickstart/server
-# from typing import Any
-# import httpx
-# from mcp.server.fastmcp import FastMCP
-
-# # Initialize FastMCP server
-# mcp = FastMCP("weather")
-
-
-# @mcp.tool()
-# async def get_personal_info(state: str) -> str:
-#     """Get weather alerts for a US state.
-
-#     Args:
-#         state: Two-letter US state code (e.g. CA, NY)
-#     """
-#     url = f"{NWS_API_BASE}/alerts/active/area/{state}"
-#     data = await make_nws_request(url)
-
-#     if not data or "features" not in data:
-#         return "Unable to fetch alerts or no alerts found."
-
-#     if not data["features"]:
-#         return "No active alerts for this state."
-
-#     alerts = [format_alert(feature) for feature in data["features"]]
-#     return "\n---\n".join(alerts)
\ No newline at end of file
diff --git a/agentic-apps/agentic-idp/requirements.txt b/agentic-apps/agentic-idp/requirements.txt
deleted file mode 100644
index d776f694..00000000
--- a/agentic-apps/agentic-idp/requirements.txt
+++ /dev/null
@@ -1,4 +0,0 @@
-langfuse
-openai
-langgraph
-
diff --git a/agentic-apps/agentic-idp/storage.py b/agentic-apps/agentic-idp/storage.py
deleted file mode 100644
index d5ae879d..00000000
--- a/agentic-apps/agentic-idp/storage.py
+++ /dev/null
@@ -1,77 +0,0 @@
-from langchain_openai import ChatOpenAI
-from langchain_core.prompts import ChatPromptTemplate, MessagesPlaceholder
-from langchain_core.messages import AIMessage, HumanMessage
-from langgraph.graph import StateGraph, START, END
-from langgraph.graph.message import add_messages
-from langgraph.checkpoint.memory import MemorySaver
-from langchain_core.messages import SystemMessage, HumanMessage
-
-from typing import Annotated, List
-from langchain.prompts.chat import HumanMessagePromptTemplate
-
-
-from typing_extensions import TypedDict
-
-import requests 
-import json
-import base64
-
-import logging
-
-from langfuse import Langfuse
-from datetime import datetime, timedelta
-import os
-import math
-import openai
-
-from PyPDF2 import PdfReader
-
-from pathlib import Path
-
-from langgraph.pregel import RetryPolicy
-
-from decision import  State
-
-# External function to store the data in s3
-async def call_store_service(text: str) -> str:
-    """
-    External function to process text through a service
-    """
-    try:
-        # Example API call - replace with your actual service endpoint
-        # response = requests.post(
-        #     "http://your-service-endpoint/process",
-        #     json={"text": text}
-        # )
-        # return response.json()
-        print(f"Making storage Call with data {text}")
-        return {"result": "success"}
-    except Exception as e:
-        logging.error(f"External service error: {str(e)}")
-        return {"error": str(e)}
-
-# Add new node for external processing
-async def external_storage_node(state: State) -> State:
-    """
-    Node that calls external processing service
-    """
-    # Get the last message content
-    # last_message = state["messages"]
-    # translated = [state["messages"][0]] + [AIMessage(content=msg.content) for msg in state["messages"][1:]]
-    ai_messages = [msg for msg in state["messages"] if isinstance(msg, AIMessage)]
-    print(f"AI Messages to Store: {json.dumps([msg.content for msg in ai_messages], indent=2)}")
-
-    
-    # [-1].content
-    print(f"Data to Store {ai_messages}")
-    print(json.dumps([msg.content for msg in ai_messages], indent=2))
-    
-    # Call external service
-    result = await call_store_service(json.dumps([msg.content for msg in ai_messages], indent=2))
-    
-    # Create new message with processed result
-    processed_message = HumanMessage(
-        content=f"External Processing Results: {json.dumps(result, indent=2)}"
-    )
-    
-    return {"messages": [processed_message]}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/AmazonQ.md b/agentic-apps/agentic_rag_milvus/AmazonQ.md
deleted file mode 100644
index 7505747b..00000000
--- a/agentic-apps/agentic_rag_milvus/AmazonQ.md
+++ /dev/null
@@ -1,72 +0,0 @@
-# Augmented LLM with MCP and RAG
-
-This project demonstrates a framework-independent implementation of an augmented Large Language Model (LLM) system that combines Model Context Protocol (MCP) for tool usage and Retrieval Augmented Generation (RAG) for enhanced context awareness.
-
-## Project Overview
-
-This application creates an AI agent that can:
-1. Retrieve relevant information from a knowledge base using vector embeddings
-2. Interact with external tools through the Model Context Protocol (MCP)
-3. Generate responses based on both the retrieved context and tool interactions
-4. Complete tasks like summarizing content and saving results to files
-
-## Architecture
-
-The system is built with a modular architecture consisting of these key components:
-
-```
-Agent → Manages the overall workflow and coordinates components
-  ├── ChatOpenAI → Handles LLM interactions and tool calling
-  ├── MCPClient(s) → Connects to MCP servers for tool access
-  └── EmbeddingRetriever → Performs vector search for relevant context
-      └── VectorStore → Stores and searches document embeddings
-```
-
-## Workflow Explanation
-
-1. **Initialization**:
-   - The system loads knowledge documents and creates embeddings using AWS Bedrock
-   - Embeddings are stored in an in-memory vector store
-   - MCP clients are initialized to connect to tool servers
-
-2. **RAG Process**:
-   - When a query is received, it's converted to an embedding
-   - The system searches for the most relevant documents using cosine similarity
-   - Retrieved documents are combined to form context for the LLM
-
-3. **Agent Execution**:
-   - The agent initializes with the LLM, MCP clients, and retrieved context
-   - The user query is sent to the LLM along with the context
-   - The LLM generates responses and may request tool calls
-
-4. **Tool Usage**:
-   - When the LLM requests a tool, the agent routes the call to the appropriate MCP client
-   - The MCP client executes the tool and returns results
-   - Results are fed back to the LLM to continue the conversation
-
-5. **Output Generation**:
-   - The LLM generates a final response incorporating tool results and context
-   - In the example task, it creates a markdown file with information about "Antonette"
-
-## Key Technologies
-
-- **LLM Integration**: Uses OpenAI API for language model capabilities
-- **MCP Implementation**: Connects to MCP servers for filesystem operations
-- **Vector Embeddings**: Uses AWS Bedrock for generating embeddings
-- **Vector Search**: Implements cosine similarity for finding relevant documents
-
-## Implementation Details
-
-- **Framework Independence**: Built without relying on frameworks like LangChain or LlamaIndex
-- **Modular Design**: Components are separated for easy maintenance and extension
-- **AWS Integration**: Uses AWS Bedrock for embedding generation
-- **Tool Orchestration**: Manages tool calls and responses through MCP protocol
-
-## Example Use Case
-
-The current implementation demonstrates a task where the agent:
-1. Retrieves information about a user named "Antonette" from the knowledge base
-2. Summarizes the information and creates a story about her
-3. Saves the output to a markdown file using the filesystem MCP tool
-
-This architecture can be extended to support various tasks requiring context-aware responses and tool usage.
diff --git a/agentic-apps/agentic_rag_milvus/README.md b/agentic-apps/agentic_rag_milvus/README.md
deleted file mode 100644
index 5a67257b..00000000
--- a/agentic-apps/agentic_rag_milvus/README.md
+++ /dev/null
@@ -1,113 +0,0 @@
-# Agentic RAG with MCP and Custom Embedding
-
-This project implements an augmented Large Language Model (LLM) system that combines Model Context Protocol (MCP) for tool usage and Retrieval Augmented Generation (RAG) for enhanced context awareness, all without relying on frameworks like LangChain or LlamaIndex.
-
-## Project Overview
-
-This application creates an AI agent that can:
-1. Retrieve relevant information from a knowledge base using vector embeddings
-2. Interact with external tools through the Model Context Protocol (MCP)
-3. Generate responses based on both the retrieved context and tool interactions
-4. Complete tasks like summarizing content and saving results to files
-
-## Architecture
-
-The system is built with a modular architecture consisting of these key components:
-
-```
-Agent → Manages the overall workflow and coordinates components
-  ├── ChatOpenAI → Handles LLM interactions and tool calling
-  ├── MCPClient(s) → Connects to MCP servers for tool access
-  └── EmbeddingRetriever → Performs vector search for relevant context
-      └── VectorStore → Stores and searches document embeddings
-```
-
-## Workflow Explanation
-
-1. **Initialization**:
-   - The system loads knowledge documents and creates embeddings using a custom embedding endpoint
-   - Embeddings are stored in a Milvus vector database
-   - MCP clients are initialized to connect to tool servers
-
-2. **RAG Process**:
-   - When a query is received, it's converted to an embedding
-   - The system searches for the most relevant documents using cosine similarity
-   - Retrieved documents are combined to form context for the LLM
-
-3. **Agent Execution**:
-   - The agent initializes with the LLM, MCP clients, and retrieved context
-   - The user query is sent to the LLM along with the context
-   - The LLM generates responses and may request tool calls
-
-4. **Tool Usage**:
-   - When the LLM requests a tool, the agent routes the call to the appropriate MCP client
-   - The MCP client executes the tool and returns results
-   - Results are fed back to the LLM to continue the conversation
-
-5. **Output Generation**:
-   - The LLM generates a final response incorporating tool results and context
-   - In the example task, it creates a markdown file with information about "Antonette"
-
-## Key Components
-
-- **Agent**: Coordinates the overall workflow and manages tool usage
-- **ChatOpenAI**: Handles interactions with the language model and tool calling
-- **MCPClient**: Connects to MCP servers and manages tool calls
-- **EmbeddingRetriever**: Creates and searches vector embeddings for relevant context
-- **MilvusVectorStore**: Interfaces with Milvus for storing and retrieving embeddings
-
-## Getting Started
-
-### Prerequisites
-
-- Node.js 18+
-- pnpm or npm
-- OpenAI API key
-- Milvus database instance
-
-### Installation
-
-```bash
-# Clone the repository
-git clone <repository-url>
-
-# Install dependencies
-pnpm install
-
-# Set up environment variables
-# Create a .env file with:
-# - OPENAI_API_KEY
-# - OPENAI_BASE_URL (optional)
-# - MILVUS_ADDRESS
-```
-
-### Usage
-
-```bash
-# Embed knowledge documents
-pnpm embed-knowledge
-
-# Embed CSV data (optional)
-pnpm embed-csv
-
-# Run the application
-pnpm dev
-```
-
-## Example Use Case
-
-The current implementation demonstrates a task where the agent:
-1. Retrieves information about a user named "Antonette" from the knowledge base
-2. Summarizes the information and creates a story about her
-3. Saves the output to a markdown file using the filesystem MCP tool
-
-## Extending the System
-
-This modular architecture can be easily extended:
-- Add more MCP servers for additional tool capabilities
-- Implement advanced Milvus features like filtering and hybrid search
-- Add more sophisticated RAG techniques like reranking or chunking
-- Implement conversation history for multi-turn interactions
-- Deploy as a service with API endpoints
-- Integrate with different LLM providers
-- Scale the vector database for production workloads
diff --git a/agentic-apps/agentic_rag_milvus/debug-auth.js b/agentic-apps/agentic_rag_milvus/debug-auth.js
deleted file mode 100644
index d411e993..00000000
--- a/agentic-apps/agentic_rag_milvus/debug-auth.js
+++ /dev/null
@@ -1,40 +0,0 @@
-import OpenAI from 'openai';
-import 'dotenv/config';
-
-// Create a simple test script to debug the API connection with authentication
-async function testConnection() {
-  console.log('Testing OpenAI API connection with authentication...');
-  console.log('Base URL:', process.env.OPENAI_BASE_URL);
-  console.log('API Key:', process.env.OPENAI_API_KEY ? 'Set (masked)' : 'Not set');
-  
-  const openai = new OpenAI({
-    apiKey: process.env.OPENAI_API_KEY,
-    baseURL: process.env.OPENAI_BASE_URL,
-    defaultHeaders: {
-      "api-key": process.env.OPENAI_API_KEY,
-      "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-    }
-  });
-
-  try {
-    // Try a simple chat completion without streaming
-    console.log('\nAttempting a simple chat completion...');
-    const completion = await openai.chat.completions.create({
-      model: 'Qwen/QwQ-32B-AWQ',
-      messages: [{ role: 'user', content: 'Hello, how are you?' }],
-      stream: false,
-    });
-    console.log('Chat completion successful:', completion);
-  } catch (error) {
-    console.error('Error with chat completion:', error);
-    
-    // Print more detailed error information
-    if (error.response) {
-      console.log('Response status:', error.response.status);
-      console.log('Response headers:', error.response.headers);
-      console.log('Response data:', error.response.data);
-    }
-  }
-}
-
-testConnection().catch(console.error);
diff --git a/agentic-apps/agentic_rag_milvus/debug-no-tools.js b/agentic-apps/agentic_rag_milvus/debug-no-tools.js
deleted file mode 100644
index 4fcbd0ae..00000000
--- a/agentic-apps/agentic_rag_milvus/debug-no-tools.js
+++ /dev/null
@@ -1,49 +0,0 @@
-import OpenAI from 'openai';
-import 'dotenv/config';
-
-// Create a test script to debug the API connection with streaming
-async function testConnection() {
-  console.log('Testing OpenAI API connection with streaming...');
-  console.log('Base URL:', process.env.OPENAI_BASE_URL);
-  console.log('API Key:', process.env.OPENAI_API_KEY ? 'Set (masked)' : 'Not set');
-  
-  const openai = new OpenAI({
-    apiKey: process.env.OPENAI_API_KEY,
-    baseURL: process.env.OPENAI_BASE_URL,
-    defaultHeaders: {
-      "api-key": process.env.OPENAI_API_KEY,
-      "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-    }
-  });
-
-  try {
-    // Try a simple chat completion with streaming
-    console.log('\nAttempting a chat completion with streaming...');
-    const stream = await openai.chat.completions.create({
-      model: 'Qwen/QwQ-32B-AWQ',
-      messages: [{ role: 'user', content: 'Tell me a short joke' }],
-      stream: true,
-    });
-    
-    console.log('Stream response started:');
-    for await (const chunk of stream) {
-      process.stdout.write(chunk.choices[0]?.delta?.content || '');
-    }
-    console.log('\nStream completed successfully');
-  } catch (error) {
-    console.error('Error with chat completion:', error);
-    
-    // Print more detailed error information
-    if (error.response) {
-      console.log('Response status:', error.response.status);
-      console.log('Response headers:', error.response.headers);
-      try {
-        console.log('Response data:', await error.response.text());
-      } catch (e) {
-        console.log('Could not read response data');
-      }
-    }
-  }
-}
-
-testConnection().catch(console.error);
diff --git a/agentic-apps/agentic_rag_milvus/debug-tools.js b/agentic-apps/agentic_rag_milvus/debug-tools.js
deleted file mode 100644
index dd2f29f3..00000000
--- a/agentic-apps/agentic_rag_milvus/debug-tools.js
+++ /dev/null
@@ -1,71 +0,0 @@
-import OpenAI from 'openai';
-import 'dotenv/config';
-
-// Create a test script to debug the API connection with tools
-async function testConnection() {
-  console.log('Testing OpenAI API connection with tools...');
-  console.log('Base URL:', process.env.OPENAI_BASE_URL);
-  console.log('API Key:', process.env.OPENAI_API_KEY ? 'Set (masked)' : 'Not set');
-  
-  const openai = new OpenAI({
-    apiKey: process.env.OPENAI_API_KEY,
-    baseURL: process.env.OPENAI_BASE_URL,
-    defaultHeaders: {
-      "api-key": process.env.OPENAI_API_KEY,
-      "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-    }
-  });
-
-  // Define a simple tool
-  const tools = [
-    {
-      type: "function",
-      function: {
-        name: "get_current_weather",
-        description: "Get the current weather in a given location",
-        parameters: {
-          type: "object",
-          properties: {
-            location: {
-              type: "string",
-              description: "The city and state, e.g. San Francisco, CA",
-            },
-            unit: {
-              type: "string",
-              enum: ["celsius", "fahrenheit"],
-              description: "The temperature unit to use",
-            },
-          },
-          required: ["location"],
-        },
-      },
-    }
-  ];
-
-  try {
-    // Try a simple chat completion without streaming
-    console.log('\nAttempting a chat completion with tools...');
-    const completion = await openai.chat.completions.create({
-      model: 'Qwen/QwQ-32B-AWQ',
-      messages: [{ role: 'user', content: 'What\'s the weather like in Seattle?' }],
-      stream: false,
-      tools: tools,
-    });
-    console.log('Chat completion successful:', JSON.stringify(completion, null, 2));
-  } catch (error) {
-    console.error('Error with chat completion:', error);
-    
-    // Print more detailed error information
-    if (error.response) {
-      console.log('Response status:', error.response.status);
-      console.log('Response headers:', error.response.headers);
-      try {
-        console.log('Response data:', await error.response.text());
-      } catch (e) {
-        console.log('Could not read response data');
-      }
-    }
-  }
-}
-
-testConnection().catch(console.error);
diff --git a/agentic-apps/agentic_rag_milvus/debug.js b/agentic-apps/agentic_rag_milvus/debug.js
deleted file mode 100644
index b4dbe53c..00000000
--- a/agentic-apps/agentic_rag_milvus/debug.js
+++ /dev/null
@@ -1,45 +0,0 @@
-import OpenAI from 'openai';
-import 'dotenv/config';
-
-// Create a simple test script to debug the API connection
-async function testConnection() {
-  console.log('Testing OpenAI API connection...');
-  console.log('Base URL:', process.env.OPENAI_BASE_URL);
-  console.log('API Key:', process.env.OPENAI_API_KEY ? 'Set (masked)' : 'Not set');
-  
-  const openai = new OpenAI({
-    apiKey: process.env.OPENAI_API_KEY,
-    baseURL: process.env.OPENAI_BASE_URL,
-  });
-
-  try {
-    // First try to list models
-    console.log('\nAttempting to list models...');
-    const models = await openai.models.list();
-    console.log('Models available:', models.data.map(m => m.id));
-  } catch (error) {
-    console.error('Error listing models:', error);
-  }
-
-  try {
-    // Try a simple chat completion without streaming
-    console.log('\nAttempting a simple chat completion...');
-    const completion = await openai.chat.completions.create({
-      model: 'Qwen/QwQ-32B-AWQ',
-      messages: [{ role: 'user', content: 'Hello, how are you?' }],
-      stream: false,
-    });
-    console.log('Chat completion successful:', completion);
-  } catch (error) {
-    console.error('Error with chat completion:', error);
-    
-    // Print more detailed error information
-    if (error.response) {
-      console.log('Response status:', error.response.status);
-      console.log('Response headers:', error.response.headers);
-      console.log('Response data:', error.response.data);
-    }
-  }
-}
-
-testConnection().catch(console.error);
diff --git a/agentic-apps/agentic_rag_milvus/explore_collection.py b/agentic-apps/agentic_rag_milvus/explore_collection.py
deleted file mode 100644
index ce9211d5..00000000
--- a/agentic-apps/agentic_rag_milvus/explore_collection.py
+++ /dev/null
@@ -1,65 +0,0 @@
-import os
-from dotenv import load_dotenv
-from pymilvus import connections, Collection
-
-# Load environment variables
-load_dotenv()
-
-# Get Milvus address from environment
-milvus_address = os.getenv("MILVUS_ADDRESS", "localhost:19530")
-milvus_host, milvus_port = milvus_address.split(":")
-
-# Collection name
-collection_name = "rag_documents"
-
-# Connect to Milvus
-print(f"Connecting to Milvus at {milvus_host}:{milvus_port}...")
-try:
-    connections.connect(
-        alias="default", 
-        host=milvus_host,
-        port=milvus_port
-    )
-    
-    # Get collection
-    collection = Collection(collection_name)
-    
-    # 1. Check the schema
-    schema = collection.schema
-    print("\n1. Collection Schema:")
-    print(f"Collection name: {collection_name}")
-    print("Fields:")
-    for field in schema.fields:
-        print(f"  - {field.name}: {field.dtype} (is_primary_key: {field.is_primary})")
-        if hasattr(field, 'params') and field.params:
-            print(f"    Vector dimension: {field.params.get('dim')}")
-    
-    # 2. Get number of entities
-    num_entities = collection.num_entities
-    print(f"\n2. Number of entities: {num_entities}")
-    
-    # 3. Examine index information
-    print("\n3. Index Information:")
-    try:
-        index_info = collection.index().params
-        print(f"Index params: {index_info}")
-    except Exception as e:
-        print(f"Could not get index params: {e}")
-    
-    # Get more detailed information about vector field indexes
-    try:
-        for field_name in collection.index_info.keys():
-            field_index = collection.index_info.get(field_name)
-            if field_index:
-                print(f"\nField '{field_name}' index:")
-                print(f"  Index type: {field_index.get('index_type')}")
-                print(f"  Metric type: {field_index.get('metric_type')}")
-                print(f"  Params: {field_index.get('params')}")
-    except Exception as e:
-        print(f"Could not get detailed index info: {e}")
-    
-    # Close connection
-    connections.disconnect("default")
-    
-except Exception as e:
-    print(f"Error exploring Milvus collection: {e}")
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diff --git a/agentic-apps/agentic_rag_milvus/images/image4.png b/agentic-apps/agentic_rag_milvus/images/image4.png
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diff --git a/agentic-apps/agentic_rag_milvus/knowledge/q_c_data.csv b/agentic-apps/agentic_rag_milvus/knowledge/q_c_data.csv
deleted file mode 100644
index e84c39dd..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/q_c_data.csv
+++ /dev/null
@@ -1,2003 +0,0 @@
-question,context
-What were the surgical complications observed in patients who underwent excision of limbal dermoids?,"Excision of limbal dermoids. We reviewed the clinical files of 10 patients who had undergone excision of unilateral epibulbar limbal dermoids. Preoperatively, all of the affected eyes had worse visual acuity (P less than .02) and more astigmatism (P less than .01) than the contralateral eyes. Postoperatively, every patient was cosmetically improved. Of the eight patients for whom both preoperative and postoperative visual acuity measurements had been obtained, in six it had changed minimally (less than or equal to 1 line), and in two it had improved (less than or equal to 2 lines). Surgical complications included persistent epithelial defects (40%) and peripheral corneal vascularization and opacity (70%). These complications do not outweigh the cosmetic and visual benefits of dermoid excision in selected patients."
-What is the most important aspect of initial treatment for Bell's palsy?,"Bell's palsy. A diagnosis of exclusion. In cases of acute unilateral facial weakness, a careful and systematic evaluation is necessary to identify the cause. Idiopathic facial paralysis (Bell's palsy) is a diagnosis of exclusion. It is also the most common cause of unilateral facial weakness seen by primary care physicians. The most important aspect of initial treatment is eye protection. Administration of systemic oral corticosteroids may lessen severity and duration of symptoms."
-How did steroid therapy help in the removal of the retained foreign body in the endobronchial region?,"Retained endobronchial foreign body removal facilitated by steroid therapy of an obstructing, inflammatory polyp. Oral and topical steroids were used to induce regression in an inflammatory, obstructing endobronchial polyp caused by a retained foreign body. The FB (a peanut half), which had been present for over six months, was then able to be easily and bloodlessly retrieved with fiberoptic bronchoscopy."
-What unusual complication of Crohn's disease was observed in the patient described in this case report?,"Recurrent buccal space abscesses: a complication of Crohn's disease. A patient is described with generalized gastrointestinal involvement by Crohn's disease. Symptoms of recurrent ulceration and mucosal tags are well-described oral manifestations of Crohn's disease; however, in our patient recurrent facial abscesses, which required extraoral drainage, also developed. This complication has not previously been reported."
-What are the key characteristics and management recommendations for intracranial fibromatosis based on the given context?,"Intracranial fibromatosis. Fibromatoses are uncommon infiltrative lesions affecting musculoaponeurotic structures, most often of the limbs and trunk. Lesions involving the cranial cavity are rare and require the same aggressive surgical management as elsewhere in the body. This case illustrates their clinical and neuroradiological features and underscores the necessity for aggressive resection to avoid recurrence. The literature is reviewed."
-What was the effect of intrathecally administered morphine sulfate on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) in awake patients?,"The effect of intrathecal morphine on somatosensory evoked potentials in awake humans. Although the effect of systemic opioids on somatosensory evoked potentials has been well described, little is known about the interaction between intrathecally administered opioid analgesics and somatosensory evoked potentials. Accordingly, the influence of intrathecally administered morphine on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) was investigated in 22 unpremedicated, awake, neurologically normal patients scheduled to undergo elective abdominal or pelvic procedures. Patients were randomly assigned to receive either preservation-free intrathecal morphine sulfate (ITMS) or placebo. After baseline PTSCEP, heart rate and, mean blood pressure were recorded, ITMS (15 micrograms.kg-1) was injected via standard dural puncture with the patient in the lateral position. PTSCEPs, heart rate, and mean blood pressure were recorded again at 5, 10, 20, 30, 60, 90, and 120 min. Control patients were treated identically (including position, sterile preparation, and subcutaneous tissue infiltration with local anesthetic), except for lumbar puncture, and were unaware of their randomization. Before administration of ITMS, PTSCEP P1, N1, P2, N2, and P3 latencies were 39.4 +/- 3.2, 47.6 +/- 3.9, 59.2 +/- 3.2, 70.4 +/- 3.7, and 84.6 +/- 5.5 ms, (mean +/- standard deviation), respectively. The corresponding P1-N1, N1-P2, and P2-N2 amplitudes were 2.4 +/- 1.1, 2.4 +/- 1.1, and 2.3 +/- 0.9 microV, respectively. There were no significant changes over time between the control and ITMS groups. PTSCEPs resulting from left-sided stimulation were not different from those elicited by right-sided stimulation. All ITMS patients had intense postoperative analgesia for at least 24 h. It is concluded that ITMS does not affect PTSCEP waveforms in the 35-90 ms latency range during the awake state."
-What is the key message of the 29th Rovenstine lecture regarding the ongoing education and approach of anesthesiologists?,"The 29th Rovenstine lecture: clinical challenges for the anesthesiologist. In conclusion, I hope that my comments have reaffirmed your biases or, even more importantly, stimulated you to think in a different way about the information explosion in our specialty and medicine in general. I believe our specialty is in a golden era that will benefit from the past and be nourished by new discoveries and understanding. We as clinicians must accept the challenge of recognizing what new information deserves incorporation into our practice, what old information deserves to be sustained, and what merits new scrutiny and perhaps should be discarded. If I had one wish, it would be that anesthesiologists would never lose their zeal to be students--their thirst for new information--as the continuum of anesthesia education is indeed a life-long process. That wish, ladies and gentlemen, is my challenge to all anesthesiologists."
-What was the purpose of the study on encainide and flecainide in patients with supraventricular arrhythmias?,"Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias. In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias."
-How do lymphokines contribute to the potential immunotherapy of cancer?,"Approaches to immunotherapy of cancer: characterization of lymphokines as second signals for cytotoxic T-cell generation. Lymphokines, the soluble molecules produced by cells of the immune system, regulate cell-cell interactions and, consequently, the functional status of the immune system. Altering immunoregulatory pathways with lymphokines in vivo may provide a mechanism for controlling a variety of immunologic disorders. Although normally produced in vivo in very small quantities, the widespread availability of recombinant lymphokines has made it possible to study the molecular signals involved in production of lymphocyte effectors with activity against tumor. For example, interleukin-2-based cancer immunotherapy programs have, in certain clinical situations, suggested that immunologic intervention can influence the regression of metastatic cancer. Ultimately the successful application of these biologic agents requires an understanding of the interaction between the immune system and tumor on a molecular level. To induce a given biologic effect, it is necessary both to classify the required lymphokines and to identify the relevant effector cell populations. This review will examine the progress made in identifying the requirements for lymphokine-induced cytotoxic T-lymphocyte function."
-What was the clinical progression and outcome of the 71-year-old woman's retinal condition associated with non-Hodgkin's large cell lymphoma?,"Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma). A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma."
-How did morphine and naloxone affect pain-related behaviors in rats with peripheral mononeuropathy?,"The 'tonic' pain-related behaviour seen in mononeuropathic rats is modulated by morphine and naloxone. This study investigated the sensitivity to pharmacological manipulations of a rating method, adapted from the formalin test, to measure the tonic component of the pain-related behaviour induced by creating a peripheral mononeuropathy with 4 loose ligatures around the common sciatic nerve. Although the adequacy of opioid substances in alleviating neuropathic pain is highly controversial, the effects of morphine (1 mg/kg i.v.) and naloxone (1 mg/and 3 micrograms/kg i.v.) were tested 1-2 weeks after the nerve ligatures were established, when pain-related behaviours were well developed. Morphine (1 mg/kg i.v.) induced a potent and prolonged decrease in the pain-rating score at week 2 after surgery. Either at week 1 or week 2, naloxone elicited a bidirectional dose-dependent action: a further increase in the pain-rating score with the high dose (1 mg/kg i.v.), and a paradoxical decrease in the score with the low dose of 3 micrograms/kg i.v. These effects are comparable to those already described in several rat models of inflammatory pain and, in the same model of neuropathy, using a phasic nociceptive test, the measure of the vocalization to paw pressure. A few differences in the effects of naloxone on tonic and phasic pain are noted and discussed."
-What cardiovascular changes were observed in patients during upper gastrointestinal endoscopy with deep sedation?,"Examination of cardiorespiratory changes during upper gastrointestinal endoscopy. Comparison of monitoring of arterial oxygen saturation, arterial pressure and the electrocardiogram. Critical events including hypoxaemia, arrhythmias and myocardial ischaemia may occur more frequently during endoscopic procedures than during anaesthesia. A study was undertaken to assess the cardiovascular changes and to evaluate suitable monitoring techniques to detect critical events during sedation and endoscopy. Twenty patients scheduled to undergo a prolonged endoscopic procedure which required deep sedation were studied. Continuous recordings of electrocardiogram, heart rate and arterial oxygen saturation were made and arterial pressure was recorded at one-minute intervals. The study commenced immediately before administration of sedatives, continued for the duration of the examination and for one hour following the examination. Oxygen saturation decreased in all patients during the examination to a mean of 82.9% (SD 11.9), and remained below baseline for the duration of the examination and into the recovery period. Statistically significant increases and reductions of systolic arterial pressure and rate-pressure product were found during the procedures compared with baseline values recorded before administration of sedatives. Sixteen of the 20 patients developed tachycardia during the examination. Ten patients developed ectopic foci which were supraventricular, ventricular or both in origin. Electrocardiogram changes resolved during the recovery period. Myocardial ischaemia was assessed by S-T segment depression and a significant correlation was found between S-T segment depression and hypoxaemia, although the magnitude of the S-T depression was small and may not have been detected clinically. No correlation was found between S-T segment depression and arterial pressure, heart rate or rate-pressure product."
-How did the presence of 4-methylpyrazole affect blood alcohol levels and methionine metabolism in the experimental groups of Golden Syrian hamsters?,"Hepatic transmethylation and blood alcohol levels. Golden Syrian hamsters that have elevated hepatic alcohol dehydrogenase activity were divided into four groups and group-fed on four different liquid diets for five weeks. Group I was fed a control diet formulated for hamsters. Group II was fed the control diet containing 20 micrograms of 4 methylpyrazole per litre. Group III was fed the hamster ethanol liquid diet (ethanol amounting to 36% of total calories). Group IV was fed the ethanol diet to which 4-methylpyrazole (20 micrograms/litre) was added. Groups I, II and III were group-fed the amount consumed by Group IV on a daily basis. Upon killing the animals, blood alcohol levels were found to be elevated in Group IV but not in Group III. Hepatic methionine synthetase (MS) was inhibited in Group IV. Betaine-homocysteine methyltransferase was induced in this group to compensate for the MS inhibition and liver betaine was lowered reflecting this induction. None of these changes were seen in Group III. Since none of the animals showed an aversion to their respective diets and gained weight normally, these data indicate that it was the elevated blood levels of ethanol rather than nutritional factors that were related to the changes in methionine metabolism."
-What are the key characteristics of memory T cells in liver inflammation?,"Memory T cells represent the predominant lymphocyte subset in acute and chronic liver inflammation. T cells can be divided into two main phenotypic subpopulations-i.e., the CD45RA-positive (2H4-positive) ""naive"" subset and the CD45RO-positive (UCHL1-positive) ""memory"" subset. In light of this recent functional reinterpretation of T-lymphocyte subpopulations, we reinvestigated the composition of the inflammatory infiltrate in liver biopsy specimens from patients with acute and chronic hepatitis. In normal liver, the few scattered mononuclear cells present in portal tracts and in the intralobular parenchyma consisted of both CD45RA-positive (2H4-positive) naive and CD45RO-positive (UCHL1-positive) memory T cells. In inflammatory liver diseases, portal tract and periportal and intralobular areas of inflammation consisted virtually only of CD45RO-positive (UCHL1-positive) memory T cells, which strongly expressed the CDw29 (4B4) antigen, and the adhesion molecules LFA-1, CD2, LFA-3, CD44 and VLA-4 and the activation marker human leukocyte antigen-DR. These results indicate that activated memory T cells represent the predominant subpopulation of lymphocytes in areas of liver inflammation. Memory T cells strongly express various homing receptors and adhesion molecules, which probably allow them to accumulate at inflammatory sites and to strengthen interaction with target cells. Furthermore, the increased number of memory T cells with enhanced interferon-gamma production in areas of liver inflammation may contribute to the maintenance and up-regulation of immune responses occurring in inflammatory liver diseases."
-What ultrastructural changes were observed in endothelial cells after intracutaneous injection of NAP-1/IL-8?,"Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study. Neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, was injected intracutaneously into human skin. Sequential biopsy specimens were taken in order to investigate the sequence of ultrastructural changes induced by the cytokine. Whereas intracutaneous injection of 100 ng of NAP-1/IL-8 per site caused no macroscopic changes, by histology infiltration with polymorphonuclear leukocytes (PMN) and monocytes was present within 1 h and increased at 3 and 5 h. No lymphocyte infiltration was noted. The first ultrastructural changes (30 min) consisted of the presence of cytoplasmic 7-nm microfilament bundles, as well as numerous protrusions of the luminal plasma membrane of endothelial cells (EC). As a striking feature, multiple 100- to 160-nm electron lucent vesicles could be observed in the EC cytoplasm. These structures differed from plasmalemmal vesicles and suggest secretory activity. When PMN and monocytes appeared in the vascular lumen (1 h and later), the number of 100-160-nm electron-lucent vesicles had decreased significantly. In contrast to C5a-injected skin sites, mast cell degranulation was absent."
-What percentage of patients in the study had squamous cell carcinoma?,"Bronchogenic carcinoma with chest wall invasion. Bronchogenic carcinoma with chest wall involvement continues to present a major clinical challenge. We have treated 52 patients since 1973, excluding those with superior sulcus tumors. There were 37 male and 15 female patients with an average age of 62.9 years. Chest pain was an initial symptom in 37%. All patients had negative mediastinoscopy results. Squamous cell carcinoma was present in 53% and adenocarcinoma in 35%. The median number of ribs resected was two (range, one to six), and only 2 patients required chest wall reconstruction. Pathologic staging was T3 N0 M0 in 83% and T3 N1 M0 in 17%. Operative mortality was 3.8%. Absolute 5-year survival was 26.3%. Patients who had N1 disease had a 5-year survival of only 11%. Radiation therapy was employed in 46% for positive nodes or close margins. Bronchogenic carcinoma with chest wall invasion remains potentially curable if N2 nodes are not involved. The role of radiation therapy has not been clearly defined. Morbidity and mortality should be minimal."
-What are the two most common electronic weapons discussed in the context?,"Electronic weaponry--a question of safety [published erratum appears in Ann Emerg Med 1991 Sep;20(9):1031] Electronic weapons represent a new class of weapon available to law enforcement and the lay public. Although these weapons have been available for several years, there is inadequate research to document their safety or efficacy. Two of the most common, the TASER and the stun gun, are reviewed. The electronic weapon was initially and still is approved by the US Consumer Product Safety Commission; its approval was based on theoretical calculations of the physical effects of damped sinusoidal pulses, not on the basis of animal or human studies. These devices are widely available and heavily promoted, despite limited research into their safety or efficiency and despite recent animal studies documenting their potential for lethality."
-What was the primary objective of surgical management for acoustic tumors in this study?,"Operative management of acoustic neuromas: the priority of neurologic function over complete resection. The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post-operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity."
-What is the potential drug interaction described in the context that may lead to cardiotoxicity?,"Torsades de pointes occurring in association with terfenadine use. Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although found in many clinical settings, torsades de pointes is most often drug induced. This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone. Measured serum concentrations of terfenadine and its main metabolite showed excessive levels of parent terfenadine and proportionately reduced concentrations of metabolite, suggesting inhibition of terfenadine metabolism. We believe that a drug interaction between terfenadine and ketoconazole resulted in the elevated terfenadine levels in plasma and in the cardiotoxicity previously seen only in cases of terfenadine overdose."
-What is the prevalence of celiac or superior mesenteric artery stenoses among male veterans evaluated for peripheral vascular disease?,"Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients."
-What were the key findings of the brain-stem auditory evoked responses (BAER's) analysis in patients with acoustic neurinoma?,"Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma. The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors. Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p less than 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p less than 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p less than 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression. Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve."
-What was the first successful heterotransplantation of a human carcinoid tumor into nude mice?,"First heterotransplantation of a human carcinoid tumor into nude mice. The first successful heterotransplantation of a human carcinoid tumor into nude mice is reported. CSH, a voluminous hepatic metastasis of a primary bronchial carcinoid tumor (CSB) was resected and transplanted into three irradiated nude (Swiss-nu/nu) mice both by subcutaneous (SC) and intramuscular (IM) routes; the success rate was five of six. Heterotransplanted tumors took 4 to 5 months to appear in the mice and 1 month to attain a width of 0.5 cm. Both human and mouse tumors (named CSH-SC and CSH-IM) were studied by light and electron microscopy. They were Grimelius-positive, neuron-specific enolase-positive, and bombesin-negative by immunocytochemistry. Furthermore, CSH-SC cells presented characteristic (pear-shaped, rod-shaped, or tadpole-shaped) neurosecretory granules. Although CSB and CSH were slightly serotonin positive by immunocytochemistry, only a few serotonin-positive cells were found in CSH-SC and none in CSH-IM, suggesting partial loss of differentiation or an increase in serotonin catabolism during transplantation."
-What was the purpose of the study on signal-averaged electrocardiogram (SAECG) reproducibility?,"A prospective evaluation of the immediate reproducibility of the signal-averaged ECG. The purpose of this investigation was to prospectively evaluate the immediate reproducibility of the signal-averaged electrocardiogram (SAECG). A total of 114 patients undergoing evaluation for ventricular arrhythmias were enrolled in this protocol. Two consecutive SAECG's (40 Hz bidirectional high-pass filtering with a computer-automated system) were performed 10 minutes apart. Abnormal SAECG parameters were defined as (1) vector QRS duration more than 120 msec, (2) terminal root mean square (RMS) voltage less than 20 microV, and (3) low-amplitude signal (LAS) duration more than 40 msec. An SAECG was defined as abnormal if at least one vector parameter was abnormal. There was close correlation between vector parameters during the two SAECG observations: QRS duration had the highest reproducibility (r2 = 0.97, p less than 0.001) followed by terminal RMS voltage (r2 = 0.92, p less than 0.001), and LAS duration (r2 = 0.90, p less than 0.001). The mean (+/- SD) percentage of change between the two recordings was 2% +/- 2% of the QRS duration, 13% +/- 22% for terminal RMS voltage, and 7% +/- 11% for LAS duration. The reproducibility of an initially normal SAECG was 92% and of an initially abnormal SAECG, 96%. Seventeen patients (15%) had a change in one of the three vector parameters between the two recordings. There were no clinically significant differences between the 17 patients in whom the SAECG was nonreproducible and the 97 patients in whom the SAECG was reproducible. However, reproducibility was significantly higher in patients with an initially normal versus an initially abnormal SAECG (92% vs 76%, p = 0.03)."
-What were the independent risk factors for stroke identified in this Chinese population study?,"Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke."
-What percentage of lung cancers showed an air bronchogram or air bronchiologram on CT scans and histologic sections in this study?,"Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors. Despite improved techniques--such as bronchoscopy and percutaneous needle biopsy--to evaluate pulmonary nodules, there are still many cases in which surgical resection is necessary before carcinoma can be differentiated from benign lesions. The present study was undertaken to determine if the presence of an air bronchogram or air bronchiologram (patent visible bronchus or bronchiole) is useful in distinguishing small lung cancers from benign nodules. Thin-section chest CT scans were obtained in patients with 20 peripheral lung cancers less than 2 cm in diameter (18 adenocarcinomas, one squamous cell carcinoma, and one large cell carcinoma) and 20 small benign nodules (eight hamartomas, seven tuberculomas, two foci of aspergillosis, one focus of cryptococcosis, one chronic focal interstitial pneumonitis, and one plasma cell granuloma). The images were compared with regard to the patency of any bronchus or bronchiole within the lesions. After surgical resection, the specimens were inflated with agar and sectioned transversely to correlate gross morphology and low-power histologic sections with the CT appearance. An air bronchogram or air bronchiologram was seen in the tumors on 65% of CT scans and 70% of histologic sections. Benign nodules had a patent bronchus or bronchiole on CT scans and histologic sections in only one case (5%). These findings suggest that the presence of an air bronchogram in a lung nodule is a useful finding to help differentiate adenocarcinomas from benign lesions."
-What were the most frequent complications observed in patients receiving long-term spinal morphine administration via Port-A-Cath?,"Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study. Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases)."
-How accurate is real-time ultrasound in detecting deep venous thrombosis (DVT) compared to contrast venography?,"Real-time ultrasound for the detection of deep venous thrombosis. PURPOSE: Accurate diagnosis of deep venous thrombosis (DVT) is a clinical problem in emergency practice. A prospective trial was conducted comparing real-time ultrasound with contrast venography in the diagnosis of proximal DVT. METHODS: Seventy patients whose clinical presentations mandated diagnostic evaluation for DVT had real-time ultrasound of the involved leg followed by contrast venography. Initial readings of ultrasound and venography were compared with each other and with final readings to assess reliability of interpretation. RESULTS: Final ultrasound readings agreed with final venogram readings in all patients. Negative initial ultrasound readings agreed with final venogram readings in 56 of 56 patients (negative predictive value, 100%; 95% confidence interval, 94 to 100). Eighteen patients had positive initial ultrasound readings compared with 14 who had positive final venogram readings (positive predictive value, 78%; 95% confidence interval, 55 to 91). CONCLUSION: Negative real-time ultrasonography reliably excludes proximal DVT. Positive ultrasound reliably diagnoses proximal DVT only in experienced hands."
-How does dual-chamber sensor-driven pacing compare to single-chamber pacing in terms of cardiac output for patients with chronotropic incompetence?,"Single- versus dual-chamber sensor-driven pacing: comparison of cardiac outputs. Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long-term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 +/- 0.3 L/min and 4.68 +/- 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 +/- 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 +/- 0.6 L/min and 7.41 +/- 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise (p less than 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value (p less than 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence."
-How does D-dimer affect the secretion of interleukin and other substances in the NOMO-1 human promonocytic leukemia cell line?,"FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line. We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation."
-What factors predict the success of stereotactic aspiration for colloid cysts?,"Stereotactic management of colloid cysts: factors predicting success. Stereotactic aspiration is a valuable surgical alternative for colloid cysts when used alone or in conjunction with microsurgical resection. Since 1981, the authors have performed computerized tomography (CT)-guided stereotactic aspiration as the initial procedure in 22 patients with colloid cysts; stereotactic aspiration alone was successful in 11 patients (50%). Of the 11 patients in whom aspiration failed, stereotactic endoscopic resection was attempted in three and was successful in one. Seven patients required a craniotomy and microsurgical removal of the cyst performed via a transcortical approach. The preoperative CT appearance in eight cases of a hypodense or isodense cyst correlated favorably with successful aspiration of the cyst in six patients. A hyperdense appearance on the preoperative CT scan in 14 cases was associated with subtotal aspiration in 13 patients; five required craniotomy for removal. Preoperative magnetic resonance (MR) imaging in eight patients provided excellent anatomical definition of the cyst and its relationship to other structures of the third ventricle, but it was not possible to correlate successful aspiration with cyst appearance on MR images with short or long relaxation time sequences. The authors' 9-year experience suggests that preoperative CT studies accurately determine size, predict viscosity, and help to define a group of colloid cyst patients for whom stereotactic cyst aspiration will likely be successful. Unsuccessful stereotactic aspiration was related to two features: the high viscosity of the intracystic colloid material (nine patients), or deviation of the cyst away from the aspiration needle due to small cyst volume (two patients). Because of its simplicity and low risk, stereotactic surgery can be offered to selected patients as the initial procedure of choice. Craniotomy can be reserved for those whose imaging studies predict failure or for those whose cyst cannot be aspirated."
-What percentage of patients with chronic demyelinating polyneuropathy showed MRI changes suggestive of demyelination?,"Cranial magnetic resonance imaging in chronic demyelinating polyneuropathy. Twenty one patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and five patients with chronic demyelinating polyneuropathy associated with benign monoclonal paraproteinaemia none of whom had signs or symptoms of central nervous system disease, had cranial magnetic resonance imaging (MRI) on a 1.5 Tesla unit. Areas of increased white matter signal intensity were seen in one of 10 patients aged less than 50 years and in five of 16 patients aged more than 50 years. In only two of the patients (8%), neither of whom had paraproteinaemia, did the appearance strongly suggest demyelination. The only clinical variable that predicted MRI changes was age (p less than 0.01)."
-How did the bleeding patterns differ between postmenopausal women receiving estradiol and norethisterone acetate versus estradiol and cyproterone acetate?,"Bleeding patterns during continuous combined estrogen-progestogen therapy. Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding."
-How does liver cirrhosis affect the metabolism and processing of lysophosphatidylcholine in rats?,"Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis. Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance."
-How many additional metastatic lymph nodes were found through serial sectioning in this study?,"The value of single versus multiple sections for detection of lymph node metastasis. This study was undertaken to determine the value of serial sectioning of lymph nodes as an aid in optimally examining cervical specimens for metastasis. The presence or absence of lymph node metastasis in 802 lymph nodes obtained from 51 consecutive neck dissection specimens were initially determined by the routine method, examination of one section from each node. This examination revealed 40 lymph nodes with metastatic involvement. Further study of the 716 lymph nodes that were initially interpreted as free of tumor by serial sectioning added only two positive nodes. Thus, serial sectioning did not contribute significantly to the detection of lymph node metastasis."
-What was the observed difference in hemolytic activity between plasma from ALS patients and normal controls?,"Cytotoxic activity in plasma from patients with amyotrophic lateral sclerosis. The present study evaluates an assay of cytotoxic effect of plasma from patients with amyotrophic lateral sclerosis. Plasma from 20 recently diagnosed ALS patients induced hemolysis of normal red blood cells with a significantly greater intensity than that of normal controls. After at least 1 month of treatment with prednisone and azathioprine, the hemolytic activity of ALS plasma was reduced but was still higher than that of control plasma."
-What are the MR imaging characteristics of giant cell tumors in patients with Paget disease of bone?,"Multiple giant cell tumors and Paget disease of bone: radiographic and clinical correlations. The clinical and radiographic findings of four patients with multicentric giant cell tumor (GCT) of bone and Paget disease were retrospectively reviewed. Three patients underwent magnetic resonance (MR) imaging evaluation; all patients underwent computed tomography (CT). The MR characteristics of the bone component in pagetic GCT appeared to reflect the pagetic phase; a sclerotic pattern was largely represented by hypointense marrow signal intensity on images obtained with both long and short repetition times (TRs) and echo times (TEs). Conversely, a tumor appearing in a mixed pagetic phase demonstrated more heterogeneous signal intensity with all pulse sequences. Extensive soft-tissue components, noted in all cases, showed largely intermediate signal intensity on short TR/TE images and foci of increased signal intensity on longer TR/TE images. In most cases, dramatic reduction in tumor bulk was noted with the use of steroids alone. An awareness of this entity is important because the appearance of lytic lesions with soft-tissue extension in patients with Paget disease does not necessarily imply a grave prognosis. Serial CT or MR imaging is helpful in monitoring the remissions and exacerbations that reflect response to therapy in Paget disease and GCT."
-What are the key MRI findings and considerations when assessing the postoperative spine in patients with degenerative disc disease?,"Magnetic resonance assessment of the postoperative spine. Degenerative disc disease. The magnetic resonance (MR) imaging findings in patients after surgery for degenerative disc disease in the lumbar and cervical spine are discussed. In the lumbar spine, changes seen in the immediate postoperative period, use of Gd-DTPA in distinguishing scar and disc and postoperative complications are reviewed. In the cervical spine, operative approaches and types, the appearance of bony stenosis, and disc herniations are demonstrated."
-What are the advantages and outcomes of using the pedicled island flap technique for repairing complicated urethral strictures?,"Urethroplasty using the pedicled island flap technique in complicated urethral strictures. Many techniques have been described for the repair of recurrent urethral strictures. Experience with 1-stage correction of hypospadias and epispadias, using a vascularized island flap technique, has led to its increased application for complicated adult urethral strictures. The advantage of the vascularized island flap technique is that reconstruction can be completed with only 1 operation, and it provides good subjective and objective results. Analysis of 50 consecutive cases treated by this approach has proved its validity. Of the 50 cases fistulas occurred in 20%, of which 12% required surgical correction, and stricture recurred in 32%. The largest proportion of recurrence was noted in patients who were primarily treated with 3 or more urethrotomies within a short time. Therefore, we recommend open surgical repair when 1 or 2 internal urethrotomies fail to produce a good result."
-What percentage of HIV-seropositive patients were found to have bullous pemphigoid (BP)-type autoantibodies in the study?,"Bullous pemphigoid autoantibodies, HIV-1 infection and pruritic papular eruption. Bullous pemphigoid (BP)-type autoantibodies were found by Western blot (WB) analysis of epidermal extracts in the serum of 38% of HIV-seropositive patients compared with 21% of HIV-seronegative patients with chronic pruritus and 76% of patients with BP. They were further identified as BP autoantibodies (BPab) by immunoprecipitation and immunoelectron microscopy. Their incidence increased from 21% in HIV infection stage II to 37% and 43% in stages III and IV, respectively. Of the patients suffering from HIV-related chronic pruritic papulovesicular eruption. 75% showed circulating BPab as compared with 29% in those without skin problems (P = 0.0066) and, among them, 30% met the diagnostic criteria for BP when histology, WB, immunofluorescence and immunoelectron microscopy techniques were used. In conclusion, this study identifies an autoimmune skin reaction that may account for, or be related to, the distressing pruritic eruptions occurring in HIV-infected patients."
-What is the significance of the DNA segment isolated from the agouti locus in mice?,Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse. Molecular characterization of a radiation-induced agouti (a)-locus mutation has resulted in the isolation of a segment of DNA that maps at or near the a locus on chromosome 2 in the mouse. This region of DNA is deleted in several radiation- or chemical-induced homozygous-lethal a-locus mutations and is associated with specific DNA structural alterations in two viable a-locus mutations. We propose that DNA probes from this region of chromosome 2 will be useful for ultimately characterizing the individual gene or genes associated with a-locus function.
-How do fish oils (EPA and DHA) affect platelet aggregation induced by nitrogen microbubbles?,"Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles. Platelet aggregation induced by N2 microbubbles (simulating microbubbles developed during deep diving) was measured in seven volunteers before and after intake of ethyl-eicosapentaenoate (-EPA, 3.5 g/day) and ethyl-docosahexaenoate (-DHA, 2.5 g/day) for 2 wk. The relative content of arachidonic acid (AA) decreased in platelets from all individuals, whereas the content of EPA and DHA increased. The decrease of AA was almost identical with the increase of EPA plus DHA. In plasma the AA content was unchanged, while EPA and DHA increased. The N2 microbubble-induced aggregation showed a significant negative correlation with the DHA content both in platelets and in plasma. Less aggregation was also observed with high EPA content in platelets or plasma. A significant correlation between AA content in platelets and aggregation was seen. Intake of marine oils may be beneficial to divers under deep diving and to patients during extracorporeal circulation, because this may reduce the microbubble-induced aggregation."
-What is midventricular obstruction and how does it relate to chronic systemic hypertension?,"Midventricular obstruction associated with chronic systemic hypertension and severe left ventricular hypertrophy. Midventricular obstruction is an uncommon finding previously defined by catheterization and angiographic techniques in patients with hypertrophic cardiomyopathy. This study describes the clinical and echocardiographic findings of 10 consecutive patients (mean age 73 years) with severe concentric left ventricular (LV) hypertrophy and the unusual finding of a dynamic systolic obstruction located in the midportion of the left ventricle. All patients were known to have chronic hypertension, and none had a history or family history of hypertrophic cardiomyopathy. In each case, a well-defined, high velocity, turbulent jet was identified by Doppler color flow imaging and subsequently confirmed with conventional Doppler techniques. Septal and posterior wall thickness averaged 1.67 and 1.57 cm, respectively. Mean LV mass index was 199 g/m2 and ejection fraction averaged 78%. Peak systolic velocity obtained by continuous-wave Doppler averaged 2.7 m/s and appeared as either a ""late-peaking"" or a ""spike and dome"" configuration. Seven of 10 patients gave a history of syncope or severe presyncope at the time of echocardiographic examination. At a mean follow-up of 1 year, syncope or presyncope had resolved in 5 patients in whom medication was adjusted based on the ultrasound study, but persisted in 2 patients in whom diuretic therapy was continued. It is concluded that obstruction to systolic flow can occur at the mid-LV level in some patients with severe concentric LV hypertrophy and avoidance of medication known to lower LV volume may relieve symptoms of transient inadequate cardiac output."
-How do blood type differences impact waiting times and graft survival in cadaveric renal transplantation?,"The impact of nonidentical ABO cadaveric renal transplantation on waiting times and graft survival. Blood type O recipients of cadaveric renal transplants have longer pretransplant waiting periods than blood type A, B, and AB recipients. To evaluate reasons for and consequences of this discrepancy, we studied both the frequency of various donor and recipient blood type combinations and their outcomes. Among 37,659 cadaveric renal transplants performed during 1983 through 1989, there were 2,625 transplants (7%) received by patients of compatible but nonidentical blood types. Of 18,575 type O donor organs, 16,784 were received by type O patients for a recipient to donor ratio of 0.9. The corresponding ratios were greater than 1.0 for all other blood types (1.02 for blood type A, 1.14 for type B, and 2.18 for type AB). This causes blood type O patients to have a lower access to transplantation and to have significantly longer waiting times than patients of all other blood types. This inequality of access diminished significantly (P less than 0.001) over the years, but did not resolve by 1989. Analysis of relative risk for first graft loss by multiple regression (Cox) showed that transplantation across compatible blood types had a 9.1% higher risk (P less than 0.1) than that of transplantation among identical blood types. Cadaveric renal transplantation within identical blood types optimizes access to transplantation and avoids further aggravating past disadvantages for blood type O recipients."
-What were the key findings of the study comparing streptokinase and recombinant tissue plasminogen activator (rTPA) in treating acute lower limb ischaemia?,"Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia. Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase."
-What rare cardiac condition did the woman present with due to metastatic melanoma?,"Metastatic melanoma to the heart presenting with ventricular tachycardia. Intraventricular tumors in adults are uncommon, and the association of these with ventricular tachycardia is even more rare. We report a case of an intracardiac metastatic melanoma in a woman who presented with syncope due to ventricular tachycardia."
-What clinical methods are used for risk stratification in patients after a myocardial infarction?,"Risk stratification after myocardial infarction. Clinical overview. Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification."
-What is the clinical significance of recurrent pericarditis in hypocomplementemic urticarial vasculitis syndrome?,"Recurrent pericarditis and cardiac tamponade in a patient with hypocomplementemic urticarial vasculitis syndrome. We describe a patient with hypocomplementemic urticarial vasculitis syndrome complicated by recurrent pericarditis and cardiac tamponade. The episodes of pericarditis were associated with urticarial vasculitis, hypocomplementemia, and circulating IgG antibodies to the collagen-like region of Clq. Histopathologic examination of the skin and pericardium demonstrated vasculitis associated with immunoglobulin and complement deposition suggesting an immune complex mediated etiology. Recurrent pericarditis should be included in the clinical spectrum of hypocomplementemic urticarial vasculitis syndrome."
-How did supplemental oxygen affect breathlessness and oxygen saturation in patients with chronic obstructive airway disease (COAD) and interstitial lung disease (ILD)?,"Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease. We have compared the symptomatic benefit of air and oxygen at rest in hypoxemic patients with chronic obstructive airway disease (COAD) or interstitial lung disease (ILD). A total of 12 severely disabled patients with COAD (mean +/- SEM, PaO2, 50.3 +/- 3.7 mm Hg) and 10 with ILD (PaO2, 48.0 +/- 3.1 mm Hg) received 28% oxygen and air by Venturi face mask, each gas on two occasions, in a double-blind randomized fashion. SaO2 increased (p less than 0.01) in both groups during oxygen breathing: COAD, 85.1 +/- 2.3% versus 93.1 +/- 1.4%; ILD, 85.5 +/- 1.7% versus 94.7 +/- 0.9%. The patients with COAD stated that air helped their breathing on 15 of 24 occasions and that oxygen helped on 22 of 24 occasions (p less than 0.05). In the patients with ILD the values were 6 of 20 and 13 of 20 occasions, respectively (p less than 0.05). In both groups of patients the severity of breathlessness recorded on a 100-mm visual analog scale was significantly (p less than 0.05) lower during oxygen breathing: COAD, 29.6 +/- 4.5 versus 45.6 +/- 6.0; ILD, 30.2 +/- 5.1 versus 48.1 +/- 4.4. Ventilation measured by magnetometers was significantly lower during oxygen breathing in the patients with COAD (8.2 +/- 1.0 versus 9.3 +/- 1.1 L/min; p less than 0.05), but the difference between oxygen and air in patients with ILD was not statistically significant (9.3 +/- 1.3 versus 11.2 +/- 1.6 L/min; p greater than 0.05)."
-What was the impact of mitomycin C (MMC) as an adjuvant treatment on survival rates in patients with resected gastric cancer after a 10-year follow-up?,"Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up. Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up."
-What are the key histological and histochemical characteristics of mucin-producing tumors in the pancreas?,"Mucin-producing tumor of the pancreas. A new pancreatic tumor, called mucin-producing tumor, has received great attention in Japan. These tumors are found inside the pancreatic duct and produce large quantities of copious mucus. The authors examined 22 cases of these tumors histologically and histochemically. In 12 malignant cases, the tumors inside the ducts consisted of cancerous lesions over small areas along with papillary or atypical hyperplasia. Tumors in ten benign cases mainly consisted of papillary hyperplasia. Except for three patients with carcinoma in situ, cancerous tumors infiltrated the pancreatic parenchyma and, in some cases, were observed invading the bile duct or duodenum. A mucous histochemical study showed evidence of sialomucin in malignant cases; neutral mucin was dominant in benign cases. Characteristics of this disease were also compared with 13 cases of mucinous cystic neoplasm. From the results, it was concluded that these two diseases can be classified into the same conceptual category."
-How was acute massive hepatic injury induced in rats in this experimental model?,"A rat model of acute liver necrosis induced by a monoclonal antibody to liver-specific antigen and complement. Acute massive hepatic injury was induced in rats by a monoclonal antibody against a rat liver-specific membrane antigen, and its histological characteristics were investigated. A single intravenous injection of murine ascites containing a monoclonal antibody produced numerous hemorrhagic foci of degenerated and necrotic liver cells predominantly in zones 1 (the periportal area) and 2 (the area of transition between the periportal zone and the perivenular zone) of the liver lobule within 10 min. Massive hepatocellular necroses were observed 1 hr later, but no inflammatory cell infiltration occurred in and around the necrotic foci. Immunohistological study demonstrated marked deposition of the third component of the complement system in the necrotic area. Serum complement activity was sharply decreased immediately after the injection of the antibody, suggesting that the hepatic necrosis is ascribable to a complement-mediated immune attack on the liver cell membrane induced by the antigen-antibody reaction. The hepatic necrosis in response to monoclonal-antibody injection did not progress to a chronic disease and healed almost completely, changing to scar tissues within 2 wk. Although it is not clear whether this hepatic injury has any clinical relevance, this antibody/complement model may be useful for investigating the cause and therapy of hepatic diseases such as fulminant hepatitis."
-What unique observation was made about the lateral rectus muscle after the silicone band transection in this case report?,"Preserved action of a rectus muscle after transection by an encircling solid silicone band. We present a case of anterior migration of a solid silicone band through a lateral rectus muscle. In this patient the action of the lateral rectus was preserved, and this is demonstrated photographically. The possible reasons for this rare complication and the possible mechanism by which lateral rectus activity remained intact are explained."
-What is the primary histologic reaction pattern in Behcet's disease?,"Clinical features of Behcet's disease. Report of four cases. Behcet's disease is a multisystem inflammatory disorder of unknown etiology. The unifying histologic reaction pattern is a leukocytoclastic vasculitis that affects predominantly the skin, oral mucosa, and eyes. Many other sites of involvement have been reported but are inconsistently found in individual patients. Early recognition and treatment of Behcet's disease may help prevent devastating permanent sequelae such as blindness. Because oral involvement is often the first manifestation of this disorder, dental practitioners are in a unique position to help these patients. We report four cases of Behcet's disease in North American patients. Diagnostic criteria and treatment options are reviewed."
-How did recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) impact neutrophil recovery and patient outcomes in autologous bone marrow transplantation for lymphoid cancer?,"Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. BACKGROUND. The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS. We conducted a randomized, double-blind, placebo-controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty-eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS. No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS. In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration."
-What differences were observed between Candida tropicalis and Candida albicans fungemia in children with leukemia?,"Candida tropicalis and Candida albicans fungemia in children with leukemia. The records were reviewed for all patients hospitalized at a pediatric oncology center for complications of leukemia (n = 822) or lymphoma (n = 290) during an 8-year period. The results of surveillance cultures (throat, rectal, and urine) and blood cultures were analyzed to identify cases of Candida tropicalis and C. albicans colonization and/or fungemia. None of the patients with lymphoma who had positive surveillance cultures for C. albicans (n = 89) or C. tropicalis (n = 23) had fungemia. Among patients with leukemia, significant fungal infection was documented in 12 of 107 colonized with C. tropicalis (11.2%) versus 14 of 700 (2%) colonized with C. albicans (P less than 0.001). The two groups of children with fungemia were similar in primary diagnoses (predominantly acute lymphoblastic leukemia) and in the frequency of several known risk factors for infection, including the duration of neutropenia (absolute neutrophil counts, less than 500/microliters). Patients with C. tropicalis fungemia all had disseminated disease compared with nine of 14 patients with C. albicans fungemia. Also, subcutaneous abscesses were unique to patients with C. tropicalis in this series. Two patients in each group died of their infection; central nervous system involvement was present in both fatal cases of C. tropicalis fungemia. A high index of suspicion and the early institution of appropriate antifungal therapy are critical to the successful management of these infections in patients with leukemia."
-What was the relationship between the degree of coronary stenosis and mortality in patients who survived an anterior wall Q-wave acute myocardial infarction?,"Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05)."
-What are the contributing factors that may lead to late bleeding after rhytidectomy?,"Late bleeding after rhytidectomy from injury to the superficial temporal vessels. Five healthy, normotensive women, whose mean age was 49.8 years, developed expanding hematomas between 8 and 10 days (average 9 days) after rhytidectomy. In each patient, the bleeding vessel could be identified: In two, it was the parietal branch of the superficial temporal artery; in two, it was the parietal branch of the superficial temporal vein; and in one, it was the superficial temporal artery immediately before its branching. Contributing factors may have been sudden physical exertion in four of the five patients and in another salicylate ingestion. Several measures can help avoid late bleeding from the superficial temporal vessels or their branches; not using a too potent vasoconstrictive agent (epinephrine) in the local anesthetic so that the vessels will be easier to visualize; not injecting the local anesthetic too deeply or incising to deeply; dividing and ligating the superficial temporal vessel and its major branches if injured; using bipolar coagulation on small branches; and instructing patients repeatedly not to engage in strenuous activity or to ingest salicylates for at least 2 weeks after operation."
-What is the current understanding of dietary fiber's effectiveness in managing constipation and diarrhea in tube-fed patients?,"Dietary fiber and bowel function in tube-fed patients. In tube-fed patients, dietary fiber is often used to manage constipation/diarrhea. Dietary fiber consists of water-soluble and insoluble plant compounds that are resistant to digestion by small-bowel enzymes but are fermented to varying degrees by colonic bacteria. Many physiologic effects of fiber may be related to the degree of fermentation. Few controlled studies of fiber-containing tube feedings have been performed. These studies have limitations and are nondefinitive as to whether fiber prevents or controls constipation/diarrhea. Constipation in tube-fed patients has not been shown to respond to mixed soluble/insoluble fiber in the few studies performed to date. Likewise, fiber may be of only limited benefit in controlling diarrhea in acute illness because of such factors as stress or medication. Fiber does play a role in maintaining gut integrity in all patients, whether they have diarrhea or not. Fiber may be recommended as part of a standard tube-feeding regimen to help assure gut mucosal integrity but not specifically to treat constipation/diarrhea. Further studies are necessary before the role of fiber in the management of constipation/diarrhea in tube-fed patients is determined."
-What was the effectiveness of fluconazole in treating hepatosplenic candidiasis in patients who did not respond to previous antifungal treatments?,"Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy."
-What abnormal vascular responses were observed in patients with hypertrophic cardiomyopathy during exercise?,"Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy. BACKGROUND. Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads. METHODS AND RESULTS. To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001). CONCLUSIONS. The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy."
-What were the significant predictors of death on the first day in the Surgical Intensive Care Unit (SICU)?,"Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications. The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU."
-What potential complications can arise from percutaneous insertion of an intra-aortic balloon pump?,"Aortoiliac dissection after percutaneous insertion of an intra-aortic balloon pump. Aortic or aortoiliac dissection may complicate percutaneous intra-aortic balloon pump insertion in various ways. Thrombosis can escape clinical recognition if no major obstruction develops. Death due to perforation after dissection is not uncommon. In this case study, aortoiliac dissection led to bilateral iliac artery stenosis, an unusual complication of percutaneous femoral cannulation for insertion of a balloon pump."
-How does heart rate affect pulmonary artery acceleration time in different levels of pulmonary artery pressure?,"Effects of heart rate and pulmonary artery pressure on Doppler pulmonary artery acceleration time in experimental acute pulmonary hypertension. Chronic pulmonary hypertension in humans is characterized by shortening of the pulmonary artery acceleration time as measured by Doppler echocardiography, such that the higher the pulmonary artery pressure, the shorter the pulmonary acceleration time. Increases in heart rate are also known to produce decreases in the pulmonary artery acceleration time. To explore the relationship between mean pulmonary artery pressure, heart rate, and Doppler pulmonary artery acceleration time, experimental acute pulmonary hypertension was created in nine Duroc swine, either by infusion of Sephadex beads with embolization of the pulmonary arterial circulation or by partially occluding the main pulmonary artery 8 to 10 cm distal to the pulmonic valve. Pulmonary artery Doppler flow velocity recordings and invasive pressure measurements were made at baseline and at paced atrial rates ranging from 60 to 160 beats per minute, in 20-beat increments. The results in this acute animal model reveal that increases in heart rate produced significant decreases in Doppler pulmonary artery acceleration time at mean pressures below 25 mm Hg. However, with mean pulmonary artery pressures greater than 25 mm Hg, both heart rate and increases in pulmonary artery pressure had no significant effect on acceleration time."
-How does hypertension and elevated cholesterol affect the fibrinolytic system?,"Hypo-fibrinolysis in patients with hypertension and elevated cholesterol. To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI."
-"How does Doppler ultrasound help in identifying a small, clinically undetectable ductus arteriosus?","Doppler ultrasound and the silent ductus arteriosus. A clinically undetectable, small ductus arteriosus was identified by Doppler ultrasonography in 21 individuals. Infants were excluded from the study and no patient had pulmonary hypertension. Persistence of the ductus arteriosus is likely to be more common than shown by less sensitive diagnostic methods. Some patients considered to have infective endocarditis with a normal heart may have a silent ductus arteriosus. Evidence of such an association would justify ligation or antibiotic cover as prophylactic measures."
-What may cause tears in the retinal pigment epithelium according to the context?,Tears of the retinal pigment epithelium: occurrence in association with choroidal effusion. Two patients developed large tears of the retinal pigment epithelium associated with choroidal effusion. One tear occurred after combined cataract/filtration surgery complicated by postoperative choroidal detachment; the second developed in a patient with idiopathic uveal effusion syndrome. Weakness of the junctions of the pigment epithelial cells secondary to the accumulation of fluid in the subretinal or suprachoroidal space may result in tearing of the retinal pigment epithelium as it is stretched.
-How did different nutritional regimens affect the cell kinetic activity of gastrointestinal tumors in this preliminary study?,"Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report. Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H-TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy."
-What was the interval between HBV infection and HCC appearance in the three reported cases?,"HBV-DNA-related hepatocellular carcinoma occurring in childhood. Report of three cases. In a series of 325 HBV chronically infected children observed over an 18-year period, three developed HCC. These three children were born in southern Italy, a region characterized by a high endemic HBV infection rate; each had been infected perinatally, developed an acute hepatitis, and became a chronic carrier. Two of the three with cirrhosis were HBsAg positive at the time their HCC was detected. The remaining case had seroconverted to HBsAb but HBV-DNA integration could be demonstrated in the absence of cirrhosis; moreover HBV antigens were not expressed in the tissue of this case. The interval between HBV infection and HCC appearance in these three cases ranged from six to 11 years. A similarity between these three Italian cases and the majority of HCC arising in chronically infected children in the Far East is noted."
-"What is the medical condition described in the context, and how long has the patient been experiencing recurrent symptoms?",Localized recurrent postoperative pernio associated with leukocytoclastic vasculitis. A patient with recurrent pernio of the right ankle for 21 years after surgery had a leukocytoclastic vasculitis localized in the area. We suggest that the various histologic descriptions of pernio in the literature and in this case represent different levels of severity of the disease.
-What advantages does the microvascular peritoneal flap offer for intraoral reconstruction?,"Intraoral reconstruction with a microvascular peritoneal flap. The microvascular peritoneal flap offers a new reconstructive option for closure of intraoral defects. The flap is easy to raise, and donor-site morbidity is low. Unlike fascial flaps, in which the raw surface may take weeks to ""mucosalize,"" the peritoneal surface heals primarily. Finally, the rectus muscle effectively covers all forms of mandibular reconstruction, and the reliable skin paddle makes possible the closure of substantial cutaneous defects."
-How does transcutaneous electrical nerve stimulation (TENS) therapy affect uterine activity in women with primary dysmenorrhea?,"Interrelation of analgesia and uterine activity in women with primary dysmenorrhea. A preliminary report. The interrelation between uterine activity and pain from primary dysmenorrhea has been of interest for many years. Objective studies of uterine activity during non-steroidal antiinflammatory drug therapy have supported the assertion that uterine activity causes pain and that reducing that activity leads to pain reduction. Unfortunately, those studies could not refute the counter-assertion that reductions in uterine activity come about because of reduced pain through central analgesia and not by direct pharmacologic action. In an effort to clarify this question, a small number of women were studied using intrauterine pressure recording and analysis to evaluate objective changes in uterine physiology during transcutaneous electrical nerve stimulation (TENS) therapy for dysmenorrhea. The preliminary studies indicated that despite successful subjective therapy with TENS, intrauterine pressure parameters remained steady or showed signs of worsening. These findings indicate that TENS provides pure analgesia by an alteration of the body's ability to receive or perceive the pain signal rather than by a direct uterine effect. It appears that the reduction in uterine activity seen in objective drug studies represents direct drug action rather than a change from reduced pain through central analgesic effects."
-What was the purpose of the laboratory study on psyllium hydrophilic mucilloid (PHM) added to enteral feeding formula?,"Flow characteristics of enteral feeding with psyllium hydrophilic mucilloid added. One therapy for managing diarrhea in patients in intensive care units who are receiving enteral nutrition is administration of psyllium hydrophilic mucilloid (PHM). This laboratory study was conducted to determine whether the addition of PHM (Metamucil) to enteral feeding formula (Entrition) adversely affected the flow characteristics of the feeding formula through a small-bore feeding tube. Descriptive data were obtained from 72 trials of feeding formula with varied infusion rates, formula osmolality and temperature, and PHM concentrations. Two thirds (n = 48) of the trials were successful (PHM did not clog the tubing and obstruct flow). The remaining one third of the trials (n = 24) were unsuccessful. Successful formula infusion was influenced by formula temperature and osmolality but not by infusion rate, PHM concentration, or flow interruption. If formula with PHM was followed by formula without PHM, the infusion was successful regardless of infusion rate or formula osmolality. Thus, the data from this laboratory study indicate that when therapeutic doses of PHM are prescribed, it is feasible for PHM to be mixed in room-temperature feeding formula and infused without clogging the feeding tube."
-How does growth hormone influence kidney growth and scarring in experimental models?,"The role of growth hormone and insulin-like growth factor-I in experimental renal growth and scarring. Recent evidence suggests a causal link between early renal/glomerular hypertrophy and late kidney scarring and glomerular sclerosis. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide likely to play a role in the development of kidney growth. We observed an increased renal IGF-I content in two experimental models of accelerated kidney growth in the rat. By contrast, diabetic renal hypertrophy is abolished in the absence of growth hormone (GH). Dietary protein manipulations affect the expression of compensatory renal growth (CRG), as well as renal IGF-I content. The renotrophic effect of a high-protein diet on CRG seems GH-dependent and IGF-I-mediated. GH also appears to have a permissive role on the development of progressive renal scarring following extensive renal ablation in rats, as dwarf rats seem somewhat resistant to the development of accelerated scarring and renal failure."
-What was the 20-year survival probability for patients with T2N0M0 stage I breast carcinoma in this long-term follow-up study?,"Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients."
-How do serum endothelin-1 (ET-1) concentrations differ between subjects with primary Raynaud's phenomenon and control subjects during cold provocation?,"Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6] degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml) than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder."
-What is the key finding of this study regarding the treatment of arteriovenous malformations with peripheral aneurysms?,"Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer. Report of three cases. The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n-butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery."
-What complication did the 36-year-old mentally retarded patient experience with his Foley catheter gastrostomy tube?,"Duodenal obstruction by a nondeflating Foley catheter gastrostomy tube. We report the case of a 36-year-old mentally retarded man who presented to our emergency department after one day of vomiting and one episode of coffee-ground emesis. The Foley catheter used as his gastrostomy tube was found to be obstructing the duodenum, and the balloon could not be deflated. Removal was accomplished by rupturing the balloon by endoscopy. Our case illustrates one of many possible complications of feeding gastrostomy tubes."
-What were the most common histologic types of soft tissue sarcomas found in the chest wall in this study?,"Soft tissue sarcomas of the chest wall. Results of surgical resection. Primary soft tissue sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. Most studies have categorized these tumors as truncal sarcomas and inferred a poor prognosis. To assess the results of surgical treatment, we reviewed our 40-year experience. Methods: Records of 189 patients admitted to our institution from 1948 to 1988 were reviewed. Pathologic material was available for review in the 149 cases (79%) that comprise this report. Survival was calculated by the Kaplan-Meier method, with comparisons by log-rank analysis and significance defined as p less than 0.05. Results: Ages ranged from 3 weeks to 86 years (median, 38 years); the ratio of male to female patients was 2:1. The initial complaint was mass or pain in 97% of the cases. Ninety sarcomas (60%) were high grade and 59 (40%) were low grade. Histologic types were as follows: desmoid tumor (n = 32, 21%); liposarcoma (n = 23, 15%); rhabdomyosarcoma (n = 18, 12%); fibrosarcoma (n = 17, 11%); embryonal rhabdomyosarcoma (n = 14, 9%); malignant peripheral nerve tumor (n = 13, 9%); malignant fibrous histiocytoma (n = 11, 7%); spindle cell sarcoma (n = 4, 3%); tenosynovial sarcoma (n = 3, 3%); hemangiopericytoma (n = 3, 3%); alveolar soft part sarcoma (n = 3, 3%); and other types (n = 12, 9%). Resection was the primary treatment in 140 cases (94%). Local recurrence developed in 27%. Metastases occurred in 52 (35%) of the cases (metachronous in 42, synchronous in 10) and were more common in patients with high-grade disease (46/90, 51%) than in those with low-grade disease (6/59, 10%). Overall 5-year survival was 66%. Five-year survival rate for those with high-grade sarcomas (49%) was significantly lower than that for low-grade sarcomas (90%, p less than 0.0001). Tumor size and age of patient were not prognostic. Conclusions: Survival of patients with primary soft tissue sarcomas of the chest wall after resection is similar to that of patients with sarcomas of the extremities. Resection alone provides acceptable survival (90% at 5 years) for those with low-grade sarcomas, but adjuvant treatment should be considered for those with high-grade sarcomas."
-"How do cephalometric measurements differ between patients with sleep apnoea, non-apnoeic snorers, and non-snoring control subjects?","Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age."
-How effective are intravascular stents in managing superior vena cava syndrome?,"Intravascular stents in the management of superior vena cava syndrome. Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome."
-"How do environmental chemicals and pollution impact public health in developing countries, particularly in relation to malnutrition and infectious diseases?","Chemicals and environmentally caused diseases in developing countries. This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of ""developing countries,"" the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries."
-What did the multivariate analysis reveal about prognostic indicators in acute spinal cord injury?,"Acute spinal cord injury: magnetic resonance imaging correlated with myelopathy. Thirty-one patients (29 males and two females, 13-87 years of age (mean, 46.7 years] with acute spinal cord injury were studied by MR (magnetic resonance) imaging and the results were correlated with neurological findings. Magnetic resonance images were obtained with a 0.5 T superconductive MR scanner (Phillips Gyroscan S5). Initial imaging was performed within 24 hours after trauma in 13 patients, 1-7 days in 13 patients and 7-14 days in five patients. Twenty-six patients underwent follow-up examinations with MR imaging. Cord abnormalities including cord compression (23 patients), cord swelling (seven patients), and abnormal signal intensities on either T1 or T2-weighted images (26 patients) were observed on initial examination. Multivariate analysis showed that cord compression and abnormal intensities on T1-weighted images were important prognostic indicators. Hyperintensity on T2-weighted images was non-specific but correlated well with clinical recovery. Magnetic resonance imaging is useful in predicting the prognosis and for planning treatment following spinal cord injuries."
-Can vitamin D deficiency cause an unusual pain syndrome with hyperesthetic characteristics?,"Can vitamin D deficiency produce an unusual pain syndrome? An unusual pain occurred in five patients in the presence of compromised vitamin D status and resolved 5 to 7 days after supplementation with vitamin D in the form of ergocalciferol. The pain had a hyperesthetic quality and did not respond to the use of analgesics, including opiate derivatives. Treatment with therapeutic levels of a tricyclic antidepressant did not bring relief of symptoms. In one case, months after treatment and subsequent improvement of vitamin D status and pain, the vitamin D status again declined and the pain recurred. The pain again resolved with vitamin D replacement and improvement of levels. There may be a pain syndrome associated with vitamin D depletion that appears as hyperesthesia worsened by light, superficial pressure or even small increments of movement. This pain restricts mobility and function and may lead to further complications, such as pressure sores."
-What was the success rate of operations for dividing atrioventricular accessory pathways in patients with Wolff-Parkinson-White syndrome?,"Operations for Wolff-Parkinson-White syndrome. Forty-six patients with symptomatic tachycardia underwent operations to divide 55 atrioventricular accessory pathways. Mean age was 29 years (range 11 to 63). Ten patients (22%) had associated cardiac disease, including two with a congenital diverticulum of the coronary sinus and six (13%) who had concomitant surgical procedures. A bipolar hand-held electrode was used in 22 operations, and simultaneous multisite mapping in the last 24 operations. Ten patients (22%) had multiple accessory pathways. A modified endocardial approach was used. The overall patient success rate was 93% with 91% to 93% of accessory pathways successfully divided. The perioperative morbidity was 17%. There were two reoperations. There were no early or late deaths. Patients have been followed up for a mean of 16 months. There were five recurrences of preexcitation (two early, three late). Two of these patients (both with a congenital diverticulum of the coronary sinus) had reoperation. One patient had late recurrence of atrial fibrillation. Operation for the Wolff-Parkinson-White syndrome has a high probability of success with a low operative risk."
-How do oral contraceptives potentially impact metabolic risk markers related to coronary heart disease?,"Oral contraceptives and coronary heart disease. In industrialized countries, coronary heart disease (CHD) is a major public health problem for both men and women. Preventive strategies for reducing the excessive mortality and morbidity associated with CHD involve the identification and modification of metabolic factors believed to be involved in the disease process. Three major areas of concern are lipid metabolism, carbohydrate metabolism and the hemostatic system. The steroid hormones contained in oral contraceptives (OCs) have been shown to interfere in all three areas. In many instances OCs have been shown to alter metabolic markers for CHD in directions associated with increased risk. Although evidence is lacking that such changes induce CHD in users of modern, low-dose OCs, it would be prudent to develop formulations with a minimal impact on metabolic risk markers. There is increasing evidence that many of the metabolic disturbances seen in CHD patients share a common origin, and the development of risk-free OCs is likely to require investigation into complex interrelationships."
-What was the purpose of this pilot study involving Fluosol and emergency coronary angioplasty in patients with anterior myocardial infarction?,"Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05)."
-What are the advantages of using the rectus abdominis free flap in head and neck reconstruction?,"The rectus abdominis free flap in head and neck reconstruction. The rectus abdominis musculocutaneous free flap, based on the deep inferior epigastric artery and vein, has been used widely in reconstruction of the breast and extremities. The number of reports on its applications in the head and neck is limited. The rectus abdominis free flap is one of the most versatile soft-tissue flaps. The deep inferior epigastric artery and vein are long, large-diameter vessels that are ideal for microvascular anastomoses. The area of skin that can be transferred is probably the largest of all flaps presently in use. The versatility of this donor site is due to the ability to transfer large areas of skin with varying thicknesses and varying amounts of underlying muscle. We have successfully used this flap in 15 consecutive patients to reconstruct defects of the neck, face, mouth, pharynx, skull base, and scalp. No major complications involving either the recipient or donor sites occurred. The literature on the use of the rectus abdominis flap in head and neck reconstruction is reviewed in detail. The advantages and disadvantages of this soft-tissue free flap are thoroughly discussed in an effort to better define its proper place among the reconstructive options available to the head and neck surgeon."
-How did the protein and fat intake affect glomerular filtration rate and urinary protein loss in patients with membranous nephropathy?,"Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome. Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake."
-How did oral ofloxacin compare to parenteral antibiotics in treating chronic osteomyelitis?,"Ofloxacin versus parenteral therapy for chronic osteomyelitis. We conducted a randomized comparison of oral ofloxacin (400 mg twice a day) and parenteral agents (cefazolin, 1.0 g intravenously every 8 h, or ceftazidime, 2.0 g intravenously every 12 h) in biopsy-confirmed, nonprosthesis osteomyelitis. A total of 19 subjects received ofloxacin for an average of 8 weeks, and 14 received parenteral antibiotics for an average of 4 weeks; both therapies were well tolerated. Infections were due to Staphylococcus aureus (40%), Enterococcus spp. (3%), Pseudomonas aeruginosa (15%), and other gram-negative organisms (42%). At the completion of therapy, one P. aeruginosa infection in the ofloxacin group persisted and the organism acquired resistance, accompanied by a resistant Acinetobacter superinfection. In the parenteral group, one S. aureus infection persisted, and there was a resolved superinfection due to S. aureus as well. Eighteen-month follow-up data have been obtained. Among those treated with ofloxacin, four subjects whose initial response to therapy was successful suffered relapses of infection, three due to S. aureus and one due to P. aeruginosa, while in the parenteral group, one subject with a P. aeruginosa infection relapsed. Long-term response to therapy was successful for 14 of 19 (74%) subjects who received ofloxacin and 12 of 14 (86%) who received parenteral antibiotics; the difference was not significant. Oral ofloxacin appears comparable to parenteral antibiotics in chronic osteomyelitis due to susceptible organisms, and oral ofloxacin offers advantages in economics and convenience."
-What are the two most common procedures used for screening hearing loss in newborns or intensive care nurseries?,"Auditory screening of infants. Within the last 20 years, infant hearing screening has progressed from a laudable goal to a state-mandated reality in many areas of the United States. The high risk register provides a means by which history and neonatal physical examination can be used to identify the infant at risk for hearing loss. Two procedures (crib-O-gram and auditory brainstem-evoked response) have been the most common methods of screening for hearing loss in the newborn or in intensive care nurseries. Evoked cochlear emissions reportedly are identifiable in 90 to 100% of normal-hearing infants. This observation has lead to the use of evoked otoacoustic emissions as a hearing screening procedure with infants."
-What was the main objective of the SWIFT trial in treating acute myocardial infarction?,"SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. OBJECTIVE--To see whether early elective angiography with a view to coronary angioplasty or bypass grafting of a stenosed infarct related vessel would improve outcome in acute myocardial infarction treated by thrombolysis with anistreplase. DESIGN--Randomised study of two treatment strategies with analysis of results over 12 months. SETTING--21 district hospitals and regional cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients presenting with clinical and electrocardiographic features of acute myocardial infarction up to three hours after the onset of major symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units followed by a standard regimen of heparin, warfarin, and timolol and (in patients so randomised) early angiography plus appropriate intervention. MAIN OUTCOME MEASURE--Death or reinfarction within 12 months. RESULTS--397 patients were randomised to receive early angiography plus appropriate intervention (coronary angioplasty in 169 cases, coronary grafting in 59) and 403 patients to receive conservative care (of these, 12 had angioplasty and seven bypass grafting during the initial admission). By 12 months mortality (5.8% (23 patients) in the intervention group v 5.0% (20) in the conservative care group; p = 0.6) and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4) were similar in the two groups. No significant differences in rates of angina or rest pain were found at 12 months. Left ventricular ejection fraction at three and 12 months was the same in both groups. Median hospital stay was longer in the intervention group (11 days v 10 days; p less than 0.0001). CONCLUSION--For most patients given thrombolytic treatment for acute myocardial infarction a strategy of angiography and intervention is appropriate only when required for clinical indications."
-What are the characteristic radiographic features of chondromyxoid fibroma that help in its identification?,"Chondromyxoid fibroma: radiographic appearance in 38 cases and in a review of the literature [published erratum appears in Radiology 1991 Aug;180(2):586] Thirty-eight cases of histologically confirmed chondromyxoid fibroma were reviewed and their radiographic features recorded. These findings, coupled with a review of the English-language medical literature, suggest that this rare, benign bone tumor has a characteristic but not specific radiographic appearance and may often mimic more common tumors. Chondromyxoid fibroma may occur anywhere in the skeleton, but almost half of the cases occur around the knee. The possibility of chondromyxoid fibroma should always be considered when a focal bone lesion is evaluated that has geographic bone destruction, a sclerotic rim, lobulated margins, and septation. The diagnosis of chondromyxoid fibroma is most likely when the patient is in the 2nd decade of life."
-How do bile acids contribute to splanchnic hemodynamics in portal hypertension?,"Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia."
-What percentage of falls resulted in a major injury in this prospective study of elderly community-dwelling persons?,"Risk factors for injurious falls: a prospective study. We conducted a prospective study of the consequences of falls in 325 elderly community-dwelling persons, all of whom had fallen in the previous year. We contacted subjects every week for one year to ascertain falls and to determine the circumstances and consequences of falls. Only 6% of 539 falls resulted in a major injury (fracture, dislocation, or laceration requiring suture), but over half (55%) resulted in minor soft tissue injury. One in ten falls left the faller unable to get up for at least 5 minutes, and one in four falls caused subjects to limit their activities. The risk of injury per fall was about the same regardless of the number of falls a person had during follow-up. The risk of major injury was increased (age- and sex-adjusted odds ratio: 5.9, 95% confidence interval: 2.3-14.9) in falls associated with loss of consciousness compared to nonsyncopal falls. In multivariate analyses of nonsyncopal falls, the risk of major injury per fall was higher in persons having a previous fall with fracture (6.7; 2.1-21.5), a slower Trail Making B time (1.9; 1.1-3.2), and in Whites (18.4; 7.5-44.6). The risk that a nonsyncopal fall would result in minor injury (versus no injury) was increased in persons with a slower hand reaction time (1.8; 1.0-3.2) decreased grip strength (1.5; 1.0-2.3), in Whites (2.0; 1.0-3.7), in falls while using stairs and steps (2.2; 1.0-5.0), and turning around or reaching (3.5; 1.7-7.3). Our findings suggest that neuromuscular and cognitive impairment, as well as the circumstances of falls, affect the risk of injury when a fall occurs."
-What was the main purpose of the study on nitroglycerin patches in patients with chronic stable angina?,"The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration. This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical."
-What were the five-year cure rates for T1 glottic squamous cell carcinoma patients who underwent laser cordectomy with and without prior radiation treatment?,"Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure."
-What is the unique aspect of the obturator foramen bypass described in this case report?,Crossover ilioprofunda reconstruction: an expanded role for obturator foramen bypass. The standard obturator foramen bypass extends from the aorta or iliac artery to the ipsilateral superficial femoral or popliteal artery. This operation has been both effective and versatile as an indirect bypass procedure for circumventing difficult vascular problems in the femoral triangle. A case is presented of a patient whose limb was salvaged by an obturator foramen bypass from the contralateral iliac artery to the profunda femoris artery. This unique case is compared to other published cases to emphasize the potential advantages of the profunda femoris as the preferred graft outflow in selected cases of arterial reconstruction through the obturator foramen.
-When is antibiotic treatment recommended for bacterial gastroenteritis?,"Antibiotic treatment of bacterial gastroenteritis. Antibiotic treatment is important in certain etiologies of bacterial gastroenteritis, both for clinical improvement and for eradication of the causative organism from stools, which is important epidemiologically. The etiology, however, is seldom known at presentation in sporadic cases of diarrhea. Thus the decision to initiate antibiotic therapy and the choice of the specific antimicrobial agents should be made on a clinical basis, before culture results are available."
-How does CD45 potentially regulate signal transduction in B cells?,"Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. CD45 is a member of a family of membrane proteins that possess phosphotyrosine phosphatase activity, and is the source of much of the tyrosine phosphatase activity in lymphocytes. In view of its enzymatic activity and high copy number, it seems likely that CD45 functions in transmembrane signal transduction by lymphocyte receptors that are coupled to activation of tyrosine kinases. The B cell antigen receptor was found to transduce a Ca(2+)-mobilizing signal only if cells expressed CD45. Also, both membrane immunoglobulin M (mIgM) and CD45 were lost from the surface of cells treated with antibody to CD45, suggesting a physical interaction between these proteins. Finally, CD45 dephosphorylated a complex of mIg-associated proteins that appears to function in signal transduction by the antigen receptor. These data indicate that CD45 occurs as a component of a complex of proteins associated with the antigen receptor, and that CD45 may regulate signal transduction by modulating the phosphorylation state of the antigen receptor subunits."
-What was the effect of isradipine on systolic and diastolic blood pressure in patients with mild-to-moderate hypertension?,"Multicenter evaluation of efficacy, tolerability and safety of a new first-line antihypertensive drug, isradipine, in a Latin-American population. Isradipine, a new antihypertensive dihydropyridine calcium antagonist, was evaluated for its efficacy, tolerability, and safety in 91 ambulatory patients who had mild-to-moderate hypertension. The design of the present study included a two-week wash-out period after confirmation of disease, followed by 12 weeks of active treatment with 2.5 mg isradipine twice daily. Patients were switched from other antihypertensive drugs, mainly diuretics and beta-blockers. The dose of isradipine remained virtually unchanged throughout the study and resulted in a mean decrease of 22 mm Hg in systolic blood pressure (SBP) (P less than .00001) and 19 mm Hg in diastolic blood pressure (DBP) (P less than .00001). Heart rate was unchanged (difference of -1 beats/min), as was the mean body weight of the study patients. Isradipine was generally well tolerated. Side effects were few and, when present, tended to diminish and eventually disappear during the treatment period. All of the clinical laboratory parameters tested and electrocardiograph intervals remained unchanged. In conclusion, these results indicate that isradipine is a novel drug which is highly effective and well tolerated in the treatment of mild to moderate hypertension in this group of patients."
-What are the potential complications for pregnancies complicated by chronic hypertension?,"Diagnosis and management of chronic hypertension in pregnancy. Pregnancies complicated by chronic hypertension are at increased risk for the development of superimposed preeclampsia, abruptio placentae, and poor perinatal outcome. The frequency of these complications is particularly increased in patients with severe hypertension and those with preexisting cardiovascular and renal disease. Such women should receive appropriate antihypertensive therapy and frequent evaluations of maternal and fetal well-being. In contrast, in patients with mild essential chronic hypertension, the maternal and perinatal benefits from antihypertensive medications are highly controversial. A review of the literature revealed two placebo-controlled studies, four trials comparing treatment versus no medication, and three comparisons of methyldopa and oxprenolol. In only one of these studies were subjects randomized in the first trimester. No differences in pregnancy outcome were found with the use of antihypertensive drugs. Evaluation of the woman with chronic hypertension who is considering pregnancy should begin before conception to establish the cause and severity of the hypertension. Appropriate management should include frequent evaluation of maternal and fetal well-being; antihypertensive medications may be useful in patients with severe disease as well as in those with target organ involvement."
-How can the relationship between gastroesophageal reflux (GER) and upper airway diseases impact patient diagnosis and treatment?,"Gastroesophageal reflux and upper airway diseases. GER can have important impacts on the upper airway passages, and in turn, upper airway obstruction can certainly aggravate reflux. This relationship should be considered in the newborn or young infant, faced with a sudden life-threatening event, and in the older child or adult presenting with chronic head and neck complaints, either unexplained or unresponsive to adequate medical therapy. A causal relationship may be difficult to establish, based first on clinical expertise as a guideline, on laboratory tests, among which pharyngeal pH monitoring could be promising, and on response to medical antireflux therapy. A better understanding of the significance of high levels of reflux and defective acid clearance, as well as a more precise knowledge of the maturation and functioning of upper airway protective mechanisms, would open the way to more accurate diagnostic procedures, to a more reliable definition of the abnormal, and to greater efficiency in the management of these patients."
-What are the potential causes and techniques for removing a Foley catheter when its balloon cannot be deflated?,"Emergency management of the nondeflating Foley catheter balloon. Inability to remove a self-retaining (Foley) catheter may result from failed attempts to deflate its balloon. In this article, the authors review the causes of inability to deflate Foley catheters as well as the various techniques for their removal."
-What was the primary finding of the study regarding the mechanism of post-prandial worsening of angina?,"Post-prandial worsening of angina: all due to changes in cardiac output? BACKGROUND--The precise mechanism leading to the post-prandial worsening of angina has yet to be adequately defined. It has been attributed to an increase in double product but is perhaps more likely to be related to an increase in cardiac output after food. This study was designed to evaluate the effects of food on patients' exercise tolerance and compare these with changes in haemodynamic variables. METHODS--23 patients with chronic stable angina who had post-prandial worsening of their angina were studied. The patients were evaluated on two occasions and at each visit they underwent two symptom limited treadmill exercise tests. They remained fasting on the first visit and were given a 1400 kcal meal 60 minutes before the second exercise test on the second visit. Time to onset of 1 mm ST segment depression, heart rate, systemic arterial blood pressure, and cardiac output were measured at rest and during exercise. RESULTS--There were no differences in any of the variables during the two exercise tests on the day the patients remained fasting. After the meal exercise tolerance fell significantly by 136 seconds and the stage at which 1 mm ST segment depression was first seen was also significantly reduced. Resting cardiac output increased significantly by 0.86 1/min with the patients sitting and by 0.89 1/min standing. The exercise times after food were significantly related to cardiac output even when fasting times were taken into account. Resting heart rate increased significantly by 8.3 beats per minute sitting and 10.4 beats per minute standing. There was little change in blood pressure and no evidence that the double product predicted the post-prandial exercise time. CONCLUSIONS--Worsening of angina was related to the increase in cardiac output after a meal and successful treatment will depend upon the prevention of this increase."
-What types of headaches were observed in patients with Arnold-Chiari malformation (ACM) in this study?,"Headache spectrum in Arnold-Chiari malformation. Exertional headaches in patients with Arnold-Chiari malformation (ACM) are well described. We report four patients with Type I ACM and recurrent headaches. These patients presented, respectively, with low spinal fluid pressure headache, migraine without aura, migraine with aura, and migraine with prolonged aura. This report suggests the need for observing patients with recurrent headaches for any physical stigmata of craniovertebral junction anomalies, and the need to exclude ACM in such patients. Possible implications of the association between ACM and different types of headaches are discussed."
-What were the key findings regarding the performance of different types of prostheses in combined mitral-aortic valve replacement after a 14-year follow-up?,"Influence of type of prosthesis on late results after combined mitral-aortic valve replacement. The influence of type of prosthesis on the late outcome of patients with combined mitral-aortic valve replacement was analyzed by comparing, at a 14-year follow-up, patients receiving two biological prostheses (group 1; n = 135), two mechanical prostheses (group 2; n = 221), or a mechanical prosthesis in the aortic position and a bioprosthesis in the mitral position (group 3; n = 97). No difference was found among the three groups in terms of actuarial survival and incidence of and freedom from valve-related deaths, thromboemboli, and hemorrhages. Patients with biological prostheses had a significantly greater incidence of structural valve deterioration, reoperations, and overall complications when compared with patients with only mechanical prostheses. The results of an extended follow-up of patients with combined mitral-aortic valve replacement indicate that mechanical prostheses perform better in the long-term owing to their superior durability when compared with biological valves. The use of bioprostheses should be confined to old patients with limited life expectancy because of their cardiac disease, provided that anticoagulants are not used. Combination of mechanical and biological prostheses in the same patient should be avoided because the advantages of each type of prosthesis are lost."
-What changes in CT scan appearance can be observed in a traumatized spleen during nonoperative management?,"CT appearance of splenic injuries managed nonoperatively. This essay illustrates the appearance of the traumatized spleen on CT scans obtained during the course of conservative treatment. Although the CT appearance of acute rupture of the spleen has been adequately described, little has been reported about the appearance of the spleen as it heals after trauma. Examples of CT studies of splenic injuries illustrate the various changes in appearance over time in the traumatized spleen that is treated nonoperatively."
-What significant legislative act was passed in 1971 that helped advance cancer research and treatment?,"Progress in cancer. Definite progress has been made against cancer since the National Cancer Act was passed in 1971. Physicians are giving increased attention to cancer prevention. The exciting changes in molecular biology provide increased knowledge about basic mechanisms in tumor growth and metastases. Detailed discussions of two common solid cancers--breast and colorectal--attest to continuing advances in cancer diagnosis and treatment. All of these augur well for further progress in oncology. Continued research, basic and clinical, is mandatory."
-What was the success rate of the percutaneous posterolateral lumbar discectomy procedure in this study?,"Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise."
-What was the overall success rate of endoprosthesis insertion for proximal malignant biliary obstruction in this study?,"Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion. For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%.Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%."
-What serious complications can occur after intravesical instillation of bacillus Calmette-Guerin (BCG)?,"Complications after intravesical instillation of bacillus Calmette-Guerin: rhabdomyolysis and metastatic infection. Two cases of adverse reaction to bacillus Calmette-Guerin (BCG) bladder instillations are reported. In both cases transient fevers and systemic symptoms developed following the instillations. After an additional instillation 1 patient had high fevers, severe myalgias and profound weakness followed by rhabdomyolysis and anuric renal failure, which required 3 weeks of hemodialysis before recovery. Extensive evaluation revealed no cause other than the BCG instillations. In the other patient a firm subcutaneous nodule gradually developed on the chest wall, which contained nonviable acid fast bacilli."
-How does the severity of prior salpingitis episodes impact the recurrence rate of ectopic pregnancy in women with a prior uterine pregnancy?,"Recurrence of ectopic pregnancy: the role of salpingitis. We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk."
-What percentage of patients reported pain relief after receiving nitrous oxide in this rural EMS system study?,"Effectiveness of nitrous oxide in a rural EMS system. Prehospital systems need a safe, effective analgesic agent for the treatment of patients suffering from pain. Recent studies have documented the efficacy of nitrous oxide in urban and rural settings. This study reviews the findings on 200 patients (157 trauma, 23 medical, 18 musculoskeletal problems) who received nitrous oxide during a 28-month period in a rural EMS system. Eighty-five percent of the patients reported pain relief. Only minor side effects were noted. Patient satisfaction was high, and there was no abuse noted among personnel."
-What is an iatrogenic epidermoid cyst and how can it occur in the parotid region following ear surgery?,Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed.
-What is an epidural blood patch and how was it used to treat subarachnoid-cutaneous fistula in the described cases?,Epidural blood patch for treatment of subarachnoid fistula in children. A subarachnoid-cutaneous fistula developed in two children after the placement of a catheter in the subarachnoid space for drainage of cerebrospinal fluid. The management of this iatrogenic complication with epidural blood patch is described.
-How does the estrogen receptor (ER) level correlate with response to tamoxifen treatment in advanced breast cancer?,"The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer."
-What were the two drugs used in the study for treating patients with Raynaud's phenomenon?,"Regional intravenous ketanserin and guanethidine therapy in Raynaud's phenomenon. The authors report the results of a study of 25 patients with Raynaud's phenomenon (primary, posttraumatic, and secondary to diffuse connective tissue diseases) treated with regional intravenous injections of guanethidine or ketanserin. These two drugs were chosen because of the different etiopathologic profiles of the conditions. All the patients showed a substantial clinical improvement with a remission of trophic lesions. Conditions secondary to connective tissue disorders did not demonstrate much improvement based on instrumental data alone, possibly because of the intrinsic limitations of the techniques used for evaluating peripheral blood flow. This specific type of pharmaceutical treatment appeared to be especially suitable for this disease owing to a combination of therapeutic efficacy and a substantial reduction in the total dosage for each patient."
-What are the two fracture patterns associated with the anteroinferior cervical vertebral body corner (teardrop) fracture?,"The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis. The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the ""teardrop"" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch."
-What were the key findings of the study comparing clinical and photographic methods for assessing facial weakness?,"Facial weakness. A comparison of clinical and photographic methods of observation. The search for an internationally acceptable facial grading system has resulted in an assessment of existing methods by several investigators. These studies were based on observations of video film taken of patients with varying degrees of facial malfunction. Although the grading systems were evaluated, the use of videotape has never been compared with clinical examination and its suitability for this type of work is, therefore, unknown. We used nine facial grading systems to compare the results of clinical observation with those of photographic methods of presentation. The latter included videotape, photographic slides, and a combination of the two. The correlation between clinical examination findings and findings of any of the photographic methods was poor, suggesting the need for a standard form of presentation when grading patients. The most consistent results were found with either clinical examination or photographic slides; videotape was the least reliable."
-How do the patterns of soft palate oscillations differ between nasal and mouth snoring?,"Pattern of simulated snoring is different through mouth and nose. Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring."
-What potential risks were identified in the study regarding self-administered sublingual nitroglycerin?,"Defining the proper role for self-administered sublingual nitroglycerin. A survey of physicians and patients. Within a half-year period, we encountered six cases of patients harmed by the adverse effects of self-administered nitroglycerin--syncope, delayed definitive medical care, and the worsening of nonischemic symptoms. We therefore surveyed 112 patients after a remote myocardial infarction, and 121 cardiologists and internists, regarding the use of sublingual nitroglycerin. Of the physicians, 84 percent routinely prescribed nitroglycerin to patients after a myocardial infarction, and 79 percent of the patients had the tablets available (83 percent of these, at all times). Most patients used the tablets less than once per month, and 37 percent of the patients who always carried nitroglycerin had not used it at all during the preceding year. Although 89 percent of the patients claimed to know when to use the drug, 57 percent had used it or would use it for symptoms such as dizziness, rapid heartbeat, or presyncope. All patients having nitroglycerin claimed it relieved their symptoms, even if the relief was only partial, the time elapsed until relief could not be specified, and the symptoms were of a type unlikely to be relieved by the drug. We suggest that the practice of routinely prescribing nitroglycerin to patients after a myocardial infarction should be reassessed."
-What was the average age of patients with osteonecrosis in the femoral condyle of the knee in this study?,"Clinical course and roentgenographic changes of osteonecrosis in the femoral condyle under conservative treatment. The history of osteonecrosis in the femoral condyle of the knee was observed in 15 knees in 14 patients, averaging 62.8 years in age (range, 23-79 years). There were nine women and five men. The average follow-up period was 4.9 years (range, one to 12 years). Spontaneous osteonecrosis was found in 11 patients and steroid-induced osteonecrosis in three. The medial femoral condyles were involved in 13 knees and the lateral femoral condyles in two. The maximum width of the lesion was measured on anteroposterior roentgenograms and an osteonecrotic lesion less than 10 mm wide was rated as small. Cases of small osteonecrotic lesions displayed no remarkable changes with respect to stages and limb alignment. The average size of the steroid-induced osteonecrotic lesions was significantly larger than that of the spontaneous type. The size of the osteonecrotic lesions at the follow-up examination was compared to that observed at the initial diagnosis in 12 knees. Eight of these lesions displayed increases in dimension of more than 18% over the initial size at diagnosis."
-What were the potential benefits of performing combined coronary angiography and angioplasty in this study?,"Safety and cost effectiveness of combined coronary angiography and angioplasty. If coronary angioplasty can be safely performed at the time of the initial diagnostic catheterization, it may result in shorter hospitalization stays and lower overall costs. Combined coronary angiography and angioplasty was performed electively on 733 patients between January 1, 1984, and September 1, 1988. These patients were divided into three major subgroups based upon their indications for angioplasty: 444 (61%) procedures were performed for restenosis; 190 (26%) procedures were performed in patients for unstable angina; and 99 (13%) procedures were performed in patients without unstable angina or previous angioplasty. A subset of 219 patients from this study who underwent elective combined coronary angiography and angioplasty during 1986 were compared with a matched population of 191 patients from the angiography and angioplasty as separate procedures). The success and complication rates were similar for both of these groups. Patients who underwent the combined procedure were hospitalized for a mean of 4.6 days with average total charges of $11,128, compared with 8.0 days and $13,160 for patients undergoing separate procedures (p less than 0.001). Significant savings were also realized with respect to total contrast dose, fluoroscopic time, and total procedural time. Thus in informed patients with suitable coronary anatomy, the strategy of combined angiography and angioplasty may present an opportunity for decreasing hospitalization stay, reducing total charges for revascularization, and reducing radiation exposure without compromising the safety or effectiveness of the procedure."
-What was the mean follow-up period for the porous-coated total hip prostheses in this study?,"Prospective study of porous-coated anatomic total hip arthroplasty. Seventy-five uncemented porous-coated total hip prostheses were implanted in 64 patients. The results were reviewed after a mean follow-up period of 47 months (range, 40-64 months). The mean preoperative rating was fair, and the mean postoperative rating was excellent. There were six dislocations. Ten patients had mild thigh pain at one year; by two years, the pain had resolved in six patients. Neither moderate nor severe limp nor significant loosening of beads was observed. Only one patient had progressive radiolucent lines. The high rate of dislocation may be related to a compromise of acetabular position to obtain bony fixation in acetabula early in the series. The clinical results were encouraging."
-How did the natriuretic response of torasemide compare to furosemide in nonazotemic cirrhotic patients with ascites?,"Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed."
-How did early thrombolytic therapy affect the incidence of ventricular late potentials in patients after acute myocardial infarction?,"Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy. Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05)."
-What was the efficacy of aztreonam in preventing urinary tract infections following transurethral resection of the prostate (TURP) in this multicenter study?,"Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study. The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure."
-What is the significance of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in Turcot syndrome and related conditions?,"Ocular findings in Turcot syndrome (glioma-polyposis). Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps."
-What is the rare complication observed in this patient with mixed connective tissue disease?,Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease.
-What was the most common symptom among patients with lower esophageal mucosal rings in this study?,"Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring."
-What is the sensitivity and specificity of duplex scanning in detecting atherosclerotic renal artery stenosis?,"Role of duplex scanning for the detection of atherosclerotic renal artery disease. To assess the accuracy of renal artery duplex scanning for the purpose of diagnosing atherosclerotic renal artery stenosis, we compared the findings of renal arteriograms to the results of duplex scanning in 41 patients. Using an increase of renal artery peak systolic flow velocity of greater than 180 cm/sec, duplex scanning was able to discriminate normal from diseased renal arteries with a sensitivity of 95% and a specificity of 90%. Using the principle that blood flow velocity across a stenosis is roughly proportional to the degree of stenosis, it appeared that a ratio of the peak velocity in the renal artery to the aorta (RAR) of greater 3.5 predicted a greater than 60% diameter reduction of that renal artery, which is felt to be a significant stenosis. Forty-eight vessels were classified as having a greater than 60% diameter reduction by arteriography. Using the RAR of greater than 3.5, duplex scanning agreed in 44 renal arteries (sensitivity 92%). In the 26 renal arteries where arteriography showed a less than 60% diameter reduction, duplex scanning agreed in 16 vessels and correctly detected a focal narrowing in nine of the remaining ten vessels. Ten of 11 occluded renal arteries were correctly identified by duplex scanning. Duplex scanning determined the location of the renal artery lesion with an accuracy of 95% (kappa 0.74). Since duplex scanning can accurately demonstrate and locate focal renal artery stenosis, we believe it may become an accurate screening test for renovascular hypertension."
-How accurate was the high frequency epicardial echocardiography in measuring coronary artery dimensions and detecting atherosclerotic lesions compared to histopathological results?,"Histopathological validation of high frequency epicardial echocardiography of the coronary arteries in vitro. The accuracy and reliability of measurement of coronary artery dimensions and detection of atherosclerotic lesions by high frequency epicardial echocardiography were compared with histopathological results. Ten pressure perfused human hearts were examined in vitro with a 10 MHz (Diasonics) transducer and a 7.5 MHz (Vingmed/Sonotron) transducer. There was close agreement between ultrasound and pathological measurements of coronary artery luminal diameter. Qualitative changes in wall structure such as diffuse wall thickening and calcification were readily identified; however, the resolution of the transducers was not high enough accurately to measure wall dimensions in normal coronary arteries. Coefficient of variation measurements for intra and inter observer variability (5.2% and 6.9% respectively) showed excellent reproducibility. The technique was accurate in identifying atherosclerotic lesions, imaging arteries distal to an occlusion, locating deeply sited arteries, and identifying complete obliteration of an artery. Intraoperative video playback and transducer miniaturisation may minimise problems caused by cardiac movement and restricted access. With these developments intraoperative assessment of coronary artery disease may become a real possibility."
-What is the typical progression and prognosis of diabetic femoral neuropathy based on this study?,"The natural history of diabetic femoral neuropathy Diabetic femoral neuropathy is an uncommon, unpleasant and sometimes disabling condition, on account of both pain and muscular atrophy, whose long-term prognosis has not previously been documented. We have reviewed a group of 27 patients up to 14 years (median 62 months) after diagnosis; 18 of these were re-examined after an average of nearly 4 years (median 45 months). The condition was more common in non-insulin-dependent diabetics (88 per cent), in men (59 per cent) and in older patients (median age at diagnosis 64 years). The neuropathy was bilateral (10 cases) or unilateral (17 cases); five patients with unilateral neuropathy developed femoral neuropathy on the opposite side, usually within a few weeks of the first episode. Recovery was apparent after 3 months and usually complete by 18 months; only two of the 27 patients had severe relapses. No patients remained disabled, although there were minor residual symptoms and signs in half of the patients (2 cm reduction in thigh circumference and diminished reflexes). The outlook for femoral neuropathy, even in its most severe form, is therefore very good: residual features are demonstrable but do not cause symptoms, and relapses after the first few weeks are very rare."
-How did participation in a cardiac rehabilitation program affect patients' psychosocial function six months after an acute cardiac event?,"Effects of a multidimensional cardiopulmonary rehabilitation program on psychosocial function. The effects of participation in a structured, outpatient cardiac rehabilitation program on psychosocial function after acute myocardial infarction or coronary artery bypass surgery, or both, were evaluated prospectively in 141 patients who were married or living with ""a significant other"" (89% men, mean [+/- standard deviation] age 63 +/- 9 years old). Forty-one patients who were participants in a 3-month cardiac rehabilitation program were compared with 100 patients who did not participate in a formal program. On average, patients in both groups were well educated, older Caucasians who had minimal cardiac dysfunction (New York Heart Association class I or II). Patients in the 2 groups were not different at baseline in sociodemographic or clinical characteristics or in any of the dependent measures of anxiety, depression, psychosocial adjustment to illness or marital adjustment. Six months after initial testing, patients who attended cardiac rehabilitation were significantly less anxious (F[1,139] = 5.09, p = 0.03), less depressed (F[1,139] = 8.39, p = 0.004), had better psychosocial adjustment (F[1,139] = 5.87, p = 0.02), and were more satisfied with their marriages (F[1,139] = 8.6, p = 0.004) than nonparticipants. The findings support the effectiveness of group cardiac rehabilitation for this subgroup of patients in facilitating their psychosocial recovery after an acute cardiac event."
-How do the adrenal glands contribute to plasma norepinephrine concentrations during cardiopulmonary resuscitation in dogs?,"Plasma norepinephrine concentrations during resuscitation in the dog. The objective of this study was to evaluate whether the adrenal glands contribute to the increase in plasma norepinephrine concentrations during cardiopulmonary resuscitation, by releasing norepinephrine and/or by secreting epinephrine that facilitates the release of norepinephrine from sympathetic nerve endings via stimulation of presynaptic beta receptors. The experiments were performed in adrenalectomized and in sham-operated dogs. In adrenalectomized dogs the increase in plasma norepinephrine concentrations during cardiopulmonary arrest and basic life support (BLS) was markedly smaller than in sham-operated dogs. Intravenous infusion of physiologic doses of epinephrine during BLS in adrenalectomized animals did not influence the plasma norepinephrine concentrations. These data indicate that, as suggested by others, the marked increase in plasma norepinephrine concentrations during BLS in dogs is mainly of adrenomedullary origin. They also suggest that presynaptic facilitation of norepinephrine release by epinephrine is not important, but further experiments using higher doses of epinephrine are necessary."
-What defects were observed in the lymphokine-activated killer (LAK) cell generation and activity among acute leukemia patients?,"Defective lymphokine-activated killer cell generation and activity in acute leukemia patients with active disease. In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease."
-What are the two unusual features of the pharyngeal pouch carcinoma cases reported in this study?,"Pharyngeal pouch carcinoma: two unusual cases. Two patients with carcinomata arising in pharyngeal pouches are reported. In one, the tumour was detected preoperatively by a contrast radiographic study. In the second the lesion was a carcinoma in situ. The English literature is reviewed with reference to these two unusual features."
-How do middle ear inflammatory mediators potentially cause sensorineural hearing loss?,"Middle ear inflammatory mediators and cochlear function. Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study."
-What percentage of patients experienced experienced cerebrospinal fluid leaks after acoustic neuroma surgery in this study?,"Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. Cerebrospinal fluid leaks and associated meningitis are the most common life-threatening complications of surgery for acoustic neuromas. This retrospective study reviews 319 patients who had surgery for 321 acoustic tumors at the Sunnybrook Health Sciences Center, University of Toronto, from April 1975 to March 1990. Cerebrospinal fluid leaks occurred after 13.4% of primary tumor operations. Surgical repair was required in 6.2% of all patients; 4.4% needed more than one operation. Meningitis occurred in 5.3% of all patients. These complications were more common in larger tumors and after the combined translabyrinthine middle fossa approach. Transnasopharyngeal eustachian tube obliteration was used to stop recurrent cerebrospinal fluid leaks in two patients."
-What restriction endonucleases were used to detect polymorphisms in the progesterone receptor gene in this study?,"Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors. We examined the progesterone receptor (PgR) gene in tissue from both primary human breast tumors and normal placentas, detecting restriction fragment length polymorphisms (RFLPs) with the restriction endonucleases Pst I/Sst I and HindIII. There was a general agreement of the Pst I and Sst I polymorphisms in any individual tumor, suggesting that they define two alleles in the human PgR locus, one being characterized by a deletion of about 300 base pairs with respect to the other. Both primary human breast tumor specimens (n = 36) and human term placentas (n = 48) displayed similar allele frequencies and typical mendelian distribution of these Pst I/Sst I alleles. The previously reported HindIII PgR RFLP was also investigated in 132 breast tumors. The HindIII PgR gene RFLP did not display typical mendelian distribution in the breast tumors; the factors affecting the HindIII allele frequencies are presently unknown. Neither the HindIII RFLP nor the deletion defined by Pst I and Sst I correlated with PgR expression as determined by a ligand-binding assay, suggesting that neither is related to the heterogeneity of PgR expression seen in breast tumors."
-What treatment is recommended when there is clinical or investigative evidence suggesting the presence of a demyelinating disease?,"Destructive lesions in demyelinating disease. Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy."
-How do T1 and T2 relaxation times change in different myocardial layers following ischemia and reperfusion?,"Transmural distribution of myocardial edema by NMR relaxometry following myocardial ischemia and reperfusion. To determine the distribution and extent of myocardial edema resulting from ischemia and reperfusion, seven open-chest dogs underwent occlusion of the left circumflex coronary artery for 2 hours (group I), and 10 underwent occlusion for 2 hours and reperfusion for 2 hours (group II). Proton nuclear magnetic resonance spectroscopy (T1 and T2 relaxation times) and percent water content were determined to quantitate the amount of edema. There was a transmural increase of the T1 relaxation time of the central ischemic zone in groups I and II, although this increase was significantly greater in group II in both the subendocardium (group I = 707.8 +/- 12.5 msec, group II = 813.2 +/- 36.2 msec; p less than 0.01) and subepicardium (group I = 641.7 +/- 20.5 msec, group II = 760.5 +/- 34.7 msec; p less than 0.01). These increases were also observed in the T2 weighted relaxation time in the subendocardium (group I = 54.7 +/- 0.8 msec, group II = 78.7 +/- 6.3 msec; p less than 0.005) and subepicardium (group I = 54.0 +/- 1.4 msec, group II = 73.1 +/- 4.0 msec; p less than 0.001). Transmural differences were evident between the myocardial layers with increased T1 relaxation times (p less than 0.01) in the subendocardium in both groups. Similar increases were noted in the percent water content of the myocardium. Thus T1 and T2 relaxation times lengthened with an increase in myocardial water content following occlusion, and these relaxation times were augmented by reperfusion. We conclude that ischemia-induced edema occurs in a transmural distribution from subendocardium to subepicardium following occlusion, and this edema is further enhanced by reperfusion."
-What potential complication can occur in the fallopian tubes following an inguinal hernia repair?,"Tubal occlusion after inguinal hernia repair. A case report. Midtubal occlusion and infertility occurred subsequent to an inguinal hernia repair. Recognition of the traumatic etiology is important because other causes of midtubal obstruction, such as endometriosis, tuberculosis and adenomatoid tumor of the oviduct, may be considered contraindications to reconstructive surgery. Once recognized, the condition is highly amendable to microsurgical reconstruction."
-How did the use of fine catheter peritoneal cytology (FCPC) and laparoscopy help improve the management of patients with acute abdominal pain in this study?,"Role of fine catheter peritoneal cytology and laparoscopy in the management of acute abdominal pain. Laparoscopy and fine catheter peritoneal cytology (FCPC) have been advocated as aids in the assessment of acute abdominal pain. In all, 411 patients admitted to a district general hospital during a 10-month period were managed using a standard protocol incorporating these techniques. After initial assessment by a surgical registrar, 151 patients were excluded from further progress through the protocol (age less than 16 years, definite diagnosis made or contraindication to FCPC. The remaining 260 patients were placed in one of four management groups: (A) urgent operation (23 patients); (B) 'look and see' (40 patients); (C) 'wait and see' (59 patients); (D) urgent operation not indicated (138 patients). Eighty-eight of 99 patients (88 per cent) in groups B and C, where the need for operation was uncertain, underwent successful FCPC and 39 patients (39 per cent) underwent laparoscopy. In these patients the initial registrar management decision proved to be incorrect in 33 cases (33 per cent), but by following the protocol the number of management errors actually made was reduced to 13 (13 per cent, P less than 0.001). This would have been reduced to 8 per cent if the protocol had not been violated in five patients. This study demonstrates the effectiveness of a protocol using FCPC and laparoscopy to improve the management of patients with acute abdominal pain."
-"What is the association between HIV infection and Salmonella typhi or Salmonella paratyphi infections in the study conducted in Lima, Peru?","Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Eight cases of typhoid and paratyphoid fever were identified during a 4-year period in a cohort of 117 patients who were positive for human immunodeficiency virus in Lima, Peru. Asymptomatic patients with human immunodeficiency virus infection and patients with the lymphadenopathy syndrome had a typical clinical presentation and response to therapy. Patients with the acquired immunodeficiency syndrome who were culture positive for Salmonella typhi or Salmonella paratyphi presented with fulminant diarrhea and/or colitis; the two patients for whom at least 2 months of follow-up were available relapsed. In our cohort there were 0.06 cases of typhoid or paratyphoid per patient year of observation; this rate is approximately 60 times that in the general population in Lima, and 25 times that in the 15- to 35-year-old age group. Our data indicate that patients who are positive for human immunodeficiency virus are at significantly increased risk for infection with S typhi and S paratyphi, and suggest that the clinical presentation of these diseases in patients with the acquired immunodeficiency syndrome differs from that seen immunocompetent hosts."
-What are the comparative outcomes of extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrostolithotomy in treating stone-containing caliceal diverticula?,"The roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in the management of pyelocaliceal diverticula. Various combinations of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy were used in the treatment of 40 stone-containing caliceal diverticula in 39 patients (16 men and 23 women). Only 1 of 26 patients (4%) treated with ESWL as a single modality became stone-free, although 9 (36%) became asymptomatic. Ten patients undergoing ESWL primarily eventually required percutaneous nephrostolithotomy due to persistence of symptoms and all became stone-free. A total of 14 patients underwent a percutaneous approach as a single modality, and the diverticula in 13 of these patients became stone-free, although 2 patients did have residual parenchymal fragments. Therefore, 21 of 24 patients (87.5%) became completely free of stones using the percutaneous approach. All patients managed with percutaneous nephrostolithotomy became free of symptoms. The complex nature of access during percutaneous nephrostolithotomy favors a 1-stage approach with direct puncture into the stone-containing diverticulum. Simultaneous fulguration of the diverticulum at percutaneous nephrostolithotomy is favored, since all 17 patients in whom this technique was used had complete obliteration of the diverticulum on followup contrast studies. These data suggest that caliceal diverticula should be managed with percutaneous nephrostolithotomy, since ESWL monotherapy is unlikely to produce a stone-free or symptom-free status."
-What was the impact of optimal debulking surgery on survival rates in patients with advanced ovarian cancer across different chemotherapy trials?,"Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery. The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin."
-What are the most common menstrual symptoms associated with pelvic endometriosis according to the study?,"Menstrual symptoms in women with pelvic endometriosis. OBJECTIVE--To investigate menstrual symptoms in relation to pelvic pathology. DESIGN--A prospective questionnaire-based study. SETTING--Aberdeen Royal Infirmary, Scotland. SUBJECTS--1250 questionnaires were sent out prior to planned admission and 1200 women (96%) brought the completed questionnaires. They comprised 598 women undergoing laparoscopic sterilization, 312 having laparoscopy because of infertility, 156 having laparoscopy because of chronic pelvic pain and 134 women undergoing abdominal hysterectomy for dysfunctional uterine bleeding. MAIN OUTCOME MEASURES--The occurrence of dysmenorrhoea, menorrhagia, menstrual regularity, premenstrual spotting, deep dyspareunia and pelvic pain in women with either endometriosis and post infective pelvic adhesions or a normal pelvis. RESULTS--Menorrhagia, menstrual irregularity and premenstrual spotting occurred with equal frequency in all groups. Deep dyspareunia, pain after intercourse and recurrent pain unrelated to menstruation or coitus was more common in women with endometriosis and those with post infective pelvic adhesions than in those with a normal pelvis. Dysmenorrhoea appears to be more prevalent among women having endometriosis. CONCLUSIONS--Menstrual symptoms, while raising a high index of suspicion for endometriosis, are not entirely reliable as indicators of disease. Dysmenorrhoea is the most common reported symptom in endometriosis sufferers. Diagnostic laparoscopy should be considered before institution of treatment in women complaining of pelvic pain and menstrual symptoms."
-How do the surface markers of monocytes change during in vitro maturation to macrophages?,"In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection. In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates."
-What was the main strategy used for managing distal ileal Crohn's disease in this study?,"Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy."
-What potential risks are associated with topical diphenhydramine administration in children with varicella-zoster infection?,"Diphenhydramine toxicity in three children with varicella-zoster infection. Diphenhydramine hydrochloride is an antihistamine with anticholinergic properties that is frequently used both orally and topically for the temporary relief of pruritus. Significant systemic absorption may occur following topical administration of diphenhydramine in patients with varicella-zoster lesions. We describe three children with varicella-zoster infection (VZI) who developed bizarre behavior as well as visual and auditory hallucinations following topical applications of large amounts of diphenhydramine to the majority of skin surfaces. In two cases, oral diphenhydramine was also administered. Serum diphenhydramine concentrations approximated or exceeded those previously reported. In each case, a complete resolution of mental status abnormalities occurred within 24 hours after discontinuation of all diphenhydramine-containing products. Pharmacists and other health professionals should be aware of the potential toxicity of topical diphenhydramine in patients with VZI."
-What medical conditions were the patients treated for before experiencing cerebral vasospasm?,Symptomatic cerebral vasospasm following tumor resection: report of two cases. The authors report two cases of symptomatic cerebral vasospasm following resection of an acoustic neuroma and a left sphenoid wing meningioma. Vascular spasm was documented by transcranial Doppler and angiography studies. Both patients responded to hypervolemic therapy. Possible mechanisms contributing to this rare complication are discussed.
-How does the posterior cricoarytenoid (PCA) muscle activity change during different breathing conditions in normal adults?,"Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation. The effect of isocapnic hypoxia and hyperoxic hypercapnia on the electrical activity of the posterior cricoarytenoid (PCA) muscle was determined in eight normal adult humans by use of standard rebreathing techniques and was compared with PCA activity during voluntary hyperventilation performed under isocapnic and hypocapnic conditions. PCA activity was recorded with intramuscular hooked-wire electrodes implanted through a fiberoptic nasopharyngoscope. During quiet breathing in all subjects, the PCA was phasically active on inspiration and tonically active throughout the respiratory cycle. At comparable increments in respiratory output, hypercapnia, hypoxia, and voluntary hyperventilation appeared to be associated with similar increases in phasic or tonic PCA activity. During quiet breathing, the onset of phasic PCA activity usually occurred before inspiratory airflow and extended beyond the start of expiratory airflow. The duration of phasic PCA preactivation and postinspiratory phasic PCA activity remained unchanged during progressive hypercapnia and progressive hypoxia. The results, in combination with recent findings for vocal cord adductors, suggest that vocal cord position throughout the respiratory cycle during hyperpnea is actively controlled by simultaneously acting and antagonistic intrinsic laryngeal muscles."
-What was the diagnostic approach and treatment for the patient with isolated adrenal cryptococcosis?,"Isolated cryptococcosis of the adrenal gland. A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination."
-What was the primary finding of the multicenter trial regarding dexamethasone therapy in neonates with chronic lung disease?,"Dexamethasone therapy in neonatal chronic lung disease: an international placebo-controlled trial. Collaborative Dexamethasone Trial Group. In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups."
-What were the hemodynamic effects of desmopressin administration in patients undergoing coronary artery bypass grafting?,"Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass. Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078)."
-What makes cutaneous metastasis from papillary thyroid carcinoma rare and challenging to diagnose?,"Cutaneous metastasis from papillary carcinoma of the thyroid gland. Cutaneous metastases from carcinoma of the thyroid gland are rare. We present the clinical, histologic, and immunohistochemical features of a solitary metastasis from papillary carcinoma of the thyroid. Our results indicate that this tumor can produce epithelial mucin and, therefore, must be differentiated from other metastatic carcinomas and from primary apocrine tumors of the skin. Positive staining for thyroglobulin confirmed the diagnosis in this case."
-What were the main findings of the histopathologic analysis of 204 fibrous gingival lesions?,"Fibrous lesions of the gingiva: a histopathologic analysis of 204 cases. Two hundred four cases of fibrous lesions of the gingiva were studied histologically for the presence of calcified tissue, the nature of the connective tissue, the type of keratinization, and the degree of epithelial thickness. Initially these lesions were subcategorized into four specific entities, namely fibrous epulis, fibroepithelial polyp, calcifying fibroblastic granuloma, and ossifying fibrous epulis. It was found that 46.5% of the lesions contained calcifications. The connective tissue was represented predominantly by either the collagenous type (50.5%) or the mixed (cellular and collagenous) type (44.6%). It was also found that 36% of the lesions were ulcerated, and, of these, 79.5% were associated with the cellular type of connective tissue and calcifications. In an attempt to subcategorize the fibrous lesions into specific entities, it was found that 32 cases (15.7%) had mixed features. This fact supports the suggestion that these lesions are stages in the spectrum of a single disease process and should collectively be termed fibroblastic gingival lesions. However, it is also suggested that the two terms, namely peripheral fibroma and fibrous epulis with and without ossification, should be retained whereas the usage of other terminologies should be avoided."
-What is the significance of ipsilateral breast tumour recurrence (IBTR) in relation to distant disease risk after breast cancer treatment?,"Significance of ipsilateral breast tumour recurrence after lumpectomy. Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy."
-What was the prevalence of peripheral neuropathy in the Parsi community of Bombay according to the survey?,"Prevalence of peripheral neuropathy in the Parsi community of Bombay. We carried out a door-to-door survey to screen for neurologic diseases, including peripheral neuropathy, in a community of 14,010 Parsis living in housing colonies in Bombay, India. The most common neurologic disorder was peripheral neuropathy with 334 cases (2,384 cases/100,000 population). The most common neuropathy was compressive, with diabetes the most common noncompressive etiology. There was no leprosy, and nutritional neuropathies were rare."
-What was the response rate to preoperative chemotherapy in patients with esophageal adenocarcinoma in this pilot study?,"A pilot study of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and postoperative radiation therapy and/or chemotherapy in adenocarcinoma of the esophagus. Fifteen patients with potentially resectable adenocarcinoma of the esophagus were treated with two cycles of preoperative chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP). Response to chemotherapy was evaluated by comparative barium swallow, computerized chest tomography, esophagoscopy, and change in clinical symptomatology. Eleven patients (73%) were resected, two (13%) were explored and found inoperable, and two (13%) were not subjected to surgery (one because of death related to toxicity and one due to progressive disease). Ten of eleven patients (91%) had gross residual tumor. One patient (9%) had residual microscopic disease only. One patient (7%) had complete clinical responses (CCR), five (33%) had partial clinical response (PCR), and nine (60%) had no response (NR). Five of 15 patients (or 45% of resected patients) remain free of disease. Median survival time was 18.47 months for all patients and 23.83 months for resected patients."
-What are the characteristic symptoms of a duodenobronchial fistula?,"Duodenobronchial fistula. Duodenobronchial fistulas are an extremely rare subgroup of abdominobronchial fistulas, which include bronchobiliary, gastrobronchial, enterobronchial, colobronchial, and splenobronchial fistulas. Only one case of a duodenobronchial fistula has been previously reported. Duodenobronchial fistulas occur as a complication of a duodenal injury. The characteristic symptoms are a cough that produces copious bilious secretions, shortness of breath, and fever. The diagnosis is made by contrast gastrointestinal studies. Treatment requires an abdominal approach with interruption of the fistula at its duodenal origin and control of the inciting inflammatory process. With prompt diagnosis and treatment, thoracic drainage or pulmonary resection should not be needed."
-What is a peritoneopericardial diaphragmatic hernia and how was it discovered in this particular case?,"Peritoneopericardial diaphragmatic hernia discovered at coronary bypass operation. A 68-year-old man was discovered to have a large peritoneopericardial hernia when operated on for coronary artery bypass. Such hernias are very unusual. The pathogenesis, clinical presentation, and management of this problem are discussed."
-What is the mortality rate and morbidity rate in the study of 23 patients with acute necrotizing pancreatitis?,"Acute necrotizing pancreatitis: management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. We reviewed our recent experience with management of 23 consecutive patients with acute necrotizing pancreatitis. All patients had documented necrotizing pancreatitis with parenchymal or peripancreatic necrosis. Our method of treatment has evolved from our previous approach of controlled open lesser sac drainage (marsupialization) to staged necrosectomy/debridement with delayed primary closure over drains. With this latter approach, hospital mortality was 4 of 23 patients (17 per cent), but significant morbidity still occurred in 12 of 23 patients (52 per cent). However, recurrent intra-abdominal abscess before discharge occurred in only one patient. We believe that this operative approach toward the severely ill patient with acute necrotizing pancreatitis who requires operative intervention will minimize the occurrence of intra-abdominal sepsis."
-What makes CT imaging of pancreatic diseases in children different from adults?,"CT of the pancreas in children. CT has become a frequently used imaging method for evaluating suspected pancreatic disease in children. Although the spectrum of CT findings in pancreatic disease is well documented in adults, there is a paucity of such information in children. Familiarity with CT patterns of pancreatic disease in childhood is important for diagnosis. In this essay, we illustrate the CT findings of pancreatic lesions in children."
-What surgical technique improvements were made in treating pectus excavatum over a 15-year period?,"Pectus excavatum: a 15-year perspective. Pectus excavatum is relatively uncommon. Our experience with 177 children during a 15-year period produced changes in our surgical technique, which now includes a small transverse incision, minimal subcutaneous flap elevation, a muscle-relaxing incision over the fifth costal cartilage, complete resection of involved cartilage, use of Adkins' strut, suspension of sternum to strut, taut reefing of intercostal muscle, no tubes or drains, epidural analgesia, a patient-controlled analgesia device postoperatively, and eventual strut removal. Use of the evolved technique gives excellent cosmetic results, good functional results with minimal discomfort, and a shorter convalescent period."
-What is a false aneurysm of the right internal mammary artery and how is it related to median sternotomy?,False aneurysm of the right internal mammary artery. False aneurysm of the internal mammary artery is an uncommon complication of median sternotomy. Clinical and radiological findings of 2 such cases are presented. At operative exploration neither was directly related to the presence of a sternal wire.
-How does the concentration of inspired CO2 (FICO2) affect cardiac resuscitation in the experimental rat model?,"Hypercarbic acidosis reduces cardiac resuscitability. BACKGROUND AND METHODS: Marked increases in myocardial hypercarbia and acidosis accompany cardiac arrest and resuscitation. To investigate whether hypercarbic acidosis independent of oxygenation is of itself detrimental to cardiac resuscitation, three groups of six Sprague-Dawley rats were ventilated with gas mixtures containing concentrations of inspired CO2 (FICO2) of 0.0, 0.3, or 0.5, with oxygen fractions held constant at 0.5. After 4 mins of ventricular fibrillation, mechanical chest compressions were initiated with a pneumatic thumper; 2 mins later, transthoracic defibrillation was attempted. RESULTS: Each animal ventilated with FICO2 of 0.0 or 0.3 was successfully resuscitated. However, none of the animals ventilated with FICO2 of 0.5, in which aortic pH was less than 6.67 and aortic PCO2 was greater than 200 torr (greater than 26.7 kPa), was resuscitated (p less than .001). This finding contrasted with a second control group of seven identically treated animals which, in the absence of cardiac arrest, demonstrated no adverse effects after ventilation with an FICO2 of 0.5. CONCLUSIONS: Increases in FICO2 to levels of 0.5 under conditions of constant arterial oxygenation and controlled coronary perfusion pressure preclude successful resuscitation in this rodent model of CPR."
-What is the effectiveness of endoscopic balloon dilatation in managing intestinal strictures caused by Crohn's disease?,"Endoscopic balloon dilatation as a therapeutic option in the management of intestinal strictures resulting from Crohn's disease. Endoscopic balloon dilatation was undertaken in seven patients who presented with obstructive symptoms resulting from Crohn's disease. Five patients had strictures from recurrent disease at the site of an ileotransverse anastomosis, one had duodenal stenosis and one a colonic stricture. The procedures were performed under intravenous sedation on one to four occasions (median 2) and were uncomplicated. Sustained improvement over an 18-24-month follow-up period was achieved in five patients, but dilatation was unsuccessful in two cases. Endoscopic balloon dilatation is a safe and effective option in selected patients with intestinal strictures resulting from Crohn's disease and may overcome the need for surgery."
-What method is considered the definitive study for evaluating the integrity of breast implants?,"Definitive diagnosis of breast implant rupture by ultrasonography. Silicone breast implantation is entering its fourth decade. Our ability to monitor the integrity of ""old"" prostheses is questioned. Clinical and mammographic examinations are reliable indicators of implant rupture only if there has been gel migration away from the implant pocket. Ultrasonography is presented as a reliable, sensitive method of evaluation of implant integrity. It should be considered the definitive study of prosthesis integrity. When sonography is added to mammographic and clinical examination, the preoperative evaluation of symptomatic augmented breasts is complete. Ultrasonography may be considered with mammography in the routine breast examination of all previously augmented patients."
-What are the key principles of managing external abdominal fistulas arising from the digestive tract?,"External fistulas arising from the digestive tract. External abdominal fistulas that arise from the digestive tract are associated with high mortality and prolonged morbidity in terms of infection, malnutrition, and skin excoriation. Such external fistulas most commonly follow anastomotic leak after gastrointestinal surgery. We identified 58 patients seen over a 5-year period at the University of Louisville Hospitals because of external abdominal fistulas that arose from the stomach (8), duodenum (4), small intestine (26), colon (14), biliary tract (9), and pancreas (7). Fifteen patients had multiple fistulas and 32 had high-output fistulas (greater than 200 mL/day). Closure was achieved in 48 patients, and eight of the 10 patients whose fistulas remained open died. Overall mortality was 19%. Principles of management include control of infection, correction of fluid and electrolyte imbalance, nutritional support, proper wound care, and often operative intervention. Multiple staged operations over many months were particularly important in managing complex wounds with large abdominal wall defects and multiple fistulas. Fistula closure is the ultimate goal, and patience is important to achieve it."
-What treatment was found to be effective in managing neurogenic pulmonary edema in a patient with subarachnoid hemorrhage?,"Neurogenic pulmonary edema: treatment with dobutamine. In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema."
-What complications did the patient develop after receiving a continuous IV infusion of vasopressin?,"Rhabdomyolysis and cutaneous necrosis following intravenous vasopressin infusion. A continuous IV infusion of vasopressin was administrated to a patient with cirrhosis of the liver and acute gastrointestinal bleeding from esophageal varices. In the first 24 hours, the patient developed rhabdomyolysis and cutaneous necrosis. Stopping vasopressin infusion resulted in relief of these lesions. The rarity of these complications suggests an idiosyncratic reaction of susceptible individuals that may be related to previous vascular disease or a failure in baroreceptor regulation."
-What are the key mental health benefits of regular aerobic exercise?,"Health benefits of aerobic exercise. Regular aerobic exercise has significant cardiovascular benefits, including a reduction in incidence of and mortality from coronary artery disease--probably because of positive effects on blood lipid levels and blood pressure. Aerobic exercise can also be an important adjunct to a weight-loss program. Many persons who continue an exercise program do so because of its positive mental benefits, including reduction in anxiety and depression and modulation of stress levels. Aerobic exercise has a place in the management of diabetes, pregnancy, and aging. The problems associated with aerobic exercise are minimal compared with its benefits."
-What makes low back pain a challenging diagnosis in emergency department settings?,"Low back pain: review of diagnosis and therapy. Low back pain is a patient complaint frequently encountered in the emergency department setting. The disease entity is often a diagnostic challenge with a subtle presentation, but can be accompanied by significant neurovascular complications. Current topics of controversy include the utility of radiologic evaluation, pharmacologic and holistic treatment strategies, as well as guidelines for urgent referral of patients with lumbar pain."
-How does Color Doppler imaging help in assessing orbital blood flow in carotid artery disease?,"Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease. Color Doppler imaging was used to evaluate the hemodynamics of the ophthalmic vasculature in a case of complete internal carotid artery occlusion. This procedure, which allows rapid, noninvasive imaging, showed a partial ophthalmic artery obstruction with absent flow in the central retinal artery, central retinal vein, and nasal posterior ciliary arteries. Although altered perfusion of the retinal vessels may be evaluated clinically, assessment of blood flow in the ophthalmic and ciliary arteries previously could be evaluated only indirectly by intravenous fluorescein angiography. The color Doppler imaging findings were confirmed by intravenous fluorescein angiography and carotid arteriography. Color Doppler imaging represents a noninvasive method to diagnose abnormal blood flow of the ophthalmic artery and its branches and to evaluate serial changes of the circulation in a noninvasive manner."
-What CT scan findings are associated with a higher probability of hypovolemia in patients with subarachnoid hemorrhage?,"Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia."
-What are the key differences in spinal nerve sheath tumors between patients with neurofibromatosis type 1 and type 2?,"Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2. Benign spinal nerve sheath tumors (neurofibromas and schwannomas) often occur on dorsal nerve roots sporadically or in neurofibromatosis types 1 and 2. These are histologically benign tumors, and distinction between them is frequently not made by clinicians. To determine if there is a correlation between the histological pattern of benign spinal nerve sheath tumors and the type of neurofibromatosis, the clinical and pathological features of these tumors (86 surgical specimens and five autopsies) in 68 patients were reviewed. The patients were classified into one of four categories: neurofibromatosis type 1, neurofibromatosis type 2, uncertain, or sporadic. The diagnostic criteria used for neurofibromatosis types 1 and 2 were established by the National Institutes of Health. Patients who did not fulfill criteria for either neurofibromatosis type 1 or 2 but who had multiple nervous system tumors or other stigmata of neurofibromatosis were designated ""uncertain."" Spinal nerve sheath tumors were considered sporadic in 42 cases (40 schwannomas and two neurofibromas). In the 14 patients with neurofibromatosis type 1, all spinal nerve sheath tumors were neurofibromas. In six of the seven patients with neurofibromatosis type 2, all spinal nerve sheath tumors were schwannomas. One patient with neurofibromatosis type 2 had a spinal nerve sheath schwannoma and a tumor with features of both tumor types. The authors conclude that spinal nerve sheath tumors in patients with neurofibromatosis type 1 are neurofibromas. In contrast, spinal nerve sheath tumors occurring in neurofibromatosis type 2 or sporadically are most frequently schwannomas. The distinct histological features of these tumors may reflect different pathogenetic mechanisms even though they arise at identical sites in neurofibromatosis types 1 and 2."
-What were the key findings comparing surgically treated and untreated patients with spinal stenosis?,"The effect of decompression on the natural course of spinal stenosis. A comparison of surgically treated and untreated patients. The clinical course of 19 untreated patients with spinal stenosis (mean age, 60 years) was compared with that of 44 patients treated surgically (mean age, 65 years). The time of follow-up was 31 and 53 months, respectively. About 80% of the patients had neurogenic intermittent claudication. In the follow-up, one third of the treated and one half of the untreated patients still had neurogenic claudication. By visual analogue-scale estimation, 60% of those treated surgically and 33% of the untreated patients felt better. Fifty-eight percent of the untreated patients were unchanged. Neurophysiologic changes showed progression in almost all cases; it was more pronounced in the treated patients. No proof of severe deterioration was found in the untreated patients, and observation for 2-3 years seems to be a good alternative to surgery."
-How does monitoring cerebral oxygenation help in managing patients with acute severe closed head trauma?,"Continuous monitoring of cerebral oxygenation in acute brain injury: injection of mannitol during hyperventilation. Global cerebral oxygenation, perfusion pressure, and expired pCO2 were continuously monitored in 10 adults with acute severe closed head trauma. Cerebral oxygenation was monitored by fiberoptic catheter oximetry, which allowed simultaneous measurements of arterial and jugular bulb oxyhemoglobin saturation. Intracranial pressure levels over 20 mm Hg were recorded several times in all patients, in spite of sedation, muscle paralysis, and profound hyperventilation. Intracranial hypertension was frequently associated with oligemic cerebral hypoxia, identified as abnormally low jugular oxygen saturation in the presence of normal arterial oxygenation. Intracranial hypertension was then managed with intravenous administration of mannitol boluses, which yielded simultaneous decreases in intracranial pressure and increases in cerebral oxygenation to highly statistically significant levels. Monitoring cerebral oxygenation was clinically useful because it allowed identification of impaired cerebral oxygenation even when cerebral perfusion pressure was normal. It is therefore proposed as a new monitoring technique, to supplement conventional monitoring of cerebral perfusion pressure."
-What were the key findings of the study on chronic neurological effects of acute organophosphate pesticide intoxication in Nicaraguan agricultural workers?,"Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group. Acute organophosphate pesticide poisonings cause substantial morbidity and mortality world wide; however, whether organophosphates cause chronic neurological sequelae has not been established. To see whether single episodes of acute unintentional organophosphate intoxication lead to chronic neuropsychological dysfunction, we carried out a retrospective study of agricultural workers in Nicaragua who had been admitted to hospital between July 1, 1986, and July 31, 1988, for occupationally related organophosphate intoxication. This ""poisoned"" group (36 men) was tested on average about two years after the episode of pesticide poisoning and compared with a matched control group. The poisoned group did much worse than the control group on all neuropsychological subtests, with significantly worse performance on five of six subtests of a World Health Organisation neuropsychological test battery and on 3 of 6 additional tests that assessed verbal and visual attention, visual memory, visuomotor speed, sequencing and problem solving, and motor steadiness and dexterity. Differences in neuropsychological performance could not be explained by other factors. The findings of a persistent decrease in neuropsychological performance among individuals with previous intoxication emphasise the importance of prevention of even single episodes of organophosphate poisoning."
-What was the accuracy of fine needle aspiration (FNA) cytology in differentiating between benign and malignant pancreatic lesions in this study?,"Preoperative and intraoperative fine needle aspiration cytology of pancreatic lesions. The aim of the present study was to describe our experience from 1976 through 1988 with fine needle aspiration (FNA) cytology of pancreatic lesions in 90 patients. Fine needle aspirations were performed preoperatively under ultrasound guidance (USG) in 46 patients, under computed tomographic guidance (CTG) in seven patients, and intraoperatively in 37 patients. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 80 patients, of whom 62 had malignant pancreatic disease (MPD) and 18 had benign pancreatic disease (BPD). The accuracy of cytologic diagnoses was verified by histologic, cytologic, and clinical findings. In 62 patients with MPD, the cytologic findings suggested malignancy in 54 patients, suspected malignancy in five, and did not reveal malignancy in three patients. Among 18 patients with BPD, all of the cytologic findings were reported as benign. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for intraoperative FNA cytologic results were 96%, 100%, 100%, 91%, and 97%, respectively, and for USG FNA cytologic results were 94%, 100%, 100%, 78%, and 95%, respectively. No complications followed the procedure. Conclusions: Both transabdominal percutaneous imaging-guided and intraoperative FNA cytology of pancreatic lesions are simple, safe, and highly accurate methods in differentiation of benign from malignant pancreatic lesions."
-What measures have been used to reduce the incidence of stress erosive gastritis in critically ill patients?,"Stress erosive gastritis. Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention."
-What were the key findings of autonomic function studies in patients with Friedreich's ataxia?,"Autonomic function in Friedreich's ataxia. Autonomic function studies were performed on 15 patients with Friedreich's ataxia, and the results compared with those of 76 healthy subjects. There was an increase in resting supine heart rate, attributed to cardiac abnormalities. Other tests of sympathetic and parasympathetic function were normal. The normal autonomic function studies are consistent with the pathological findings of degeneration predominantly of large diameter myelinated fibres with sparing of small myelinated and unmyelinated fibres."
-What was the incidence of tracheostomal stenosis in patients who underwent total laryngectomy with immediate tracheoesophageal puncture compared to the control group?,"Tracheostomal stenosis after immediate tracheoesophageal puncture. The incidence of tracheostomal stenosis in a group of patients after total laryngectomy with or without pharyngectomy plus immediate tracheoesophageal or tracheogastric puncture was compared with that of a control group without puncture. The stenosis rate of the puncture group was significantly higher than that of the control group (19% vs 6%). The other probable etiologic factors for stomal stricture were similar in both groups. Analysis of the risk factors in the puncture group suggested a higher tendency of stenosis in females (43% vs 16%) and in patients receiving postoperative radiotherapy (29% vs 14%), although the difference failed to reach statistical significance."
-What was the primary objective of the Systolic Hypertension in the Elderly Program (SHEP) study?,"Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group OBJECTIVE.--To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. DESIGN.--Multicenter, randomized, double-blind, placebo-controlled. SETTING.--Community-based ambulatory population in tertiary care centers. PARTICIPANTS.--4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. INTERVENTIONS.--Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. MAIN OUTCOME MEASURES.--Primary.--Nonfatal and fatal (total) stroke. Secondary.--Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. RESULTS.--Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. CONCLUSION.--In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000."
-What were the two antibiotic regimens compared in this clinical trial for treating children with ruptured appendicitis?,"A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis. This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis. Ninety-seven children were randomized. Forty-seven were assigned to the AGC regimen and 50 received CC. Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS). There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization. Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint. We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy."
-What are the limitations of physical examination techniques in diagnosing splenomegaly according to the context?,"The clinical diagnosis of splenomegaly. Assessing for the presence of splenomegaly is an important component of the physical examination. Although several methods of palpation and percussion of the spleen have been described, until recently they have not been validated by noninvasive imaging techniques such as ultrasonography, radionuclide scanning, and computed tomography that offer objective means to assess splenomegaly. We review the literature comparing various physical examination techniques with noninvasive imaging modalities and conclude that palpation and percussion of the spleen are complementary but frequently insensitive and that further studies are needed to evaluate the efficacy of specific diagnostic methods."
-What are the various surgical procedures recommended for treating cubital tunnel syndrome?,"The failed ulnar nerve transposition. Etiology and treatment. Various procedures have been recommended for the treatment of cubital tunnel syndrome. Simple decompression in situ, medial epicondylectomy, subcutaneous transposition, intramuscular transposition, and submuscular transposition all have their advocates. The results of the surgical treatment for cubital tunnel syndrome are related to the severity of the compressive neuropathy at the time of diagnosis and to the adequate decompression of the nerve at all sites of potential compression at the time of surgical treatment. Fourteen patients who had previously undergone surgical treatment for cubital tunnel syndrome were evaluated because of persistent pain, paresthesia, numbness, and motor weakness. All patients had documented persistent compression of the ulnar nerve on clinical and electromyographic evaluation. The indication for repeat surgical exploration in all patients was unremitting pain despite nonoperative treatment. All patients had been treated by neurolysis and submuscular transposition of the ulnar nerve as described by Learmonth. The causes of continued pain after initial surgery included retention of the medial intermuscular septum, dense perineural fibrosis of the nerve after intramuscular and subcutaneous transposition, adhesions of the nerve to the medial epicondylectomy site, and recurrent subluxation of the nerve over the medial epicondyle after subcutaneous transposition. Revision surgery was found to be highly successful for relief of pain and paresthesias; however, the recovery of motor function and return of sensibility were variable and unpredictable."
-How does verapamil help protect against renal injury at the cellular level?,"Role of calcium channel blockers in protection against experimental renal injury. The available evidence indicates that the first generation calcium channel blocker verapamil has a protective effect against both acute and chronic renal failure. At the cell membrane, verapamil helps minimize the effects of excess calcium influx after ischemic injury, evidenced by reduced uptake of 45Ca, thus lessening tubular injury from both calcium-activated phospholipases and mitochondrial calcium overload. In experimental chronic renal failure, the long-term administration of verapamil protects against renal dysfunction and damage, independent of any effect on systemic mean arterial pressure. Protective effects of verapamil are delineated in several models, supporting the presented hypothesis of the pathogenesis of renal failure."
-What was the clinical significance of microsporidia detection in HIV-1-infected patients with chronic diarrhoea?,"Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals To assess the importance of microsporidiosis of the small intestine in the pathogenesis of chronic diarrhoea in HIV-1-infected individuals, duodenal biopsy samples from the following three patient groups were prospectively evaluated for bacterial, viral, and parasitic pathogens by standard methods, and for microsporidia by light microscopy: 55 consecutive HIV-1-antibody-positive subjects with unexplained diarrhoea of at least 3 weeks duration (group A); 38 HIV-1-seropositive subjects without diarrhoea (group B) who consecutively underwent upper gastrointestinal endoscopy for various reasons; and 7 patients without known risk factors for HIV infection with chronic unexplained diarrhoea (group C). In groups A and B most subjects had had previous AIDS-defining opportunistic infections and the median peripheral blood CD4 lymphocyte count was less than 0.1 x 10(9)/l. Microsporidia were detected as the single pathogen in 15 of the group A compared with 1 (in whom diarrhoea subsequently developed) of the group B patients (p = 0.001) and none of the group C patients. With the exception of 4 of the group A patients, no other intestinal pathogens were identified in any of the patients. The median peripheral blood CD4 count was significantly lower in patients with detectable microsporidia than in those without microsporidiosis (0.03 x 10(9)/l vs 0.06 x 10(9)/l; p = 0.03); in all patients with microsporidiosis, the CD4 count was equal to or less than 0.1 x 10(9)/l. 13 patients with microsporidiosis were treated with metronidazole, in 10 of whom treatment led to a substantial improvement or disappearance of diarrhoea within days of starting therapy, but did not result in eradication of the parasite in the 5 patients who underwent repeat biopsy. The findings suggest that small-intestinal microsporidiosis is an important cause of chronic unexplained diarrhoea in HIV-1-infected individuals with pronounced cellular immune deficiency. This infection should therefore be added to the list of AIDS-defining opportunistic infections."
-What are the key differences in vascular reactivity between norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure?,"Differences in vascular reactivity in models of ischemic acute renal failure. To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded."
-What is the significance of S100-positive sustentacular cells in determining the malignancy of pheochromocytomas?,"S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. The absence or presence of S100-positive sustentacular cells has been previously shown to be correlated with benign and malignant pheochromocytomas and paragangliomas. We evaluated a total of 17 malignant and recurrent or locally aggressive adrenal pheochromocytomas for their quantity of sustentacular cells. An absence of sustentacular cells was demonstrated in the majority of malignant cases, while the locally aggressive or recurrent group usually contained an abundance of these cells. However, in one malignant case a constant moderate number of sustentacular cells in the primary site and in two sequential metastases was found. We conclude that the absence of sustentacular cells in pheochromocytomas may indicate a lesion with a greater potential for metastasis and that sustentacular cells, when they are present in a malignant pheochromocytoma, are an integral part of the tumor."
-What is the proposed solution for facilitating Nd-YAG laser hyaloidotomy in eyes prone to developing malignant glaucoma after surgery?,"Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation. Three cases of malignant glaucoma following extracapsular cataract extraction with 7 mm one-piece posterior chamber intraocular lens implantation are presented. Nd-YAG laser hyaloidotomy was successfully performed in all eyes, but was difficult and required several sessions in two eyes. In the third eye, which had a sector iridectomy, laser hyaloidotomy applied over the edge of the lens optic through the iridectomy resulted in brisk deepening of the anterior chamber and reduction of intraocular pressure. We propose that the one-piece 7 mm optic posterior chamber intraocular lens may constitute an obstacle to successful hyaloidotomy, mainly owing to its large size, as it may block aqueous percolation from the vitreous into the anterior chamber. Eyes prone to develop malignant glaucoma after surgery should have a sector or large peripheral iridectomy to facilitate postoperative Nd-YAG laser hyaloidotomy if required."
-What were the main indications for emergency pulmonary resection in the patients described in this context?,"Emergency pulmonary resection for pneumonia. High morbidity and mortality. Emergency pulmonary resection was performed because of complicated pneumonia in eight patients (5 pneumonectomies, 2 lobectomies, 1 bilobectomy) over a 2-year period. The patients' age range was 5 months to 43 years. The indications were rapid aggravation of respiratory insufficiency in children with staphylococcal pneumonia and enlarging pneumatoceles, and massive hemoptysis in patients with chronic destructive pneumonia. Two patients died after pneumonectomy, one from contralateral aspiration and one from cardiogenic shock. Postoperative complications occurred in four cases--bronchopleural fistula and pyopneumothorax in three and thoracic empyema with massive chest-wall infection in one. Only two patients had an uneventful postoperative course. Complications of pulmonary necrosis in pneumonia may dictate urgent pulmonary resection, often pneumonectomy. Surgery will be life-saving in most cases, but high morbidity is to be expected."
-What are the key risk factors for myocardial rupture after acute myocardial infarction?,"Myocardial rupture. Your patient's survival may depend on you. Myocardial rupture is the second leading cause of in-hospital death from acute myocardial infarction. It is most likely to occur in the elderly, women, and patients with transmural infarction and no previous history of angina. A high index of suspicion is critical to the diagnosis. Myocardial rupture should be suspected when recurrent chest pain or hemodynamic instability develops after myocardial infarction. Rapid intervention and appropriate infarct-limiting therapy may reduce the mortality rate of this catastrophic complication."
-What are the key contributing factors for developing an abdominal wall Actinomyces abscess associated with an intrauterine device?,"Abdominal wall Actinomyces abscess associated with an intrauterine device. A case report. An abdominal wall Actinomyces abscess occurred in a woman with an intrauterine device. Contributing factors were local trauma, spread from surrounding colonized body sites and symbiotic growth of other anaerobes. The diagnosis was based on the histologic finding of the sulfur granule. Special studies may be needed to distinguish this condition from other, similar ones (Nocardia, botryomycosis)."
-How does radionuclide ventriculography help in assessing prognosis after acute myocardial infarction?,"Radionuclide assessment of ventricular function and risk stratification after myocardial infarction. Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction."
-What uncommon complication occurred in a 38-year-old woman 7 days after lumbar myelography with iohexol?,"Intracerebral hemorrhage after lumbar myelography with iohexol: report of a case and review of the literature. Intracranial hemorrhage is an uncommon complication of dural puncture. In most instances, hematomas are subdural; they may be unilateral or bilateral. Rarely are intraparenchymal cerebral hemorrhages related to dural puncture. This report describes a delayed occurrence of bilateral intraparenchymal hemorrhages in a 38-year-old woman 7 days after lumbar myelography with iohexol. A review of the literature is presented."
-How does activity level modify the relationship between serum cholesterol level and coronary heart disease risk in older persons?,"Is the serum cholesterol-coronary heart disease relationship modified by activity level in older persons? Although coronary heart disease remains a leading cause of death and disability in old age, the relationship of serum cholesterol level to risk of coronary heart disease in old age is controversial. Data for 2,388 white persons aged 65-74 who participated in the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study (NHEFS) were examined to determine the relationship of serum cholesterol level to coronary heart disease incidence and whether activity level would modify this relationship. While there was no overall relationship between serum cholesterol level and coronary heart disease risk in either men or women, the relationship between serum cholesterol level and coronary heart disease differed within activity groups. For persons who were more active, serum cholesterol level was associated with a graded increase in risk of coronary heart disease, from 1.3 (95% CI 0.7, 2.3) in those with serum cholesterol level of 4.7-5.1 to 1.7 in those with serum cholesterol level of 6.2 mmol/L or more (95% CI 1.0, 2.7), when compared with those with serum cholesterol level below 4.7. For the least active persons, all levels of cholesterol were associated with a significant inverse relative risk, including cholesterol of 6.2 mmol/L or more (Relative risk = 0.4 (95% CI 0.2, 0.7]. These data suggest that factors such as activity level may modify the serum cholesterol-coronary heart disease association in old age. The serum cholesterol-coronary heart disease association in more active older persons resembles that seen in younger populations, whereas the association in less active persons is that of serum cholesterol level and risk of cancer or death. The modification of the serum cholesterol-coronary heart disease association by activity level may have implications for appropriate clinical management as well as appropriate design of research studies of this association."
-What evidence suggests an increase in GABA-ergic neurotransmission in patients with hepatic encephalopathy due to fulminant hepatic failure?,"Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure BACKGROUND. Increased gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathogenesis of hepatic encephalopathy. The mechanism by which GABA-ergic activity is increased in hepatic failure is unclear, but recent studies in animals with encephalopathy due to fulminant hepatic failure suggest that GABA-ergic neurotransmission may be increased by the presence of elevated concentrations of benzodiazepine agonists such as diazepam and N-desmethyldiazepam. METHODS AND RESULTS. Samples of frontal cortex were obtained at autopsy from 11 patients with hepatic encephalopathy who died of acetaminophen-induced fulminant hepatic failure and 8 patients who died of cardiovascular disease or trauma. None of the 19 patients had received benzodiazepines while hospitalized. Chromatographic analyses of extracts of these samples revealed 4 to 19 peaks representing substances that inhibited the binding of a radiolabeled imidazobenzodiazepine ([3H]flumazenil) to its receptors. Several of these peaks had retention times corresponding to those of known 1,4-benzodiazepines. Ultraviolet- and mass-spectroscopic analysis confirmed that two of these peaks represented diazepam and N-desmethyldiazepam. The patients who died of fulminant hepatic failure could be divided into two groups: six who had had significantly elevated brain concentrations (2-fold to 10-fold higher than normal) of substances inhibiting the binding of [3H]flumazenil and five who had normal concentrations. CONCLUSIONS. Brain concentrations of substances inhibiting the binding of [3H]flumazenil to its receptors are increased in some patients with hepatic encephalopathy due to fulminant hepatic failure. The origin of these substances is unknown, but these findings provide a rational basis for trials of benzodiazepine-receptor antagonists in the management of this disorder."
-What method did the researchers use to detect hepatitis B virus DNA in liver tissue samples?,"Detection of hepatitis B virus DNA in paraffin-embedded liver tissues in chronic hepatitis B or non-A, non-B, hepatitis using the polymerase chain reaction. We developed a polymerase chain reaction assay for the direct detection of hepatitis B virus in paraffin-embedded liver tissue and applied this assay to determine whether hepatitis B virus DNA exists in livers with chronic hepatitis non-A, non-B. Fifty five liver biopsy samples were studied: 11 from patients with HBeAg-positive chronic hepatitis (paraffin-embedded) and 44 from patients with chronic hepatitis non-A, non-B (21 paraffin-embedded; 25 fresh frozen). Thirty three (75%) of the non-A, non-B cases were positive for hepatitis C virus antibodies. Approximately 1 to 10 ng of DNA was extracted from the paraffin-embedded tissue and amplified using oligonucleotide (23-mer) primers specific for the S gene (positions 261 to 692). The beta-globin gene was used as an internal control for sensitivity because this is a single copy gene and allows for relative quantification. In each of the chronic hepatitis B livers, the expected 432-base-pair amplification product for hepatitis B virus DNA and beta-globin gene product were both detected. On the other hand, in the 21 paraffin-embedded chronic hepatitis non-A, non-B livers, no hepatitis B virus DNA was detected, although beta-globin gene was observed in all. Furthermore, in all 25 frozen non-A, non-B livers, beta-globin gene was observed, but no hepatitis B virus band was seen. The limit of detection of hepatitis B virus DNA by this method was estimated to be one genomic copy of hepatitis B virus DNA per cell."
-What is the potential advantage of the step-down method of FSH administration for ovulation induction in women with polycystic ovarian syndrome (PCOS)?,Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome. The step-down method can be an alternative method of ovulation induction in women with PCOS. This protocol can induce ovulation with a smaller dose of FSH and with lower incidence of excessive ovarian enlargement in comparison with the traditional fixed-dose administration method.
-What were the key findings of the 12-week trial of fluoxetine in patients with borderline or schizotypal personality disorders?,"Fluoxetine in the treatment of borderline and schizotypal personality disorders. Twenty-two patients meeting the criteria for borderline or schizotypal personality disorder or both participated in a prospective, nonblind 12-week trial of fluoxetine. There were significant reductions in self-injury and in scores on the Hopkins Symptom Checklist regardless of diagnosis. The results suggest that controlled trials of fluoxetine and investigations of the serotonergic system in these disorders would be useful."
-What is the proposed term for the special variant of dermatofibroma described in the case report?,"Atypical polypoid dermatofibroma: report of two cases. Two cases of a hitherto undescribed special variant of dermatofibroma are reported. A man and a woman, aged 57 and 52 years, respectively, had slowly growing cutaneous tumors on the lower extremities. The tumors were exophytic and polypoid, 10 and 6 cm in maximal diameters, respectively; they were covered by rough nonulcerated skin and were joined by a short pedicle to an indurated base. Histologic examination showed some features of an otherwise conventional dermatofibroma, whereas the polypoid component was hypercellular and showed striking atypia and scattered mitotic figures. After 32 and 28 months' follow-up, the lesions did not recur after surgical excision. We suggest the term atypical polypoid dermatofibroma to summarize the special clinicopathologic features of these tumors."
-What was the average hospital stay for patients with pelvic fractures in this study?,"Pelvic fracture from major blunt trauma. Outcome is determined by associated injuries. Pelvic hemorrhage has been implicated as the cause of death in 50% of patients who die following pelvic fractures. To establish correlates of morbidity and mortality from pelvic fractures due to blunt trauma, we reviewed 236 patients treated during 4 years. The average age of the 144 men and 92 women was 31.5 years, the average Injury Severity Score was 21.3, the average blood requirement was 5 units, and the average hospital stay was 16.8 days. One hundred fifty-two patients (64.4%) were injured in motor vehicle accidents, 33 (14%) had motor vehicle-pedestrian accidents, 16 (6.8%) had crush injuries, 12 (5.1%) each had either motorcycle accidents or falls, and 11 (4.6%) had miscellaneous accidents. Eighteen patients (7.6%) died, with seven (38.9%) deaths due to hemorrhage. Only one death was caused by pelvic hemorrhage. Other deaths were due to hemorrhage from other sites (6), head injury (5), sepsis or multiple-organ failure (4), pulmonary injury (1), and pulmonary embolus (1). None of the septic deaths was related to a pelvic hematoma. Multivariate multiple regression analysis showed that the severity of injury was correlated with indices of severity of pelvic fractures such as fracture site (p less than 0.0001), fracture displacement (p less than 0.005), pelvic stability (p less than 0.0001), and vector of injury (p less than 0.01). However death could not be predicted on the basis of these indices of severity (p greater than 0.28). Of the nine patients who underwent pelvic arteriography, three required embolization of actively bleeding pelvic vessels, but seven had intra-abdominal hemorrhage that required laparotomy, and eight developed a coagulopathy. Massive bleeding from pelvic fractures was uncommon, and the major threat of hemorrhage was from nonpelvic sites. Furthermore, although injury severity was correlated with the severity of the pelvic fracture, hospital outcome was determined by associated injuries and not by the pelvic fracture."
-What is the estimated yearly risk of Giardia infection for water systems using polluted waters compared to pristine waters?,"Risk assessment and control of waterborne giardiasis. BACKGROUND: Waterborne giardiasis has been increasing in the United States with 95 outbreaks reported over the last 25 years. The Safe Drinking Water Act has mandated control of this pathogen. METHODS: A risk assessment model was developed to estimate risk of infection after exposure to treated waters containing varying levels of Giardia cysts. The model was defined by a dose-response curve developed from human feeding studies for Giardia and assumed 2L of water consumption per day. Data on concentrations and distribution of the organism in source waters were used to assess exposure after varying reductions achieved through treatment. RESULTS: In surveys reporting prevalence and levels of Giardia cyst contamination, average levels of cysts in surface waters ranged from 0.33 to 104/100L; from pristine watersheds (protected from all human activity) 0.6 to 5/100L. Yearly risks were 4.8 x 10(-3) for systems using polluted waters and 1.3 x 10(-4) for pristine waters with a 10(-3) treatment reduction. CONCLUSION: Public Health officials will need to work with the water industry to ensure a risk of less than 1/10,000 for source waters with 0.7 to 70 cysts per 100 liters through treatment achieving reduction of 10(-3) to 10(-5), respectively, of Giardia cysts."
-What rare medical condition is described in this case report involving the cauda equina?,Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis.
-What unique mitochondrial DNA characteristics were found in the muscle biopsy specimens of the two children with combined Kearns-Sayre and MELAS syndrome features?,"Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression."
-What were the key psychiatric disorders found to be more prevalent in men with chronic low back pain compared to the control group?,"Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study. This study used structured diagnostic interviews and DSM-III criteria to assess lifetime prevalence and pre-morbid risk of psychiatric disorder in a sample of men with long-standing chronic back pain (CLPB) attending a primary care clinic. A control group of age and demographically matched men without history of back pain was also studied. Compared to controls, men with CLBP had significantly higher lifetime rates of major depression (32% vs. 16%), alcohol use disorder (64.9% vs. 38.8%), and a major anxiety disorder (30.9% vs. 14.3%). Almost all CLBP men ever experiencing a mood disorder reported recurrent, not single, episodes. The 6 month point prevalence of major depression, but not other disorders, was also significantly elevated for men with CLBP. In CLBP, the first episode of major depression generally (58.1%) followed pain onset. While the initial major depressive episode usually commenced within the first 2 years of established pain, late onset mood disorder was also common. By comparison in most cases (81%) onset of alcohol use disorders considerably preceded pain. When an age-matching procedure was used to gauge relative vulnerability to psychiatric illness in patients and controls, CLBP patients had significantly higher pre-pain rates of alcohol use disorder but not depression. After age of pain onset, CLBP subjects had over 9 times the risk of developing major depression, but had similar rates of developing alcoholism. We conclude that (1) alcohol use disorders rather than depression may increase risk of developing CLBP, and (2) risk of new onset and recurrent major depression remains high for men throughout their pain career. This suggests that psychological adaptation to long-standing pain may be less successful than previously thought, especially with regard to recurrent mood disorder."
-What are the two conflicting views regarding the nature of the transmissible agent in spongiform encephalopathies like scrapie?,"A 'unified theory' of prion propagation. There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleic acid. On the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the PrPc gene, it has been suggested that a nucleic acid must be a component of the agent. Can the two views be reconciled?."
-How do the regulatory elements within the 475-base-pair fragment of the sevenless gene contribute to its specific expression pattern during Drosophila eye development?,"Analysis of the enhancer element that controls expression of sevenless in the developing Drosophila eye. The sevenless gene encodes a protein-tyrosine kinase receptor expressed in a complex pattern during the development of the Drosophila melanogaster eye. We have previously shown that this pattern is regulated transcriptionally by an enhancer located in the body of the sevenless gene. Here we extend our analysis of the sevenless enhancer, defining a 475-base-pair fragment that contains elements necessary for the correct qualitative and quantitative expression of the sevenless gene. Within this fragment are sequence elements conserved in the sevenless gene of a distantly related Drosophila species and protected from DNase I digestion by nuclear extracts isolated from adult heads and imaginal discs. Partial deletions of the 475-base-pair fragment result in preferential loss of expression in different subsets of cells. These results suggest that the normal pattern of expression is generated by the combined action of separate cell-specific regulatory elements."
-What were the two major patterns of severe Helicobacter pylori infection identified in the CT scans?,"Helicobacter pylori gastritis mimicking gastric carcinoma at CT evaluation. The abdominal computed tomographic (CT) scans from 61 patients with biopsy-proved Helicobacter (formerly Campylobacter) pylori gastritis were retrospectively reviewed. The CT scans were interpreted on the basis of the original report of the findings at CT examination and without knowledge of the results of biopsy. Of 19 patients (31%) with gastric abnormalities at CT, 14 (74%) had inflammatory changes initially reported as suspicious for gastric malignancy; malignancy was entertained as the primary diagnosis in four of those patients. In five of the 19 abnormal cases (26%), the diagnosis with CT was gastritis. The two major patterns of severe H pylori infection identified were (a) circumferential antral wall thickening and (b) thickening of the posterior gastric wall along the greater curvature, with or without evidence of ulceration. Thickening averaged 1.5-2.0 cm in cases suspicious for malignancy. The majority of abnormalities involved the gastric antrum (68%). No cases demonstrated significant adenopathy, obliteration of fat planes, or invasion of adjacent organs."
-How do micrometastases of gastric cancer impact patient survival rates after node dissection?,"Non-ominous micrometastases of gastric cancer. So-called R2 or wider meticulous node dissection was performed in 1368 patients with resected gastric cancer invading beyond the submucosa but without distant metastases. Survival rates were similar in subsets of patients with or without microscopic node metastases and macroscopically normal lymph nodes. The extent of node metastases has previously been shown to be one of the two most important prognostic factors in gastric cancer without distant metastases, and its lack of impact in these patient groups was not explained by the imbalance of other prognostic factors. The findings indicate that micrometastases of gastric cancer are curable by a wide node dissection made in the absence of palpable abnormality. They also offer the possibility that an extensive node dissection may yield good stage-specific survival rates, in part because of upstaging of patients. The findings should influence the recording of node metastases for evaluation of stage-specific treatment results and for research purposes."
-What was the main finding regarding cardiovascular mortality in diabetic patients treated with diuretics for hypertension?,"Excess mortality associated with diuretic therapy in diabetes mellitus OBJECTIVE. To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN. Cohort analytic study with a median follow-up of 4.5 years. SETTING. Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS.--There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS.--Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS.--In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population."
-What are the key differences between radiation and pagetic osteogenic sarcomas compared to classical osteogenic sarcoma?,"Radiation and pagetic osteogenic sarcomas. Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition."
-What was the response rate and overall survival of patients with refractory lymphomas and cutaneous T-cell lymphoma treated with pentostatin in this Phase II trial?,"Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease. Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers."
-What were the main causes of bilateral blindness in the Central African Republic according to the study conducted between 1985 and 1989?,"Causes of blindness and visual handicap in the Central African Republic. The causes of bilateral blindness (best visual acuity less than 3/60) in 1371 people in the Central African Republic seen between 1985 and 1989 who attended eye clinics in 10 out of the 16 prefectures across the country are given. The main causes of bilateral blindness were cataract (51%), glaucoma (12.7%), and onchocerciasis (8.1%). In 710 patients with unilateral blindness the main causes were cataract (38%), glaucoma (10%), iritis (7.5%), and trauma (6.3%). Bilateral blindness in children was rarely seen. The causes of visual impairment (vision between 6/18 and 3/60) in 424 patients were cataract, including aphakia (38%), maculopathy (14%), and onchocerciasis (7%)."
-How does sucralfate enhance gastroduodenal protection and mucosal defense mechanisms?,"Mechanisms of gastroduodenal protection by sucralfate. Over the past 5-10 years, a number of studies have shown that topical sucralfate enhances a number of gastric and duodenal mechanisms, e.g., the ""mucus-bicarbonate barrier,"" mucosal hydrophobicity, mucosal blood flow, cell viability, and local production of prostaglandins, as well as endogenous mediators of tissue injury and repair. It seems likely that the complex actions of sucralfate are in part related to direct interaction between the drug or its components (aluminum, sucrose, and sulfate) and gastric mucosal tissues, and in part related to effects of the drug on the various mucosal mediators of tissue injury and repair. Local actions may play a role in accelerating healing of ulcer-damaged mucosa, but this does not explain the protective actions of sucralfate on normal mucosa. Thus sucralfate appears to enhance the protective function of the ""mucus-bicarbonate"" barrier by actions on both components. This may depend in part on an interaction with the unstirred layer overlying gastric epithelium. Sucralfate has also been shown to increase the hydrophobicity of mucus gel. There is little doubt that sucralfate increases local production and release of protective prostaglandins (PGs), but the precise role played by these agents in mediating mucosal protection and in chronic ulcer healing remains uncertain. Currently, the mechanism of action of sucralfate on vascular integrity remains unknown and the role of PGs in this protective function is unclear. There is little evidence that epidermal growth factor plays any role in mediating mucosal protection by sucralfate, but it may be important in its ulcer-healing action. Sucralfate has been shown to be truly ""cytoprotective"" in that it protects isolated epithelial cells from damage by noxious agents. In animals treated with sucralfate, the surface epithelial cells were disrupted, but necrotic lesions in the deep proliferative zone were virtually absent. It seems likely that investigations of the actions of sucralfate and its components will move ever closer to defining the target cells, the intracellular events, and the mediators that bring about its protective and ulcer-healing activity."
-What is the correlation between histological grade and bromodeoxyuridine (BUdR) labeling index in astrocytomas?,"Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases. The histological grade and the bromodeoxyuridine (BUdR) labeling index of 60 astrocytomas of ""ordinary"" cell types (fibrillary, protoplasmic, gemistocytic, and anaplastic astrocytomas and glioblastomas) were compared to determine whether the grading system reflects the proliferative potential of the tumors. The tumor grade was based on the presence or absence of four criteria (nuclear abnormalities, mitosis, necrosis, and vascular endothelial proliferation): Grade 1, no criterion, Grade 2, one criterion, Grade 3, two criteria; and Grade 4, three or four criteria. The BUdR labeling index, or percentage of S-phase cells, was calculated in paraffin-embedded tumor sections after in situ labeling by intraoperative intravenous infusion of BUdR, 200 mg/sq m. Exponential regression analyses showed a positive correlation between the histological grade and labeling index (r = 0.88, p less than 0.001) that was stronger than the correlations between log labeling index and age (r = 0.55, p less than 0.001) and between grade and age (r = 0.55, p less than 0.001). These results indicate that the histological grading system reflects the proliferative potential of ""ordinary"" astrocytomas."
-What are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease?,"Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the ""symptom index."" Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain."
-What percentage of infectious agents were identified in the study of acute infectious erythemas in children?,"Acute infectious erythemas in children: a clinico-microbiological study. One-hundred children with an acute illness comprising fever and widespread erythematous rash were prospectively studied to determine whether clinical presentations are helpful in defining the causative agent and to identify the most appropriate microbiological specimens. An infectious agent was identified in 65 children; 72% were viruses, 20% were bacteria, 5% were Mycoplasma pneumoniae and in 3% both viruses and bacteria were detected. The most common infectious agents were picornaviruses, an atypical presentation of measles and Group A beta-haemolytic Streptococcus. Different patterns of rash occurred with each of these infections. The clinical presentation of a child with an acute febrile illness and rash was unhelpful in defining the causative agent. Routine management should include a throat swab for bacterial investigation and in selected cases a blood sample for IgM viral titres."
-What was the relationship between serum cholesterol concentration and mortality from coronary heart disease in the Shanghai population studied?,"Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. OBJECTIVE--To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE--Death from coronary heart disease and other causes. RESULTS--The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION--Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a ""low"" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death."
-What was the primary aim of the study on renovascular hypertension?,"The value of tests predicting renovascular hypertension in patients with renal artery stenosis treated by angioplasty. The aim of this study was to evaluate tests predicting renovascular hypertension. This was done by relating the results of renal vein renin tests, the captopril test, and renal scintigraphic tests to the blood pressure outcome 12 months after relief of renal artery stenosis by percutaneous transluminal renal angioplasty in 31 patients. Cure was seen in eight (26%). Improved blood pressure was obtained in 12 patients (39%), and in 11 patients (35%), the result for blood pressure was a failure. The accuracies of the two mathematical models used to analyze the renal vein renin assays were 44% and 60%. The captopril test showed a sensitivity of 36% and an accuracy of 43%. Renal captopril technetium Tc 99m-labeled pentetic acid scintigraphy gave a sensitivity of 60%. Stepwise logistic regression analysis of clinical variables in relation to blood pressure response revealed age as the only factor significantly related to blood pressure outcome. We conclude that the tests used are unfit for helping select patients for percutaneous transluminal renal angioplasty and that age may have an important influence on outcome."
-What are the two surgical approaches used for treating congenital atresia of the external auditory canal in this study?,"Surgical approaches to congenital atresia of the external auditory canal. During the past 4 years, 22 patients with congenital atresia of the external auditory canal underwent 24 initial operations by either an anterior or transmastoid approach. No attempt at randomization was made, but the two groups were similar in number and pathology (in 14 cases approach was anterior and in 10 cases approach was transmastoid). Followup ranged from 6 months to 4 years. Hearing results were similar in the two groups (71% with air-bone gap less than 30 dB). There were no instances of facial nerve injury or sensorineural hearing loss. Facial nerve monitoring was used. Complications of stenosis and drainage were more common with the transmastoid approach. In both groups, hearing results were accomplished with the patients' intact ossicles or prosthetic reconstructions. Meticulous soft-tissue technique, with split-thickness grafts covering all exposed bone, is the key to preventing stenosis. For the three cases of patients with thick, acellular atresia plates, a different approach was developed. Maintaining proper orientation during the medial dissection is more difficult in these cases. By opening the antrum primarily and identifying the lateral canal, ossicles, and facial nerve, an ear canal can then be created anteriorly with these landmarks in view. An intact canal wall-like procedure is carried out. Although hearing results are similar, the anterior approach, because of fewer postoperative complications, is now our procedure of choice. Proper orientation and soft-tissue technique are the keys to successful correction of the congenitally atretic ear canal."
-How does brief hypoxia affect the afterdischarge mechanism in conscious humans?,"Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans. After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the ""afterdischarge."" Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing."
-What potential surgical complication occurred during the left radical nephrectomy for renal cell carcinoma?,"Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma. The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions."
-Can moderately mentally retarded adults improve their cardiovascular fitness through a minimally supervised exercise program?,"Effects of a minimally supervised exercise program for mentally retarded adults. Previous exercise studies that attempted to improve the cardiovascular fitness (CVF) of mentally retarded (MR) adults were flawed with methodological shortcomings that prevented conclusive results. At issue in these training studies were fitness test validity and reliability, exactness of duration and intensity of training, and an inordinate amount of supervision. Therefore, we sought to determine whether moderately MR adults (seven males, five females; IQ = 61 +/- 3, age = 25 +/- 3 yr) could improve their CVF through a minimally supervised 16-wk training program. Each subject repeated exercise tests twice on two different modes of exercise, the treadmill (TM) and Schwinn Air-Dyne ergometer (SAE), before training to ensure validity and reliability of initial CVF levels. Intensity and frequency of exercise were closely monitored. An observer was present during the training bouts, but, following initial instructions, no additional encouragement or instructions were given. Although the training program significantly increased peak VO2 (29.2 +/- 8 to 33.5 +/- 9 ml.kg-1.min-1) and peak ventilation (73 +/- 26 to 81 +/- 231.min-1) when assessed on the TM, significant changes in these same parameters were not seen when assessed on the SAE. The importance of these results was discussed."
-What was the overall 30-day postoperative cardiac mortality rate for patients aged 80 years and older undergoing cardiac surgery during the study period?,"Cardiac surgery in the octogenarian: perioperative outcome and clinical follow-up The perioperative and follow-up results of cardiac operations employing extracorporeal circulation and cold cardioplegic arrest were examined in 191 consecutive patients greater than or equal to 80 years of age having surgery over a 5 year period (1982 to 1986). Most patients had severe preoperative symptoms with functional class III (39.8%) or IV (57.1%) limitation. The overall 30 day postoperative cardiac mortality rate was 15.7%. The total in-hospital mortality rate was 18.8%; the mean postoperative hospital stay was 16.4 +/- 13.3 days. The perioperative mortality rate for elective operations was as follows: coronary artery bypass (5.6%), aortic valve replacement (9.6%), aortic valve replacement with coronary bypass (17.9%) and mitral valve surgery with or without coronary bypass (21.4%). Urgent operations were performed in 39 patients (20.4%) with a total perioperative mortality rate of 35.9%; urgent coronary artery bypass was performed in 26 patients (67%) with an in-hospital mortality rate of 23.1%. Clinical evidence of left ventricular failure, functional class IV symptoms, left ventricular ejection fraction less than 50%, mitral valve repair or replacement for severe mitral regurgitation and urgent operation were associated with an increased perioperative mortality rate. Follow-up study in all 155 patients surviving postoperative hospitalization at 22.6 +/- 14.8 months showed significant improvement in symptom status in all surgical subgroups. There were 18 follow-up deaths (11.6%); 10 were noncardiac. The actuarial survival rate of the entire study group was significantly better than that in age- and gender-matched control subjects (p = 0.037)."
-What did the study reveal about the relationship between ethnic identity and pain perception?,"Interethnic differences in pain perception. While several investigators have reported relationships between ethnic background and expression of pain, such relationships are in fact highly problematical. Few studies of pain and ethnicity have used quantitative measures of pain combined with multivariate methods of data analysis. Most have focussed on populations which, unlike many in the United States today, are characterized by highly distinct ethnic groups. The study reported here interviewed 536 persons recently treated for forms of cancer known to cause significant pain. Pain was assessed using standard, well validated instruments, including Graphic Rating Scales anchored in several alternative time-frames and the McGill Pain Questionnaire. The study took place in an area with a low proportion of recent immigrants and only small concentrations of distinct ethnic minorities. No statistically significant relationships were observed between ethnic identity and measures of pain sensation. However, pain described in affective terms according to the McGill Pain Questionnaire did vary among ethnicities. This observation suggests that cultures associated with specific ethnic identities still condition individual expression of pain despite the high degree of assimilation that has occurred among ethnic groups in the United States."
-"What is the role of platelet activating factor (PAF) in shock, sepsis, and multiple organ failure?","The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure. PAF has been implicated as a mediator of shock, sepsis and MOF. The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage. These effects are prevented by PAF antagonists. PAF induces many of the characteristic changes of MOF, including functional impairment in the lung, kidney, gastrointestinal tract and heart. PAF antagonists will inhibit these adverse effects. PAF antagonists are now being manufactured by a number of pharmaceutical companies studying the beneficial effects of PAF antagonists in human disease. Data from these studies promise valuable information with significant clinical relevance to the practicing surgeon."
-What were the effects of tocopherol and tocotrienol on rat mammary tumors induced by DMBA and NMU?,"A comparison of tocopherol and tocotrienol for the chemoprevention of chemically induced rat mammary tumors. Two forms of vitamin E, tocopherol and tocotrienol, were tested for chemopreventive activity in two chemically induced rat mammary-tumor models. When mammary tumors were induced by 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg), only the tocotrienol group had a statistically significant increase in tumor latency. There was no effect of either compound on tumor multiplicity. When tumors were induced by N-nitrosomethylurea (NMU, 30 mg/kg), neither analogue of vitamin E modified latency, whereas tocotrienol increased tumor multiplicity. In summary, neither vitamin analog had a major impact on mammary-tumor development after tumor induction with either DMBA or NMU."
-How do calcium-channel blockers like verapamil and diltiazem affect ventricular function differently in control hearts versus failing hearts?,"Increased negative inotropic effect of calcium-channel blockers in hypertrophied and failing rabbit heart. The effects on ventricular function of calcium channel blockers and isoproterenol were studied in isovolumically beating perfused control rabbit hearts and in hearts subjected to a double pressure plus volume overload studied at the early phase of heart failure. In control hearts, isoproterenol produced an increase of systolic ventricular function and relaxation that was maximal at 10(-7) M. In failing hearts, inotropic state increase in response to isoproterenol was significantly smaller (P less than .01) with no observed lusitropic effect. In control hearts, verapamil and diltiazem produced dose-dependent decreases of ventricular function which were larger with verapamil than with diltiazem (median drug concentration50 of developed pressure was, respectively, 1163 +/- 131 nM and 4524 +/- 451 nM, P less than .001). In failing hearts, contractility decrease was larger than in control hearts (median drug concentration50 of developed pressure was 604 +/- 69 nM and 2691 +/- 580 nM with verapamil and diltiazem, respectively). In contrast, Ro 40-5967, a new calcium-channel blocker, did not produce reductions of inotropic state with concentrations up to 10(-5) M. All three calcium-channel blockers produced a 2-fold increase of coronary flow at 10(-6) M. We conclude that the deleterious effect of verapamil and diltiazem in heart failure is due, at least in part, to a direct depressant effect of these drugs on contractility, which is larger than in control hearts. Additionally, the in vivo sympathetic compensation is probably reduced, as indicated by the decreased ventricular responsiveness to isoproterenol."
-What were the actuarial survival rates for children who underwent heart transplantation according to the international survey?,"Heart transplantation in children: an international survey. A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor."
-What is sclerotherapy and how is it used in the treatment of large varicose veins?,"Practical phlebology. Sclerotherapy of large veins. A practical, step-by-step guide for the sclerotherapy of large varicose veins is offered. First, an orientation regarding the place of sclerotherapy and surgery in the total treatment of varicose veins is given, with a practical clinical classification of varicose veins. This is followed by a detailed discussion of patient education before sclerotherapy, material to be used with recommended concentrations, injection technique, compression after sclerotherapy, instructions to the patient after injection, and procedures at subsequent visits."
-What did the nuclear magnetic resonance spectroscopy reveal about brain pH in patients after cardiac resuscitation?,"Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation. We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining."
-What is the significance of this case report regarding intraocular hemangiopericytoma?,"Supraciliary hemangiopericytoma. A 10-year-old black girl complaining of pain and decreased vision in the left eye was found to have a smoothly elevated ciliochoroidal mass involving the superonasal quadrant of the left eye. The mass appeared circumscribed and uniformly dense by computed tomography. The tumor was hyperintense to vitreous and cerebral white matter on T1-weighted magnetic resonance imaging but was hypointense to vitreous and hyperintense to white matter on T2-weighted magnetic resonance imaging. Results of gross examination of the enucleated eye showed a sharply circumscribed, tan, intraocular mass arising equatorially. Results of histopathologic examination showed a well-vascularized spindle cell proliferation with a sinusoidal pattern characteristic of hemangiopericytoma. This is the third reported case of intraocular hemangiopericytoma and the first in a pediatric patient."
-What is the proposed modification to the definition of early gastric cancer according to the study?,"Problems in the definition and treatment of early gastric cancer. Radical operation with extensive dissection of lymph nodes (R1, 48 patients; R2, 196 patients; R3, one patient) was performed in 245 out of 247 patients with early gastric cancer. The 5-year survival rate was only 73.2 per cent in the 34 patients with lymph node metastases (31.8 per cent). Analysis of factors influencing recurrence revealed that not only lymph node metastases but also the depth of cancer invasion could affect prognosis in early gastric cancer. This study suggests that radical operation with complete dissection of the first and second group of lymph nodes (R2 resection) is a safe and appropriate treatment even for early gastric cancer. We propose that the definition of early gastric cancer be modified to 'carcinoma with invasion confined to the mucosa or submucosa and without evidence of lymph node metastases'."
-What is the purpose of using the Cavitron ultrasonic surgical aspirator in resecting residual mediastinal germ cell masses?,"Resection of residual mediastinal germ cell masses with the Cavitron ultrasonic surgical aspirator. Residual mediastinal masses after chemotherapy for germ cell tumors should be resected. Complete excision of bulky residual masses may sometimes be difficult because of problems with exposure in the region of the great vessels and important nerves. Two cases are presented in which the Cavitron ultrasonic surgical aspirator (Valleylab Inc., Surgical Systems Division, Stamford, Conn.) facilitated excision of large masses after intensive chemotherapy. We found that the collapsed pseudocapsule remaining after aspiration of tumor mass allowed early improved exposure and safer dissection from neighboring vessels and neural structures. Complete excisions were accomplished and no viable tumor was found, so that the patients were spared the immediate need for further therapy. Both had uneventful recoveries."
-What relationship did the study find between platelet membrane fluidity and stroke risk factors in Alzheimer's disease patients?,"Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease. We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease."
-What were the key findings of the study on total knee arthroplasty using the posterior stabilized condylar prosthesis?,"Results of total knee arthroplasty using the posterior stabilized condylar prosthesis. A report of 137 consecutive cases. One hundred thirty-seven consecutive posterior stabilized total knee arthroplasties (TKAs) were reviewed. Average age of the patient was 61.1 years and length of postoperative follow-up period was 29.2 months. Patients were evaluated using the Hospital for Special Surgery (HSS) knee rating scores. Average preoperative scores improved from 52 to 92, postoperatively. Ninety-eight percent of patients had no pain or mild occasional pain postoperatively compared with 99% of patients experiencing severe to disabling pain preoperatively. Complications included one myocardial infarction, two deep venous thrombosis, one urinary tract infection, one patellar dislocation, and four wound problems. There were two incidences of seroma, one hematoma, and one deep infection requiring revision after joint debridement and systemic antibiotics. Also noted was one incidence of ligamentous laxity and one patella fracture."
-How does precordial ST segment depression impact the prognosis of patients with inferior myocardial infarction?,"Precordial ST segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. The impact of associated precordial ST segment depression in inferior myocardial infarction on angiographic and clinical outcomes after thrombolytic therapy and selective coronary angioplasty was studied in 583 patients with acute myocardial infarction. Anterior infarction (Group I), inferior infarction with precordial ST segment depression (Group II) and inferior infarction without precordial ST segment depression (Group III) were present in 289, 135 and 159 patients, respectively. Precordial ST segment depression was more frequent in circumflex than right coronary infarct-related arteries (44 [71%] of 62 versus 91 [40%] of 230; p = 0.000). Although acute patency rates were not statistically different, there was a trend toward different patency rates at day 7 (Group I 88%, Group II 84%, Group III 80%; p = 0.089) partly because of insignificantly higher reocclusion rates in inferior infarction without precordial ST segment depression (Group I 11%, Group II 10%, Group III 18%, p = 0.104). Infarct zone regional wall motion (standard deviations/chord) in inferior infarction was lower with precordial ST segment depression, both acutely (Group I -2.8 +/- 0.9, Group II -2.5 +/- 1.2, Group III 2.0 +/- 1.1; p = 0.000) and at day 7 (Group I -2.2 +/- 1.1, Group II -2.3 +/- 1.1, Group III -1.9 +/- 1.3; p = 0.011). Precordial ST segment depression was associated with a lower ejection fraction in inferior infarction both acutely (Group I 47 +/- 11%, Group II 53 +/- 11%, Group III 58 +/- 9%; p = 0.000) and at day 7 (Group I 49 +/- 12%, Group II 53 +/- 10%, Group III 58 +/- 8%; p = 0.000). Complication rates tended to be higher in inferior infarction when precordial ST segment depression was present. Mortality rates for Groups I, II and III were 8%, 6% and 5%, respectively. These results suggest that precordial ST segment depression in inferior infarction predicts a worse ventriculographic and clinical outcome despite reperfusion therapy."
-What was the primary finding of the study regarding the combination of verapamil and recombinant tissue plasminogen activator in preventing postoperative adhesions?,"Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model. Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route."
-What are the key muscle-related complications observed in patients with sickle cell anemia?,"Myonecrosis and myofibrosis as complications of sickle cell anemia. Painful crises in sickle cell anemia are associated with infarction and subsequent fibrosis of many different organs. Myonecrosis secondary to muscle infarction during a crisis and subsequent fibrosis are often not recognized as complications of sickle cell anemia. We describe four patients, all of whom had recurrent episodes of symmetric proximal muscle pain and swelling as prominent features of their crises. Muscle biopsies showed acute myonecrosis with a minimal inflammatory reaction as well as myofibrosis with abundant collagen deposition. Chronic sequelae consisted of muscle induration, atrophy, and contractures."
-How does chronic ethanol feeding affect the composition of high-density lipoprotein (HDL) subfractions in rats?,"Effect of chronic ethanol feeding on high density lipoprotein subfractions in rats. We have reported previously that chronic alcohol consumption in the rat produced elevated total serum high density lipoprotein (HDL) fraction, but HDL particles of the alcohol-fed rat were deficient in apolipoprotein (apo) E. In that report, serum HDL particles were prepared by successive ultracentrifugation method and there were concerns that the apo E deficiency in HDL particles was artificially produced by centrifugal forces. In the present report, apo Al affinity column chromatography was used instead of successive ultracentrifugation and it likewise yielded HDL particles from alcohol-fed rats that exhibited lower apo E: apo Al ratio than HDL from control rats (0.185 +/- 0.016 vs. 0.303 +/- 0.017, respectively). When the total serum lipoprotein fraction (d less than 1.21) was analyzed by high performance liquid chromatography (HPLC), both HDL and VLDL peaks were higher in alcohol-fed rats than controls. The size of apo E deficient HDL particles from alcohol-fed rats determined by HPLC did not differ from that of normal HDL particles. When HDL (1.063 less than d less than 1.21) was subfractionated into HDL2 (1.063 less than d less than 1.125) and HDL3 (1.125 less than d less than 1.21), only HDL2 of alcohol-fed rats showed lowered apo E: apo Al ratio when compared with same HDL subfraction of control animals. Therefore, the molecular structure of only HDL2 (but not HDL3) was affected by alcohol-feeding. Another HDL subpopulation which is enriched with apo E, i.e. HDL1 (1.054 less than d less than 1.063), was also prepared."
-How does echocardiography help in managing patients with chronic ischemic heart disease?,"Use of echocardiography for patient management in chronic ischemic heart disease. Myocardial ischemia causes regional myocardial contractile and relaxation abnormalities. The extent of ischemia is determined by the distribution and severity of coronary artery stenoses. In coronary heart disease, two powerful predictors of prognosis are the coronary anatomy and ventricular function. Management in coronary heart disease is directed by accurate diagnosis and individualized objectives. Echocardiography at rest and exercise, combined with Doppler and color flow imaging, are properly applied to the differential diagnosis of common clinical syndromes in ischemic heart disease, the identification of the proximal coronary arteries, and the effects of ischemia and prior infarction. Subsequent use of coronary arteriography partially depends on the philosophy regarding the applicability of coronary surgery or angioplasty in an individual patient. Prediction of multivessel, left main, or proximal left anterior descending coronary artery disease by extensive wall motion abnormalities or an abnormal left ventricular ejection fraction may direct the clinician to coronary arteriography to select among coronary surgery, angioplasty, or medical management."
-What were the key findings of the study comparing MOPP and MOPP/CABS treatment for advanced-stage Hodgkin's disease?,"Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP. One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival."
-What is the significance of HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension (IPH)?,"HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension. Immunohistochemical characteristics and relation to portal phlebosclerosis. We recently reported that HLA-DR antigen was expressed on the microvasculature of portal tracts more frequently in idiopathic portal hypertension (IPH) than in normal livers or in other hepatic diseases, and that this HLA-DR expression may be involved in the development of the portal venopathy characteristic of IPH. The present study was performed to evaluate the relationship between the HLA-DR expression and portal tract lesions, as well as to investigate the immunohistochemical characteristics of the HLA-DR-positive microvasculature using liver wedge biopsy specimens obtained from 32 patients with IPH. According to the degree of phlebosclerosis of the portal veins, the portal tracts were divided into three groups: mild, moderate, and severe. The microvasculature in portal tracts was positive for HLA-DR in 21 (66%) of the 32 specimens and in 133 (44%) of 302 portal tracts. In the 21 specimens, there was no significant difference in the prevalence of HLA-DR-positive microvasculature among the three groups: it occurred in 57 (66%) of 86 portal tracts in the mild group, 53 (61%) of 87 portal tracts in the moderate group, and 23 (49%) of 47 portal tracts in the severe group. The HLA-DR-positive microvasculature was positive for type IV collagen and receptors of Ulex europaeus lectin I, suggesting that HLA-DR-positive microvessels are blood vessels. These findings suggest that HLA-DR antigen is already expressed on portal microvessels in the incipient stage of IPH, and that HLA-DR expression persists during the progression of portal phlebosclerosis. The HLA-DR expression may be an initiating factor leading to immunologic assault on portal microvessels in IPH."
-What methods were used to prevent thromboembolic complications in urological surgery in this study?,"A prospective comparison of thromboembolic stockings, external sequential pneumatic compression stockings and heparin sodium/dihydroergotamine mesylate for the prevention of thromboembolic complications in urological surgery. Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66% of the patients undergoing a major urological operation. Thromboembolic stockings, external sequential pneumatic compression stockings and anticoagulant agents, such as heparin sodium plus dihydroergotamine mesylate, have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli. A total of 74 evaluable patients undergoing a major urological operation was randomized to receive either thromboembolic stockings, external sequential pneumatic compression stockings, or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli. 111Indium-labeled platelet scans, performed preoperatively and on days 1, 3 and 6 postoperatively, were used to diagnose deep venous thrombosis and pulmonary emboli. Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease. Deep venous thrombosis was detected in 5 of 25 patients (20%) with thromboembolic stockings, 3 of 24 (12.5%) with external sequential pneumatic compression stockings and 2 of 25 (8%) with heparin plus dihydroergotamine. There was no difference in blood loss or complications among the groups. Although statistical significance among the treatment groups was not reached in this study, the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine, and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli."
-What distinguishes patients with obstructive sleep apnea (OSA) from heavy snorers in terms of upper airway morphology?,"Why don't all heavy snorers have obstructive sleep apnea? Patients with obstructive sleep apnea (OSA) and heavy snorers without apnea both show intrathoracic suction pressures during sleep that exceed their static upper airway closing pressures. Complete airway occlusion, however, occurs only in the former patient group. We hypothesized that the kinetic properties of the airflow would be different in these two types of patients because of differences in upper airway morphology. The pharyngeal computed tomography (CT) was used to measure the cross-sectional areas of the upper airways in 15 patients with OSA, 25 nonapneic heavy snorers, and 14 control subjects while they were awake. Nocturnal breathing was monitored with the static charge-sensitive bed (SCSB). The patients with OSA had a narrower airspace at the velopharyngeal (VP) level than the controls (p less than 0.01); the nonapneic snorers did not differ from the other groups. At the tongue base (TB) and the hyoid bone (HB) levels there was no difference between the OSA and the control groups, but the nonapneic snorers had narrower airways at both of these levels compared with control subjects (p less than 0.01) and at the hyoid bone level compared with the OSA group (p less than 0.05). The VP/HB ratio was the parameter that best distinguished the patients with OSA from the nonapneic snorers (lower in the OSA group, p less than 0.001). We suggest that airway collapse during sleep is favored by a narrow velopharynx associated with large hypopharynx. Some heavy snorers may not have an oropharyngeal collapse because the peak inspiratory suction pressure could already be damped down at the level of the relatively narrow hypopharyngeal airways."
-What rare complication did the patient develop after internal jugular vein catheterization?,"Internal mammary artery subclavian vein fistula following internal jugular vein catheterization. A case report and review of the literature. We have recently treated a patient with an arteriovenous fistula that developed after a right internal jugular vein catheterization. The patient was found to have a pulsatile hematoma and a bruit five days after removal of a temporary pacemaker catheter. Digital subtraction arteriography documented a fistula between the right internal mammary artery and subclavian vein. The fistula was surgically repaired via the cervical route. To our knowledge, an arteriovenous fistula between the internal mammary artery and subclavian vein has not been previously described as a complication of a percutaneous internal jugular vein catheterization."
-What was the aim of the experiments in this animal model study of gluten-induced enteropathy?,"Animal model of gluten induced enteropathy in mice. The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy."
-What potential complications can arise from intralesional corticosteroid therapy for periocular capillary hemangiomas?,"Adrenal suppression and growth retardation after injection of periocular capillary hemangioma with corticosteroids. Adrenal suppression and/or growth retardation were noted in two patients after injection of periocular capillary hemangiomas with corticosteroids. Parents should be warned of these two potential complications of intralesional corticosteroid therapy. Baseline and posttreatment adrenal function should be monitored. If iatrogenic adrenal suppression occurs, supplemental systemic corticosteroids may be necessary in situations involving systemic stress such as infection or surgery."
-What is idiopathic myointimal hyperplasia of mesenteric veins and what are its key clinical characteristics?,"Idiopathic myointimal hyperplasia of mesenteric veins. Nonthrombotic occlusion or stenosis of the mesenteric veins is a rare cause of intestinal ischemia that usually occurs in association with systemic vasculitis. The current report includes four male patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins and their intramural branches; neither vasculitis nor arterial involvement were present. Three of the four patients were less than or equal to 38 years of age; the fourth was 67. All four patients were previously healthy and had no history of drug use of any kind. Clinical findings included abdominal pain, diarrhea, bloody stools, and colonic strictures discovered by barium enema. The intima of the mesenteric and intestinal mural veins was focally thickened by a marked increase in cells and matrix between the endothelium and internal elastic lamina, whereas the vessel walls external to the thickened intima appeared normal. Histochemistry and immunoreactivity with antibodies to muscle-specific actins (HHF-35) disclosed that the intimal thickening was caused by proliferation of smooth muscle cells in a proteoglycan matrix. All patients recovered completely after segmental resection of the ischemic portion of the colon and had no recurrence of intestinal symptoms on follow-up of up to 7 years. These unusual venous lesions do not appear to have been previously described; their etiology and pathogenesis remain unknown."
-What were the long-term outcomes of menstrual cycles and fertility for patients with different types of secondary amenorrhea after a 10-year follow-up?,"Ten-year follow-up of patients with secondary amenorrhea and normal prolactin. A group of 46 patients with secondary amenorrhea without galactorrhea or hyperprolactinemia were studied retrospectively after being clinically categorized into four groups with the use of progesterone-induced uterine bleeding and measurement of serum gonadotropins and prolactin levels. The ability to have regular spontaneous menstrual cycles and to conceive was assessed after a follow-up period of 10 years. Patients who had been classified as having hypothalamic pituitary ""failure"" (hypoestrogenic amenorrhea) with low levels of circulating estradiol had a greater rate of recovery of spontaneous ovulation and menses when compared with patients who had been classified as having only hypothalamic pituitary dysfunction (euestrogenic amenorrhea). The patients with diagnosis of hyperandrogenic chronic anovulation or polycystic ovary syndrome generally required clomiphene citrate for induction of ovulation and almost all the patients with premature ovarian failure (hypergonadotropic amenorrhea) remained estrogen-deficient and unable to ovulate. Hyperprolactinemia or an identifiable pituitary adenoma has not developed in any of the patients to date."
-What motor abnormalities were observed in the second patient that could potentially promote bacterial overgrowth in the Roux limb?,"Could recurrent cholangitis after Roux-en-Y hepaticojejunostomy be explained by motor intestinal anomalies? A manometric study. The aim of this study was to describe the motor patterns found in two patients with recurrent cholangitis episodes after Roux-en-Y hepaticojejunostomy. In one patient, cholangitis was due to a stenosis of the anastomosis between the limb and the left intrahepatic bile duct, while motility of the limb, duodenum, and distal jejunum was normal. In the second patient, no anatomical explanation was found for cholangitis attacks. However, although the duodenal motor activity was normal, the motility of the limb and of the jejunum below the jejunojejunal anastomosis was grossly abnormal: permanent minute rhythm, phase IIIs absent or rare and slowly propagated, all motor abnormalities that could promote bacterial overgrowth in the limb. This stresses the interest in performing motor studies of the Roux-limb when cholangitis remains unexplained after Roux-en-Y hepaticojejunostomy."
-What did the study reveal about eosinophil infiltration in orbital pseudotumor compared to control specimens?,"Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis."
-What is the primary purpose of using superselective embolization in treating arteriovenous fistulas in renal transplant patients?,"Arteriovenous fistulas complicating biopsy of renal allografts: treatment of bleeding with superselective embolization. The use of superselective embolization was assessed as a treatment for bleeding from postbiopsy arteriovenous fistulas (AVFs) in renal transplants. AVFs commonly occur after biopsy procedures in renal transplants, but severe bleeding is rare. Transcatheter embolization can be used to control bleeding, but unless it is sufficiently selective, the procedure results in loss of significant amounts of renal parenchyma. During a 4-year period, embolization procedures were attempted in seven patients 30-65 years old. All had AVFs shown on arteriography. Five patients underwent embolization; occlusion occurred only in the branch supplying the AVF. In one patient with three large AVFs, two were found to have occluded the day after embolization was attempted. In another, an AVF occluded when superselective catheter position was achieved but before embolization. Catheter manipulation in these cases may have precipitated occlusion. In five cases, coaxial embolization techniques were used. Embolization materials consisted of coils in three cases: 0.038 in. (0.97 mm) in one case, 0.025 in. (0.64 mm) in one case, 0.018 in. (0.46 mm) in one case; 0.038 in. (0.97 mm) coils and gelatin foam particles in one case; and localized contrast extravasation in one case. Serum creatinine level was measured before and after embolization in all patients, and radionuclide studies were undertaken in three cases. In all patients, bleeding was effectively controlled. None of the patients showed an increase in serum creatinine level after embolization, and in four, significant improvement was seen. Nuclear medicine studies showed no loss of renal function and a dramatic improvement in one patient. No complications due to the procedure were seen. Our experience suggests that superselective embolization with coaxial catheter techniques is an effective method of treating bleeding from postbiopsy AVFs in renal transplants with minimal loss of renal parenchyma."
-How does preexisting cerebral ischemia affect the sympathetic nervous system's response to increased intracranial pressure?,"Effect of preexisting brain ischemia on sympathetic nerve response to intracranial hypertension. The performance of the sympathetic nervous system during sustained moderate cerebral ischemia (CI) was examined in the present study. For this purpose, a Cushing response was elicited repeatedly during incomplete global CI in anesthetized artificially ventilated cats after vagotomy and baroreceptor denervation. In control animals without CI, sympathetic activity in response to brief elevation of intracranial pressure (ICP) showed a well-repeatable two-phase reaction. During CI there was a progressive deterioration of background sympathetic nerve discharge (SND) over a period of 30 min. SND response to repeated elevation of ICP was initially similar to control response but later with progression of CI was seriously changed. 1) Instead of the usual hyperactivation, sympathetic nerve activity was depressed during intracranial hypertension. 2) The characteristic desynchronized activity either appeared later during the reperfusion period or remained absent. The progressive loss of SND response to raised ICP in developed CI was compared with the changes seen in experiments in which repeated ICP elevations were superimposed on asphyxia. These findings suggest that the sympathetic component of the Cushing reaction strongly depends on the actual state of brain stem autonomic circuits and may be seriously altered in pathological situations involving ischemic brain injury."
-How does the intracellular free magnesium concentration differ between normal brain tissue and brain tumor tissue?,"Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T. We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain."
-What are the potential otolaryngologic symptoms associated with gastroesophageal reflux (GER)?,"Otolaryngologic manifestations of gastroesophageal reflux. The exact incidence of gastroesophageal reflux (GER) is unknown, although it is estimated that at least 25% of patients with GER have head and neck symptoms alone. These symptoms may consist of one or more of the following: excess salivation, hoarseness, ""post-nasal drip,"" voice change, persistent coughing, food sticking in the throat, globus hystericus, otalgia, throat clearing, neck pain, sore throats, the sensation of a lump in the throat, choking spells, and bronchospasm. Carcinoma of the larynx and upper aerodigestive tract may be a consequence of chronic reflux. GER, especially when the classic symptoms of reflux are absent, is frequently overlooked as a cause of these problems. This article reviews the symptoms and pathophysiology of these conditions. The diagnostic and therapeutic modalities available to us in managing these patients are also discussed."
-What are the current limitations of using blood flow velocimetry in obstetric practice?,"The current status of maternal and fetal blood flow velocimetry. Significant progress has been achieved in regard to normative data for uteroplacental and fetal blood flow velocity and the factors which may affect these observations. Associations have been demonstrated between abnormal indices of maternal and fetal blood flow velocity and pregnancy-induced hypertension, fetal growth retardation, fetal blood gas measures, and intrapartum clinical fetal distress. However, in general, the predictive power is modest and no evidence has yet been provided to indicate that these measures can be used as a screening test in the general obstetric population. Continuing research is highly desirable. At the present time, the use of Doppler assessment of blood flow in pregnancy should be limited to the investigational setting."
-What is the relationship between drusen of the optic disc and central retinal vein occlusion in this case study?,"Central retinal vein occlusion associated with drusen of the optic disc. A 43-year-old man had gradual visual changes OD. Funduscopic examination revealed central retinal vein occlusion OD. Complete ocular examination revealed bilateral drusen of the optic disc, confirmed by b-scan ultrasonography. Complete systemic evaluation showed no other etiology for the central retinal vein occlusion. Over a ten-year follow-up, in the absence of systemic disease or other local ocular anomalies, we concluded that central retinal vein occlusion can arise from external compression secondary to drusen of the optic disc."
-What are the key differences observed in the clinical outcomes of the two girls with congenital sideroblastic anaemia?,"Congenital sideroblastic anaemia in two girls. Transfusion dependent congenital sideroblastic anaemia occurred in infancy in two unrelated girls. One girl developed early organ failure which was not prevented by standard chelation treatment. The combination of modest iron burden and putative intrinsic mitochondrial dysfunction could have accounted for the clinical picture. The other girl remained well, receiving regular transfusion and standard chelation treatment. She had normal liver function and no other evidence of organ damage. The syndrome is unlikely to be due to extreme lyonisation in carriers of the usual X-linked condition. The contrasting clinical patterns seen in these two patients suggest that transfusion dependent congenital sideroblastic anaemia may comprise a heterogeneous group of disorders. It is suggested that such children be carefully monitored for evidence of increasing iron overload so that organ damage can be prevented."
-What novel cell line and experimental model did the researchers establish for studying human pancreatic carcinoid tumors?,"Novel therapy for the treatment of human carcinoid. Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS."
-What changes in magnetic resonance imaging can help diagnose spinal cord infarcts at different stages?,"Magnetic resonance imaging of human spinal cord infarction. Magnetic resonance images obtained in two cases of spinal cord infarction are described: one with hemorrhagic thoracic cord infarct, the other with ischemic cervical cord infarct with sequential magnetic resonance imagings. An enlarged cord with strand-shape or longitudinal hypointensity on both T1- and T2-weighted images was noticed in the hemorrhagic infarct; hypointensity on the T2-weighted image was thought to be due to hemosiderin, which shortens T2 relaxation. In the ischemic infarct, a small, round area of hypointensity on T1-weighted images, and of hyperintensity on T2-weighted images, noted 9 hours postictus (""early infarct"") changed on the 22nd day to a cephalocaudal strandlike hypointensity on T1-weighted image, which was enhanced by Gd-DTPA. The hypointensity suggested ""pencil-like softening"" in ""medium"" age infarct. On postictal day 49, it showed an extensive homogeneous hypointensity involving several segments of the cord on T1-weighted images and hyperintensity on T2-weighted images with negative Gd-DTPA enhancement suggesting ""late transverse infarct."" We considered that these changes are of value in diagnosing spinal cord infarcts on magnetic resonance imagings."
-What is the incidence of portal thrombosis after splenectomy in patients with idiopathic portal hypertension (IPH) compared to patients with cirrhosis of the liver?,"High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension. Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough."
-What was the overall occurrence rate of gastroduodenal mucosal damage in this study of critically ill patients receiving total parenteral nutrition?,"Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients."
-What is the effectiveness of intraperitoneal thrombolytic agents like urokinase or streptokinase in treating relapsing or persistent peritonitis in CAPD patients?,"Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis. Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis."
-"How do the expression levels of c-jun, jun-B, and c-fos RNA transcripts differ between primary melanocytes and metastatic melanoma cell strains?","Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas. Analysis of the regulation of c-jun, jun-B, and c-fos RNA transcript expression was performed in human primary melanocytes and metastatic melanoma cell strains. The medium requirements for human melanocyte in vitro growth are phorbol esters, agents that elevate intracellular cAMP levels, hormones, and growth factors. Cellular jun, jun-B, and c-fos gene expression are known to be affected by growth promoting agents. In primary melanocytes, the expression of c-jun, jun-B, and c-fos RNA transcripts was dependent on the growth-promoting agents present in the medium. Uniformly high c-jun, jun-B, and c-fos RNA transcript levels were observed in melanocytes cultivated in complete medium. Higher levels of c-jun RNA transcripts and low levels of c-fos RNA transcripts were observed in melanocytes cultivated in plain medium. In contrast, a range of c-jun, jun-B, and c-fos RNA transcript levels was detected in metastatic melanoma cell strains cultivated in medium with or without serum. In general, an increase in jun-B and c-fos RNA transcript expression and a decrease in c-jun RNA transcript expression was observed in metastatic melanomas compared to neonatal melanocytes. These data suggest a potential role for c-jun, jun-B, and c-fos genes in the transformation of melanocytes to malignant melanoma."
-What was the primary objective of the study on pain characterization in cancer patients?,"Pain characterization in cancer patients and the analgetic response to epidural morphine. In 48 patients with pain related to malignancy, a pain characterization was performed during oral opioid therapy. After an optimal epidural morphine regimen had been established, the alteration in pain relief was evaluated by means of a visual analogue scale. The CSF and plasma morphine concentrations at minimum steady state were then analysed in 28 patients and related to the degree of pain relief. The efficacy of the spinal treatment ranked in the following order: somatic greater than visceral greater than radiating = 0, but the difference was only significant between the somatic and radiating pain groups. There was a tendency for continuous pain to be better relieved than intermittent pain. No correlations were found between the CSF or plasma morphine concentrations and the degree of pain relief, suggesting that not all pain impulses are modulated in a dose-dependent manner by morphine at the spinal level. Pain characterization may be instrumental in providing an optimal spinal opioid analgesia in malignancy. Moreover, there is a need for better defined diagnostic criteria for clinical pain characterization."
-How can small DNA alterations or abnormalities be detected in genetic diseases using restriction endonuclease techniques?,"Diagnosis of genetic disease by primer-specified restriction map modification, with application to cystic fibrosis and retinitis pigmentosa Detection of small alterations or abnormalities in genomic DNA (eg, point mutations or small deletions) has become increasingly important in the diagnosis of genetic disease and polymorphism. When a mutation or polymorphism creates a new restriction endonuclease site, it can easily be identified by polymerase chain reaction (PCR) amplification of the DNA region of interest, followed by digestion with the restriction endonuclease. However, useful restriction sites are the exception, and a variety of specialised techniques have been developed to identify subtle DNA abnormalities. We have shown that where a DNA mutation does not create a useful novel restriction site, such a site can be introduced by PCR and specially chosen primers. The approach is simple and inexpensive and should be broadly applicable in the diagnosis of genetic polymorphism and mutation. The technique is illustrated here by the three base-pair deletion responsible for most cases of cystic fibrosis and by detection of the point mutation in the rhodopsin gene that has been associated with some cases of autosomal dominant retinitis pigmentosa."
-What is the significance of the mitral valvuloplasty performed 5 years after the repair of a sinus venosus atrial septal defect?,"Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty."
-What quantitative nucleolar features were found to be most useful in distinguishing between follicular adenoma and follicular carcinoma of the thyroid?,"Value of quantitative nucleolar features in the preoperative cytological diagnosis of follicular neoplasias of the thyroid. Nucleolar prevalence, size, and outline were investigated on cytological material from cold thyroid nodules obtained by fine needle aspiration. The percentage of nucleolated nuclei in follicular adenoma (32 cases) was less than in follicular carcinoma (26 cases). In adenoma most nuclei contained one nucleolus, and nuclei with two or more nucleoli were less common than in carcinoma where most cases showed the highest nucleolar diameter values. There was some overlap between adenomas and carcinomas, however, when the mean of the 10 largest values of the major nucleolar diameter was considered. In follicular carcinoma the percentage of marginated nucleoli--that is, those touching the nuclear membrane--was, in general, greater than 20%; in adenoma the values were equal to or lower than 16%. The overlap index showed that the percentages of marginated nucleoli and nucleolated nuclei are the two best discriminatory features between adenoma and carcinoma."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-How does the masseter muscle respond to respiratory stimuli like hypercapnia and inspiratory loading?,"Respiratory-related recruitment of the masseter: response to hypercapnia and loading. To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway."
-What are the key characteristics of acute pandysautonomic neuropathy according to the given context?,"Acute pandysautonomic neuropathy. Acute pandysautonomic neuropathy is characterized by severe postganglionic sympathetic and parasympathetic dysfunction, with relative or complete sparing of motor and sensory function. Of four reported cases with sural nerve biopsies, two were normal and two abnormal, revealing loss of small myelinated and unmyelinated fibers. We present a patient with pandysautonomic neuropathy and elevated CSF protein whose sural nerve biopsy showed active axonal degeneration."
-What are the most prominent clinical signs of aseptic meningitis syndrome observed in cardiac transplant patients?,"Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction."
-What criteria were used to determine when patients could be weaned from mechanical ventilation and extubated after transsternal thymectomy for myasthenia gravis?,"Extubation after transsternal thymectomy for myasthenia gravis: a prospective analysis. Recommendations concerning postoperative extubation after thymectomy for myasthenia gravis are presently based upon retrospective chart reviews. We present the results of a prospective investigation of time to extubation after thymectomy for 14 patients over a 12-month period based upon a protocol that included preoperative immunologic therapy, combined epidural and general anesthesia, postoperative epidural narcotic analgesia, and a standardized approach to discontinuation of ventilatory support. After a neurologist took measures to optimize preoperative neuromuscular function, all 14 patients received agents to produce lumbar epidural anesthesia and light general anesthesia. Muscle relaxants were avoided in all but one patient. Postoperative analgesia was initially maintained with epidural hydromorphone, then therapy was switched to patient-controlled intravenous morphine sulfate. Criteria for weaning from mechanical ventilation, first measured at the end of anesthesia, were partial pressure of oxygen (arterial) greater than or equal to 90 mm Hg (fraction of inspired oxygen = 0.40), partial pressure of carbon dioxide (arterial) less than or equal to 50 mm Hg, pH greater than or equal to 7.30, and respiratory rate less than or equal to 30 breaths/min. If these criteria were not met, ventilatory support was continued postoperatively with intermittent mandatory ventilation, and the patient was weaned gradually from this support. Criteria for extubation included meeting the criteria for weaning, vital capacity greater than or equal to 10 mL/kg, and inspiratory pressure better than -30 cm H2O. Criteria for reintubation included tachypnea (respiratory rate greater than 40 breaths/min), respiratory acidosis not due to narcotics, or vital capacity less than or equal to 8 mL/kg. The mean time to extubation was 9 hours (range, 0.75 to 25 hours). Mean preoperative vital capacity was 2.59 +/- 0.64 L (range, 1.90 to 4.20), which decreased approximately 50% to 1.19 +/- 0.39 L (range, 0.70 to 2.0) at the time of extubation. No patient required reintubation. Half of the patients required postoperative anticholinesterase therapy based upon serial neurologic examinations; there were no instances of cholinergic crisis. Thirteen patients returned to the ward on the first postoperative day, and one on the second day. Thirteen patients preferred epidural analgesia to patient-controlled analgesia. The time to extubation and average length of stay in an intensive care setting were markedly reduced compared to those reported in previous retrospective studies. We conclude that a multidisciplinary approach that optimizes neuromuscular function and decreases poststernotomy pulmonary insult will shorten the time to extubation and decrease the length of stay in the intensive care or recovery room after thymectomy."
-What was the laser technique used for treating ovarian endometriomas in this study?,"The use of potassium-titanyl-phosphate laser for laparoscopic removal of ovarian endometrioma. From January 1989 through January 1990, 31 patients thought to have ovarian endometrioma at ultrasonography were treated by operative laparoscopy and potassium-titanyl-phosphate laser. The endometriomas ranged from 2 to 9.2 cm in diameter by preoperative transvaginal ultrasonography. The operative procedure used was a three-puncture technique with a 600 micron fiber attached to a potassium-titanyl-phosphate laser. The power setting was 10 W with a continuous pulse. In all cases endometriomas were opened, drained, and irrigated, and the potassium-titanyl-phosphate laser was used to vaporize or remove the entire cyst lining. The ovarian edges were inverted with the laser at the end of the procedure. With one exception, there was no recurrence of endometrioma at 1, 3, and 6 months after the procedure, on the basis of transvaginal ultrasonography or laparoscopy. In one case, 4 months after the initial laparoscopic procedure, exploratory laparotomy was performed for resection of a large, recurrent endometrioma. The use of the potassium-titanyl-phosphate laser allows the laparoscopic surgeon an aggressive approach to ovarian endometriomas that in the past necessitated exploratory laparotomy."
-What percentage of patients experienced vasovagal reactions during breast-imaging procedures in this study?,"Localization and needle aspiration of breast lesions: complications in 370 cases. A prospective study of the immediate complications of 370 consecutive breast-imaging procedures (203 wire localizations and 167 radiographically or sonographically guided fine-needle aspirations) is reported. Vasovagal reactions occurred in 27 (7%) of 370 cases, ranging in severity from syncope (four of 370, 1%) to mild light-headedness. These vasovagal reactions were independent of procedure type or use of local anesthesia, but were more common in younger patients. Other complications included prolonged (5 min or longer) bleeding (three of 370, 1%) and extreme pain (two of 370, 1%). One patient was found to have malignant hypertension. We conclude that wire localizations and imaging-guided aspirations are generally well tolerated procedures. However, vasovagal reactions are frequent enough to warrant close observation of patients. Radiologists and breast-imaging personnel should be able to recognize and treat vasovagal reactions."
-What imaging technique was crucial in identifying the pontine glioma in this patient with hemifacial spasm?,"Occult pontine glioma in a patient with hemifacial spasm. Hemifacial spasm due to an intracranial mass lesion is rare. We describe a 29-year-old man with hemifacial spasm successfully treated with botulinum A toxin injections for 2 years. The development of acquired diplopia secondary to acquired sixth cranial nerve palsy prompted investigation. Computed tomography done at the time of original diagnosis and on three other occasions (concentrating on the brain stem and cerebellopontine angle) failed to demonstrate an intracranial mass lesion. Magnetic resonance imaging (MRI) showed a large mass lesion in the pons presumed to be a glioma. Patients with hemifacial spasm who have atypical features, especially those with associated neurologic findings, should be screened for tumours. Our case illustrates the superiority of MRI in demonstrating pontine gliomas causing hemifacial spasm."
-How do monoclonal antibodies help in visualizing myocardial necrosis in dogs and humans?,"Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains. The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis."
-What was the success rate of treating primary vesicoureteric reflux using subureteric injection of Polytef paste in this study?,"Primary vesicoureteric reflux: treatment with subureteric injection of Polytef paste. A series of 34 children with 40 primary refluxing ureters were treated endoscopically with a subureteric injection of polytetrafluoroethylene paste (Polytef). The amount injected ranged between 0.1 and 0.8 ml (mean 0.3). A single injection cured the reflux in 26 ureters (65%) and the grade of reflux improved in a further 9 ureters. Seven ureters required a second injection and reflux was cured in 6 of these. The overall cure rate was therefore 80% after the second injection. There was one complication due to self-limiting ureteric obstruction following injection. The procedure is quick, easy to perform and effective. We have some reservations about the long-term efficiency and safety of subureteric Polytef injection in children."
-What serum biomarkers were studied in patients with metastatic renal cell carcinoma and what were their key findings?,"Serum biomarkers in metastatic renal cell carcinoma. To identify possible clinically valuable markers of metastatic renal cell carcinoma, we measured the serum concentrations of several commercially available biomarkers in 117 patients with this disease. The alpha-fetoprotein level was measured in 75 patients and was elevated in 8 (11%); elevation did not correlate with the presence of liver metastasis. Beta subunit of human chorionic gonadotropin levels increased in 8 of 83 patients tested (10%). C-terminal parathyroid hormone levels were measured in 79 patients and were elevated in 15 (19%); their serum creatinine level was normal. Thirteen of this group had normal serum calcium levels, whereas 7 patients with hypercalcemia and no clinically evident bone metastasis had normal parathyroid hormone levels. In only 2 of 72 patients, serum lactate dehydrogenase and its isoenzyme 1 were elevated. Only 1 of 85 patients had mildly elevated serum carcinoembryonic antigen, in contrast to 3 of 7 patients with metastatic transitional cell carcinoma of the renal pelvis who had moderately elevated carcinoembryonic antigen. Elevations in alpha-fetoprotein, human chorionic gonadotropin, and parathyroid hormone correlated with the course of the disease in 13 patients for whom follow-up measurements were available; measurement of these markers, however, is only useful in a small proportion of patients with metastatic renal cell carcinoma."
-What was the purpose of the study comparing Trisdine bladder instillations and O'Neil catheters in patients with acute spinal cord trauma?,"Bladder instillations of trisdine compared with catheter introducer for reduction of bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma. An open, prospective, randomised trial was conducted to compare the incidence of significant bacteriuria following 2 methods of intermittent urethral catheterisation in patients with acute spinal cord trauma. Twenty-two patients were catheterised with a Nelaton catheter and 50 ml of Trisdine were instilled into the bladder and left there immediately prior to withdrawal of the catheter. Fifteen patients were catheterised with a Nelaton catheter with a special introducer to improve asepsis (O'Neil catheter). The mean incidence of significant bacteriuria in males and females who received Trisdine bladder instillations was 0.58 and 0.48% per catheterisation respectively; in males and females catheterised with the O'Neil catheter it was 1.16 and 2.93% per catheterisation respectively. The instillation of Trisdine into the bladder after each passage of a catheter resulted in a significantly lower incidence of bacteriuria compared with that which resulted from the use of the O'Neil catheter. The former method is therefore to be preferred for aseptic intermittent urethral catheterisation in patients with acute spinal cord trauma."
-What percentage of patients survived long-term after receiving the Bio-Medicus ventricular assist device during cardiac surgery?,"Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients."
-What method did the researchers use to estimate the pressure difference between arms and legs in patients with suspected recoarctation of the aorta?,"Estimation of Doppler gradients at rest and during exercise in patients with recoarctation of the aorta. In patients with suspected recoarctation of the aorta the estimation of the pressure difference between the arms and legs is an important part of the examination. Because this difference is often augmented when the circulation is stressed by exercise, exercise tests are a useful part of the evaluation. Doppler echocardiography was used to estimate this pressure difference in 16 adult patients in whom simultaneous pressure and Doppler recordings were made both at rest and during exercise. There was a close correlation between the invasive peak instantaneous gradient and the Doppler gradient both at rest and during exercise. There was only a moderate correlation between the invasive peak to peak gradient and the Doppler gradient at rest and during exercise. Doppler echocardiography is recommended as an easy and accurate method of estimating the peak instantaneous gradient both at rest and during exercise in patients with suspected recoarctation."
-"How does abdominal surgery affect protein, RNA, and nucleotide synthesis in lymphocytes?","Stimulation of protein, RNA, and nucleotide synthesis in lymphocytes after abdominal surgery is not affected by postoperative amino acid supply. The effects of abdominal surgery on protein, RNA, and de novo purine nucleotide synthesis in lymphocytes, and modification of these changes by postoperative amino acid supply, were investigated in 24 patients undergoing cholecystectomy (n = 12) or removal of gastric cancer (n = 12). Mono-nuclear cells were isolated from the peripheral venous blood and incubated with radioactive tracers in vitro. Protein and RNA synthesis, as measured using [14C] glycine and [3H]uridine, respectively, increased postoperatively. Nucleotide synthesis determined by the incorporation of radioactivity from [14C] glycine into nucleotides increased simultaneously. The concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP) estimated by the incorporation of [14C]adenine into nucleotides also increased. These changes were greater and of longer duration in patients with cancer operation than in those with cholecystectomy. In neither case were they affected by the amount of amino acid intake, or increases in energy intake. These results suggest that abdominal surgery stimulates protein and ribonucleic acid (RNA) synthesis in lymphocytes. Increased RNA synthesis may be ensured by increased synthesis of nucleotides, and increased PRPP concentrations appear to regulate the rate of nucleotide synthesis. The responses are apparently dependent upon the severity of surgery, but unrelated to the amount of amino acid supplied postoperatively."
-Does intravenous aminophylline reduce the risk of relapse in patients with decompensated chronic obstructive pulmonary disease (COPD)?,"Aminophylline in the outpatient management of decompensated chronic obstructive pulmonary disease. The objective of this study was to determine if IV aminophylline reduces the risk of relapse after treatment of decompensated COPD in an ED. Forty-six visits in which IV aminophylline was given (T visits) were compared with an equal number of visits in which it was withheld (N visits) with respect to pretreatment serum theophylline level, number of treatments with nebulized bronchodilators and use of parenteral beta-adrenergic drugs, IV corticosteroids and prednisone. The difference in 48-h relapse rates for T and N visits was examined by McNemar's test. No differences were found between T and N visits with respect to vital signs, pretreatment FEV1, arterial blood gas values, hematocrit level or blood leukocyte count. The 48-h relapse rate for T visits (22.2 percent) was significantly higher than for N visits (6.7 percent; p = 0.035). Aminophylline does not appear to be beneficial for outpatients with decompensated COPD and may be harmful."
-How does the administration of estradiol and progesterone affect luteinizing hormone (LH) pulse frequency in women with polycystic ovarian disease?,"Reduction of gonadotropin-releasing hormone pulse frequency is associated with subsequent selective follicle-stimulating hormone secretion in women with polycystic ovarian disease. Polycystic ovarian disease (PCO) is characterized by hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. Mean plasma FSH concentrations are low, while LH is elevated in a majority of patients. LH pulsatile secretion has been shown to occur at rapid follicular phase frequencies (approximately one pulse per h) in PCO, suggesting persistent rapid frequency GnRH secretion in this disorder. Anovulatory women with PCO were given estradiol (E2; Estraderm skin patches) and progesterone (P; vaginal suppositories) to produce midluteal concentrations for 21 days. The aim was to determine if E2 and P would slow LH (GnRH) pulse frequency and if this would result in augmented FSH secretion and follicular development after withdrawal of E2 and P. Plasma LH was measured every 10 min for 8 h before, during (days 10 and 20), and 7 days after withdrawal of E2 and P (day 28). On each of these study days FSH was measured hourly, and E2 and P were measured every 2 h. After sampling, GnRH (25 and 250 ng/kg, iv) was given to assess pituitary responsiveness. Follicular development was monitored by vaginal ultrasound through day 34 of the study. Basal LH frequency was 8.5 +/- 0.5 pulses/8 h (mean +/- SEM). During E2 and P, LH pulse frequency fell to 3.3 +/- 1.0 (10 days) and 2.3 +/- 0.8 (20 days), 39% and 27% of the basal value, respectively, and subsequently increased to 5.6 +/- 0.7 (66% of basal) 7 days after withdrawal of E2 and P. LH pulse amplitude (basal, 7.2 +/- 1.5 IU/L) was not reduced until day 20, but remained suppressed (3.9 +/- 1.1 IU/L) on day 28. As a result, mean LH (basal, 21.0 +/- 3.5 IU/L) fell progressively during E2 and P, to 3.8 +/- 1.2 IU/L on day 20, and remained low (39% of basal) 7 days after steroid withdrawal. Mean plasma FSH (basal, 7.1 +/- 0.9 IU/L) also fell during steroid administration, but in contrast to LH, had risen to 93% of the basal value by 7 days after E2 and P. LH release in response to exogenous GnRH revealed marked initial responses which did not decrease until day 20, but remained suppressed (8% of basal) after withdrawal of E2 and P. FSH responses were also suppressed on day 20, but had increased to 75% of the basal value by day 28. Initiation of follicular development occurred in all patients, and the lead follicle measured 12.3 +/- 0.8 mm 13 days post-E2 and P. Ovulation occurred in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What is circumspinal decompression and how does it address thoracic myelopathy caused by ossification of the posterior longitudinal ligament and ligamentum flavum?,"Circumspinal decompression for thoracic myelopathy due to combined ossification of the posterior longitudinal ligament and ligamentum flavum. Ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the ligamentum flavum (OLF) in the thoracic spine can result in serious myelopathy, leading to circumferential compression of the spinal cord in advanced stages of the disease. The authors performed circumspinal decompression (circumferential decompression of the spinal cord) on these patients. This operation consists of two steps: posterior and lateral decompression of the spinal cord by removal of the OLF (first step) and anterior removal of the OPLL for anterior decompression (second step), followed by interbody fusion. In the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura to easily and safely remove the OPLL anteriorly at the second step. In the second step, the surgical approach varies according to the affected level; costotransversectomy in the upper thoracic spine and standard thoracotomy in the middle or lower thoracic spine. According to the authors, circumspinal decompression is not an easy procedure, but from their results in 10 patients, they identify it as a radical and promising surgical procedure."
-What percentage of patients with pulmonary embolism experienced dyspnea or tachypnea?,"Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. The history, physical examination, chest radiograph, electrocardiogram and blood gases were evaluated in patients with suspected acute pulmonary embolism (PE) and no history or evidence of pre-existing cardiac or pulmonary disease. The investigation focused upon patients with no previous cardiac or pulmonary disease in order to evaluate the clinical characteristics that were due only to PE. Acute PE was present in 117 patients and PE was excluded in 248 patients. Among the patients with PE, dyspnea or tachypnea (greater than or equal to 20/min) was present in 105 of 117 (90 percent). Dyspnea, hemoptysis, or pleuritic pain was present in 107 of 117 (91 percent). The partial pressure of oxygen in arterial blood on room air was less than 80 mm Hg in 65 of 88 (74 percent). The alveolar-arterial oxygen gradient was greater than 20 mm Hg in 76 of 88 (86 percent). The chest radiograph was abnormal in 98 of 117 (84 percent). Atelectasis and/or pulmonary parenchymal abnormalities were most common, 79 of 117 (68 percent). Nonspecific ST segment or T wave change was the most common electrocardiographic abnormality, in 44 of 89 (49 percent). Dyspnea, tachypnea, or signs of deep venous thrombosis was present in 107 of 117 (91 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain or atelectasis or a parenchymal abnormality on the chest radiograph was present in 115 of 117 (98 percent). In conclusion, among the patients with pulmonary embolism that were identified, only a small percentage did not have these important manifestations or combinations of manifestations. Clinical evaluation, though nonspecific, is of considerable value in the selection of patients in whom there is a need for further diagnostic studies."
-What are the key challenges in managing osteogenic sarcoma in children and adolescents?,"Management of osteogenic sarcoma in children and adolescents. The management of osteogenic sarcoma in children has made a fantastic step on the survival rate, but there still remains unexpected late metastatic recurrence even in initially good responders to chemotherapy and lower survival rate in the bad responder group. Therefore, the research on etiology and on the understanding and rating of oncologic power of the tumoral cells as well as other kinds of treatment (vaccine, immunotherapy, and other types of chemotherapy) must be increased. The initial function after replacement is good and is often excellent but increasing deterioration is noticed during each follow-up evaluation. A considerable effort is still to be done for bone and joint replacement. Biocompatible material with mechanical strength and resistance to wear will be used for a long time because of the young age of the patients. There must be better use and understanding of the allograft revascularization, as well as a better biologic connection between the bone host and replacement device. This will probably be used in the future with less cement and more of a modular system. The final prognosis will remain for a long time in the perfect cooperation between the various members of the teams (oncologist, surgeon, imager, pathologist, and research team) who treat the patients."
-What was the total morbidity rate for complications in the study of long-term seizure monitoring using subdural strip electrodes?,"The morbidity of long-term seizure monitoring using subdural strip electrodes. The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%."
-What were the significant predictors of event-free survival after balloon aortic valvuloplasty?,"Predictors of event-free survival after balloon aortic valvuloplasty. BACKGROUND. Balloon aortic valvuloplasty was developed as an alternative to aortic-valve replacement in selected elderly patients with aortic stenosis. The use of this procedure is limited, however, by a high incidence of restenosis. METHODS. Between December 1985 and April 1989, valvuloplasty was performed in 205 patients. We evaluated 40 demographic and hemodynamic variables as univariate predictors of event-free survival by Cox regression analysis and identified independent predictors of event-free survival by stepwise multivariate analysis. RESULTS. Early hemodynamic results indicated a decrease in the peak transaortic-valve pressure gradient from 67 +/- 28 to 33 +/- 15 mm Hg after valvuloplasty and an increase in aortic-valve area from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2 (P less than 0.001 for both comparisons). The rate of event-free survival (defined as survival without recurrent symptoms, repeated valvuloplasty, or aortic-valve replacement) was 18 percent over the mean (+/- SD) follow-up period of 24 +/- 12 months (range, 1 to 47). Significant predictors of event-free survival included the left ventricular ejection fraction and the left ventricular and aortic systolic pressure before valvuloplasty, and the percent reduction in the aortic-valve pressure gradient; the pulmonary-capillary wedge pressure was inversely associated with event-free survival. Although the predicted event-free survival rate for the entire patient group was 50 percent at one year (95 percent confidence interval, 43 to 57 percent) and 25 percent at two years (95 percent confidence interval, 19 to 31 percent), the probability of event-free survival at one year varied between 23 and 65 percent when patients were stratified according to three independent predictors: the aortic systolic pressure, the pulmonary-capillary wedge pressure, and the percent reduction in the peak aortic-valve gradient. CONCLUSIONS. The most important predictors of event-free survival after balloon aortic valvuloplasty were related to base-line left ventricular performance. The best long-term results after valvuloplasty were observed among patients who would also have been expected to have excellent long-term results after aortic-valve replacement."
-"What medical condition did the pregnant young woman experience, and how was it treated?","Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. We describe a pregnant young woman with branch retinal arteriolar occlusions, encephalopathy, and hearing loss in whom we demonstrated a patent foramen ovale. She improved while receiving anticoagulants and no immunosuppressive therapy. The microangiopathic syndrome of retinopathy, encephalopathy, and deafness may be due to a disturbance of coagulation and/or microembolism."
-What are the key characteristics of eosinophilic pustular folliculitis?,"Eosinophilic pustular folliculitis. Eosinophilic pustular folliculitis is characterized by the spontaneous development of recurrent, sterile papules, pustules, and plaques on the face, trunk, arms, and occasionally the palms and soles. Although the large majority of the reported cases have occurred in Eastern Asians, most patients in the United States have been infants or men seropositive for human immunodeficiency virus. We describe a North American woman with eosinophilic pustular folliculitis who was neither seropositive for human immunodeficiency virus nor of Asiatic descent."
-What medical condition did the 44-year-old male present with in the emergency department?,"Delirium and lactic acidosis caused by ethanol and niacin coingestion. A 44-year-old male presented to the emergency department with altered mental status. He was receiving niacin therapy for hypercholesterolemia, and 16 hours earlier had ingested a large quantity of wine. Past medical history was otherwise unremarkable; physical examination revealed paranoid ideation and asterixis. Laboratory evaluation was significant for metabolic acidosis with a calculated anion gap of 39. Liver enzymes were elevated, and lactic acid level was 9.5 mmol/L (normal: 0.5 to 2.2 mmol/L). White blood cell count was 23,100, but all cultures were negative, and all other diagnostic studies, including bilirubin, prothrombin time, and ammonia were normal. The patient recovered rapidly with hydration and administration of thiamine and magnesium. After psychiatric evaluation, a diagnosis of toxic delirium due to niacin and ethanol coingestion was made. This is the first case reporting toxic delirium and lactic acidosis due to niacin and ethanol coingestion. This occurred in the absence of significant hepatic impairment. Possible mechanisms for the observed derangements are discussed."
-What factors determine the severity and management of bacterial skin and soft tissue infections?,"Treatment of bacterial skin and soft tissue infections. Bacterial skin infections occur commonly and range in severity from mild to life threatening. The severity of skin infections, and their management and prognosis, can depend on the mechanism of infection, the skin structures involved and the infecting organism or organisms. Primary skin infections result from invasion of microorganisms through tiny breaks in the epidermis or from the spread of microorganisms through the bloodstream. Secondary infections arise from pre-existing trauma, burns or surgical wounds; infections involving the soft tissues underlying the skin are also discussed. These also frequently occur in areas of trauma, operation or ischemia. The cause, bacteriologic factors and management of skin infections were studied, with special attention to pyodermas, infections of the foot in diabetic patients and necrotizing soft tissue infections. Choice of appropriate antibiotic agents depends in large part on the infecting organism and patterns of antibiotic susceptibility. In necrotizing soft tissue infections, survival or limb salvage may depend on prompt surgical intervention. In these instances and in some of advanced primary skin infections in which bacteremia is involved, parenteral antibiotics are required. The available options are discussed and a report on the data with the combination agent ticarcillin disodium and clavulanate potassium is presented."
-What was the technical success rate of placing self-expandable stents in treating iliac artery obstruction or stenosis?,"Iliac artery stenosis or obstruction after unsuccessful balloon angioplasty: treatment with a self-expandable stent. Obstruction or stenosis of the iliac artery was treated by placement of a self-expandable stent in 91 patients. A total of 100 lesions was treated. All patients had had poor results of balloon angioplasty including residual stenosis, iliac occlusion, and dissection. The stent used in all cases was a self-expandable stainless steel endoprosthesis mounted on a 7- or 9-French catheter and covered by an invaginated tubular rolling membrane. The diameter of the expanded stent varied from 7 to 12 mm. A total of 129 stents was placed. Technical success was 97%. Thromboses occurred immediately after placement in two patients and within the first month in six; these were mainly due to residual obstruction. Eighty-two (93%) of 88 patients with a follow-up longer than 3 months had no recurrent symptoms. Restenosis caused by intimal hyperplasia inside the stent occurred in 10 patients; these required repeated intervention in only four cases. In the remaining six patients, no further complications occurred. Our results show that self-expanding endoprostheses are of value for improving the results of inadequate percutaneous transluminal angioplasty."
-How does ulinastatin affect polymorphonuclear leukocyte elastase levels and pulmonary vascular resistance after esophageal cancer surgery?,"Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations. To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment."
-How does platelet angiotensin II binding differ between normotensive and hypertensive pregnant women?,"Platelet angiotensin II binding sites in normotensive and hypertensive women. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy."
-What challenges do cytologists face when interpreting gastrointestinal cytology specimens?,"Gastrointestinal cytology. Since the development of the fiberoptic endoscope, laboratories have received cytologic specimens obtained from all segments of the gastrointestinal tract in increasing numbers to identify infectious agents and neoplasms. Adenocarcinomas generally are easily diagnosed and distinguished from reparative atypia, but their precursor lesions, dysplasia and adenomas, provide greater interpretive challenges. The same is true for such entities as malignant lymphomas. Most mesenchymal tumors remain outside the diagnostic capabilities of most cytologists."
-How do the expression patterns of alpha smooth muscle actin and desmin in perisinusoidal cells change between normal adult liver tissue and pathological liver conditions?,"Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs."
-What percentage of women in the Charleston tricounty area reported having a mammogram within the past year?,"Breast cancer screening in a biracial community: the Charleston tricounty experience. Breast cancer remains a major cause of death among women in South Carolina. Mammography, breast self-examination, and clinical breast examination are effective methods for early detection and subsequent mortality reduction. The Tricounty Breast Cancer Screening Survey assessed knowledge of these methods and recommendations among 503 women in the Charleston area. While 57% of all respondents reported performing breast self-examination at least once per month, 13% of blacks and 6% of whites reported that they do not know how to perform the procedure. Clinical breast examinations within the past year were reported by 69%, yet 11% of blacks and 4% of whites reported that they had never had the examination. More than one third (40%) of all 503 women reported ever having had a mammogram, and 22% reported having had one within the past year. However, 18% of the blacks and 5% of whites reported never having heard of the procedure. The major barriers to mammography appear to be the belief that women do not need regular mammograms and the lack of recommendations by their physicians. Survey results support the need for educating women about what the procedures are, the importance of using them regularly, and the means to comply with them."
-What was the primary objective of the study examining skin test reactivity in patients with lung and breast cancer?,"Skin test reactivity in patients suffering from lung and breast cancer. Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer."
-How does isradipine potentially protect against thromboembolic diseases in patients with mild hypertension?,"Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism. Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity."
-How do mothers adjust their babies' clothing and bedding in response to different temperatures and seasons?,"How mothers keep their babies warm. Details of room temperature, clothing, and bedding used by night and by day and in winter and in summer were recorded for 649 babies aged 8 to 26 weeks. Room temperature at night was significantly related to outside temperature and duration of heating. Total insulation was significantly related to outside temperature and to minimum room temperature, but there was wide variation in insulation at the same room temperature. High levels of insulation for a given room temperature were found particularly at night and in winter, and were associated with the use of thick or doubled duvets and with swaddling. At least half the babies threw off some or all of their bedding at night, and at least a quarter sweated. Younger mothers and mothers in the lower social groups put more bedclothes over their babies, and the latter also kept their rooms warmer. Many mothers kept their babies warmer during infections."
-What percentage of patients with a closed mastoid cavity were satisfied with their hearing aid?,"Use of hearing aids by patients with closed mastoid cavity. Twenty-five patients who had undergone a closed-cavity tympanomastoidectomy in our Unit and wore a hearing aid in the operated ear were reviewed, and information was recorded on the use of the aid, and the patients' impression about it. The information obtained was analysed and compared with similar data from 39 hearing aid users of similar age with no history of ear surgery. Eighty per cent of the patients with a closed mastoid cavity were satisfied with the aid, and no significant difference was found between the two groups regarding the impression about the aid (chi square 3.06, p = 0.08), or the problems with it, which, in most of the cases, were related to several changes of mould (chi square 2.19, p = 0.13). The various recorded parameters are discussed, and it is concluded that the patients with a closed mastoid cavity can tolerate a hearing aid in the operated ear at least as well as the control subjects with no ear surgery."
-What is the frequency of T-cell receptor delta gene recombination observed in acute lymphoblastic leukemias (ALL)?,"T-cell receptor delta gene recombination in common acute lymphoblastic leukemia: preferential usage of V delta 2 and frequent involvement of the J alpha cluster. A high frequency (greater than 80%) of acute lymphoblastic leukemias (ALL) exhibit a recombination of the T-cell receptor (TCR) delta chain locus. Interestingly, distinct TCR delta elements are preferentially used in immunologic subtypes. In a recent series of 201 children with common ALL (cALL) we observed a TCR delta rearrangement in 162 patients, 57% of the latter showing a hybridization pattern in Southern blots suggestive of a V delta 2 to D delta 3 recombination. To verify this interpretation and to elucidate in more detail the diversity of this common type of TCR delta recombination we amplified and sequenced the junctional region of nine cALL patients and cell line REH-6 by polymerase chain reaction (PCR). A V delta 2 D delta 3 recombination was confirmed in all cases; convincing evidence for the participation of D delta 1 or D delta 2 elements was not obtained. Eight of nine patients and REH-6 showed complete 5' D delta 3 boundaries within V delta 2 D delta 3 segments, a limitation of junctional diversity also detected in 50% of peripheral blood cell clones derived from two healthy probands. Notably, sequence identity at the V delta 2 D delta 3 junction was demonstrated for a cALL and one of the control clones. Another group of 35 of 162 cALL patients was characterized by V delta 2 rearrangements and biallelic deletion of J delta and C delta sequences. Using a J alpha consensus primer, PCR-directed sequence analysis demonstrated V delta 2 D delta 3 J alpha recombinations in all four cases analyzed by this approach. The J alpha segments of these patients differed, but were identical or homologous to published J alpha elements. Our data suggest a recombination pathway of the TCR delta/alpha locus leading to chimeric TCR alpha molecules, containing V delta and, remarkably, also D delta sequences."
-What were the antiproliferative effects of cytokines on squamous cell carcinoma of the head and neck cell lines in this study?,"Antiproliferative effects of cytokines on squamous cell carcinoma. A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly."
-What are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease?,"Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the ""symptom index."" Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain."
-What were the response rates and median survival times for patients in the chemotherapy arm (arm A) and the best supportive care arm (arm B) in this randomized trial of advanced non-small-cell lung cancer?,"A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer. From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy."
-How do tocotrienols affect liver cell damage and enzyme activities in rats treated with 2-acetylaminofluorene (AAF)?,"Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats. The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis."
-How does thrombolysis affect the incidence of late potentials in patients within 10 days of acute myocardial infarction?,"Effect of thrombolysis on the evolution of late potentials within 10 days of infarction. Patients with late potentials in the signal averaged electrocardiogram are more at risk of lethal arrhythmias in the period after acute myocardial infarction. To test the effects of thrombolysis on the incidence and evolution of late potentials, 158 consecutive patients were prospectively studied during the first 10 days after acute myocardial infarction. The study population consisted of two groups: 93 control patients treated conservatively and 65 patients treated with intravenous thrombolysis. Recordings of signal averaged electrocardiogram were obtained within two days and 7-10 days after infarction. The incidence of late potentials in the first two days after infarction was not significantly different in the thrombolytic and control groups (14% v 11.8%). By 7-10 days the incidence of late potentials among patients who underwent thrombolysis remained unchanged (14%); however, it increased significantly in the control group (11.8% to 22.5%). Thus thrombolysis seems to reduce the evolution of late potentials within 10 days of infarction. Because the risk of fatal arrhythmias is higher in patients with late potentials this study may partly explain the reduced mortality after thrombolysis."
-What is the rare condition described in this case report involving a patient with Sjogren's disease and a choroid plexus mass?,"Inflammatory pseudotumor of the choroid plexus in Sjogren's disease. We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjogren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass."
-What potential risks were associated with the colic medication mixture given to the eight infants in the study?,"Colic medication and apparent life-threatening events. Eight infants with histories of apnea and cyanosis were referred to the Southwest SIDS Research Institute for evaluation of apparent life threatening events (ALTE). All of the infants had been treated for colic with a 1:1 concentration of dimenhydrinate (Dramamine) and phenobarbital, hyoscyamine sulfate, atropine sulfate and scopolamine hydrobromide (Donnatal). The medication was pre-mixed by local pharmacists. A comprehensive work-up failed to reveal a cause for the ALTE in any infant. The Dramamine/Donnatal mixture was withdrawn and polygraphic evaluation was conducted. Cardiorespiratory abnormalities were identified in all eight infants and significant gastroesophageal reflux (GER) was documented in four. The possibility that colic medication contributes to cardiorespiratory instability and GER in vulnerable infants requires serious consideration and further evaluation."
-How did acetazolamide therapy impact the visual acuity and macular edema in this pseudophakic patient?,"A direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy. We report the case of a patient with pseudophakic cystoid macular edema whose visual acuity improved promptly with oral administration of 500 mg of acetazolamide extended-release capsules BID for two weeks. However, vision worsened again within two weeks of discontinuation of the treatment. On resumption of acetazolamide therapy for three weeks, and its slow withdrawal during the following three weeks, the macular edema eventually resolved, and vision returned to normal. Our observation provides a direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy and shows the importance of tapering the doses of this regimen."
-"What was the prevalence of headache with migrainous features among low-tension glaucoma, primary open-angle glaucoma, and normal subjects in this Japanese study?","Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese. We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients."
-How does high-resolution ultrasound help in evaluating cervical esophageal motility in patients with progressive systemic sclerosis?,"Cervical esophageal motility: evaluation with US in progressive systemic sclerosis. High-resolution ultrasound (US) showed that initial peristalsis propelled ingested soda smoothly and rapidly in 20 volunteers without symptoms who met both manometric and radionuclide esophageal scintigraphic (RES) criteria for normal motility. Twenty-eight patients with progressive systemic sclerosis were classified according to results of RES as follows: group 1, normal esophageal motility (three patients [11%]); group 2, hypomotility of the esophagus, excluding the cervical esophagus (18 patients [64%]); and group 3, hypomotility of the cervical esophagus (seven patients [25%]). In the seven patients of group 3, US demonstrated that an incomplete peristalsis sequence or a feeble peristalsis propelled the soda in a slow and/or to-and-fro motion with low velocities. In the other 21 patients (75%), the soda passed through the esophagus smoothly and rapidly. Retention of soda in the cervical esophagus was not limited to patients with hypomotility of the cervical esophagus. It is concluded that US is useful in evaluation of cervical esophageal motility."
-How does tumor-bearing affect albumin synthesis and degradation in mice compared to non-tumor-bearing animals?,"Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition. Hepatic albumin synthesis, serum albumin turnover, and hepatic albumin messenger RNA (mRNA) content were evaluated in mice bearing a transplantable low differentiated tumor (MCG 101). Results obtained on tumor-bearing mice were compared with results obtained from non-tumor-bearing animals that were either freely fed, food restricted so that their body composition was similar to tumor-bearing animals (pair-weighed), fed a protein-free diet for 5 days, or fasted for 48 hours. Tumor-bearing animals became hypoalbuminemic (33 +/- 5 vs. 44 +/- 3 g/L in freely fed mice), which could be explained by both depressed albumin synthesis (1.95% +/- 0.20% vs. 2.67% +/- 0.27%/h in freely fed mice) and increased albumin degradation. Pair-weighed and protein-calorie malnourished controls had reductions in albumin synthesis (1.81% +/- 0.18% and 1.67% +/- 0.17%/h, respectively) similar to tumor-bearing animals, and the starved controls had the lowest synthetic rates (1.07% +/- 0.10%/h). Albumin degradation was increased only in tumor-bearing animals. Hepatic albumin mRNA in undernourished animals was less (tumor bearing, 32% +/- 5%; pair weighed, 47% +/- 4%; 48 hours fasted, 18% +/- 2%; and protein-calorie malnourished, 26% +/- 3%) than 50% of the mRNA content in the livers of freely fed control mice. Messenger RNA-directed synthesis of albumin in vitro was also depressed to a variable degree in tumor-bearing and malnourished non-tumor-bearing controls. The hypoalbuminemia in tumor-bearing animals could not be prevented by daily injections of a prostaglandin synthesis inhibitor (indomethacin, 1 microgram/g body wt), but the hepatic acute phase protein serum amyloid P decreased from 157 +/- 12 to 103 +/- 9 micrograms/mL in indomethacin-treated tumor-bearing mice (P less than 0.01). It is concluded that increased albumin degradation seen in tumor-bearing animals cannot be explained by associated malnutrition, whereas tumor-associated malnutrition can explain to a large extent the depressed albumin synthesis. Decreased albumin synthesis in tumor-bearing animals correlated in part with a decreased quantity of liver albumin mRNA. The results of the current study are consistent with either a reduced transcription of the albumin gene or a change in albumin mRNA processing and stability communicated by anorexia and malnutrition."
-What is Cogan's syndrome and what are its potential neurological complications?,"Cogan's syndrome complicated by lacunar brain infarcts. Cogan's syndrome, nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction, is an uncommon disease of young adults, probably a manifestation of vasculitis. A 32 year old woman with this syndrome developed a thalamic syndrome with amnesia and dysphasia due to lacunar infarcts."
-"How does autologous bone marrow (ABM) infusion impact neutrophil count recovery in patients receiving high-dose cyclophosphamide, etoposide, and cisplatin?","Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin. Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients."
-What were the main findings of the endoscopic and histological examination in people with and without dyspepsia in this Norwegian population-based study?,"Prevalences of endoscopic and histological findings in subjects with and without dyspepsia OBJECTIVE--To examine the association between dyspeptic symptoms and endoscopic and histological diagnoses. DESIGN--Cross sectional study of people with dyspepsia and controls matched for age and sex identified by questionnaire survey of all inhabitants aged 20 to 69. Endoscopy and histological examination was performed with the examiner blind to whether or not the patient had dyspepsia. SETTING--Population based survey in Sorreisa, Norway. SUBJECTS--All people with dyspepsia and age and sex matched people without dyspepsia were offered endoscopy. A total of 309 people with dyspepsia and 310 without dyspepsia underwent endoscopy, giving 273 matched pairs. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses made according to internationally accepted standards. RESULTS--In all, 1802 of 2027 (88.9%) people returned the questionnaire. Of the 163 subjects who refused endoscopy, 114 were controls. Of five endoscopic and four histological diagnoses only peptic ulcer disease, endoscopic duodenitis, and active chronic gastritis were diagnosed significantly more often in people with dyspepsia. In all, 30% to 50% of the diagnoses of mucosal inflammation and peptic ulcer disease were made among subjects without dyspepsia, and only 10% of both those with and those without dyspepsia had normal endoscopic findings. CONCLUSIONS--The diagnostic findings, with possible exceptions of peptic ulcer disease and endoscopic duodenitis, showed no association of clinical value with dyspeptic symptoms. The small number of ""normal"" endoscopic findings in both those with and those without dyspepsia challenge well accepted endoscopic and histological diagnostic criteria with relation to the upper gastrointestinal tract."
-How are atrial natriuretic factor mRNA levels correlated with plasma concentrations and heart pressures in patients with heart failure?,"Transcription, storage and release of atrial natriuretic factor in the failing human heart. 1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure- and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atrial are related to left ventricular filling pressures in the failing human heart."
-What makes this case of Hodgkin's disease unique in the context of HIV-seropositive patients?,"Intracerebral Hodgkin's disease in a human immunodeficiency virus-seropositive patient. Intracerebral involvement of Hodgkin's disease (HD) is rarely described, with only 42 cases in the literature. Since the outbreak of the acquired immune deficiency syndrome (AIDS) epidemic, there has been an increasing number of human immunodeficiency virus (HIV)-infected (HIV+) persons who have diffuse non-Hodgkin's lymphoma and, more recently, atypical aggressive HD. The authors report the case of a patient with a history of intravenous drug abuse (IVDA) and Stage IVB HD who, after a drug-induced clinical remission, had intracerebral mixed-cellularity HD. This appears to be the first report of intracerebral HD in a person who is HIV+."
-How do enterocytes from patients with inflammatory bowel disease (IBD) differ from normal enterocytes in their interaction with T cells?,"Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment."
-What is the relationship between leukoaraiosis and ventricular size in patients with ischemic stroke?,"Leukoaraiosis and ventricular enlargement in patients with ischemic stroke. We studied the relationship between ventricular size and nonspecific periventricular lucency on computed tomograms (leukoaraiosis) in 192 patients with ischemic stroke. Leukoaraiosis did not occur in 21 patients less than 50 years of age; ventricular size could not be measured in an additional 29. Leukoaraiosis was graded from 0 to 4 on a semiquantitative scale; bicaudate, frontal horn, and posterior horn indices were used as measures of ventricular size. Patients with leukoaraiosis were older (difference between means 7 years, t = 5.3, df = 140, p less than 0.0001) and had larger bicaudate indices (difference between means 0.023, t = 3.54, df = 140, p = 0.0007) than patients without leukoaraiosis. Multiple regression analysis demonstrated that the effects of age and leukoaraiosis were independent. No effect of lesion type (cortical or lacunar infarct, or both) on bicaudate index could be demonstrated. Larger values for the bicaudate index were associated with a predominantly anterior location of leukoaraiosis. The frontal horn and occipital horn indices increased with age, but we could not find an effect of leukoaraiosis on these indices."
-What was the primary objective of the Canadian Atrial Fibrillation Anticoagulation (CAFA) Study?,"Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other ""positive"" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17)."
-What is the importance of anticoagulation therapy after stent implantation in venous bypass grafts?,"The importance of adequate anticoagulation to prevent early thrombosis after stenting of stenosed venous bypass grafts. Stent implantation in native coronary arteries may be complicated by acute thrombosis, despite the use of stringent anticoagulation. Thrombotic occlusion of stented venous grafts may occur less frequently, possibly because of the larger caliber of these grafts. We report our experience with 46 stents (Wallstent, Medinvent, Lausanne, Switzerland) implanted in 35 lesions of 24 consecutive patients (mean age 64 years, range 43 to 75). Two overlapping stents were implanted in seven patients, and three overlapping stents were positioned in two. After implantation, activated partial thromboplastin time was maintained at two to three times the control level by intravenous administration of heparin (160 to 550 mg daily) until thrombotest values were reduced 5% to 10% by acenocoumarol. Impending thrombotic occlusion was recognized in two suboptimally anticoagulated patients: patient A after implantation of four stents and patient B after anticoagulation therapy was discontinued because of acute upper gastrointestinal bleeding. Coronary artery bypass grafting was performed successfully in both patients. A third patient had a myocardial infarction on day 7 after stent implantation, in spite of adequate anticoagulation and optimal medical drug therapy. It is concluded that stringent anticoagulation therapy appears mandatory to maintain graft patency after stent implantation."
-How does the consumption of fish and sea mammals relate to blood pressure during pregnancy among Inuit women in the Keewatin region?,"Blood pressure during pregnancy in Canadian Inuit: community differences related to diet. OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted."
-Can early anti-pseudomonas chemotherapy prevent chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis patients?,"Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy."
-What is the relationship between the severity of primary biliary cirrhosis and pulmonary function in non-smoking patients?,"Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked. We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjogren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity."
-What are the major barriers that impede access to health care for millions of residents in the United States?,"Access to health care. One neurologist's perspective. Millions of residents of the United States have difficulty obtaining health care. Barriers impeding access to care include poverty, physical unavailability of health care services, absence of health insurance, and physicians unwilling to care for uninsured patients. Many patients do not successfully use health services because of educational, cultural, and language barriers. A major access barrier is lack of health insurance. Over 30 million people in the United States have none, the so-called medically indigent. Among them are over 3 million people with neurologic disorders. They have additional barriers to overcome because often they cannot work, cannot drive, have difficulty using public transportation, and have major cognitive and communication impairments. Medical and governmental bodies are debating solutions to the health care access crisis. Physicians should actively participate in this national debate. Neurologists should address the special needs of patients with neurological disorders."
-How did enflurane anesthesia affect the inducibility of ventricular tachycardia in patients undergoing cardiac ablation?,"Effects of enflurane on inducibility of ventricular tachycardia. The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventricular tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age +/- standard deviation 55 +/- 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with high-energy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before (""baseline study I"") and the second at the beginning of the ablation procedure (""baseline study II"") while the patient was awake and nonsedated. The third programmed stimulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide (""enflurane study""). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesia, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia."
-What was the mean age of patients diagnosed with endometrial adenocarcinoma in this Norwegian study?,"Endometrial adenocarcinoma in Norway. A study of a total population. Fifteen hundred sixty-six patients with adenocarcinoma of the endometrioid type (AC) were studied. These accounted for 78.9% of all 1985 patients with confirmed endometrial carcinoma diagnosed in Norway in the period 1970 through 1978. Four hundred and sixty-nine patients (29.9%) had well-differentiated tumors, 677 (43.2%) were moderately and 420 (26.8%) poorly differentiated. Eighty-one percent of the patients had surgicopathologic Stage I disease, 11% Stage II, 6% Stage III, and 2% Stage IV. Mean age at diagnosis was 62.1 years (range, 36 to 91). The crude 5-year and 10-year survival rates for all patients were 74.1% and 62.2%, respectively. Five-year crude survival was 86.8% for Grade 1 and 58.3% for Grade 3 tumors. The 5-year crude survival for patients with intramucosal tumors was 88.7% as opposed to 46.9% for patients with tumors infiltrating to the serosa. Sixty-six percent of the patients with vessel invasion survived for 5 years in contrast to 88.6% for patients without vessel invasion. Histologic grade, myometrial infiltration, vessel invasion, and lymphocyte reaction surrounding the tumor were strongly interrelated. Multivariate analysis showed that the age of the patient at the time of diagnosis was the most important single prognostic factor. Disregarding age, survival in operated patients was more dependent on the depth of myometrial invasion than on grade and stage of disease."
-What are the key characteristics of pain perception and coping strategies in patients with noncardiac chest pain (NCCP)?,"Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain."
-What problem can occur following craniofacial procedures involving periosteum stripping over the zygomatic maxillary complex?,"Periosteal suspension of the lower eyelid and cheek following subciliary exposure of facial fractures. Following craniofacial procedures that involve stripping of the periosteum and soft tissue over the zygomatic maxillary complex, descent of soft tissue with a decrease in anterior projection over the malar area and increase in fullness in the nasolabial fold have been seen to be a problem by these authors. Simple repositioning of the soft tissues to their normal anatomic position may be used to alleviate this problem."
-What is the primary advantage of using an uncemented porous-coated anatomic (PCA) hip system in total hip arthroplasty?,"Noncemented porous-coated anatomic total hip arthroplasty. In 1984, as an alternate to the acrylic fixation of the components of total hip arthroplasty, the use of an uncemented porous-coated anatomic (PCA) hip system with a beaded porous coating to achieve biologic fixation was initiated. Since then, 44 patients with cementless acetabular components and 35 patients with cementless femoral components have been followed for a minimum of 24 months and an average of 37 months. Harris hip scores averaged 90.5 at most recent follow-up intervals. No reoperations were necessary for failures of fixation or change in position of the acetabular component. Ominous roentgenographic signs such as progressive bead shedding, progressive radiolucencies, or progressive component migration have not occurred. Two femoral component revisions have been necessary: one for intractable pain and one for pain and roentgenographic loosening. Although thigh pain has been prevalent (20%), all patients have been accommodated and have retained stable hip scores. Progressive radiolucencies and progressive implant subsidence have been rare occurrences. The authors continue to use the cementless acetabular component in all cases of total hip arthroplasty in which initial stability can be obtained. It is their preference to cement the femoral component in patients over 65 or when initial stability cannot be achieved."
-What are interferons and how do they modulate the immune response?,"Immunologic effects of interferon. Interferons can be defined as a family of induced proteins sharing the capacity to exert pleiotropic effects on cell functions and to render cells resistant to virus infection. They are activating genes coding for a number of enzymes, most of which have not yet been characterized, and also by enhancing the synthesis of cell surface components. This enables interferons to modulate the immune response at different levels. This article will focus on the effects of interferon on antigen presentation, regulation of the immune response, activation of macrophage functions, and on its role in the pathogenesis of some diseases."
-What percentage of patients with neurosarcoidosis experienced seizures as the first manifestation of the disease?,"Clinical implications of seizures in neurosarcoidosis. Seizures are a recognized manifestation of neurosarcoidosis, but their clinical relevance is not well established. We reviewed the characteristics, clinical correlations, and prognosis of seizures in 79 patients with neurosarcoidosis. Thirteen (15%) of the 79 patients had seizures, and in eight patients (10%) a seizure was the first manifestation of neurosarcoidosis. These seizures were generalized tonic-clonic seizures in 12 patients (92%) and partial seizures in four patients (31%). The patients with neurosarcoidosis with seizures were more likely to have a progressive or relapsing clinical course and intracranial mass lesions (four patients [31%]), encephalopathy or vasculopathy (eight patients [62%]), or hydrocephalus (five patients [38%]). These central nervous system disorders, rather than the seizures per se, were responsible for most of the serious morbidity and the two deaths (15%) among our patients with seizures. Indeed seizure control was good in 11 (85%) of 13 patients treated with combinations of steroids and antiepileptic medications. Seizures are an important sign in neurosarcoidosis because they are associated with more severe and progressive or relapsing forms of central nervous system sarcoidosis and may be an early manifestation of such disorders."
-What were the MR imaging findings for hepatocellular carcinoma lesions before and after percutaneous ethanol injection (PEI)?,"Small hepatocellular carcinoma treated with percutaneous ethanol injection: MR imaging findings. Fifty-seven magnetic resonance (MR) imaging examinations were obtained at 0.5 T in 19 patients before and after percutaneous ethanol injection (PEI) for 23 hepatocellular carcinoma (HCC) lesions less than 3.5 cm in diameter. Seventeen patients also underwent MR imaging 6 months after completion of therapy. In 11 patients, computed tomography was performed before and after treatment. After PEI, fine-needle biopsy specimens were obtained in all cases. Before treatment, HCC lesions had low signal intensity on T1-weighted images in 13 cases, had the same signal intensity as normal liver parenchyma in six, and had high signal intensity in four; all 23 tumors had high signal intensity on T2-weighted images. After treatment and at 6-month follow-up, all 21 lesions that contained no malignant cells at fine-needle biopsy had high signal intensity on T1-weighted images and had low signal intensity on T2-weighted images. The remaining two HCC lesions in which tumor necrosis was not achieved with PEI displayed a different MR pattern, since the residual neoplastic tissue showed no change in signal intensity on either T1- or T2-weighted images. The authors conclude that MR imaging may be useful for evaluating the effectiveness of PEI in achieving tumor regression."
-"How does nicotine affect gastric mucosal damage, and what protective measures were found to reduce its harmful effects?","Nicotine induced gastric injury. A quantitative macroscopic and microscopic analysis of the protective effects of sucralfate and feeding. Nicotine, while an important component of cigarettes, does not cause gross gastric mucosal damage, although its microscopic effect remains unknown. We have evaluated the histology and the microvascular permeability of (a) the effect of nicotine alone or in combination with ethanol on the gastric mucosa of rats and (b) the effect of feeding and sucralfate on the mucosa of rats treated with nicotine and ethanol. Mucosal injury was assessed histologically by the depth of injury and microvascular permeability by the leakage of fluorescein isothiocyanate-labelled albumin. Our results show that nicotine induced microscopic mucosal damage and accentuated the damage induced by alcohol. The damaging effects on mucosa of nicotine and ethanol, alone or in combination, were reduced by pretreatment with sucralfate. Similarly, feeding reduced the degree of mucosal injury. Nicotine and ethanol increased leakage of albumin into the interstitium and the leakage was reduced after sucralfate pretreatment. This study substantiates the adverse effect of smoking on mucosal damage. Vascular factors are probably involved in the pathogenesis."
-How do fibroblasts from kidneys with interstitial fibrosis (FKIF cells) differ from normal kidney fibroblasts (NKF cells) in terms of growth and collagen synthesis?,"Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. Fibroblast cultures from normal human kidneys (NKF cells) and kidneys affected with interstitial fibrosis (FKIF cells) were analyzed for in vitro growth, differentiation dynamics, and collagen synthesis. FKIF cells are characterized by hyperproliferative growth, resulting in a prolonged mitotic lifespan, by an altered differentiation pattern, and by the expression of the FKIF cell-specific protein ""fibrosin"" (molecular weight 53 kd, isoelectric point [pi] 6.1). Furthermore, FKIF cells synthesize four to five times more total collagen per cell as compared with NKF cells, and the relative amounts of the collagen types produced (type I, III, and V) are significantly different from controls. Thus, the in vitro cell system of FKIF cells may help to elucidate the underlying mechanisms triggering the induction and progression of renal interstitial fibrosis in vivo."
-What is iniencephaly and how was the infant in this case report treated?,"Deformity correction and long-term survival in an infant with iniencephaly. Case report. The authors describe the case of a male infant who was diagnosed prenatally as having iniencephaly. Since birth, the child has grown, thrived, and undergone two successful operations to correct his cervical deformity. This case demonstrates that the iniencephaly defect is not uniformly fatal and that neurosurgical intervention may offer significant improvement in the cervical deformity."
-What did the statistical analysis reveal about the timing of chest pain onset in patients with myocardial infarction?,Circadian variation in the frequency of onset of chest pain in acute myocardial infarction. The time of onset of chest pain was studied prospectively in 1154 consecutive patients admitted to a coronary care unit with myocardial infarction during a five year period. Statistical analysis confirmed a previous finding in a retrospective study of a bimodal frequency distribution with peaks in the time of onset of chest pain between 2330 and 0030 hours and between 0630 and 0830 hours.
-How do angiotensin converting enzyme inhibitors like perindopril affect vascular resistance in spontaneously hypertensive rats (SHR)?,"Angiotensin converting enzyme inhibitors, regional vascular hemodynamics, and the development and prevention of experimental genetic hypertension. During the development of hypertension in young spontaneously hypertensive rats (SHR) vascular resistance is increased, particularly in the renal circulation, and, to a lesser extent, in the splanchnic bed. Treatment with angiotensin converting enzyme inhibitors in young SHR reverses the renovascular abnormalities more effectively than simple vasodilators, suggesting that the resistance changes may depend on angiotensin II. Perindopril treatment during the development of hypertension causes a reduction in blood pressure as a result of a fall in total peripheral resistance, which persists long after treatment is stopped. These long-term effects can be prevented by replacing angiotensin during perindopril treatment. Not all organs share the long-term resistance changes following perindopril treatment, which are most marked in the renal, splanchnic, and cerebral circulations. The heterogeneous patterns of regional vascular resistance during the development and after prevention of hypertension with angiotensin converting enzyme inhibitors in SHR suggest that local factors, for example, angiotensin II related to the tissue renin-angiotensin system or local adrenergic activity, may be important in the genesis of high blood pressure in this genetic model."
-How do oral glycopyrrolate and oral atropine compare in preventing cardiovascular depression during halothane anesthesia induction in infants?,"Is premedication with oral glycopyrrolate as effective as oral atropine in attenuating cardiovascular depression in infants receiving halothane for induction of anesthesia? The authors conducted a double-blind study to compare premedication with oral glycopyrrolate and oral atropine in prevention of bradycardia and hypotension during induction of anesthesia with halothane-N2O in 90 outpatient infants and children aged 1-18 mo who were randomized into three groups to receive either an oral placebo, oral atropine (0.02 mg/kg), or oral glycopyrrolate (0.05 mg/kg) approximately 1 h before induction of anesthesia. Heart rate and mean arterial pressure were measured before drug administration, just before induction of anesthesia, and every minute until surgical stimulation occurred. Glycopyrrolate, at the dose used, was significantly less effective than atropine in attenuating bradycardia during induction; neither glycopyrrolate nor atropine altered the incidence or degree of hypotension. Antisialagogic activity and side effects were comparable, except for significantly more flushing with atropine."
-What unusual hemorrhagic manifestations did the 19-year-old man with sickle cell anemia develop during a painful crisis?,"Case report: epidural and bilateral retroorbital hematomas complicating sickle cell anemia. Early in the course of a painful crisis, a 19-year-old man with known sickle cell anemia (SCA) developed a clinical picture that resembled either early cavernous sinus thrombosis or retroorbital and bifrontal microinfarcts. A brain computer tomography scan demonstrated bilateral retroorbital hemorrhages along with a left frontal epidural hematoma. In the absence of trauma, thrombocytopenia, or any other detectable hemostatic defect, this type of hemorrhagic manifestation in the setting of SCA has not, to our knowledge, been previously reported in the literature."
-What are the key differences between vigorous and classic achalasia according to the study?,"Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. Compared with classic achalasia, vigorous achalasia has been defined as achalasia with relatively high esophageal contraction amplitudes, often with minimal esophageal dilation and prominent tertiary contractions on radiographs, and with the presence of chest pain. However, no study using current manometric techniques has compared manometric, radiographic, and clinical findings in vigorous and classic achalasia or questioned the usefulness of making this distinction. Fifty-four cases involving patients with achalasia whose radiographic and manometric studies were performed within 6 months of each other were available for review. Patients with vigorous achalasia (n = 17), defined by amplitude greater than or equal to 37 mm Hg, and patients with classic achalasia (n = 37), defined as amplitude less than 37 mm Hg, had substantial overlap in radiographic parameters of esophageal dilation, tortuosity, and tertiary contractions. Manometric properties of repetitive waves and lower esophageal sphincter pressure and clinical aspects of chest pain, dysphagia, heartburn, and satisfactory responses to pneumatic dilation were similar in both forms of achalasia. A separate analysis of patients with mean contraction amplitude greater than 60 mm Hg revealed similar findings. It is concluded that use of amplitude as a criterion for classifying achalasia is arbitrary and of dubious value."
-What was the prevalence of obesity among American Indian adults according to the 1987 National Medical Expenditure Survey?,"Prevalence of obesity in American Indians and Alaska Natives. Obesity is an important risk factor for cardiovascular diseases and non-insulin-dependent diabetes, which are chronic diseases that afflict American Indians and Alaska Natives today. Because American Indians are not represented in most national health and nutrition surveys, there is a paucity of data on actual prevalence of obesity in American Indians. We estimated prevalence of overweight and obesity for American Indian adults, school-age children, and preschool children from existing data. The prevalence of obesity in adults was estimated from self-reported weights and heights obtained from a special survey of American Indians performed as part of the 1987 National Medical Expenditure Survey. Prevalence of obesity in American Indians was 13.7% for men and 16.5% for women, which was higher than the US rates of 9.1% and 8.2%, respectively. Obesity rates in American Indian adolescents and preschool children were higher than the respective rates for US all-races combined."
-How does dipyridamole echocardiography test (DET) help in detecting jeopardized myocardium after thrombolytic therapy?,"Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy. BACKGROUND. We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS. Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS. DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention."
-What percentage of postmenopausal women experienced persistent side effects from tamoxifen treatment in this study?,"Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance."
-What were the significant risk factors related to an obstructing tumor in Japanese patients with colorectal cancer?,"Prognostic factors in Japanese patients with colorectal cancer: the significance of large bowel obstruction--univariate and multivariate analyses. In order to define prognostic factors in colorectal carcinoma, univariate and multivariate analyses were carried out on data from 113 Japanese patients treated in a typical general hospital in Japan. In the univariate analysis, a poor prognosis was seen in those with poorly differentiated adenocarcinoma, in tumors that perforated the visceral peritoneum or that invaded directly other organs or structures (T4), in metastasis to the nodes along the main vascular pedicle (N3), in lymphatic permeation, in blood vessel invasion, in peritoneal dissemination, in Dukes C stage, and in those with lesions presenting with large bowel obstruction. Of these, only lymph node metastasis and peritoneal dissemination had an independent prognostic significance when a multivariate Cox analysis was performed. The significant risk factors related to an obstructing tumor were determined by multivariate logistic regression analysis. The significant variables were patient's age, nodal involvement and peritoneal dissemination. Since lymph node metastasis and peritoneal dissemination proved significant in both multivariate analyses, we propose that the presence of large bowel obstruction is not an independent prognostic factor in patients with colorectal carcinoma. In poor-risk patients who have an obstructing tumor, a staged operation should be attempted for definitive curative surgery."
-How do the clinical manifestations of loiasis differ between endemic and non-endemic populations?,"Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis."
-What percentage of elderly patients in the primary care setting reported having at least weekly heartburn?,"Prevalence of gastroesophageal reflux in elderly patients in a primary care setting. Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER--none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed."
-What percentage of laboratory and nursing training programs made the hepatitis B vaccine available to their students?,"Availability and use of hepatitis B vaccine in laboratory and nursing schools in the United States. Hepatitis B is a well-documented occupational hazard for health care workers, including both laboratory and nursing personnel. Since the development of effective hepatitis B vaccines, the Immunization Practices Advisory Committee (ACIP) has recommended that health care workers receive the vaccine. In this study, 78 laboratory training programs and 83 nursing training programs were surveyed regarding availability and usage of hepatitis B vaccine. The hepatitis B vaccine was made available to students in 81 percent of the laboratory programs and 23 percent of the nursing programs. In those programs making the vaccine available, only 59 percent of the laboratory programs and 5 percent of the nursing programs reported a high (greater than 75 percent) use by students. Concern about cost and payment for the vaccine was the most common reason (80 percent) noted by laboratory schools that did not have hepatitis B vaccination programs for students. Of the nursing schools that did not have vaccine programs, 58 percent had not yet considered a program. At laboratory schools with vaccination programs, who paid for the vaccine (hospital or school versus student) was among the most important determinants for vaccine usage by students. These findings point out that some laboratory schools and many nursing schools have not applied the ACIP recommendations to their own programs. Educational efforts and creative payment plans for the vaccine are needed to increase the availability and use of hepatitis B vaccine among laboratory and nursing students."
-What was the purpose of using polymerase chain reaction in this study of multiple sclerosis patients?,"Analysis of retroviral sequences in the spinal form of multiple sclerosis. The polymerase chain reaction was used, in a blind study, to look for retroviral sequences in DNA extracted from the peripheral blood mononuclear cells of 11 patients with the spinal form of multiple sclerosis (MS). Control subjects consisted of 7 patients with other neurological diseases and 5 healthy blood donors. Three sets of oligonucleotides were used. They could detect all known human oncoretroviruses, lentiviruses, or spumaretroviruses. The primers recognized conserved sequences in the long terminal repeats of the proviral DNA. Control experiments showed that the primers crossreacted within the human immunodeficiency virus or human T-cell lymphotropic virus group and that they provided the expected level of sensitivity. Therefore the assay could have detected not only known human retroviruses but also new related members. In spite of this, no retroviral sequences were detected in either the MS or the control specimen."
-What was the main objective of the clinical trial involving the E5 murine monoclonal IgM antibody?,"A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated."
-How does complete Freund's adjuvant (CFA) treatment affect diabetes onset and insulitis in NOD mice?,"Prevention of insulitis and diabetes onset by treatment with complete Freund's adjuvant in NOD mice. In studies of immune cell defects in autoimmune diabetes mellitus, we observed that complete Freund's adjuvant (CFA) prevented the onset of diabetes when injected into 8- to 10-wk-old prediabetic nonobese diabetic (NOD) mice. The prevalence of the onset of diabetes in the CFA-injected versus uninjected NOD mice was 2 of 81 (2.5%) vs. 231 of 379 (61%) among females and 2 of 44 (4.5%) vs. 83 of 336 (25%) among males, respectively. The incidence of histologically identifiable insulitis was significantly reduced in CFA-treated prediabetic female NOD mice (18%) compared with the incidence in female age-matched controls (70%). Splenocytes or Mac-(1+)-enriched splenocytes from CFA-treated NOD mice, when cotransferred with splenocytes from diabetic mice, reduced the incidence of diabetes provoked by diabetic splenocytes in vivo. In the spleen, CFA injection induced sustained increases in cell proliferation and an associated major increase in the numbers of an immature cell type that expressed the Mac-1 surface antigen. In CFA-treated NOD mice, lymphocytes derived from the spleen failed to respond in vitro to stimulation by the mitogen concanavalin A or by anti-CD3. When cocultured, Mac-1+ cells, enriched from the splenocytes of CFA-treated mice, suppressed concanavalin A- or anti-CD3-induced proliferation of T lymphocytes derived from either the spleen or thymus of untreated NOD mice. Therefore, treatment with CFA prevents the development of diabetes, and concomitantly, insulitis while stimulating the generation of splenic suppressor cells that are capable of suppressing diabetogenic T-lymphocyte function in vivo and in vitro."
-What was the purpose of the study comparing intermittent intravenous injections and patient-controlled analgesia for sickle cell crisis pain in the emergency department?,"Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department. BACKGROUND.--The purpose of this study is a prospective assessment of morphine sulfate administration by intermittent intravenous (IV) injections (Int-IV) vs patient-controlled analgesia (PCA) in patients in the emergency department (ED) with sickle cell crisis pain. METHODS.--Patients were at bed rest and received intravenous hydration. Linear analog scale for pain intensity and verbal pain scale, level of alertness, and vital signs were assessed prior to therapy, every 60 minutes thereafter, and at the time of discharge from the ED. Patients were randomized to Int-IV or PCA. During phase 1, patients in the Int-IV group received morphine sulfate 4 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 2 mg bolus then 1.0 mg with a 6-minute lockout. During phase 2, patients in the Int-IV group received morphine sulfate 8 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 5 mg bolus then 2.7 mg with a 10-minute lockout. Data were analyzed by unpaired t test, general linear modeling, Mann-Whitney U test, and chi 2 test. RESULTS.--During phase 1, 10 patients (28.3 +/- 7.3 years) received Int-IV and 10 patients (33.9 +/- 12.5 years) received PCA. Treatment groups did not differ significantly regarding duration of pain, amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, level of alertness, or vital signs except for a significantly lower final respiratory rate with Int-IV. In phase 2, 12 patients (28.4 +/- 5.6 years) received Int-IV and 13 patients (26.8 +/- 8.1 years) received PCA. The PCA groups had a significantly shorter elapsed time between onset of pain and treatment (7.3 +/- 6.5 hours) when compared with the Int-IV group (18 +/- 16.9 hours). Treatment groups did not differ significantly with respect to total amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, vital signs, or level of alertness. The PCA group had a significant reduction in length of stay in the ED during phase 2 when compared with phase 1. The ED discharge rate and the incidence of side effects did not differ significantly between groups. CONCLUSION.--At both the low- and high-dose regimens, PCA is equally safe and effective and may be used in place of Int-IV administration of morphine in the ED treatment of sickle cell crisis pain."
-What was the main finding of the study regarding alcohol consumption and supraventricular tachyarrhythmias?,"Alcohol consumption of patients with supraventricular tachyarrhythmias other than atrial fibrillation. We studied the recent alcohol consumption and other possible precipitating factors in 99 consecutive patients (53 men and 46 women) all under 65 years of age with sustained re-entry and automatic supraventricular tachyarrhythmias and compared them with those of two groups of controls. One control group was derived from the Emergency Room patients and matched for age and sex; the other group (44 men, 22 women, mean age 48.7 years) was randomly selected from the general out-of-hospital population. There were 50 patients with supraventricular tachycardia, 30 with atrial flutter, and 19 with paroxysmal atrial tachycardia. Coronary heart disease (14% of patients), hypertension (10%), and dilated cardiomyopathy (6%) were the most prevalent cardiovascular diseases associated with the arrhythmias. The self-reported alcohol consumption of patients with arrhythmias during the week preceding the arrhythmia did not differ significantly from that of hospital or population controls, although significantly more patients than controls had liver enzyme levels above normal; neither were there any significant differences between the groups regarding prevalence for alcoholism as judged by the CAGE questionnaire. The results were essentially similar when patients with supraventricular tachycardia and those with intra-atrial tachyarrhythmias (flutter and paroxysmal tachycardia) were separately compared with the controls. We conclude that alcohol consumption, although a risk factor for atrial fibrillation, is not associated with the induction of other supraventricular tachyarrhythmias in patients of working age."
-What are the potential health risks associated with prolonged inhalation of mineral spirits?,"Mineral spirits inhalation associated with hemolysis, pulmonary edema, and ventricular fibrillation. A previously healthy 42-year-old woman developed severe dyspnea, chest discomfort, and malaise several hours after prolonged exposure to concentrated vapors from mineral spirits. On the way to the hospital, she sustained a cardiopulmonary arrest; on arrival several minutes later, she was found to be in ventricular fibrillation and was resuscitated. Her hospital course included slowly resolving cardiac abnormalities, amnesia, noncardiogenic pulmonary edema, abrupt hemolytic anemia, sustained rhabdomyolysis, and other metabolic abnormalities. It is highly probable that this syndrome represented acute and near-lethal toxicity caused by the inhalational exposure to the petroleum distillate known as mineral spirits. It is important that physicians be aware of this syndrome in order to recognize it on presentation and to warn patients of the risk of such toxic exposure."
-What was the outcome of ciprofloxacin treatment for patients with refractory chronic bacterial prostatitis caused by Escherichia coli?,Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months. A total of 16 men suffering from refractory chronic bacterial prostatitis caused by Escherichia coli was treated with ciprofloxacin for 4 weeks. After a median followup of 30 months (range 21 to 36 months) 10 of the 16 patients were considered cured as judged by bacteriological results and clinical symptoms. In 2 men a second ciprofloxacin regimen obviously showed success also. In 2 patients ciprofloxacin therapy failed and in 2 therapy had to be discontinued due to side effects of the central nervous system.
-What are the four categories of hypertension in pregnancy?,"Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years? High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive."
-What are the key characteristics of desmoplastic small cell tumors based on microscopic and immunohistochemical findings?,"Desmoplastic small cell tumors of the peritoneum coexpressing mesenchymal and epithelial markers. Desmoplastic small cell tumors arising diffusely within the abdomen and lacking an apparent organ of origin are rare. Most previously reported cases occurred in children, but young adult patients also have been described. Light microscopic examination shows the tumors to be composed of nests of small cells surrounded by an abundant desmoplastic stroma. Immunohistochemical findings reveal multidirectional differentiation with coexpression of cytokeratin, milk fat globule, neuron-specific enolase, Leu-7, desmin, and vimentin. Electron microscopic examination demonstrates paranuclear condensations of intermediate filaments. The authors describe two patients who died of their disease, despite aggressive chemotherapy and surgical intervention."
-What were the mortality rates for ischaemic heart disease and cerebrovascular disease among different ethnic groups in England and Wales during the 1970s and 1980s?,"Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade."
-What was the average peak effect of botulinum toxin treatment for tremors in this study?,"Botulinum toxin treatment of tremors. We report the results of an open trial of botulinum toxin (Botox) in the treatment of 51 patients with disabling tremors, classified as dystonic (14), essential (12), combination of dystonic and essential (22), parkinsonian (1), peripherally induced (1), and midbrain (1). The average age of the patients was 55.8 years, and duration of symptoms was 13.9 years. During a total of 160 treatment visits, an average of 242 +/- 75 units of Botox was injected per visit in cervical muscles of 42 patients with head tremor and 95 +/- 38 in forearm muscles of 10 patients with hand tremor; one patient was injected in both. The average peak effect for all patients was rated as 3.0 (0 to 4 scale). Thirty-five (67%) patients improved (peak effect greater than or equal to 1). The average latency from injection to response was 6.8 days, and the average duration of maximum improvement was 10.5 weeks. Local complications, lasting an average of 20.6 days, were noted in 17 (40%) patients injected for head tremor, consisting chiefly of dysphagia in 12 (29%), transient neck weakness in four (10%), and local pain in two (5%). Six (60%) patients with hand tremor had transient focal weakness. EMG recordings showed decreased amplitude of EMG bursts after Botox treatment. The results of this pilot study indicate that Botox injections can be used to control tremor in patients in whom other forms of therapy have failed."
-What complications did the patients with chickenpox pneumonia experience in this case report?,"Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation."
-How does tumor cell DNA content (ploidy) relate to recurrence rates in colorectal cancer patients?,"A prospective evaluation of the effect of tumor cell DNA content on recurrence in colorectal cancer. Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy."
-What are the key challenges emergency physicians face when treating patients with headaches?,"Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache."
-What genetic modifications cause the nonsecretory alpha-chain disease plasma cells to produce only membrane-form alpha-chain?,"Gene deletions force nonsecretory alpha-chain disease plasma cells to produce membrane-form alpha-chain only. We studied a case of nonsecretory alpha-chain disease. The proliferating plasma cells contained a short transcript coding for a truncated membrane-form alpha 1-chain. The productive alpha-gene bore several noncontiguous deletions affecting the VHDJH and CH1 regions. Two deletions were accompanied with peculiar insertions containing duplications. The first insertion contained an acceptor splice site and was present in part in the mature transcript, thus coding for an abnormal aminoterminal peptide. Another deletion located 3' to CH3 eliminated the polyadenylation site of secreted-form alpha-mRNA. As a result, only membrane-form alpha mRNA was present in the tumoral plasma cells, thus explaining the nonsecretory phenotype of the disease. Comparison of cDNA and genomic sequences showed that the previously undescribed human alpha membrane region is encoded by a single exon, beginning with two alternate acceptor splice sites, and comprises either 65 or 71 amino acids."
-What is the purpose of the anterior sternal retraction technique in reoperative median sternotomy?,Anterior sternal retraction for reoperative median sternotomy. The incidence of reoperative median sternotomy for repeat cardiac surgery is increasing. Reoperative median sternotomy is associated with a higher morbidity and mortality than first-time cardiac surgery. A portion of this morbidity and mortality may be due to direct injury to the heart and great vessels in the process of reopening the sternum. We report a new technique utilizing anterior sternal retraction that allows division of adhesions between the undersurface of the sternum and the heart and great vessels under direct vision. This technique enables the surgeon to minimize the risk of serious injury to these underlying structures during reoperative cardiac surgery.
-How does physical overdistension of the ventricular wall affect the production of atrial natriuretic peptide (ANP) in cardiomyocytes?,"Physical overdistension converts ventricular cardiomyocytes to acquire endocrine property and regulate ventricular atrial natriuretic peptide production. Atrial natriuretic peptide (ANP) is present in adult atria but at very low concentrations in normal adult mammalian ventricles. In the atria, the production of ANP is regulated by physical distension of the atrial wall. The same phenomenon was investigated in the ventricles of rats and men. Cardiac tissues from human ventricular aneurysm (n = 5), spontaneously hypertensive rats (n = 30), and rats that had overloaded left ventricles induced by surgery (n = 84) were studied with the methods of light microscopic immunocytochemistry, electron microscopic immunogold staining, and RNA-RNA tissue in situ hybridization. It was found that the levels of ANP gene expression, ANP immunoreactivity, and ANP-containing specific granules in the overburdened ventricles were elevated and their degrees of fluctuation were directly proportional to the force of physical distension applied to the ventricular cardiomyocytes. In rats, ANP mRNA and ANP immunoreactivity returned to the control level seven days after the ventricular overload was surgically released. The changes of ANP and its mRNA in the ventricles were related more closely to the changes of intraventricular pressure than to cardiocytic hypertrophy. In addition, ANP immunoreactivity was demonstrated in Purkinje cells and periarteriolar cardiomyocytes in the ventricles of normotensive rats. In conclusion, physical overstretch of the ventricle wall is likely to be the triggering factor affecting ventricular cardiomyocytes to acquire endocrine property, and also to regulate the production of ventricular ANP, thereby contributing to the control of the blood volume and the blood pressure."
-What were the key functional outcomes observed in children with sickle-cell disease who had experienced strokes?,"Functional outcomes of children with sickle-cell disease affected by stroke. The nature and degree of functional recovery after stroke in children with sickle-cell disease (SCD) has not been extensively investigated. The purpose of this study was to evaluate retrospectively the functional status of 14 SCD children who had had strokes and to compare them with age-matched and gender-matched SCD children who had not had strokes. By doing so, we would be able to quantify the eventual physical and cognitive functional outcomes of survivors of stroke secondary to SCD and assess the impact of stroke on these patients. These children (five boys and nine girls) with SCD and stroke(s) were 11.6 +/- 4.3 years of age (range five to 18 years). They experienced one to three strokes at a mean age of 6.1 +/- 5.2 years (range one to 17 years). A series of tests were administered to these subjects to evaluate physical and psychosocial functions. These tests were performed at least one year after the latest stroke. This study showed that all of the SCD-stroke children were physically independent. Only a few had impairments of hand functions and mild difficulties in self-care activities. However, most of these children demonstrated intellectual deficits ranging from borderline to moderate mental retardation, reduced language functions ranging from low normal to retarded range, and problems in adjustment. Intelligence quotient of the children with SCD-stroke(s) was significantly lower than those of age-matched and gender-matched nonstroke SCD children, suggesting that stroke caused an adverse effect on the cognitive functioning of these children. The results indicate that in the SCD-stroke children psychosocial deficits outweighed physical disabilities."
-What percentage of appendicitis cases were perforated during the 5-year review at the Guthrie Medical Center?,"Acute appendicitis. A 5-year review. A startling 31 per cent rate of perforated appendicitis in 1984 prompted a 5-year review at the Guthrie Medical Center. An increase over previous rates of 13 per cent and 0 per cent in 1964 and 1944 was confirmed in this study. Perforation accompanied 44 of 240 cases of appendicitis (18.3%); diagnostic accuracy in 295 cases undergoing operation was 81.4 per cent. Groups at risk for perforation were patients in the first decade of life (34.3% with perforations) and those over 50 years of age (48% perforated). Perforation rates were generally inversely related to accuracy. Accuracy was poorest in women in the second to fourth decade or those in the mid-portion of the menstrual cycle. When the appendix was not perforated, complications occurred in 8.7 per cent of patients while 29.5 per cent with a perforation had a complication. The mean hospital stay was prolonged by 2.5 days if the appendix was perforated. An increased awareness of the risk by both the public and physicians is essential to reduce the number of perforations."
-What method did the study suggest for determining the optimal time to remove a nephrostomy tube?,Intrarenal pressure following pyeloplasty or percutaneous surgery. In a study of 37 patients it was shown that recording the intrapelvic pressure is a safe and reliable means of judging the best time to remove a nephrostomy tube. No post-operative complications were encountered and the procedure has the added advantage of avoiding the use of X-rays.
-What is oncocytic metaplasia of the pharynx and how was it typically discovered in the reviewed cases?,"Oncocytic metaplasia of the pharynx. Oncocytic metaplasia of the pharynx has been infrequently described, with only two previous cases in the literature. With the advent of panendoscopy during the last decade, however, a better understanding of this histopathologic diagnosis is desirable. Thirty-three cases are reviewed, with thirty occurring in the nasopharynx. This was most commonly discovered as an unrelated finding during endoscopic evaluation of a head and neck mass or malignancy in twenty-two patients, either histologically after random biopsy or after biopsy of small but visible lesions. An additional eight cases manifested otitis media or eustachian tube dysfunction. The histology, terminology, and benign clinical nature of these lesions are discussed."
-How did the researchers use a cholera toxin transgene to study the effects of cAMP on pituitary growth hormone-producing cells?,"Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering."
-What was the outcome of the balloon dilatation attempts on fetuses with critical aortic stenosis?,"Balloon dilatation of the aortic valve in the fetus: a report of two cases. Because they had irreversible damage to the left ventricular myocardium none of 12 patients with critical aortic stenosis diagnosed prenatally survived after postnatal treatment. This experience prompted three attempts at intrauterine balloon dilatation of the aortic valve in two fetuses with this condition. On each attempt the balloon catheter was successfully delivered to the left ventricle. In the first fetus the aortic valve was not crossed and the fetus died the next day. In the second fetus the balloon was correctly positioned across the aortic valve and inflated in the valve ring. After delivery, a further balloon angioplasty was performed; this relieved the stenosis but the patient died five weeks later from persisting left ventricular dysfunction related to endocardial fibroelastosis. Balloon angioplasty is feasible in fetal life but the prognosis depends on the ability of the relief of stenosis to limit, prevent, or allow regression of left ventricular damage before delivery."
-What is the new method described for dealing with late-presenting spontaneous esophageal ruptures?,"New method for dealing with late-presenting spontaneous esophageal ruptures. A new technique is described for dealing with late-presenting spontaneous esophageal ruptures. This method requires only a short period of general anesthesia to drain the periesophageal abscess by a drainage tube inserted into the abscess cavity from the esophagus with the aid of a gastroscope and fluoroscopy. Gastric fluids are diverted from the esophageal rupture with a gastrostomy, and a jejunostomy is used for enteral feeding. The esophagus is retained, and closure of the fistula with resumption of normal swallowing is documented with serial sinograms."
-What anaesthetic technique was used for a parturient with severe mitral stenosis and pulmonary hypertension during an urgent Caesarean section?,"Alfentanil for urgent caesarean section in a patient with severe mitral stenosis and pulmonary hypertension. We present the case of a parturient with severe mitral stenosis and pulmonary hypertension who received general anaesthesia using alfentanil for urgent Caesarean section. Alfentanil promoted haemodynamic stability and allowed immediate postoperative extubation. Epidural morphine provided postoperative analgesia. This combination permitted early ambulation and prevention of thromboembolism. A disadvantage of this technique, neonatal respiratory depression, was promptly reversed with a single dose of naloxone. The anaesthetic management of mitral stenosis in pregnancy is discussed and the neonatal pharmacokinetics of maternally administered alfentanil are presented."
-What is the specific genetic mutation identified in the patient with adenosine deaminase deficiency (ADA-SCID)?,"Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). We have identified a previously unrecognized missense mutation in a patient with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The mutation is a G646-to-A transition at a CG dinucleotide and predicts a glycine-to-arginine substitution at codon 216. Computer analysis of secondary structure predicts a major alteration with loss of a beta-pleated sheet in a highly conserved region of the protein. The basepair substitution also generates a new site for the restriction enzyme BstXI in exon 7 of the genomic DNA. Digestion of genomic DNA from the patient and from his parents revealed that he was homozygous for the mutation and that his mother and father were carriers. This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase. Analysis of DNA from 21 additional patients with ADA-SCID and from 19 unrelated normals revealed that, while none of the normal individuals showed the abnormal restriction fragment, two of the 21 patients studied were heterozygous for the G646-to-A mutation."
-What are the key factors for survival in cases of spontaneous abdominal arteriovenous fistulae?,"Spontaneous abdominal arteriovenous fistulae: report of eight cases and review of the literature. The spontaneous rupture of an abdominal aneurysm into an adjacent major vein results in a profound and rapidly worsening haemodynamic disturbance. Survival depends on prompt diagnosis and closure of the fistula at operation. Eight cases are reported and modes of presentation, diagnostic criteria and management principles are reviewed in a detailed analysis of 148 cases in the English literature."
-How does the acidity of nebulized salbutamol solution affect oxygen levels in wheezy infants?,"Hypoxaemia after nebulised salbutamol in wheezy infants: the importance of aerosol acidity. The effect of nebulised iso-osmolar, preservative free, but acidic salbutamol solution was studied in 34 acutely wheezing infants aged 1-17 months. Transcutaneous oxygen pressure (TcPO2) and oxygen saturation (SO2) fell significantly during the first five minutes after nebulisation with further deterioration at 15-20 minutes. Ten of these infants were followed up for another two hours and showed slight improvement. Even after the second hour TcPO2 had not reached baseline values. Three months later the response to salbutamol and a placebo of equal acidity (pH 3.9) was studied in 11 infants from the same group, now free of symptoms. Lung function tests were included and showed no significant changes in specific conductance and volume corrected maximum expiratory flows (Vmax at functional residual capacity/thoracic gas volume). However, hypoxaemia occurred after the acidic placebo with a significant drop of TcPO2 (mean 0.9 kPa); SO2 decreased similarly but this did not reach significance. After salbutamol there was a further significant deterioration of mean TcPO2 (1.4 kPa) and of SO2. These results show that beside a possible pharmacological effect of salbutamol the acidity of the aerosol also induces hypoxaemia in infants."
-How does the study validate the technique for quantifying myocardial blood flow using oxygen-15-labeled carbon dioxide and positron emission tomography?,"Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. BACKGROUND. Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. METHODS AND RESULTS. The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001). CONCLUSIONS. PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients."
-What was the average cost of averting death or severe disability through neurosurgical intervention in this study?,"Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community."
-What morphological abnormalities were observed in the sural nerves of patients with inherited tendency to pressure palsy (ITPP)?,"Uncompacted inner myelin lamellae in inherited tendency to pressure palsy. Nerves in patients with inherited tendency to pressure palsy (ITPP) are susceptible to degrees of traction or compression which in nonaffected persons do not induce neuropathic symptoms or deficits, conduction block of fibers, or electromyographic changes characteristic of the disorder. Two observations suggest a widespread asymptomatic abnormality of nerves: 1) low conduction velocity of clinically unaffected nerves, and 2) focal thickenings (tomacula) on teased myelinated fibers of clinically unaffected sural nerves. Sural nerves from five patients and five healthy subjects were assessed for morphologic abnormality in ITPP that might account for the susceptibility of nerves to compression. Teased nerve fibers showed a higher frequency of segmental demyelination or remyelination, or both (p less than 0.003). The mean frequency of fibers showing focal myelin thickenings was 57 +/- 10% in ITPP and 0% in controls. In electron micrographs, regions of uncompacted myelin lamellae, usually affecting the innermost lamellae and extending for a variable distance averaging 9 +/- 4 microns were seen in 11 +/- 4% of fibers in ITPP. None were found in the control nerves. The finding of uncompacted myelin lamellae may suggest an abnormality of myelin composition or of interaction of Schwann cells and axons accounting for the increased susceptibility to pressure palsy, tomaculous formation, or demyelination. From electron microscopic evaluation of serial skip sections we infer that myelin of tomaculae is in continuity with internodal myelin and is reduplicated (full-thickness or cleaved layers are longitudinally or circumferentially folded-back on themselves)."
-What are the key characteristics of mouse mannose-binding proteins A and C based on their molecular characterization?,"Molecular characterization of the mouse mannose-binding proteins. The mannose-binding protein A but not C is an acute phase reactant. Mannose-binding proteins play a role in first line host defense against a variety of pathogens. We report the molecular cloning of two mouse mannose-binding proteins designated A and C based on their close identity with their rat homologues. The deduced amino acid sequence of the mouse mannose-binding proteins, as with rat and the human forms, have an NH2 terminus that is rich in cysteine that stabilizes a collagen alpha helix followed by a carboxyl- terminal carbohydrate binding domain. We further show that the mouse mannose-binding protein A mRNA, as with the human, is induced like the acute phase reactant serum amyloid P protein, yet the expression of mouse mannose-binding protein C mRNA is not regulated above its low baseline level. The expression of both mannose-binding proteins A and C mRNA is restricted to the liver under basal and stress conditions."
-What is the purpose of the clinical trial involving Cronassial in patients with Chagas' disease?,"Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo."
-What is the clinical significance of nonvisualization in HIDA scans after endoscopic retrograde sphincterotomy in patients with and without cholelithiasis?,"Biliary patency imaging after endoscopic retrograde sphincterotomy with gallbladder in situ. Clinical impact of nonvisualization. We prospectively performed nuclear biliary patency imaging (HIDA scanning) in 62 patients who had undergone endoscopic retrograde sphincterotomy for management of pancreaticobiliary disease with their gallbladders in situ. Elective cholecystectomy was not recommended because of advanced age, comorbidity, or absence of gallstones. All patients had patent cystic ducts at endoscopic retrograde cholangiopancreatography balloon cholangiography. Eighteen (29.1%) of 62 patients had nonvisualizing HIDA scans, and in 44 (70.9%) of 62 visualization was normal or delayed. Six cholecystectomies were required for colic (n = 1), acute cholecystitis (n = 4), and acute cholecystocholedochal fistula with cholangitis (n = 1). Among the patients with cholelithiasis and nonvisualization (n = 13), five (38.5%) required surgery, whereas only one (4.8%) of 21 patients with cholelithiasis and visualization required surgery. Nonvisualizing HIDA scans are frequent (30%) after endoscopic retrograde sphincterotomy and have no clinical relevance in patients without cholelithiasis but predict the need for cholecystectomy within 16 months in 38.5% of patients with cholelithiasis."
-How did damage to the fornix affect memory function in the two patients after colloid cyst removal?,"Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans."
-What was the outcome of autologous bone marrow transplantation (ABMT) for patients with neuroblastoma in this study?,"High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method."
-What innovative approach was used to place a stent in a patient with malignant biliary obstruction complicated by ascites?,"Malignant biliary obstruction complicated by ascites: transjugular insertion of an expandable metallic endoprosthesis. Although the transjugular approach has long been used to provide safe access to the liver, it has not been used for placement of stents in biliary obstruction. The recent development of an expandable metallic endoprosthesis now makes this method more feasible. The case of a patient with malignant biliary obstruction complicated by ascites is presented herein. Palliation was achieved with an expandable biliary endoprosthesis placed by the transjugular-hepatic vein approach."
-How do spousal caregivers and adult children differ in their caregiving responsibilities and support received for brain-impaired adults?,"Time spent caregiving and help received by spouses and adult children of brain-impaired adults. Caregivers for brain-impaired adults differ in living arrangements, amount of time spent giving care, and assistance received from family and friends and from paid help depending on their kin relationship and employment status. Spousal caregivers devote large amounts of time to caregiving, and husbands spend no less time than wives. Most caregivers receive little assistance from other family members and friends, but husbands receive more than others. Employed spouses receive more paid help than those without jobs, but employment does not affect the amount of paid help received by adult daughters."
-How can surgical interventions help manage epilepsy in patients with brain tumors?,Epilepsy and brain tumors: implications for treatment. Primary intraparenchymal tumors of the brain are important etiologic factors in partial or focal epilepsy. Indolent low-grade gliomas may be associated with a long-standing seizure disorder refractory to medical treatment. Surgical resection of the neoplasm and the epileptogenic area may render patients seizure-free. Removal of the tumor alone may also be associated with an excellent survival rate and surgical outcome. Conventional neurosurgical procedures are restricted in patients with tumors that are deep-seated lesions or involve functional cerebral cortex. Computer-assisted stereotactic surgical procedures have been developed for biopsy and resection of intra-axial brain-mass lesions. Stereotactic tumor resection may allow pathological determination of intracranial lesions and produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.
-What is labyrinthitis ossificans and how does it potentially impact cochlear implantation?,"Labyrinthitis ossificans: histopathologic consideration for cochlear implantation. Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased."
-What health risks can welding pose to workers according to the given context?,Fume fever and reactive airways dysfunction syndrome in a welder. I have reported a case of fume fever and concurrent reactive airways dysfunction syndrome (RADS) after welding. The RADS should be added to the list of potential hazards associated with welding.
-What are the key immunohistochemical findings in carcinosarcomas of the uterus and ovary?,"Carcinoma (malignant mixed mullerian [mesodermal] tumor) of the uterus and ovary. Correlation of clinical, pathologic, and immunohistochemical features in 29 cases. We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed mullerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases."
-How does Borrelia burgdorferi stimulate glioma cells to secrete interleukin-6 in the context of neuroborreliosis?,"Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6. Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors."
-What percentage of eyes maintained visual acuity at 20/60 or better after cataract extraction following brachytherapy for choroidal malignant melanoma?,"Cataract extraction after brachytherapy for malignant melanoma of the choroid. Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid."
-What unique finding was observed in the cardiac examination of a 29-year-old man and his 4-year-old son?,"Familial aneurysms of the interventricular septum. Congenital aneurysms of the interventricular septum were found in a 29 year old man and his four year old son. Both were symptom free. In both, M mode and cross sectional echocardiography showed an aneurysm in the mid-muscular trabecular portion of the ventricular septum with considerable paradoxical motion of the aneurysmal segment. Otherwise the chamber dimensions, intracardiac structures, and cardiac function were normal for age. Congenital aneurysm of the interventricular septum is rare and these familial cases may be unique."
-What was the mean increase in graft diameter observed in the ultrasound measurements compared to the manufacturer's recorded box size?,"Clinical significance of aortic graft dilation. To determine if there is a relationship between aortic graft dilation and graft complications, 443 serial ultrasound studies performed on 106 patients were analyzed. Of 443 studies, 243 were done retrospectively on 59 patients from 3 to 144 months (mean, 38 months) after graft implantation. Forty-seven additional patients were studied prospectively, with direct measurement of external graft diameter after aortic clamp release. Subsequent ultrasound examinations at 3, 6, 9, and 12 months and then annually (n = 200) were routinely performed. Mean follow-up was 12 months (range, 3 to 48). Knitted double velour Dacron prostheses were used in all cases reported in this study. This cohort was culled from our ongoing graft surveillance program, which includes grafts of other materials and manufacturers. Comparison of the manufacturer's recorded box size with follow-up ultrasound measurements in all cases demonstrated a mean increase in graft diameter of 3.7 mm (23%). Little dilation occurred after 1 year. In 47 patients with direct graft diameter measurements taken after declamping, an immediate mean increase of 1.7 mm (11%) was noted. Dilation was not related to surgical indication (aneurysm vs occlusive disease) or hypertension. Analysis of the 10% segment of the series with the greatest dilation (mean, 39%) did not demonstrate a predilection for graft complications. No significant dilation was noted in the single cases encountered of femoral and iliac anastomotic aneurysms and perigraft seroma. Although dilation of knitted Dacron grafts is to be anticipated, no association between graft dilation and graft complications was found in this series."
-How can quantitative motor performance tests help in early detection of Parkinson's disease?,"Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are ""at risk for"" Parkinson's disease and other related disorders."
-What were the independent prognostic factors identified in the multivariate analysis of primary sclerosing cholangitis patients?,"Natural history and prognostic variables in primary sclerosing cholangitis. The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation."
-What were the two major psychological insights about orthognathic surgery patients that emerged from this research?,"Psychological aspects of orthognathic surgery: how people respond to facial change. This study was undertaken to explore the motivations and problems shared by adult orthognathic surgical patients over the age of 25. Objective findings included demographic information and reasons for seeking surgery. The majority of 65 respondents cited functional problems as their primary reason for seeking treatment. Eighty-nine percent were pleased with esthetic changes, and 83% responded that the functional problem had been corrected. For most, the greatest discomfort related to the surgery was the postoperative intensive care unit. Two of the most common side effects of the surgery were the loss of sensation in the lips and chin area and a short period of depression. Women had depression more often than men but were more enthusiastic about the final results of the procedure. Two major areas of interest to surgeons emerged from the research. First, although women have functional problems, the majority seem to have a desire for cosmetic improvement. Having a functional problem seemed to provide the psychological permission necessary to spend the time and money for a cosmetic change. The second point focused on the need for good communication between surgeon and patient. The patients who were more positive toward the procedure and more satisfied with the results were those who were better informed and who thought they had a good system of communication with the orthodontist, surgeon, and their respective staffs."
-How does partial ischaemia affect free-radical damage compared to total ischaemia in rabbit skin flaps?,"Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals. 1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-"How does the volume of low-grade, latent prostate cancer tissue relate to the incidence of high-grade clinical cancer?","Low-grade, latent prostate cancer volume: predictor of clinical cancer incidence? We hypothesize that each cell in low-grade (Gleason grade 1-3) prostate cancer tissue is at risk of transformation into a cell which produces a high-grade (Gleason grade 4-5) clinical cancer after a short period of growth. As a consequence, the volume of low-grade, latent cancer tissue in the prostate glands of men at any age determines their incidence rate for high-grade, clinical cancer a few years later. Autopsy and incidence data for both white men and black men support this conclusion, with a tumor growth period of about 7 years. The transformation rate is similar for black men and for white men, about 0.024 high-grade cancers per year per cm3 of low-grade, latent cancer volume. Our hypothesis explains the infrequent occurrence of clinical cancer despite the high prevalence of latent cancer, the steep rise of clinical cancer incidence with age despite the slow rise of latent cancer prevalence with age, and the disparities in clinical cancer incidence among some populations despite their similar latent cancer prevalence. This hypothesis suggests that low-grade cancer volume is a critical determinant of clinical cancer risk."
-"What were the electrophysiologic effects of UK-68,798 in a canine model of sudden coronary death?","The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent. The electrophysiologic and antifibrillatory properties of UK-68,798 were studied in vivo in a conscious canine model of sudden coronary death. Electrophysiologic testing was performed on conscious male mongrel dogs (14.5-21.5 kg) 3 to 5 days after surgical induction of an anterior myocardial infarction by occlusion (2 h)-reperfusion of the left anterior descending coronary artery. Compared to saline-treated control animals, UK-68,798 at a dose of 0.9 mg/kg i.v. did not (P = .083) suppress the induction of ventricular tachycardia by programmed electrical stimulation. Six of 12 UK-68,798-treated dogs remained inducible, whereas 10 of 12 vehicle-treated dogs responded to electrical induction of arrhythmia. When compared to predrug inducibility, UK-68,798 significantly (P = .007) reduced the incidence of programmed electrical stimulation-induced ventricular tachycardia. In five of the six dogs inducible after UK-68,798 administration, the cycle length of the induced ventricular tachycardia was prolonged (P = .007) compared to the predrug cycle length. Heart rate, PR interval and QRS duration were not affected by UK-68,798 administration. The rate-corrected QT interval was prolonged (P less than .05) by UK-68,798. The ventricular effective refractory period was increased by UK-68,798 (158 +/- 7 msec, predrug vs. 185 +/- 7 msec, postdrug). Subsequent to programmed electrical stimulation, a 150 microA anodal current was applied to the luminal surface of the left circumflex coronary artery to induce transient episodes of posterolateral ischemia in response to electrolytic injury of the vessel wall."
-What is the significance of the leucocyte alkaline phosphatase (LAP) score in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS)?,"Use of leucocyte alkaline phosphatase (LAP) score in differentiating malignant from benign paraproteinaemias. The leucocyte alkaline phosphatase (LAP) score of peripheral blood neutrophils was examined in 20 patients with multiple myeloma and compared with the score in 18 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean (95% confidence limit) LAP score in those with multiple myeloma was 186 (169-218) compared with 92 (64-120) in the MGUS group. In the multiple myeloma group all but one patient had a high LAP score, irrespective of disease. No cause for raised LAP, such as infection, was present in any of the patients with multiple myeloma. In the MGUS group six patients had a raised LAP score; in two of them another cause for such a rise was present (autoimmune haemolytic anaemia and primary thrombocythaemia). In neither group did the LAP score correlate with duration of the disease, bone marrow plasma cell count, paraprotein concentration, haemoglobin, total white cell or neutrophil count. It is concluded that a normal LAP count in patients with paraproteinaemia suggests a benign condition, but a raised count does not indicate a malignant condition."
-How do ATP-dependent K+ channels modulate pulmonary vascular responses during severe hypoxia in ferret lungs?,"ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 less than or equal to 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs [( glucose] less than 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14 +/- 0.4 mM had the same effect. As a result, initial vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCl, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events."
-What is the cost-effectiveness of periodic colonoscopic surveillance after the removal of an adenomatous colon polyp?,"Colonoscopic surveillance after polypectomy: considerations of cost effectiveness. OBJECTIVE: To assess the cost effectiveness of the current recommendation that persons who have had an adenomatous colon polyp removed have periodic colonoscopic surveillance at fixed and regular intervals. DESIGN: Cost-effectiveness analysis using data from the medical literature in a simulation model to estimate the costs of and the risk for perforation associated with periodic colonoscopic surveillance for a 50-year-old man followed for 30 years. MAIN RESULTS: A program of colonoscopy every 3 years would incur cumulatively a 1.4% risk for colon perforation, a 0.11% risk for perforation-related death, and direct physician costs of $2071 for colonoscopy (discounted at 5%). If a 50-year-old man's cumulative remaining risk for death from cancer is 2.5% after the removal of a single small adenoma and if effectiveness of colonoscopic surveillance every 3 years is 100%, then one death from cancer could be prevented by doing 283 colonoscopies, incurring 0.6 perforations, 0.04 perforation-related deaths, and direct physician costs of $82,000. If surveillance were 50% effective and the cumulative remaining risk for death from cancer were 1.25%--a plausible scenario--1131 colonoscopies would be required to prevent one death from cancer, incurring 2.3 perforations, 0.17 perforation-related deaths, and physician costs of $331,000. CONCLUSIONS: The cost effectiveness of colonoscopic surveillance is very sensitive to estimates of the cumulative remaining risk for death from cancer after polypectomy as well as to surveillance efficacy. For persons whose remaining risk for death from cancer may be low, such as persons with a single small adenoma, recommendations for colonoscopic surveillance at fixed and regular intervals may be excessively costly."
-What was the purpose of asking donors questions about gastrointestinal symptoms during blood donation screening?,"Screening blood donors for gastrointestinal illness: a strategy to eliminate carriers of Yersinia enterocolitica. Recent reports of fatal transfusion-associated Yersinia enterocolitica sepsis prompted a study of the feasibility of adding a question to the routine donor health history as a method of reducing this risk. In three American Red Cross blood centers, 11,323 donors were asked one of two questions about gastrointestinal symptoms during their health history screenings. Affirmative responses were obtained from 0.6 or 4.0 percent of the donors, depending on how the question was asked. In one center, more than 6 percent of donors gave affirmative answers. The efficacy of asking a relatively simple question about gastrointestinal symptoms as a way of preventing Y. enterocolitica should be evaluated further, because relatively large numbers of donors may respond affirmatively. Other methods of reducing the risk of transfusion-associated Y. enterocolitica infection should be pursued."
-What were the key findings of the study comparing chorionic villus sampling and amniocentesis as prenatal genetic diagnostic procedures?,"Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis. Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital."
-How can an immunocytochemical (ICC) panel help improve the diagnostic accuracy of cytologic examination in serous effusions?,"Immunocytochemical panel for the identification of malignant cells in serous effusions. The cytologic diagnosis of malignancy in serous effusions can be challenging. An immunocytochemical (ICC) panel using commercially available antibodies (to carcinoembryonic antigen [CEA], epithelial membrane antigen [EMA], B72.3, Leu-M1, cytokeratin [CK], leukocyte common antigen [LCA], S-100 protein, and vimentin) was applied to cell blocks fixed in methyl Carnoy's solution that were from 55 consecutive pleural, peritoneal, and pericardial fluid specimens. The results were correlated with data from clinical records and routine cytologic studies. Final cytologic diagnoses included 26 of adenocarcinoma and 1 of mesothelioma. The remaining 28 cases were considered to be benign (reactive) proliferations. EMA, CEA, B72.3, and Leu-M1 were present in 96%, 77%, 58%, and 42% of adenocarcinomas, respectively. These determinants were absent in the mesothelioma and the reactive effusions, although anti-CEA yielded strong background staining of inflammatory cells. The CK markers identified malignant cells in 93% of cases, but consistently stained mesothelial cells as well. Antivimentin strongly labeled mesothelial cells in all cases, with weak to absent staining of malignant cells. In 3 of 26 carcinoma cases (12%), the ICC panel identified malignant cells that were not recognized initially on routine cytologic examination. In 1 of 26 cases (4%), the panel was falsely negative. Use of this approach can improve the diagnostic accuracy of cytologic examination of serous fluids. The ICC panel is especially helpful when atypical mesothelial proliferation is present, or in cases that are clinically suspect for malignancy, but cytologically negative because there are only a few malignant cells, or those that are cytologically bland."
-What was the cause of the patient's failure to regain consciousness after a total hip replacement surgery?,"Failure to awaken after general anaesthesia secondary to paradoxical venous embolus. A patient is presented who failed to regain consciousness after an apparently uneventful nine-hour revision of a total hip replacement. There were no clinically important haemodynamic changes during the operation, and oxygen saturation, capnography and acid base balance were normal throughout. Postop CT of the head showed a large left MCA infarct with midline shift. At autopsy, the patient was found to have a previously unsuspected patent foramen ovale, and a venous embolus in the left internal carotid artery, which probably had originated from the periprostatic venous plexus with a large infarct in the distribution of the left anterior and middle cerebral arteries. The authors conclude that massive paradoxical venous emboli can occur during surgery with minimal haemodynamic changes."
-How did the healing rates of gastric ulcers compare between enprostil and ranitidine in this clinical study?,"Gastric ulcer healing: a comparison of enprostil versus ranitidine. Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers."
-How does the Fos-Jun protein complex potentially suppress osteocalcin gene transcription during osteoblast proliferation?,"Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the proliferation period of osteoblast phenotype development. We present evidence that AP-1 (HeLa cell-activating protein 1) sites residing within two promoter elements of the osteocalcin gene bind the Fos-Jun protein complex: the osteocalcin box (OC box; nucleotides -99 to -76), which contains a CCAAT motif as a central element and influences tissue-specific basal levels of osteocalcin gene transcription, and the vitamin D-responsive element (VDRE; nucleotides -462 to -440), which mediates enhancement of osteocalcin gene transcription. Gel electrophoretic mobility-shift analysis demonstrated high AP-1 binding activity in proliferating osteoblasts and dramatic changes in this activity after the down-regulation of proliferation and the initiation of extracellular-matrix mineralization in primary cultures of normal diploid osteoblasts. Methylation interference analysis established at single nucleotide resolution that purified recombinant Fos and Jun proteins bind in a sequence-specific manner to the AP-1 sites within the VDRE and OC box. Similarly, an AP-1 motif within a putative VDRE of the alkaline phosphatase gene, which is also expressed after the completion of proliferation, binds the Fos-Jun complex. These results support a model in which coordinate occupancy of the AP-1 sites in the VDRE and OC box in proliferating osteoblasts may suppress both basal level and vitamin D-enhanced osteocalcin gene transcription as well as transcription of other genes associated with osteoblast differentiation--a phenomenon we describe as phenotype suppression. This model is further supported by binding of the Fos-Jun complex at an AP-1 site in the type alpha I collagen promoter that is contiguous with, but not overlapping, the VDRE. Such a sequence organization in the collagen VDRE motif is compatible with vitamin D modulation of collagen but not with osteocalcin and alkaline phosphatase expression in proliferating osteoblasts."
-What potential therapeutic effect of pentoxifylline was observed in patients being treated for claudication of the lower extremities?,Pentoxifylline in the treatment of vascular impotence--case reports. Vascular impotence is a common medical problem for which available therapies are limited. Three impotent patients observed in the authors' practice who were receiving pentoxifylline for treatment of claudication of the lower extremities spontaneously reported improved sexual function. A controlled trial of pentoxifylline for vascular impotence may be warranted.
-How can gonadotropin-releasing hormone analogs help improve ovulation and pregnancy rates in patients with polycystic ovary syndrome?,"Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs. Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog."
-What are the common pathologic features shared by ANCA-associated vasculitides?,"Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. Antineutrophil cytoplasmic autoantibodies (ANCA) are a useful diagnostic serologic marker for the most common forms of necrotizing vasculitis, provide a means of categorizing vasculitides so that diagnostically useful shared pathologic and clinical characteristics can be recognized, and offer insight into the pathogenesis of previously idiopathic diseases. ANCA-associated vasculitides can be categorized into a number of distinctive clinicopathologic categories, eg, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary renal syndrome, microscopic polyarteritis nodosa, leukocytoclastic angiitis, and necrotizing and crescentic glomerulonephritis. At least the latter four syndromes can also be caused by other ANCA-negative immunopathogenic mechanisms, eg, immune complex deposition. Therefore, thorough diagnostic classification requires both an assessment of clinicopathologic category, as well as an assessment of immunopathologic category. Although different ANCA-associated vasculitic syndromes have distinctive clinical and pathologic features, all ANCA-associated vasculitides share a number of common pathologic features, ie, focal distribution, necrosis, and neutrophil infiltration. ANCA assays have very good sensitivity and specificity for ANCA-associated diseases, but the prevalence of these diseases in the patient population being analyzed must be taken into consideration when determining the predictive value of a test result. As with all serologic tests, ANCA results must be integrated with other clinical and pathologic data in order to reach the most accurate diagnostic conclusion."
-How does chronic xerostomia affect esophageal acid exposure and potential injury?,"Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency."
-What immunohistochemical markers were used to distinguish sarcomatoid liver carcinomas from true sarcomas?,"An immunohistochemical study of sarcomatoid liver carcinomas. Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver."
-What were the main causes of death in patients who underwent emergency surgery for colorectal cancer?,"Outcome after emergency surgery for cancer of the large intestine. The data for 77 patients with colorectal cancer who underwent emergency surgery for acute intestinal obstruction (57 patients) or perforation (20 patients) within 24 h of admission were evaluated. The patients were older and had more advanced disease than patients undergoing elective surgery for colorectal cancer. Emergency surgery for carcinoma of the right colon consisted of primary resection in 95 per cent of cases and was followed by a 28 per cent mortality rate. Perforated tumours of the left colon and rectum were managed by primary resection in 82 per cent of cases with a 22 per cent mortality rate. In contrast, obstructing tumours of the left colon and rectum were treated by primary resection in 38 per cent of cases with a 6 per cent mortality rate, and by primary decompression in 62 per cent of cases with a 25 per cent mortality rate. The overall postoperative mortality rate was 23 per cent and increased with advanced tumour disease, perforation and peritonitis. Cardiac decompensation and intraabdominal sepsis were the major causes of death. Although the long-term survival rate following emergency surgery was worse than after elective surgery, improvements in outcome should be achieved by better management of the initial emergency situation."
-What are the key characteristics of pain perception and coping strategies in patients with noncardiac chest pain (NCCP)?,"Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain."
-What are the key diagnostic features of superficial thrombophlebitis?,"Acute venous thrombosis. Therapeutic choices for superficial and deep veins. Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence."
-What were the key findings of the decision-analysis study on prophylactic intravenous immune globulin in chronic lymphocytic leukemia patients?,"Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia [see comment] BACKGROUND. A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS. We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality-adjusted life expectancy. RESULTS. Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS. Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective."
-What was the key finding regarding pain perception during gastric distension in patients with chronic idiopathic dyspepsia?,"Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research."
-What percentage of lower respiratory tract infections in Thai children were associated with viral infections and Chlamydia trachomatis during the study period?,"A study of nonbacterial agents of acute lower respiratory tract infection in Thai children. From January 1986 to December 1987, 596 children less than 5 years of age with lower respiratory tract infection (LRI)--manifested as laryngitis, croup, bronchitis, bronchiolitis, and pneumonia--were studied for evidence of infection with respiratory tract viruses Mycoplasma pneumoniae, and Chlamydia trachomatis. Of the 596 children in the study, 315 were ambulatory and 281 were hospitalized. Virologic studies included isolation and rapid diagnosis of virus from specimens of nasopharyngeal aspirate (NPA) and serologic studies of blood samples. Cultures of NPA for C. trachomatis were performed for children less than 6 months of age who had pneumonia. Of the LRI cases, 45% were associated with viral infections of the respiratory tract and 12.1% were associated with C. trachomatis. Respiratory syncytial virus (RSV) accounted for 45.2% of infections with viral agents and was associated with acute bronchitis, acute bronchiolitis, and pneumonia. Parainfluenza type 3 virus was the most common virus found in conjunction with laryngitis and croup. The incidence of infections due to RSV peaked in July and August, while that of infections due to parainfluenza viruses peaked in February and March; influenza viruses and adenoviruses were isolated throughout the year."
-What are the key considerations for physicians when managing febrile seizures and counseling parents?,Febrile seizure. Caring for patients--and their parents. Management of febrile seizure involves diagnosis and treatment of the underlying cause and assessment of risk factors for recurrence. What should physicians tell anxious parents about this frightening occurrence? Is prophylaxis with anticonvulsant agents appropriate? The authors address these questions and discuss the changing approach to management of febrile seizure.
-What was the miss-rate of large colorectal polyps found in this prospective blinded trial of tandem colonoscopy?,Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps. We prospectively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring tandem colonoscopy. Sixty-three lesions greater than or equal to 1 cm in size were discovered and none were missed. Confidence intervals of 95% are a miss-rate of 0 to 4.6%. We conclude that less than 5% of large colorectal polyps are missed during the index colonoscopic examination in a well-prepared colon.
-What was the outcome of the six-year-old boy with symptomatic cerebral swelling complicating diabetic ketoacidosis?,"Symptomatic cerebral swelling complicating diabetic ketoacidosis documented by intraventricular pressure monitoring: survival without neurologic sequela. A six-year-old boy developed symptomatic cerebral swelling four hours after the initiation of treatment for newly diagnosed diabetes mellitus complicated by ketoacidosis. Ventriculostomy documented intracranial pressure over a two-day period. Increased intracranial pressure unresponsive to controlled hyperventilation and sedation was treated by administering a diuretic and by drainage via a ventriculostomy. Intracranial pressure monitoring was a useful adjunct in management of this rare, but often lethal, complication of diabetes mellitus. One year later, both school performance and the results of a neurologic examination were normal."
-What were the independent predictors of heart failure identified in the study using multivariant stepwise logistic regression analysis?,"Predicting left heart failure after a myocardial infarction: a preliminary study of the value of echocardiographic measures of left ventricular filling and wall motion. Heart failure occurs from both systolic and diastolic dysfunction. To determine whether simple Doppler echocardiographic measures of left ventricular filling could improve upon the ability of systolic function to predict heart failure after infarction, patients with acute myocardial infarction were studied within the first 36 hours by Doppler and two-dimensional echocardiography. Forty-eight patients who did not have heart failure before the Doppler echocardiographic study and who did not have myocardial revascularization, moderate or severe mitral regurgitation, or other complications during recovery were monitored for 6 months or to the onset of heart failure (n = 10). The univariate predictors of heart failure were age (p less than 0.05), anterior infarction (p less than 0.05), early diastolic peak filling velocity (p = 0.05), filling velocity with atrial systole (p less than 0.05), the ratio of these velocities (p less than 0.001), the percentage of filling with atrial systole (p less than 0.001), and the wall motion score index (p less than 0.001). However, the only independent predictors of heart failure by use of multivariant stepwise logistic regression analysis were the wall motion score index (p less than 0.05) and either the ratio of early and late peak filling velocities (p less than 0.001) or the percentage of filling with atrial systole (p less than 0.001). The combined use of a measure of systolic function and measures of the relative contribution of atrial systole to ventricular filling were useful predictors in identifying patients likely to develop subsequent heart failure after myocardial infarction."
-What were the key clinical patterns observed in paediatric urolithiasis across different stone types in this retrospective study?,"Clinical patterns of paediatric urolithiasis. A series of 270 paediatric stone patients was studied retrospectively according to the clinical pattern of urolithiasis (age and sex, stone location, stone analysis, recurrence rate) and aetiology of stone disease (infection, anatomical, metabolic or idiopathic). Infection stones occurred earliest and more commonly in males and were usually upper tract struvite calculi related to Proteus infection. Anatomical stones were most commonly associated with pelviureteric junction (PUJ) obstruction and had a high recurrence rate, despite surgical correction of obstruction. Idiopathic stones most resembled those found in adult urolithiasis by virtue of occurring latest, being sited in the ureter more often and being more frequently composed of calcium oxalate. Metabolic stones were most frequently calcium phosphate or cystine and virtually all were renal. They comprised the smallest group but had the highest recurrence rate."
-How did the response to desflurane differ between normal and malignant hyperthermia-susceptible swine in the study?,"Desflurane is a trigger of malignant hyperthermia in susceptible swine. Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility."
-How does dipyridamole improve the specificity of thallium-201 single-photon emission computed tomography in detecting coronary artery disease in patients with left bundle branch block?,"Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole. Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB."
-"How are depression, chronic fatigue, and chronic pain interconnected in terms of their psychological and neurobiological factors?","Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery."
-What prognostic factors were found to be associated with a higher recurrence rate in papillary carcinoma of the thyroid in this retrospective study?,"Prognostic factors in papillary carcinoma of the thyroid. In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hurthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men."
-How does local thrombin synthesis contribute to platelet recruitment and thrombus stabilization in heparinized blood?,"Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization."
-How does the p53 gene mutation correlate with the progression of chronic myelocytic leukemia (CML) in this patient's case study?,Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
-What is the relationship between silent myocardial ischemia and autonomic dysfunction in diabetic patients?,"Detection of silent myocardial ischemia in diabetes mellitus. The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as greater than or equal to 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as greater than or equal to 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia."
-What was the purpose of the study comparing the use of dexapolyspectran drops in one ear versus the control ear after tympanostomy tube insertion?,"Use of prophylactic otic drops after tympanostomy tube insertion. In a 1-year prospective study, 60 patients with chronic serous otitis media underwent bilateral tympanocentesis with tube insertion. The right ear was treated with dexapolyspectran (a solution consisting of polymyxin B sulfate, neomycin sulfate, sulfonamide, and hydrocortisone) intraoperatively and for 72 hours afterward, and the left ear served as the control. All patients were followed up at weekly intervals for the first month. Five (8.3%) out of 60 experimental ears had purulent otorrhea within the first 14 days after surgery, compared with eight (13.3%) out of 60 control ears. Statistical analysis showed no difference between the two groups."
-What was the treatment approach for the patient with pancreatic islet cell carcinoma and how long did the remission last?,"Pancreatic islet cell carcinoma with hypercalcemia: complete remission 5 years after surgical excision and chemotherapy. A 45-yr-old man who presented with hypercalcemia was found to have an abdominal mass that was a pancreatic islet cell carcinoma. Although clinical features were suggestive of primary hyperparathyroidism, his parathyroid hormone level was not elevated. The patient underwent a radical resection of the pancreatic neoplasm which was situated in the tail of the gland. After surgery, the serum calcium fell within the normal range, suggesting that the tumor was responsible for production of a parathyroid hormone-like substance. Because of malignant histologic features of the lesion, a chemotherapeutic regimen including 5-fluorouracil and streptozotocin was indicated. Five years later, the tumor has remained in total remission."
-What specific mitochondrial DNA mutation was found to be associated with myoclonus epilepsy and ragged-red fibers (MERRF) in this study?,"Rapid detection of the A----G(8344) mutation of mtDNA in Italian families with myoclonus epilepsy and ragged-red fibers (MERRF). We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy (Shoffner et al. 1990). We confirmed this association in five of seven Italian MERRF pedigrees. The mutation was specific for the MERRF trait, because it was never found in mtDNA of non-MERRF individuals, including 14 normal and 110 diseased controls. Our study corroborates the idea that the A----G(8344) mutation is the most frequent and widespread genetic cause of MERRF."
-What is the relationship between arachidonic acid metabolism and brain edema in different types of brain pathologies?,"""Ex vivo"" release of eicosanoid from human brain tissue: its relevance in the development of brain edema. The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The ""ex vivo"" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05)."
-How does pentoxifylline affect intestinal microvascular blood flow during resuscitation from hemorrhagic shock?,"Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock. We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow."
-What was the primary aim of the study investigating the antihypertensive effects of ketanserin?,"The acute and chronic antihypertensive effects of ketanserin cannot be explained by blockade of vascular serotonin, type 2, receptors or alpha 1-adrenergic receptors. The mechanism underlying the antihypertensive effect of acute and chronic administration of ketanserin was investigated in eight hypertensive patients. Intrabrachial artery infusions of serotonin and the selective alpha 1-adrenergic receptor agonist methoxamine were given before and 1 hour after a single oral dose of 20 mg ketanserin and after 4 weeks of treatment with 20 to 40 mg twice daily. Blood pressure was reduced by ketanserin both after the initial dose (p less than 0.01) and after 4 weeks of treatment (p less than 0.01). During placebo, serotonin, 1 ng/kg/min, increased forearm blood flow by 51% +/- 9% (p less than 0.01), whereas the highest dose induced a decrease in flow (-33% +/- 6%; p less than 0.01). Methoxamine elicited a vasoconstriction (p less than 0.001). These effects of serotonin and methoxamine were not influenced by either the initial dose of ketanserin or after 4 weeks of treatment. It is concluded that serotonin cannot be considered a general endogenous pressor agent in these patients. The antihypertensive effects of ketanserin cannot be attributed to either vascular alpha 1-receptor or serotonin, type 2, receptor blockade."
-What was the survival rate of patients with paracetamol overdose who underwent liver transplantation in this study?,"Liver transplantation after paracetamol overdose. OBJECTIVE--To evaluate the role of liver transplantation after paracetamol overdose. DESIGN--Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING--Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES--Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS--30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION--Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol."
-What medical condition did the 31-year-old alcoholic woman suffer from and how was it treated?,The perils of Pauline: visual loss in a tippler [clinical conference] A 31-year-old alcoholic woman who smoked had subacute visual loss. She was treated for tobacco-alcohol amblyopia with subsequent improvement in vision.
-Does delaying antibiotic therapy by 48 hours affect the recurrence rate of group A beta-hemolytic streptococcal (GABHS) pharyngitis?,"Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate."
-What are the endocrine and reproductive effects observed in patients after total body irradiation for haematological malignancy?,"Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. The endocrine and reproductive sequelae of total body irradiation for haematological malignancy have been studied in 21 patients (11 male) who were treated with 10 Gy in five fractions or 12 or 13.2 Gy in six fractions over 3 days. Eighteen patients (eight male) aged 16-49 years underwent dynamic tests of the hypothalamic-pituitary axis with insulin hypoglycaemia, thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone stimulation and basal measurement of prolactin, sex steroids and thyroid hormones. Growth hormone responses (mean peak 64 +/- 36 mU/l, range 21-146 mU/l) and cortisol responses (mean peak 831 +/- 122 nmol/l, range 626-1105 nmol/l) were all within the normal range. Two patients had minimally elevated serum prolactin levels (445 and 588 mU/l, normal less than 350 mU/l). Serum thyroxine levels (57-133 nmol/l) were normal but six patients had elevated basal thyrotrophin (TSH) levels (6-9 mU/l) and seven had an exaggerated TSH response to thyrotrophin releasing hormone, indicating radiation-induced damage to the thyroid. Amenorrhea developed within 3 months of irradiation in all females and oestradiol levels were low, at 37-108 pmol/l (mean 58 +/- 22 pmol/l). Severe oligospermia or azoospermia was noted in men tested 5-70 months after irradiation and testicular volume was below the normal adult range in five of seven men assessed. Serum testosterone levels (12.4-35 nmol/l) were normal. Gonadotrophin-releasing hormone-stimulated gonadotrophin levels were elevated in all patients. However, two men have fathered two children each; one has refused semen analysis, but the other has a sperm count of 7 x 10(6)/ml (60 per cent motile, 20 per cent abnormal forms) 70 months after irradiation. When given by the above fractionated regimens, the endocrine sequelae of total body irradiation are limited to gonadal failure requiring oestrogen replacement in women and severe impairment of fertility in men. Subclinical thyroid dysfunction has been seen in 39 per cent of patients there is no evidence of direct damage to the hypothalamic pituitary axis."
-What is the key treatment approach for the patient with steroid-responsive tubular aggregate myopathy described in this case report?,"Steroid-responsive tubular aggregate myopathy. We report a man with an acute myalgia/cramp syndrome and tubular aggregates on his muscle biopsy. He was placed on prednisone and was found to be exquisitely sensitive to the drug, with changes of only 5 mg precipitating recurrence of symptoms. He was eventually tapered off all steroids, without symptoms, and repeat biopsy showed no tubular aggregates. We recommend similar patients be given a trial of high-dose steroids."
-What did the study find about the relationship between racial differences and the incidence of hypertensive end-stage renal disease (HT-ESRD)?,"Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease? Prospectively collected data on the incidence of treated hypertensive end-stage renal disease (HT-ESRD) were analyzed to investigate whether the higher rate of HT-ESRD in blacks compared with whites is due to differences in putative ESRD risk factors. The overall age-adjusted relative risks of HT-ESRD for black compared with white residents in the Maryland Regional ESRD Registry (Network 31) Catchment Area were 7.4 (95% confidence interval, 5.9 to 9.4) and 9.9 (95% confidence interval, 7.4 to 13.1) for men and women, respectively. In a population level analysis, race-specific HT-ESRD incidence rates in the black and white populations of 13 regions in Network 31 were related to the prevalence of putative ESRD risk factors in those populations. The latter were estimated from the 1981-1982 Maryland Statewide Household Hypertension Survey. Black populations had a 5.6-fold (95% confidence interval, 3.9 to 8.1) higher unadjusted incidence of HT-ESRD than white populations. The HT-ESRD incidence in a population was also directly related to that population's prevalence of hypertension, severe hypertension, and diabetes mellitus and inversely related to measures of socioeconomic status and mean age at diagnosis of hypertension. When adjusted simultaneously for age, prevalence of hypertension, severe hypertension, diabetes, and level of education, the risk of HT-ESRD was still 4.5 (95% confidence interval, 3.2 to 6.2) times higher for black compared with white populations. Our findings failed to support the hypothesis that race-related differences in the prevalence, severity, or age at onset of hypertension, in the prevalence of diabetes or in socioeconomic status, explain the well-recognized black-white differences in the HT-ESRD incidence."
-What oral lesions were found to be more prevalent in HIV-infected homosexual and bisexual men compared to HIV-negative subjects?,"The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts. To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status."
-How does streptokinase treatment affect chest pain duration in patients with acute myocardial infarction?,"The effect of streptokinase on chest pain in acute myocardial infarction. Treatment with intravenous streptokinase is known to restore blood flow to the ischaemic myocardium in patients with acute myocardial infarction. However, little is known about its effect on chest pain. In a retrospective cohort study, 76 patients treated with streptokinase were compared to 76 patients not treated with streptokinase. All patients had acute myocardial infarction and less than 6 h of cardiac symptoms. Patients treated with streptokinase had a significantly lower need for nicomorphine (median 20 mg) than patients not treated with streptokinase (median 41 mg). Correspondingly, the median duration (3.5 h) of pain was reduced significantly in patients treated with streptokinase compared to patients not treated (24 h). We conclude that intravenous streptokinase given in the acute phase of myocardial infarction is effective in reducing the duration of cardiac chest pain."
-What was the disease-free survival rate for patients with Stage I and II Hodgkin's disease treated with subtotal nodal irradiation in this study?,"Cure of early-stage Hodgkin's disease with subtotal nodal irradiation. Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure."
-How does prolonged hemorrhagic shock affect the regeneration of plasma coagulant masses in rabbits?,"Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit. BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration."
-What specific genetic abnormalities have been identified as potentially important in the progression from normal to malignant colonic mucosa?,"Genetics of colon cancer. Strikingly rapid advances in the identification of genetic events that are important in colonic carcinogenesis have been made in the past several years. Specific inherited (adenomatous polyposis coli gene) and acquired (ras gene point mutations; c-myc gene amplification; allelic deletion at specific sites on chromosomes 5, 17, and 18) genetic abnormalities appear to be capable of mediating steps in the progression from normal to malignant colonic mucosa. Understanding these genetic factors and how they influence cellular function will have a profound effect on medical practice. High-risk populations will be (and are being) identified by genetic markers, thus allowing prevention and screening to be more precisely targeted to the population at risk; intervention strategies will be designed on the basis of the known cellular defects of neoplastic colonic mucosa; and new molecular preventive and therapeutic approaches can be developed."
-What rare intrathoracic complications can occur in acute pancreatitis according to the given context?,Rare intrathoracic complications in acute pancreatitis. Ascites and pleural effusions may complicate pancreatitis but pericarditis with pericardial effusion and tamponade is rare and necrosis of mediastinal fat has not been described before. All these complications occurred in the case reported here.
-How does the expression of TNF receptors on neoplastic B-CLL cells change when cultured in vitro compared to their state in vivo?,"Receptors for tumor necrosis factor on neoplastic B cells from chronic lymphocytic leukemia are expressed in vitro but not in vivo. Recombinant tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces proliferation of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms involved in regulating TNF responsiveness, we have examined TNF receptor expression on neoplastic B-CLL cells. We have demonstrated that freshly isolated neoplastic B cells from patients with CLL did not express TNF receptors. After 1 day of incubation in culture medium, TNF receptors were detectable in the range of 540 to 1,500/cell. Kinetic experiments revealed that receptor expression was half-maximal after 3 hours of culturing and required de novo protein synthesis. The Scatchard plots of TNF-alpha binding indicated a single set of high-affinity TNF receptors with a dissociation constant of 70 pmol/L. TNF receptor expression in vitro was found in all examined cases. All cytokines tested, with the exception of IL-2, did not influence the expression of TNF receptors. The TNF receptor expression is enhanced in B-CLL cells cultured in the presence of interleukin-2 when compared with the receptor expression of cells cultured in medium alone. Our data suggest that neoplastic B-CLL cells in patients with stable disease do not express TNF receptors in vivo and that an unknown mechanism suppressing TNF receptor expression in vivo may play a role in growth regulation of neoplastic B cells."
-What were the initial surgical techniques used for patients before balloon angioplasty in this study?,"Balloon angioplasty for recurrent coarctation of aorta. Immediate and long-term results BACKGROUND. As angioplasty techniques have been refined and larger low-profile balloons developed, a nonsurgical approach to recoarctation has become available. Several reports have documented both the efficacy and safety of this procedure. However, there are little data available on the long-term follow-up of these patients. This report details the initial results and long-term evaluation of both the relief of obstruction and the presence of hypertension after balloon angioplasty for recurrent coarctation. METHODS AND RESULTS. Balloon angioplasty for recurrent coarctation of the aorta was performed 29 times in 26 patients at a median age of 4 years and 9 months (range, 4 months to 29 years), with eight patients less than 1 year old. Initial surgical techniques were end-to-end anastomosis in 11 patients, subclavian flap aortoplasty in 11 patients, and patch aortoplasty in four patients. Angioplasty was performed at a median interval of 2 years and 7 months (range, 4 months to 23 years) after surgery. Mean peak systolic pressure difference across the coarctation decreased from 40.0 +/- 16.8 to 10.3 +/- 9.5 mm Hg (p less than 0.05) after the initial angioplasty, and mean diameter of the aortic lumen at the coarctation site increased from 5.8 +/- 3.5 to 9.0 +/- 4.3 mm (p less than 0.05). There was no mortality, and only one patient developed an aneurysm (4%). Three patients underwent repeat angioplasty for a pressure difference of more than 20 mm Hg. Long-term follow-up is available on 24 of 26 patients with a mean follow-up of 42 +/- 24 months (range, 12-88 months). Mean peak systolic pressure difference across the area of coarctation decreased from 40.3 +/- 17.4 before angioplasty to 8.5 +/- 8.3 mm Hg after final angioplasty (p less than 0.05) and 7.5 +/- 7.5 mm Hg at follow-up. Mean peak systolic blood pressure in the upper extremities decreased from 133.1 +/- 14.9 before angioplasty to 111.1 +/- 14.1 mm Hg at long-term follow-up (p less than 0.05). CONCLUSIONS. Balloon angioplasty should be considered the treatment of choice for relief of recurrent aortic coarctation."
-What is the relationship between syringomyelia and congenital intraspinal lipoma in this case study?,Syringomyelia secondary to congenital intraspinal lipoma. Preoperative evaluation using serial magnetic resonance imaging was performed on an infant with lumbosacral lipoma. Syrinx formation arising just above the lipoma was observed in conjunction with rapid growth of the lipoma. Definite shrinkage of syringomyelia was obtained after radical excision of the lipoma. The syrinx formation was possibly caused by compression from the extramedullary lipoma.
-How does persistent measles virus infection affect endothelin 1 signaling in C6 rat glioma cells?,"Loss of the endothelin signal pathway in C6 rat glioma cells persistently infected with measles virus. Endothelin 1 causes a strong Ca2+ signal in C6 rat glioma cells as measured by fura-2 fluorescence. This endothelin 1-induced Ca2+ signal was not observed when the cells were persistently infected with a measles virus strain of subacute sclerosing panencephalitis (SSPE, strain Lec). Binding of 125I-labeled endothelin 1 to the C6/SSPE cells was less than 5% of the binding to the C6 control cells, suggesting that the impairment in signal transduction was due to a loss of binding sites for endothelin 1. Treatment of the C6/SSPE cells with measles antiserum resulted in the loss of expression of viral proteins located in the membrane as well as inside the cells (antigenic modulation), but it restored neither the endothelin 1-induced Ca2+ rise nor the 125I-endothelin 1 binding. Cocultivation of uninfected C6 cells with C6/SSPE cells (9:1 ratio) resulting in contact-mediated transmission of measles virus showed that the 125I-endothelin 1 binding activity was gradually lost as a consequence of persistent virus infection."
-What is the incidence of stroke during pregnancy according to the study conducted at Parkland Memorial Hospital?,"Cerebrovascular accidents complicating pregnancy and the puerperium. The decreasing incidence of direct causes of maternal death over the past half century has led to a heightened awareness of nonobstetric factors responsible for maternal mortality. For example, cerebrovascular accidents are an important nonobstetric cause of maternal morbidity and mortality. During the 6.5-year period from 1984 to mid-1990, we encountered 15 women in whom pregnancy or the puerperium was complicated by an acute cerebrovascular accident. Six of these women had hemorrhagic strokes and nine had ischemic strokes. During this same time, approximately 90,000 women were delivered at Parkland Memorial Hospital, and thus the incidence of stroke was about one in 6000 pregnancies. Chronic hypertension or preeclampsia was causative in three cases of hemorrhagic stroke. It is important that 20% of the women died as a result of stroke, and of the 12 survivors, 40% have residual neurologic deficits. An aggressive work-up to define the etiology of stroke is necessary in order to implement cause-specific management, with subsequent reduction in morbidity and mortality."
-What were the key differences in clinical outcomes between patients who underwent mitral valve replacement with and without preservation of the posterior leaflet?,"Clinical results of mitral valve replacement with and without preservation of the posterior mitral valve leaflet and subvalvular apparatus. In this study we attempted to investigate the importance of posterior leaflet preservation during mitral valve replacement (MVR). One hundred and forty randomly selected patients with isolated mitral insufficiency were studied, half of whom had MVR with preservation of the posterior leaflet (Group I), whereas in the other half conventional MVR was performed, without preservation of the posterior leaflet (Group II). Within these two groups there were no in hospital deaths, but 5 patients in Group II were admitted to the hospital with congestive heart failure and 3 of them died after approximately 6 months. Long term mortality rate was 4.2% in Group II. Ejection fraction (EF) decreased postoperatively from 56% to 50% in Group I (p less than 0.05), and from 59% to 49% in Group II (p less than 0.05). Fifteen patients in each group and aged below 30 with sinus rhythm and in the first functional capacity according to the New York Heart Association classification (NYHA) were subjected to exercise study, 18 months after the operation. After exercise EF increased from 47% to 64% in Group I and decreased from 51% to 47% in Group II. These findings suggested that MVR with the preservation of the chordae tendineae can be done with a low morbidity and mortality rate in the early and late postoperative period."
-How does platelet-activating factor (PAF) contribute to complement activation and tissue injury in mice?,"Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice. We previously showed that TNF and endotoxin (LPS) synergize to activate the complement system and produce shock and bowel injury in normal mice. However, C5-deficient mice were protected from these adverse effects. In this study, we show that in mice, platelet-activating factor (PAF) antagonist prevents TNF- and LPS-induced complement activation, bowel injury, and death, indicating that PAF mediates the actions of TNF and LPS. We then examined the role of the complement system in PAF-induced shock and tissue injury. We found that 1) PAF (3 micrograms/kg) induces shock, hemoconcentration, bowel necrosis, and death in normal mice, whereas C5-deficient mice are protected from these effects. (Protection was abrogated when the dose of PAF was raised to 5 micrograms/kg.) Furthermore, when C5-deficient mice were reconstituted with normal serum, they also developed shock, bowel injury, and death in response to PAF. Thus, C5 is required for PAF to induce injury. 2) PAF activates the complement system in vivo, but not in vitro. The mechanism of complement activation by PAF is unclear. Inasmuch as PAF stimulates neutrophils to release protease that may activate the complement system, we examined the effect of neutrophil depletion on PAF-induced injury and complement activation. We found that neutrophil depletion fails to prevent PAF-induced complement activation, although PAF-induced lethality is much reduced. We conclude that PAF causes complement activation, and acts in synergy with active complement fragments to produce shock and tissue injury. Neutrophils probably do not play the pivotal role in PAF-induced complement activation."
-What was the purpose of the study on the Graseby patient-controlled analgesia system?,Evaluation of the Graseby PCAS. A clinical and laboratory study. The Graseby patient-controlled analgesia system was evaluated in the laboratory and in clinical use. The problems encountered with eight examples used to treat 510 patients are reported. Laboratory performance revealed the unit to be accurate at infusion volumes of 1 and 2 ml.
-What is the purpose of the review by the Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee?,"Occupational and industrial toxin exposures and the gastrointestinal tract. Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee. The subcommittee on Gastrointestinal Toxicology of the Patient Care Committee of the American College of Gastroenterology has reviewed potential effects of exposures to occupational and industrial hazards on the gastrointestinal tract, liver and pancreas. This review is presented to 1) share clinical data concerning gastrointestinal toxicology, 2) emphasize the paucity of available information to the practicing clinician, and 3) stimulate basic research interest in this field."
-What is the recommended initial antibiotic combination for treating necrotizing fasciitis according to the review?,Necrotizing fasciitis. Ten cases of necrotizing fasciitis are reviewed. Three patients died but only two of these deaths were due to uncontrolled septicaemia. All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice. Prompt and aggressive surgical debridement remains the cornerstone of management.
-What was the total possible loss of calcium during the preparation of paraffin blocks and slide preparation in the study of breast specimen microcalcifications?,"Breast specimen microcalcifications: radiographic validation and pathologic-radiologic correlation. A prospective analysis of specimens from location and biopsy of mammographically suspect microcalcifications in 108 patients was carried out to determine if microcalcifications were lost during histopathologic processing and the clinical relevance of such loss. Nine hundred sixty-eight paraffin blocks were prepared from 425 gross tissue slices containing calcifications identified at radiography of the specimens. Calcium was apparently lost both during preparation of the blocks (13.6%) and after slide preparation (12.6%), for a total possible loss of 26.2%. All specimens demonstrated calcification histologically. One pathology report was amended because of information obtained after recuts, but all cancers were detected on original slides whether or not calcifications were identified initially. The results indicate that, by following the suggestions offered to ensure adequate histopathologic sampling of calcification seen at mammography, most if not all of the calcification present can be detected on the original slide."
-What is the significance of the zinc finger protein gene cluster deletion in the mouse embryonic lethal mutation tw18?,A cluster of related zinc finger protein genes is deleted in the mouse embryonic lethal mutation tw18. We report that a number of related zinc finger protein genes are closely linked on mouse chromosome 17. At least four of these genes are transcribed in the 8.5-day postcoitum embryo and are deleted in the t complex early acting embryonic lethal mutation tw18. We have evidence that additional finger protein genes are located in this region. These findings demonstrate that related finger protein genes can be clustered in the murine genome and identify genes that may be considered as candidates for the tw18 mutation.
-How does regional cerebral blood flow differ between aphasic stroke patients and control subjects during a functional naming test?,"Remote cortical dysfunction in aphasic stroke patients. We studied the effect of deep-seated left hemispheric lesions on cortical blood flow in 18 right-handed aphasic stroke patients. Regional cerebral blood flow was measured at rest and during the performance of a functional naming test using the two-dimensional xenon-133 inhalation method. Compared with 10 controls, at rest the patients showed regional cortical hypoperfusion in the left frontoparietal region. In the controls, activation patterns from the rest to the test condition involved mainly the left hemisphere areas. In the patients, a lack of blood flow change was observed in several areas that were usually hypoperfused at rest. However, in patients with slight verbal expression disorders there were obvious blood flow increases in other brain regions in both hemispheres. Such cortical functional reorganization and the presence of a remote cortical dysfunction could play a role in the pathophysiology of language disorders."
-How did the researchers study the chemosensory responses of the carotid body in this in vitro preparation?,"In vitro perfused-superfused cat carotid body for physiological and pharmacological studies. An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible."
-What was the efficacy of different oral doses of ondansetron in preventing nausea and emesis in breast cancer patients receiving cyclophosphamide-doxorubicin chemotherapy?,"Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy. We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related."
-What challenges can arise when differentiating between germ cell tumors and central nervous system sarcoidosis?,"Germ cell tumors masquerading as central nervous system sarcoidosis. The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis."
-What did the researchers discover about circulating ICAM-1 isoforms in the study of healthy young volunteers?,"Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Intercellular adhesion molecule-1 (ICAM-1, CD54) is an important early marker of immune activation and response. Evidence on its role has come from immunohistological staining of tissues, since no free circulating ICAM-1 has been detected. By means of monoclonal antibodies against ICAM-1 and a sensitive chemiluminescence technique, free circulating ICAM-1 was detected in serum from sixteen healthy young volunteers. The concentrations varied among the subjects. Non-denaturing gel separation methods showed that ICAM-1 circulates in at least three isoforms, the proportions of which also varied. These findings have important implications for the investigation, diagnosis, and therapeutic monitoring of various inflammatory, neoplastic, and immune disorders."
-What makes pancreatic cancer a particularly challenging disease to treat?,"Biology of pancreatic cancer. Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer."
-How do the bile acid compositions differ between intrahepatic and extrahepatic brown pigment stones?,"Microanalysis of bile acid composition in intrahepatic calculi and its etiological significance. Brown pigment stones in the intrahepatic bile ducts were compared with those found in the extrahepatic bile ducts with special reference to the bile acids modified by bacterial intervention, that is, unconjugated, glucuronidated, secondary, and ketonic bile acid fractions. The former showed significantly lower amounts of total bile acids (P less than 0.01) and lower proportions of unconjugated bile acid fraction (P less than 0.01), secondary bile acid fraction (P less than 0.05), and ketonic bile acid fraction (P less than 0.05) to total bile acids than the latter. The discriminant analysis using these bile acid parameters led to complete separation between intrahepatic and extrahepatic stones in the case of brown pigment stones. In contrast, cholesterol stones in the intrahepatic bile ducts showed the bile acid composition close to those found in the extrahepatic ducts and gallbladder. The above data show that the bacterial infection plays a less important role in the formation and ensuing growth of most intrahepatic brown pigment stones than in extrahepatic stones, and that factors other than or in addition to bacterial infection are involved."
-What were the independent predictors of respiratory failure in patients undergoing thoracoabdominal aortic aneurysm repair?,"A prospective study of respiratory failure after high-risk surgery on the thoracoabdominal aorta. From June 1960 to September 1990, 1414 patients underwent repair of thoracoabdominal aortic aneurysms, of whom 112 (8%) had pulmonary complications requiring respiratory support with tracheostomy; subsequently 45 (40%) died in the hospital. We determined by stepwise logistic regression analysis, in a prospective study of high-risk type I and II thoracoabdominal aortic aneurysms repairs, the independent predictors of respiratory failure, defined as respiratory ventilation exceeding 48 hours after operation. In 98 patients studied, 38 (39%) were women, 60 (61%) were men, 54 (55%) had type II thoracoabdominal aortic aneurysms, 34 (35%) had aortic dissection, 19 (19%) were nonsmokers, 40 (41%) exsmokers, and 39 (40%) active smokers. Before operation, 55 (56%) had chronic pulmonary disease with respiratory failure developing in 58% (p = 0.0005 versus no chronic pulmonary disease, 10/43, 23%), and of the 26 patients in the lower quarter of forced expiratory volume (1 sec) (FEV1 less than or equal to 1.45 L) respiratory failure developed in 61% (p = 0.035). In-hospital survival was 98% and 83% (p = 0.008), respectively, and cumulative survival at 6 months by Kaplan-Meier analysis was 96% and 80% (p = 0.004, log-rank test), respectively, for patients without respiratory failure (N = 56/98, 57%) and with respiratory failure (N = 42/98, 43%). On univariate analysis, the following were associated with respiratory failure (p less than 0.05): FEV1, FEV1% predicted, FVC, FEF25, FEF25% predicted, FEF25-75, FEF25-75% predicted, PaCO2 Pao2, symptoms, smoking history, chronic pulmonary disease, cryoprecipitate volume, postoperative neuromuscular deficit, cardiac complications, reoperation for bleeding, renal complication, stress ulceration, postoperative creatinine level, postoperative dialysis, and postoperative encephalopathy. The independent predictors of respiratory failure were (p less than 0.05): chronic pulmonary disease, smoking history, cardiac and renal complications. In patients with chronic pulmonary disease, the only independent predictor was FEF25 (p = 0.030). These observations may be of value in selecting patients for elective operation."
-How did electrical muscle stimulation affect periodic leg movements in sleep for the patients in the study?,"Nonpharmacologic treatment of periodic leg movements in sleep. The effects of a 30-minute stimulation of the dorsiflexors of the feet and toes before bedtime were investigated in eight patients with periodic leg movements in sleep (PLMS). None were taking medications at the time of the investigation. All subjects were treated with the EMS-250 Neuromuscular Stimulator, which has a maximum output per channel of 1.5mA and a frequency of 47Hz. Stimuli were delivered via a pulse train (on for 1.5sec and off for 1.8sec). A single all-night polysomnogram after this stimulation showed that all patients responded to stimulation, with reduction of leg movements from an average pretreatment PLMS index of 44.6 per hour to a posttreatment PLMS index of 14 per hour (p less than .01). Nocturnal leg movements were primarily reduced during the non-REM sleep. Multiple indices of sleep continuity did not change significantly, although there was a trend toward better sleep consolidation."
-What is the relationship between absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery and the development of necrotising enterocolitis?,"Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis. Absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery were identified in 25 high risk pregnancies. In six pregnancies the fetus was abnormal and all but one of these ended in perinatal death. Of the 19 morphologically normal fetuses, three died in utero and there were four neonatal or infant deaths. The mortality rate was 48% for all pregnancies and 37% for those with morphologically normal fetuses. There was a highly significant increased risk for the development of necrotising enterocolitis in these morphologically normal fetuses with AREDF (53%) compared with controls (6%) who did have umbilical artery end diastolic flow velocities in fetal life. There were no significant differences between the matched pairs for parameters of neonatal outcome chosen to reflect neonatal morbidity. These findings demonstrate the close association between AREDF and necrotising enterocolitis that appears to be independent of other variables such as degree of growth retardation, prematurity, and perinatal asphyxia."
-How do interpersonal conflicts differ in their impact on chronic pain for patients with arthritis versus those with myofascial disorders?,"The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology. This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed."
-What makes the dislocation of an osseointegrated screw a rare event?,Total avulsion of an osseointegrated screw. The close union achieved between pure grade titanium and healthy bone makes dislocation a rare event. We report the case of the total avulsion of an apparently well-integrated implant from a healthy mastoid bone.
-What was the key finding regarding chromosome 14 inheritance in the patient with a Robertsonian translocation?,"Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. A 9-year-old mentally retarded girl with multiple congenital anomalies was found to carry a balanced 13/14 Robertsonian translocation [45,XX,t(13q14q)] which was also present in her father. Her mother carried a balanced reciprocal translocation between chromosomes 1 and 14 [46,XX,t(1;14) (q32;q32)]. Both of her parents were phenotypically normal. Molecular studies were carried out to determine the parental origin of chromosomes 1, 13, and 14 in the patient. Using probes for D14S13 and D14S22, we could show that the patient inherited both chromosomes 14 from her father and none from her mother. Similar studies using probes for chromosomes 1 (D1S76) and 13 (D13S37) loci showed the presence of both maternal and paternal alleles in the patient. Our findings indicate that paternal uniparental heterodisomy for chromosome 14 most likely accounts for the phenotypic abnormalities observed in our patient. It is suggested that uniparental disomy may be the basis for abnormal development in at least some phenotypically abnormal familial balanced-translocation carriers."
-What factors were found to be most strongly correlated with sleep problems in the South Australian community health survey?,"Sleep difficulties, pain and other correlates. A multiple regression analysis was used with variables relevant to sleeping problems from a large community health survey in South Australia. The variables that were found to be most strongly correlated with sleep problems were, in order of importance, pain, anxiety, age, somatic health and annual household income, all of which accounted for 22% of the variance. Weight problems, depression and sex of the respondent were not so important in this analysis. Arthritis, which often increases with age, appeared to be most strongly associated with pain, explaining in part why sleeping problems increase with age. Anxiety, pain and poor somatic health were most strongly associated with lying awake at night or sleeping badly, and anxiety and pain were most strongly correlated with taking longer to get to sleep. Poor somatic health and anxiety were most strongly associated with waking early, and age and pain were the most important variables in taking tablets to aid sleep."
-What are the key findings of the study regarding patient-controlled analgesia in children?,Long-term patient-controlled analgesia in children. Three children who received patient-controlled analgesia for periods of up to 41 days are described. In each case patient-controlled analgesia allowed pain control to be achieved in difficult situations. No patient developed tolerance or clinical signs of dependence. This use of long-term patient-controlled analgesia warrants further evaluation.
-What are the key findings of the study regarding infectious disease transmission in outpatient healthcare settings?,"Transmission of infectious diseases in outpatient health care settings. Increased provision of health care in outpatient settings and concerns about occupational transmission of infections have focused attention on the risk of transmission of infectious diseases in ambulatory health care settings. In contrast to inpatient nosocomial infections, infections transmitted in outpatient settings are neither systematically monitored nor likely to be detected by routine qi surveillance. To better define the spectrum of such events, we reviewed the literature to identify cases and clusters of infections associated with outpatient health care. In this review, we identified and epidemiologically characterized 53 such reports that occurred from 1961 through 1990. Transmission occurred in general medical offices, clinics, and emergency departments (23); ophthalmologists' offices and clinics (11); dental offices (13); and alternative-care settings (six). Our findings suggest that inpatient infection-control practices should be extended to outpatient health care settings by assigning specific responsibility for infection control and by adapting surveillance methods and prevention measures."
-How do Staphylococcus epidermidis and Escherichia coli compare in their ability to induce inflammatory responses and physiological changes in rabbits?,"Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli. Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism."
-"What complication occurred in the patient who underwent endoscopic variceal sclerotherapy, and how was it discovered?","Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence. Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy."
-What were the three major inclusion criteria for patients in this deep vein thrombosis prevention study?,"Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of Logiparin and standard heparin. H.B.P.M. Research Group. A total of 1290 patients were enrolled in a randomized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin, Logiparin, in the prevention of deep vein thrombosis (DVT) in general surgery. Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT. Patients were randomized to receive unfractionated heparin (UH) 5000 units b.d., Logiparin 2500 units daily or Logiparin 3500 units daily. Each treatment was given subcutaneously 2 h before surgery and continued for 7-10 days. Daily 125I-labelled fibrinogen uptake tests (FUTs) were performed from day 2 to day 7 to detect DVT, and phleboangiography was used to confirm the diagnosis. The wound was examined on a daily basis to check for haematoma formation, and all patients were followed up for 1 month after operation. All three treatment arms were well matched for age, sex, weight, diagnosis and type of operation performed. The three major inclusion criteria in the trial were malignancy, age over 60 years and a history of varicose veins. Positive FUTs (UH = 4.2 per cent, Logiparin 2500 units daily = 7.9 per cent, Logiparin 3500 units daily = 3.7 per cent) and positive angiograms (UH = 3.0 per cent, Logiparin 2500 units daily = 5.6 per cent, Logiparin 3500 units daily = 2.3 per cent) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups. The rates of major complications (severe haemorrhage, death, pulmonary embolism, reintervention) were similar in the three groups."
-What treatment was found to be effective for a 28-year-old woman with pulmonary endometriosis after surgical procedures and other treatments failed?,"Treatment of pulmonary endometriosis with a long-acting GnRH agonist. We report the case of a patient who was successfully treated with a long-acting GnRH agonist for pulmonary endometriosis. This 28-year-old woman had symptomatic pleural endometriosis, documented by biopsies, as well as symptomatic pelvic endometriosis. Two surgical procedures, consisting of excision of pleural endometriotic tissue and partial pleurectomies, failed to relieve her chest symptoms. Little relief was achieved with pseudopregnancy treatment. Satisfactory symptomatic improvement was obtained with danazol, but this medication had to be discontinued because of severe side effects. Trial of a GnRH agonist, leuprolide acetate, achieved complete remission of her chest symptoms; in addition, the patient became pregnant immediately after cessation of therapy. Gonadotropin-releasing hormone agonist therapy may be an important therapeutic alternative for women with pulmonary endometriosis who cannot tolerate danazol treatment and in whom surgical therapy fails to relieve the chest symptoms."
-What was the patient and graft survival rate in this study of primary liver transplants using FK 506?,"One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults. An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration."
-How did the hepatic perfusion index (HPI) change before and after mesenteric revascularization in this patient with mesenteric angina?,"Hepatic perfusion index (HPI) in mesenteric angina and following successful revascularization. This is a case report of a 45 year old man who had previously undergone a small bowel resection for acute mesenteric ischaemia. He subsequently suffered from mesenteric angina due to stenosis of the origin of the superior mesenteric artery and intermittent claudication due to aorto-iliac atheroma. The patient underwent a successful aorto-bifemoral Y graft and small bowel revascularization with a saphenous vein graft between the Y graft and the accessible proximal portion of the superior mesenteric artery. Before vascular reconstruction, the hepatic perfusion indices (HPI) in both the fasted and fed states were elevated; after mesenteric revascularization the HPI values were substantially lowered. The hepatic perfusion index may, by demonstrating functional abnormality, be useful in the diagnosis of mesenteric ischaemia and also in the assessment of treatment. Further evaluation of HPI in patients with suspected mesenteric ischaemia is therefore required."
-What are the key cardiac complications associated with Kawasaki disease?,"Diagnosis and management of Kawasaki disease. Kawasaki disease is an acute vasculitis characterized by mucosal inflammation, rash, cervical adenopathy, indurative edema of the hands and feet, and late membranous desquamation of the fingertips. Early cardiac effects include myocarditis (occasionally with congestive heart failure), pericardial inflammation, and, rarely, valve involvement. Coronary artery aneurysms are a long-term concern because coronary thrombosis with myocardial infarction can be a late manifestation. The origin of Kawasaki disease is unknown, but an infectious agent is most likely. Management consists of aspirin for control of fever and inflammatory manifestations and intravenous gamma globulin for the prevention of coronary aneurysm formation. Careful late follow-up is required, especially for patients with persistent coronary abnormalities. Giant aneurysms (greater than 8 mm) are more likely to progress to coronary obstructive disease, and coronary bypass grafts have been required for some patients. Late coronary artery manifestations in patients with mild early coronary dilatation have not been described. However, since long-term epidemiologic studies have not yet been performed, it is prudent to consider childhood Kawasaki disease to be a potential risk factor for coronary disease, especially in atherosclerosis-prone Western societies."
-What was the localization and pattern of HPV 16 E4 protein expression observed in cervical biopsy tissues?,"Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation."
-How did actigraphic monitoring help in understanding the potential risks of discontinuing lithium treatment in bipolar patients?,"Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles. In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation."
-What blood conservation techniques were used in this study of 500 consecutive coronary artery bypass operations?,"Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations. With use of a nonpharmacological, simple, and inexpensive program for blood conservation, 500 consecutive patients underwent elective coronary artery bypass grafting without need of homologous red cell transfusions in 493 (98.6%). At least one internal mammary artery was grafted in all but 1 patient, with supplemental saphenous vein grafts. Intraoperatively, autologous heparinized blood was removed before bypass and retransfused at the conclusion of extracorporeal circulation. The volume remaining in the oxygenator and tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after operation. The mean postoperative mediastinal blood loss was 643 +/- 354 mL, whereas 624 +/- 296 mL was autotransfused. Thirteen patients (2.6%) needed reexploration for bleeding, of whom 7 (7/500, 1.4%) received homologous blood. No other patients required red cell transfusions. In addition, 9 patients were given a mean of 2.6 units of fresh frozen plasma because of suspected coagulopathy. No platelets were transfused, and no cryoprecipitate therapy was undertaken. Thus, in total, 484 patients (96.8%) were not exposed to any homologous blood products during the hospital stay. At discharge, the mean hemoglobin concentration was 121 +/- 14 g/L (12.1 +/- 1.4 g/dL) and the hematocrit, 0.36 +/- 0.04. Postoperative complications were few. There was one in-hospital death (0.2%)."
-What was the outcome of the study on patients with gastro-oesophageal reflux disease without oesophagitis?,"Natural history of gastro-oesophageal reflux disease without oesophagitis. This retrospective study was undertaken to characterise the clinical course and reflux pattern of patients with gastro-oesophageal reflux without evidence of oesophagitis. We investigated 33 patients (12 women, 21 men; mean age 36 years) with typical symptoms, a negative oesophagoscopy, and a 24 hour oesophageal pH-metry indicative of pathological gastro-oesophageal reflux. All patients received antacids or prokinetic drugs or both for three to six months. Nineteen of 33 patients still had symptoms at the end of treatment, of whom five had developed erosive changes of the oesophageal mucosa. The other 14 discontinued treatment and remained asymptomatic during a six month follow up period. Comparison of the pretreatment pH-metry data of the 19 symptomatic patients and the 14 asymptomatic patients showed no differences in the pattern of gastro-oesophageal reflux in the two groups. We conclude that in a substantial proportion of patients with pathological reflux without oesophagitis symptoms may persist and mucosal lesions may develop during conventional treatment without any apparent change in the reflux. Patients who developed endoscopic oesophagitis did not have a more severe pretreatment pattern of gastro-oesophageal reflux when compared with those who did not develop oesophageal mucosal damage."
-How does copper loading affect the recovery of heart function after ischemia and reperfusion in an isolated rat heart model?,"Copper loading of hearts increases postischemic reperfusion injury. We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal."
-What were the key findings regarding gastric cancer incidence and mortality in Scotland between 1978 and 1987?,"Gastric cancer in Scotland: changing epidemiology, unchanging workload. OBJECTIVE--To determine the changes in incidence of and mortality from gastric cancer in Scotland between 1978 and 1987 and in the operative workload in Lothian between 1979 and 1988. DESIGN--Analysis of national incidence statistics for gastric cancer derived from the Scottish national cancer registry, deaths from gastric cancer recorded by the registrar general for Scotland, and Lothian surgical audit data. SETTING--Scotland and Lothian Health Board area. PATIENTS--Patients in Scotland with gastric cancer during 1978 to 1987 inclusive; patients in Scotland with gastric cancer recorded on their death certificate as cause of death during 1978 to 1987; patients who had an operation in Lothian for gastric cancer during 1979 to 1988. MAIN OUTCOME MEASURES--Changes in incidence of and mortality from gastric cancer in Scotland from 1978 to 1987 and in the number of operations performed for gastric cancer in Lothian from 1979 to 1988. RESULTS--Mortality from gastric cancer in Scotland fell by about 25% over the 10 years. The incidence and standardised incidence of gastric cancer showed a marginal decline of about 9%. The differences in trends between incidence and mortality were significant (p less than 0.05). CONCLUSIONS--This study shows that the surgical workload associated with gastric cancer is not declining. This is because the incidence has remained almost static, which may be due to the relative increase in the numbers of older people in the population, who are at greater risk of developing gastric cancer. Gastric cancer should not be regarded as a disease in decline. Incidence and workload should determine resources allocated to this disease rather than mortality statistics."
-What is the definition of a mucin-hypersecreting tumor of the pancreas according to the study?,"Mucin-hypersecreting tumor of the pancreas with mucin extrusion through an enlarged papilla. Patient records, imaging films, macroscopic and microscopic features, and clinical follow-up data of seven Japanese patients with a mucin-hypersecreting tumor of the pancreas were reviewed. The mucin-hypersecreting tumor was defined as an enlarged major or minor papilla with a dilated orifice and visible mucin oozing on endoscopy. The series consisted of six men and one woman ranging from 47 to 79 yr old. The excretion of mucin through a patulous orifice of the enlarged ampulla of Vater was seen in six patients and of the enlarged minor papilla in the other patient with pancreas divisum. The main pancreatic duct was dilated in all patients. Amorphous mucin was seen in the dilated duct of five patients, and papillary nodules were present in two patients. Computed tomography and/or ultrasonography showed dilatation of the main pancreatic duct with multilocular cysts in six patients and with a solid tumor in the other patient. The tumor was located diffusely in the main pancreatic duct in one patient, whereas it was confined to branches in the head (four patients), body (one patient), or tail (one patient) of the pancreas in the six other patients. Histopathologic diagnosis was a cyst lined by hyperplastic mucus-secreting epithelium in one patient, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in two. Five patients underwent resection and have survived for 1-46 months after the operation. The authors would like to emphasize this endoscopic syndrome because about half of mucin-hypersecreting tumors are malignant with a favorable prognosis."
-What was the correlation between immunological reactions and the time course of cerebral vasospasm in the primate model?,"The correlation between immunological reaction in the arterial wall and the time course of the development of cerebral vasospasm in a primate model. To investigate the role of immunological reactions in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH), the authors studied the correlation between immune/inflammatory reactions in the arterial wall and the time course of vasospasm in primates. Twenty monkeys were divided into four groups of 5 animals each: 1) a control group of sham-operated animals, 2) animals subjected to angiography 3 days after the induction of SAH (3-day SAH), 3) animals subjected to angiography 7 days after SAH (1-week SAH), and 4) animals subjected to angiography 7 and 14 days after SAH (2-week SAH). To induce SAH, the main cerebral arteries on the right were dissected free of the arachnoid, and an autologous blood clot was placed around the arteries. To evaluate vasospasm, all animals underwent a baseline angiogram before SAH; angiography was repeated at different intervals in each group, as outlined above. Histopathological changes and the deposition of the immunoglobulin IgG in the arterial wall were evaluated immunohistochemically in each group. The cerebral arteries on the side of the clot showed evidence of mild vasospasm (-24.6% reduction) on the angiogram performed on Day 3, severe vasospasm (-51.7%) on Day 7, and mild vasospasm (-12.8%) on Day 14. The infiltration of inflammatory cells was most marked in the spastic arterial wall in the 1-week SAH group. In the 2-week SAH group, severe myonecrosis and intimal disruption were observed, even in the vessels that showed only mild vasospasm, and the inflammatory reactions had almost abated."
-How does the length of the waiting list impact the survival benefit of cardiac transplantation for outpatients?,"Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. Many patients are accepted for cardiac transplantation during a period of clinical instability associated with a high risk of death, even though most can be discharged home to await transplantation. As the waiting lists lengthen, priority is awarded solely on the basis of the waiting time of outpatients, who now usually undergo transplantation after they have already survived a major period of jeopardy. To determine the impact of the current waiting times and priority system on the previously expected benefit offered by transplantation, 1-year actuarial survival without transplantation was recalculated after each month without transplantation for 214 potential candidates with an ejection fraction of 0.17 +/- 0.05 discharged on tailored medical therapy after evaluation. These data were compared with the 1-year survival data of 88 outpatients who underwent transplantation. Actuarial survival after 1 year was 67% on tailored therapy compared with 88% after transplantation (p = 0.009). Death without transplantation was sudden in 43 of 51 patients, resulting from hemodynamic decompensation in 8. For outpatients already surviving 6 months without transplantation, actuarial survival over the next 12 months was 83% without transplantation. Thus, the expected improvement in survival after transplantation would be only 5% over the subsequent year for patients waiting 6 months, which is the waiting time for many outpatients. Such patients should be reevaluated to determine whether transplantation remains indicated during the next year."
-How many cases of occipital meningoceles in patients with Dandy-Walker syndrome have been reported in this study?,"Occipital meningoceles in patients with the Dandy-Walker syndrome. Occipital cephaloceles in the Dandy-Walker syndrome are not rare. To date, 28 cases have been reported. We report on 8 cases of associated occipital meningocele, totalling 16% of all patients with the Dandy-Walker syndrome in our series. In all patients, communication existed between the posterior fossa cyst and the occipital meningocele. In 2 patients, the occipital meningocele disappeared after cerebrospinal fluid shunting and never required surgical repair. It appears that the cranial defect had ossified and resulted in self-closure. Poor intellectual development in persons with the Dandy-Walker syndrome is associated with the presence of other central nervous system and systemic abnormalities and not with occipital meningoceles alone."
-How do intermediate biomarkers help in understanding the predisposition to gastrointestinal cancer?,"Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: introduction and perspective. In this article, abnormalities in the proliferation and differentiation of gastrointestinal cells are described in diseases that increase predisposition to gastrointestinal cancer. Recent findings related to the effects of calcium on gastrointestinal cell proliferation, differentiation, and tumor occurrence in rodent models and in human subjects are summarized."
-What is the primary cause of malnutrition in patients with malignant disease?,"Nutritional support of patients with cancer of the gastrointestinal tract. Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established."
-What percentage of subjects reported symptom relief after using a neutral-angle wrist splint for carpal tunnel syndrome?,"Carpal tunnel syndrome: objective measures and splint use. One hundred five adults with carpal tunnel syndrome (CTS) were studied to assess the efficacy of a neutral-angle wrist splint, and to identify criteria for splint referral. Ten observations before and after treatment were analyzed with descriptive and inferential statistics. After splint use, 67% of the subjects reported symptom relief. T-test comparison of sensory latency of values before and after treatment indicated improvement for the total group. Chi-square and t-tests failed to reveal significant differences between relief and no-relief groups for gender, affected hand, presence of concomitant conditions, duration of symptoms before treatment, age, length of time between pretreatment and posttreatment nerve conduction testing, initial nerve latency of motor and sensory fibers, or the difference between pretreatment and posttreatment sensory latencies. A significant difference was found for motor latency; the relief group improved and the no-relief group deteriorated. Data suggest that splinting is most effective if applied within three months of symptom onset. Those with damage to the wrist structures or median nerve were least responsive to splinting."
-What was the typical duration of antibiotic treatment for patients with Whipple's disease in this study?,"Short-term antibiotic treatment in Whipple's disease. We report the results of short-term antibiotic treatment in 19 patients with Whipple's disease (WD). The diagnosis was based on clinical features and on a characteristic small bowel biopsy. Patients received treatment for a mean of 7.9 weeks (range 4-20). Fourteen were treated with de-methyl-chlortetracycline (600 mg/day), and 1 also received chloramphenicol (1 g/day); 1 was treated with ampicillin (2 g/day), and 4 were treated with amoxicillin (1.5 g/day). In all patients, the clinical response was rapid and excellent, body weight increased significantly, diarrhea subsided, and fecal fat values returned to normal. Intestinal biopsies obtained after treatment was completed showed significant improvement based on a decrease in the number of macrophages staining positive with periodic acid-Schiff (PAS), normalization of villous structure, and decreased dilatation of lymphatic channels; free bacilli were absent, as shown both by light and electron microscopy. Seventeen patients have been followed for a mean of 99.4 months (range 6-300). Two died 30 and 72 months after diagnosis of Whipple's disease, 1 of laryngeal carcinoma and the other of colonic carcinoma. Fifteen patients are in excellent health. Three patients treated with tetracycline have had clinical and/or histologic relapses. In our experience, short-course antibiotic treatment with tetracycline or ampicillin and derivatives can be effective in WD, with few relapses and excellent outcome. No neurologic symptoms, either initially or during follow-up were observed."
-What was the overall prevalence rate of dementia among individuals aged 85 years and older in the Leiden community survey?,"Prevalence of dementia in the 'oldest old' of a Dutch community. OBJECTIVE: To estimate the prevalence rate of dementia in subjects 85 years of age and over. DESIGN: A two-phase design with the Mini-Mental State Examination (MMSE) in the screening phase and the Geriatric Mental State Schedule (GMS) in the diagnostic phase. SETTING: Community survey including subjects in residential care. SUBJECTS: All (n = 1,259) inhabitants of Leiden, The Netherlands, aged 85 years and over on December 1, 1986. First phase participation rate was 71% (17% dropout due to death); second phase participation rate was 82%. MAIN OUTCOME MEASURE: DSM-III diagnosis of dementia without further specification of the etiology of the dementia. RESULTS: An overall prevalence rate of 23% (95% C.I.: 19%-26%) was found. This included 12% mild dementia, 7% moderate and 4% severe dementia. The prevalence rate was higher among women (24%) than among men (18%). It increased with age from 19% (95% C.I.: 16%-22%) in the group of 85-89 years to 32% (95% C.I.: 26%-39%) in the group of 90-94 years to 41% (95% C.I.: 25%-58%) in the 95+ group. CONCLUSION: A fifth of the 85+ and a third of the 90+ population suffer from dementia with an indication that half of the 95+ population is affected. With the expected steep rise in the number of the oldest old, dementia will stay a major health problem in the near future."
-What was the purpose of the study on mastoid cavities and how was the symptom score determined?,"Mastoid misery: quantifying the distress in a radical cavity. Seventy-eight mastoid cavities were studied in 39 patients who required revision surgery for troublesome symptoms. A retrospective questionnaire was used to assign a symptom score to each patient in his pre and post-operative condition. The 5 leading symptoms of pain, wax, discharge, smell and giddiness were reviewed. A score of 15 points represented the worst case and zero the best. The average improvement after surgery was 4.7 points. Hearing was not considered in this study."
-What was the average lifetime benefit of chemotherapy for 45-year-old and 60-year-old women with node-negative breast cancer according to the decision-analysis model?,"Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. A decision-analysis model. BACKGROUND. In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. METHODS. Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. RESULTS. For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of $18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups. CONCLUSIONS. Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients' risk preferences."
-What percentage of patients with civilian craniocerebral gunshot wounds survived with a good outcome?,"Civilian craniocerebral gunshot wounds. Experience with 120 patients who incurred a gunshot wound to the head with dural penetration is presented. All of the patients were managed by a standard resuscitation protocol and assigned a clinical grade based on their level of consciousness both at the time of presentation and at 2 to 4 months after injury. Fifty patients (42%) underwent surgery. Twenty-eight patients (23%) had a good recovery, 19 (16%) were moderately disabled, 6 (5%) were severely disabled, and 67 (56%) died. All patients who were alert and awake with a normal or near normal neurological examination at the time of admission survived with a good outcome. All but 4 patients who were comatose at the time of admission died. Nine patients, however, who were not comatose at the time of admission died from potentially preventable causes. In 3 of these patients, a more aggressive diagnostic approach (including cerebral angiography) may have altered their ultimate outcome. An expeditious approach to the trauma victim with a comprehensive management scheme after injury may have altered the course in the remainder of these patients."
-What were the key findings of the study on total androgen ablation using Zoladex plus flutamide compared to orchiectomy in prostate cancer patients?,"Total androgen ablation: European experience. The EORTC GU Group. Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups."
-What percentage of nursing home residents in the study had a nutrient-modified diet prescription?,"Use of modified diets in nursing homes. Randomly chosen medical charts of 212 elderly subjects in 11 nursing homes were reviewed to determine which characteristics of the subjects were most closely associated with their diet prescriptions. The chart reviews indicated that 104 (49.0%) of the 212 subjects had some type of nutrient-modified diet prescription. Eight patients who were tube fed were not included in subsequent analyses. Sodium restriction was the most common modification (60 [29.4%] of the remaining 204 patients) and calorie-controlled diets were also common (52 [25.5%] of the patients). Of the 55 patients with hypertension, 31 (56.4%) had no sodium restriction. Only 10% of all low-sodium diets limited sodium to 2 g per day. Of the 38 patients with diabetes, 7 (18.4%) had no prescription for calorie control, and there was no indication that increased dietary fiber was encouraged for diabetic patients. Only one of the 121 subjects with a diagnosis of coronary heart disease or atherosclerosis had a prescription for a cholesterol-lowering diet. Characteristics of the subjects not specifically related to diet or diagnosis, such as age, sex, duration of stay, and level of care, had no significant relationship to diet prescription. These findings suggest that the practitioners in our sample were not convinced of the efficacy of modified diets to control disease for most nursing home residents."
-What improvements in lung function were observed in patients who underwent thoracoscopic carbon dioxide laser treatment for bullous emphysema?,"Thoracoscopic carbon dioxide laser treatment of bullous emphysema. A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation."
-What is the relationship between methotrexate cumulative dose and the progression of liver disease in patients with rheumatoid arthritis or psoriatic arthritis?,"Methotrexate and histologic hepatic abnormalities: a meta-analysis. STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS: A total of 636 patients from 15 studies. RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity."
-What is the recommended strategy to manage nitrate tolerance in patients?,"A practical guide to nitrate use. Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension."
-What types of tumors were most commonly associated with radial nerve paralysis in this review?,"Radial nerve paralysis and tumor. This paper presents ten cases of radial nerve paralysis because of tumor and reviews 38 previously reported cases. The tumor distribution was 35 lipomas, four neurofibromas, four ganglions, three neuromas, one fibroma, and one neurilemoma. Malignant tumors are not discussed in this review. Electromyography is of value if diagnostic problems occur. Postoperative results are normally good."
-What was unusual about the ECG findings in this patient with fulminant hepatic failure?,"Massive ST-segment elevation without myocardial injury in a patient with fulminant hepatic failure and cerebral edema. A 49-year-old woman presented in fulminant hepatic failure. The ECG showed dramatic ST-segment elevation, suggesting diffuse myocardial injury. However, echocardiography, creatine phosphokinase enzyme determinations, and examination of the heart at autopsy (six days later) failed to demonstrate any physiologic, anatomic, or histologic evidence of abnormality. The appearance of ST-segment elevation in this setting should not prompt treatment for cardiac disease or limit the candidacy for liver transplantation of such critically ill patients."
-What is the proposed pathophysiological reason for the rarity of peripheral neuropathy in sickle cell disease?,Mononeuropathy in sickle cell anemia: anatomical and pathophysiological basis for its rarity. Peripheral neuropathy is a rare complication of sickle cell disease. We report a young black woman with sickle cell anemia who developed a proximal median mononeuropathy in the setting of sickle cell crisis. The clinical and electrodiagnostic features are consistent with an ischemic mechanism from the sickling process. The pathophysiological basis for the rarity of this complication may be related to the rich anastomotic microvasculature of peripheral nerve and the unique large size of the capillaries of this vascular network.
-What was the success rate of scleral buckling surgery for rhegmatogenous retinal detachments in patients with severe myopia during the study period?,"Scleral buckling for rhegmatogenous retinal detachment associated with severe myopia. From Jan. 1, 1980, to Dec. 31, 1989, we performed scleral buckling surgery on 48 eyes of 46 patients for rhegmatogenous retinal detachments associated with severe myopia (greater than 5.00 diopters). Forty eyes of 38 patients were observed for at least six months, and the mean follow-up period was 46 months. Intraoperative complications occurred in four of 48 eyes (8%) and included retinal incarceration (two eyes), choroidal hemorrhage (one eye), and choroidal detachment (one eye). Three of the 40 eyes (7.5%) followed up for more than six months developed a recurrent retinal detachment and underwent a revision of the scleral buckle. At the last follow-up examination, the retinas of all 40 eyes were totally reattached. Final visual acuity of 20/40 or better was attained in 26 of 40 eyes (65%). Because of the low rate of intraoperative complications and the high rate of success, scleral buckling is recommended for most patients with rhegmatogenous retinal detachments associated with severe myopia."
-What are the five breast cancer screening strategies compared in the cost-effectiveness analysis in Japan?,"Cost-effectiveness analysis of mass screening for breast cancer in Japan. The official Japanese recommendation for breast cancer screening is physical examination by a physician, in contrast to US recommendations of mammography. In this analysis of breast cancer screening, the authors used Japanese data in a cost-effectiveness model to compare the following five strategies: (1) no screening (N); (2) physical examination alone (PE); (3) mammography (MG); (4) PE followed by MG if PE findings were abnormal (PE----MG); and (5) PE combined with MG for all screened women (PE + MG). None of these programs would save medical expenditures. The total discounted net costs per patient (in US dollars) were as follows: N, +54; PE, +412; MG, +517; PE----MG, +340; and PE + MG, +731. The number of years of life saved per cohort of 100,000 asymptomatic Japanese women would range from 708 (PE----MG) to 3724 (PG + MG). The additional cost of each strategy (compared with N) per additional year of life would be +49,700 for PE, +40,400 for PE----MG, +14,300 for MG, and +18,000 for PE + MG. The least costly screening option (PE----MG) does not have the lowest cost per additional year of life saved (MG does). MG would be preferable to the current Japanese recommendation of PE alone."
-What was the key finding regarding c-erbB-2 gene product expression in lobular breast neoplasia?,"C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Lobular carcinoma in situ (LCIS) has uncertain malignant potential; biologic markers that will identify patients at risk for a poor clinical outcome have been sought actively. Amplification of the c-erbB-2 protooncogene has been correlated with poor prognosis in invasive mammary carcinoma, and immunohistochemical evaluation for expression of the oncogene protein has been correlated with gene amplification. The authors retrospectively evaluated 62 cases of lobular neoplasia for expression of the c-erbB-2 gene product on formalin-fixed, deparaffinized sections, using two monoclonal anti-erbB-2 (p185) antibodies (c-neu Ab3 and m-erb) and one polyclonal anti-erbB-2 antibody (pAb 1) by the avidin-biotin-peroxidase method. All 62 cases were negative with the pAb 1 antibody; one of 62 cases was weakly positive with the c-neu Ab3 in a membranous pattern. Expression of c-erbB-2 gene product was identified on adjacent invasive ductal carcinoma in one case and in adjacent ductal carcinoma in situ in another. None of 15 cases if infiltrating lobular carcinoma was positive with either of the two anti-c-erbB-2 antibodies. Strong positivity was found on benign epithelium in one case, demonstrating epitheliosis. In summary, evidence of expression of the c-erbB-2 gene product was found in one of 57 cases of LCIS and none of 15 cases of invasive lobular carcinoma. This suggests that, in contrast to reported data concerning intraductal and invasive ductal carcinoma, c-erbB-2 oncogene amplification and/or overexpression does not play a significant role in the progression of lobular breast neoplasia."
-What percentage of head and neck squamous cell carcinoma patients had elevated carcinoembryonic antigen (CEA) levels in this study?,"Carcinoembryonic antigen and head and neck cancer. Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated (greater than or equal to 2.5 ng/ml). Only 13% of the patients had clearly elevated CEA levels (greater than 5 ng/ml). CEA levels were significantly higher in patients with advanced, e.g. stage IV, disease but a correlation between serum CEA concentration and prognosis was not found. Patients who smoked had significantly higher serum CEA levels than non-smoking patients. In the serial determinations slight CEA elevations could be found in only 50% of patients with tumour recurrence. Combined with the data from the literature we conclude that serum CEA determination is not useful in predicting the outcome in patients with a head and neck squamous carcinoma."
-What diagnostic imaging technique was used to identify the spinal cord herniation and intradural spinal arachnoid cyst?,"Spinal cord herniation associated with an intradural spinal arachnoid cyst diagnosed by magnetic resonance imaging. Two rare cases of spinal cord herniation associated with intradural spinal arachnoid cyst are reported. A preoperative magnetic resonance imaging scan demonstrated the presence of spinal cord herniation, identified as a protrusion continuous with the spinal cord. Surgery upon the intradural spinal arachnoid cyst improved progressive neurological dysfunction. The authors postulate that spinal cord herniation occurred for the following reason: The pressure of the intradural arachnoid cyst on the dorsal aspect of the spinal cord caused thinning of the dura, leading to a tear and, thus, the development of an extradural arachnoid cyst. Along with the enlargement of intradural arachnoid cyst, the spinal cord herniated through the tear in the dura into the extradural arachnoid cyst."
-How did the researchers use pulsed Doppler technique to evaluate blood flow velocity in the pulmonary artery of dogs with acute pulmonary hypertension?,"Intraluminal pulsed Doppler evaluation of the pulmonary artery velocity time curve in a canine model of acute pulmonary hypertension. The velocity pattern of the blood flow in the pulmonary artery was investigated in an animal model of acute pulmonary hypertension. Nine anesthetized, open-chest dogs were embolized with polystyrene microspheres, and the velocity pattern of the blood flow in the pulmonary artery was studied with use of an invasive pulsed Doppler technique. Phasic intraluminal velocity was recorded with use of a miniature piezoelectric crystal activated by 20-MHz Doppler pulses and mounted on the tip of a needle probe introduced into the pulmonary artery. The recorded Doppler quadrature signals were processed by spectral analysis. Significant increases occurred in mean, systolic, and diastolic pulmonary arterial pressures (p less than 0.0002), in pulmonary vascular resistance (p less than 0.005), and in negative velocity time (duration in milliseconds that the mean velocity was directed toward the pulmonic valve) (p less than 0.002). Significant decreases occurred in right ventricular ejection time (p less than 0.006) and in positive velocity time (duration in milliseconds that the mean velocity was directed away from the pulmonic valve) (p less than 0.005). A significant shortening in the time to peak velocity (acceleration time) was found (p less than 0.005). Second-order regression analyses demonstrated an inverse correlation between the ratio of positive velocity time to negative velocity time and the mean pulmonary artery pressure in all animals (r = 0.71). These findings should be compared with the velocity patterns of the blood flow in the pulmonary artery obtained under pulmonary hypertensive conditions due to various causes to facilitate interpretation and understanding of clinical investigations."
-How does the energy state of pig lungs change under different levels of oxygen and cyanide exposure?,"Energy state and vasomotor tone in hypoxic pig lungs. To evaluate the role of energy state in pulmonary vascular responses to hypoxia, we exposed isolated pig lungs to decreases in inspired PO2 or increases in perfusate NaCN concentration. Lung energy state was assessed by 31P nuclear magnetic resonance spectroscopy or measurement of adenine nucleotides by high-pressure liquid chromatography in freeze-clamped biopsies. In ventilated lungs, inspired PO2 of 200 (normoxia), 50 (hypoxia), and 0 Torr (anoxia) did not change adenine nucleotides but resulted in steady-state pulmonary arterial pressure (Ppa) values of 15.5 +/- 1.4, 30.3 +/- 1.8, and 17.2 +/- 1.9 mmHg, respectively, indicating vasoconstriction during hypoxia and reversal of vasoconstriction during anoxia. In degassed lungs, similar changes in Ppa were observed; however, energy state deteriorated during anoxia. An increase in perfusate NaCN concentration from 0 to 0.1 mM progressively increased Ppa and did not alter adenine nucleotides, whereas 1 mM reversed this vasoconstriction and caused deterioration of energy state. These results suggest that 1) pulmonary vasoconstrictor responses to hypoxia or cyanide occurred independently of whole lung energy state, 2) the inability of the pulmonary vasculature to sustain hypoxic vasoconstriction during anoxia might be associated with decreased energy state in some lung compartment, and 3) atelectasis was detrimental to whole lung energy state."
-Does aerobic exercise training provide significantly better physical performance improvements compared to light exercise for patients recovering from acute myocardial infarction?,"Effect of early programmes of high and low intensity exercise on physical performance after transmural acute myocardial infarction. Does a programme of light exercise training after acute myocardial infarction produce the same improvement in treadmill performance as aerobic exercise training? Three hundred and eight men from a consecutive series of 479 men with transmural (Q wave) acute myocardial infarction, admitted to a single coronary care unit, were randomly allocated to eight weeks of group aerobic exercise training or group light exercise. Groups were well matched for all characteristics other than site of infarction, which did not significantly affect results. Mean (SD) physical working capacity (metabolic equivalents) determined by treadmill testing at the start of the study (in the third week after infarction) was 6.8 (2.2) v 6.7 (2.5) METs, at the end (in the eleventh week after infarction) 10.8 (2.3) v 9.9 (2.4) METs, and at 12 month review 10.8 (2.4) v 10.7 (1.9) METs for the exercise training group and the light exercise group respectively. The difference of 0.9 METs at the end of the study was the only significant difference between groups. There were no significant intergroup differences at any stage in resting and maximal heart rate, resting and maximal systolic blood pressure, or rate-pressure product. Apart from a small temporarily greater physical working capacity, the physical benefits of aerobic exercise training were equally well achieved by group light exercise."
-What were the key findings regarding nocturnal body temperature in women with premenstrual syndrome (PMS) and late luteal phase dysphoric disorder (LLPDD)?,"High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder. OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects."
-What specific HLA-DQ alleles were found to be associated with insulin-dependent diabetes mellitus (IDDM) susceptibility in Japanese and white populations?,"Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites. Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups."
-What was the success rate of tumor destruction in patients with colorectal villous adenomas using endoscopic resection and Nd:YAG laser photocoagulation?,"Endoscopic treatment by snare electrocoagulation prior to Nd:YAG laser photocoagulation in 85 voluminous colorectal villous adenomas. The association of endoscopic resection with Nd:YAG laser photocoagulation was used to treat benign colorectal villous adenomas. Eight-five patients were included: 49 with surgical contraindications, 35 for whom surgical resection appeared to be too hazardous, and 1 who refused surgery. Forty-five tumors had an axial extension between 1 and 3 cm, and 40 tumors had an axial extension of at least 4 cm. Diathermic snare resection was performed to remove large tumoral fragments prior to laser photocoagulation of the residual flat lesions. Treatments were repeated every 15 days until total tumor destruction was achieved. A carcinoma was detected in biopsy specimens obtained during endoscopic treatment of five patients. Two patients were lost to follow-up. Treatment results could be analyzed in 78 patients. Successful treatment was achieved in 67 patients. Tumor destruction was complete in 77 percent of patients who had lesions of at least 4 cm diameter and in 93 percent of patients with smaller lesions. The axial extension of the tumor was the main factor affecting the results of treatment. No major complications occurred. During the average 103-week follow-up period, 21 percent of the patients with total tumor destruction had a recurrence. The risk of recurrence was correlated with the number of initial treatment sessions and previous surgery treatment. It would appear that the treatment with endoscopic resection prior to Nd:YAG laser photocoagulation is a safe and effective method in the destruction of colorectal villous adenomas."
-How do the fixed-reference and floating-reference systems differ in their assessment of wall motion abnormalities in patients with myocardial infarction?,"Reference systems in echocardiographic quantitative wall motion analysis with registration of respiration. Registration of respiration allows analysis at the end-expiratory phase and may thus favor the use of the fixed-reference system versus the floating-reference system in echocardiographic quantitative wall motion analysis. Analysis is performed on two-dimensional echocardiograms of 44 normal subjects, 38 patients with anterior myocardial infarction, and 17 patients with posterior myocardial infarction. Two different models for wall motion analysis are applied, each using the fixed-reference system and the floating-reference system, respectively. In patients with anterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the anterior, septal, and apical walls, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. In patients with posterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the posterior wall, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. These findings indicate that the fixed-reference system is superior to the floating-reference system in quantification of wall motion of end-expiratory two-dimensional echocardiograms."
-"In the study comparing diamorphine and morphine, what was the overall finding regarding the speed of onset of analgesic effect?","Comparison of speed of onset of analgesic effect of diamorphine and morphine. In a random, double-blind crossover trial using an ischaemic limb pain model we have assessed the speed of onset of analgesia after an i.v. bolus of equipotent doses of diamorphine and morphine in 12 healthy male volunteers. Pain and its subsequent relief were assessed by means of a visual analogue scale. Two of the subjects found diamorphine acted quicker than morphine, one found no difference and nine found that morphine was quicker than diamorphine. The mean time to diamorphine effect was 53% greater than for morphine (P less than 0.005, Wilcoxon rank sum test). These findings suggest that, for rapid relief of pain, morphine is more suitable than diamorphine."
-What unique neurological condition was observed in the 30-year-old woman that suggested a potential loss of nerve growth factor (NGF) trophic action?,"New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides. A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF."
-How does left ventricular hypertrophy (LVH) relate to cardiovascular disease risk in patients with hypertension?,"Left ventricular hypertrophy in hypertension. Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography, and with this technique it has been shown that evidence of LVH is an important independent risk factor for cardiovascular disease. The major cause of death in patients with hypertension and LVH is coronary artery disease. Therefore an understanding of the interrelationships between these two disorders is fundamental, and it is now clear that the hypertrophied ventricle is vulnerable to myocardial ischemia. Appreciation of the mechanisms of sudden death has also increased, although the exact situation in patients with LVH remains to be clarified. Regression of LVH is known to occur with the use of several different antihypertensive drugs. Recent studies indicate that the calcium blocking agent nicardipine, in addition to beta-blocking drugs and angiotensin-converting enzyme inhibitors, brings about LVH regression without any deterioration of left ventricular function. However, further studies are needed to assess the long-term benefits of this regression."
-What medical condition did the 27-year-old man with osteogenesis imperfecta develop after sustaining a femoral fracture?,Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.
-What treatment method was used to achieve tumor regression in patients with gastrointestinal leiomyosarcoma liver metastases?,Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.
-What is the Damus-Kaye-Stansel operation and what type of heart conditions is it used to treat?,"The Damus-Fontan procedure. The Damus-Kaye-Stansel operation is a useful technique for the treatment of complex cyanotic congenital heart disease when there is obstruction between the systemic ventricle and the aorta. Modifications of the technique include transection of the aorta and the pulmonary artery, anastomosis of the contiguous aortic and pulmonary walls, and connection of the distal aorta to the perimeter of the new bivalved proximal great artery. In addition, the bidirectional cavopulmonary shunt technique can be used with or without the Fontan procedure. Six patients underwent a Damus-Fontan operation, and all survived. Two patients underwent the Damus-cavopulmonary shunt (hemi-Fontan) procedure, and 1 survived. The postoperative status of the 7 survivors is good to excellent. Follow-up ranges from 2 months to 7 1/2 years."
-What is the proposed mechanism of anastomotic obstruction after stapled enteroanastomosis in this medical case report?,Anastomotic obstruction after stapled enteroanastomosis. We have recently treated two cases of anastomotic obstruction after side-to-side stapled enteroanastomosis. Complete obstruction of a stapled small-bowel anastomosis has not been reported to our knowledge. The mechanism of the obstruction appears to be the healing together of the cut edges of viable bowel beyond the inverted stapled lines. An alternative method of constructing the functional end-to-end enteroanastomosis that is offered is intended to prevent the occurrence of postoperative anastomotic obstruction.
-What percentage of children at the Children's Hospital in Bangkok were found to have bloody diarrhea?,"Epidemiologic aspects of shigellosis and other causes of dysentery in Thailand. Nearly 20% of children seen in the outpatient department of Children's Hospital in Bangkok, Thailand, for diarrheal disease had bloody diarrhea. Shigella species and enteroinvasive Escherichia coli--isolated from 13% and 2% of children with diarrhea, respectively--were the most frequent causes of bloody diarrhea. Campylobacter species and nontyphoidal Salmonella species were also isolated frequently but were much less often associated with bloody diarrhea. Shigella species were rarely isolated from patients who did not have diarrhea, while Campylobacter and Salmonella species were isolated frequently from well children. None of the species isolated always caused bloody diarrhea. Studies on infection with Campylobacter suggest that natural immunity may prevent bloody diarrhea and in fact may eventually prevent all disease due to this organism. Studies of endemic Shigella flexneri and epidemic Shigella dysenteriae 1 in Thailand have shown that immunity may also explain an age-related decrease in rates of S. flexneri infection but not in rates of S. dysenteriae 1 isolation."
-How does hypertension impact stroke risk in the black population?,"Cerebrovascular disease in hypertensive blacks. There is convincing evidence that all grades of persistent diastolic hypertension, especially in blacks, should be treated in order to prevent stroke and other cardiovascular complications. Studies are now in progress to gather additional information concerning isolated systolic hypertension, especially in the aged. Inasmuch as at least one half or more of stroke deaths in blacks develop as the result of hypertension, lowering blood pressure offers the perfect opportunity to reduce considerably the frequency of this devastating illness. The recent dramatic fall in U.S. stroke mortality, greatest in the black female, is a commendable achievement, but the flattening of the declining mortality curve over the past several years should be a cause for alarm and intensive investigation."
-What are gastrointestinal lipomas and how are they typically identified during radiologic examination?,"Gastrointestinal lipomas: a radiologic and pathologic review. Lipomas of the gastrointestinal tract are an infrequent finding on radiologic examination; however, they occur often enough to warrant consideration in the differential diagnosis of mass lesions of the gut. In many instances, their morphologic characteristics allow the specific diagnosis of a lipoma. In this report, we review gastrointestinal lipomas with an emphasis on their radiologic and pathologic correlation."
-How did the researchers classify patients with orthostatic disorders based on their blood pressure and heart rate responses when standing?,"Spectrum of orthostatic disorders: classification based on an analysis of the short-term circulatory response upon standing. 1. In 31 consecutively referred patients (20 females, 11 males) with overt or suspected orthostatic disorders, the changes in blood pressure and heart rate that occur in the first 2 min of standing were analysed. 2. Blood pressure was measured continuously by Finapres. The blood pressure and heart rate responses after 1-2 min of standing (early steady-state response) were used to classify the patients as follows: group I (n = 17, age 42 +/- 17 years), normal early steady-state blood pressure and heart rate responses; group II (n = 5, age 40 +/- 14 years), combination of normal early steady-state blood pressure and postural tachycardia; group III (n = 9, age 51 +/- 14 years), hypotensive orthostatic response with (4/9) or without (5/9) postural tachycardia. We examined whether additional information could be obtained by beat-to-beat analysis of the initial circulatory response (first 30 s). It was quantified by identifying the blood pressure trough and overshoot and the maximum heart rate and relative bradycardia. 3. The initial drop in systolic and diastolic blood pressures did not differ between the three groups. A recovery of blood pressure with a systolic and/or diastolic blood pressure overshoot was present in all group I and II patients, but was absent in all except two patients in group III. The initial maximum heart rate increase did not differ between the three groups. The relative bradycardia was less in groups II and III than in group I. 4. We conclude that analysis of the beat-to-beat blood pressure changes in the first 30 s after the onset of standing provides almost all the information that is necessary to determine abnormalities in orthostatic circulatory control."
-How does atrial appendectomy affect the secretion of atrial natriuretic polypeptide in dogs with high-output heart failure?,"Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide? The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure."
-What type of adverse skin reaction did the patient experience when taking medications containing pseudoephedrine and norephedrine hydrochloride?,"Systemic contact dermatitis from pseudoephedrine. A patient with rhinitis developed systemic contact dermatitis when starting oral treatment with Rhinalair, containing pseudoephedrine hydrochloride. A few months later, another oral treatment Rinutan, containing norephedrine hydrochloride, provoked a more severe generalized eczema. Patch test reactions were strongly positive to ephedrine and pseudoephedrine, slightly positive to phenylephrine and negative to epinephrine. Norephedrine was not tested."
-What were the two antibiotic combinations compared in this study for prophylaxis of infection following colorectal surgery?,"Colorectal surgery: short-term prophylaxis with clindamycin plus aztreonam or gentamicin. A randomized study was conducted to compare the effectiveness of aztreonam plus clindamycin with that of gentamicin plus clindamycin for prophylaxis of infection following colorectal surgery. A total of 138 patients undergoing elective colorectal surgery were randomized to treatment with clindamycin (600 mg) plus either aztreonam (1 g) or gentamicin (80 mg) 30 minutes before and 8 and 16 hours after surgery. The study included 122 patients (88.4%) with colorectal carcinoma. Samples from the abdominal cavity and from the subcutaneous tissues were taken for bacteriologic study. All samples from the abdominal cavity yielded microorganisms; both aerobic and anaerobic bacteria were isolated. Wound infections occurred in eight patients (12.1%) in the aztreonam group and in 12 patients (16.7%) in the gentamicin group. Escherichia coli, Bacteroides species, enterococci, and staphylococci were isolated most frequently from wounds and were often isolated from bacteriologic samples from the abdominal cavity of the same patients. The incidence of septic complications reflected the extent of nutritional and immunologic impairment. No significant differences were found between groups in the rate of urinary tract or lower respiratory tract infections. Aztreonam/clindamycin appears to be a valid alternative to gentamicin/clindamycin for the prophylaxis of infections following colorectal surgery."
-What percentage of patients with CHARGE Association had upper airway abnormalities beyond choanal atresia and cleft lip and palate?,"Incidence and management of airway problems in the CHARGE Association. The airway problems associated with anaesthesia in patients with the CHARGE Association have been underreported. We undertook a retrospective review of 50 cases, of which anaesthetic records were available for 37 patients. Apart from choanal atresia and cleft lip and palate, 56% of patients has some other upper airway abnormality. There appeared to be greater difficulty in tracheal intubation with increase in age in four patients. The incidence and management of airway abnormalities are discussed."
-What potential complications can arise from overfeeding critically ill patients according to the context?,"Report of a hidden case of overfeeding. Nutritional support is essential to the care of the critically ill patient, but complications of overfeeding can occur. Precise metabolic measurement by indirect calorimetry can detect problems of nutrition and allow adjustment in caloric intake. This case study illustrates the complications of carbon dioxide retention and inability to wean from mechanical ventilation with subsequent prevention of further complications."
-Why was trimethoprim-sulfamethoxazole (TMP-SMX) ineffective in treating experimental enterococcal endocarditis in the rat model?,"Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis. To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection."
-What significant finding was made regarding the p53 gene in a patient with an intracranial ependymoma?,"Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited."
-What was the relationship between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram in patients with acute myocardial infarction?,"Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction. This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery."
-How does insulin resistance affect inhibin levels in women with polycystic ovary syndrome (PCOS) compared to control subjects?,"Serum inhibin levels in polycystic ovary syndrome: effect of insulin resistance and insulin secretion. Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women."
-What were the findings of the study regarding the presence of human papillomavirus (HPV) DNA in cervical adenocarcinoma?,"Absence of human papilloma virus in cervical adenocarcinoma determined by in situ hybridisation. A few studies using DNA technology have suggested that human papillomavirus (HPV) may be an aetiological factor for adenocarcinoma of the uterine cervix. Twenty one cases of cervical adenocarcinoma were studied by in situ hybridisation using biotinylated DNA probes for HPV types 6, 11, 16 and 18 and a streptavidin, biotinylated alkaline phosphatase detection system. Intranuclear HPV DNA was detected in none of the adenocarcinomas, while positive controls gave a clear intranuclear signal. Adjacent areas of normal, koilocytic, and dysplastic squamous epithelium also gave positive results. It may be that squamous epithelium contaminates adenocarcinomas reported as positive by Southern blotting. Our results showing absence of detectable HPV DNA within adenocarcinomas suggest that HPV infection may not have a major role in the aetiology of adenocarcinoma of the uterine cervix."
-How does combined treatment with pulsatile LH-RH and hMG affect follicular development in patients with polycystic ovaries?,"Treatment with pulsatile luteinizing hormone-releasing hormone modulates folliculogenesis in response to ovarian stimulation with exogenous gonadotropins in patients with polycystic ovaries. Combined treatment with pulsatile LH-RH and hMG, given to eight patients who had anovulation associated with PCO and resistant to CC, significantly reduced the number of large follicles induced by hMG alone. A direct effect of pulsatile LH-RH on the ovary is postulated. This combined treatment eased the problems of multifollicular development, thereby increasing efficiency and reducing complications in patients with PCO stimulated by gonadotropins."
-What were the initial findings of the clinical study on granisetron for treating migraine headaches?,"First clinical study of the selective 5-HT3 antagonist, granisetron (BRL 43694), in the acute treatment of migraine headache. Granisetron (BRL 43694), a selective 5-HT3 receptor antagonist, was assessed as acute therapy for the first time in migraine patients. In an open pilot study 7 migraine attacks were treated in 6 patients. All but 1 patient experienced marked and rapid relief from the headache, and nausea and vomiting were rapidly resolved in the 6 cases where these symptoms accompanied the attack. No side effects were recorded. Development of granisetron for migraine was suspended during the study for extraneous reasons."
-"What are the differences in the expression of Tn, sialosyl Tn, and T antigens across normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma?","Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis."
-How does QTc prolongation relate to the risk of sudden death in patients with and without cardiac dysfunction?,"QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. BACKGROUND. QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. METHODS AND RESULTS. In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. CONCLUSIONS. These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death."
-"What were the key findings regarding adverse events in children who completed treatment for acute lymphoblastic leukemia across studies VIII, IX, and X?","Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X. We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure."
-What is the purpose of the educational device described in the context related to Mohs micrographic surgery?,An educational device for Mohs micrographic surgery. A three-dimensional model of basal cell carcinoma. Mohs micrographic surgery for skin cancer (fresh-tissue technique) involves the processing of tissue in a complex fashion. The advantages of this method relate to the asymmetric three-dimensional growth of basal cell carcinoma (BCC). A device is described here based on published knowledge about the growth of BCC. The model demonstrates the precise way in which Mohs surgery varies from other surgical approaches to yield higher cure rates in specific circumstances. This device may be helpful in educating residents and medical students about Mohs surgery and in preparing patients for this procedure.
-What was the incidence of ischemic injury to the spinal cord or lumbosacral plexus following abdominal aorta operations during the study period?,"Ischemic injury to the spinal cord or lumbosacral plexus after aorto-iliac reconstruction. Between January 1, 1980, and June 30, 1989, 9 patients (6 males and 3 females) developed ischemic injury to the spinal cord or lumbosacral plexus following 3,320 operations on the abdominal aorta (0.3%). The incidence of this complication was 0.1% (2 of 1,901) after elective and 1.4% (3 of 210) after emergency abdominal aortic aneurysm repair, and 0.3% (4 of 1,209) after repair for occlusive disease. Three of the latter had prior clinical evidence of distal embolization. Eight grafts were bifurcated (aorto-iliac:four, aorto-femoral: three, aorto-ilio-femoral:one). One patient underwent extra-anatomic revascularization. Only two patients had supraceliac aortic cross-clamping and one patient underwent exclusion of both internal iliac arteries. Four patients had hypotension. Early mortality was 22% (two of nine). Severe perioperative complications, mostly due to associated visceral and somatic ischemia and sepsis, were present in seven of the nine patients. The extent and type of the neurologic injury correlated with long-term outcome. Patients with ischemic injury of the lumbosacral roots or plexus had better recovery. Attention to the pelvic circulation and the collateral blood supply is important. Use of gentle technique to prevent embolization, avoidance of hypotension and prolonged supraceliac cross-clamping, revascularization of at least one internal iliac artery, and the use of heparin may decrease but not eliminate paraplegia. Once this unexpected complication occurs, careful neurologic evaluation should be done to localize the lesion and aid prognosis."
-What is the significance of Agrobacterium radiobacter peritonitis in the two patients on chronic peritoneal dialysis?,"Agrobacterium radiobacter peritonitis in two patients maintained on chronic peritoneal dialysis. We report two patients with end-stage renal disease maintained on chronic peritoneal dialysis who developed peritonitis in which the infecting organism was Agrobacterium radiobacter, normally a rare pathogen in humans. Both patients initially responded to antibiotics, but later relapsed and required catheter removal. Neither had been exposed to soil or plant material. A radiobacter is yet another of a growing list of unusual organisms that infect the peritoneal cavity of peritoneal dialysis patients."
-How does calcium potentially help in reducing the risk of colon cancer according to the given context?,"Modulating effects of calcium in animal models of colon carcinogenesis and short-term studies in subjects at increased risk for colon cancer. A substantive amount of evidence from animal models supports the hypothesis that dietary fat is an etiological factor in colon cancer. Although various theories account for possible mechanisms, it is clear that under the influence of a basic colonic pH, fatty acids and bile acids may become highly surfactant in the colon, causing cell loss and compensatory hyperproliferation. Calcium likely reduces lipid damage in the colon by complexing with fat to form mineral-fat complexes or soaps. It has been shown in an increasing number of animal experiments that calcium has the ability to inhibit colon cancer. In limited studies in man, the colonic hyperproliferation associated with increased risk for colon cancer has been reversed for short periods by administration of supplemental dietary calcium. Taken together the available evidence suggests that increases in the daily intake of calcium in the diet may provide a means of colorectal-cancer control."
-What is the recommended treatment approach for symptomatic cavernous malformations of the brain stem?,"Cavernous malformations of the brain stem. Once they become symptomatic, cavernous malformations of the brain stem appear to cause progressive morbidity from repetitive hemorrhage, and can even be fatal. Twenty-four patients with long-tract and/or cranial nerve findings from their cavernous malformations of the brain stem were seen for initial evaluation or surgical consultation and thereafter received either surgical or continued conservative treatment. The decision to operate was based on the proximity of the cavernous malformation to the pial surface of the brain stem, the patient's neurological status, and the number of symptomatic episodes. Sixteen patients were treated by definitive surgery directed at excision of their malformation. In four patients, associated venous malformations influenced the surgical approach and their recognition avoided the risk of inappropriate excision of the venous malformation. Although some of the 16 patients had transient, immediate, postoperative worsening of their neurological deficits, the outcome of all except one was the same or improved. Only one patient developed recurrent symptoms: a new deficit 2 1/2 years after surgery required reoperation after regrowth of the cavernous malformation. She has been neurologically stable since the second surgery. One patient died 6 months postoperatively from a shunt infection and sepsis. The eight conservatively treated patients are followed with annual magnetic resonance imaging studies. One has a dramatic associated venous malformation. Seven patients have either minor intermittent or no symptoms, and the eighth died from a hemorrhage 1 year after his initial presentation. Based on these results, surgical extirpation of symptomatic cavernous malformations of the brain stem appears to be the treatment of choice when a patient is symptomatic, the lesion is located superficially, and an operative approach can spare eloquent tissue. When cavernous malformations of the brain stem are completely excised, cure appears permanent."
-What chromosomal translocation was observed in the meningioma cells of patient MN32?,"A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene. Cytogenetic analysis of meningioma cells from one particular patient (MN32) displayed the stem-line karyo-type 45, XY, -1, 4p+, 22q-, 22q+, which thus had rearrangements of both chromosomes 22. The 22q+ marker appeared as a dicentric: 22 pter----q11::1p11----qter. The reciprocal product of this translocation has presumably been lost because it lacked a centromere. The 22q- chromosome also appeared to have lost sequences distal to band q11. We assumed that this marker could have been the result of a reciprocal translocation between chromosomes 4 and 22. To investigate the 4p+ and 22q- chromosomes in more detail, human-hamster somatic cell hybrids were constructed that segregated the 22q- and 4p+ chromosomes. Southern blot analysis with DNA from these hybrids showed that sequences from 22q were indeed translocated to 4p+ and that reciprocally sequences from 4p were translocated to 22q-, demonstrating a balanced t(4;22)(p16;q11). On the basis of these results we presume that in this tumor a tumor-suppressor gene is deleted in the case of the 22q+ marker and that the t(4;22) disrupts the second allele of this gene. The latter translocation was mapped between D22S1 and D22S15, a distance of 1 cM on the linkage map of this chromosome. The area in which we have located the translocation is within the region where the gene predisposing to neurofibromatosis 2 has been mapped."
-How does the activity of calcium-independent plasmalogen-selective phospholipase A2 change during myocardial ischemia?,"The rapid and reversible activation of a calcium-independent plasmalogen-selective phospholipase A2 during myocardial ischemia. Recent studies have demonstrated the existence of two members of a novel family of calcium-independent plasmalogen-selective phospholipases A2 in mammalian myocardium (Wolf, R. A., and R. W. Gross. 1985. J. Biol. Chem. 260:7295-7303; and Hazen, S. L., D. A. Ford, and R. W. Gross. 1991. J. Biol. Chem. 266:5629-5633). To examine the potential role of these calcium-independent phospholipases A2 in mediating membrane dysfunction during early myocardial ischemia, the temporal course of alterations in phospholipase A2 activity during global ischemia in Langendorf perfused rabbit hearts was quantified and compared with traditionally accepted markers of myocytic ischemic injury and anaerobic metabolism. We now report that membrane-associated calcium-independent plasmalogen-selective phospholipase A2 activity increased over 400% during 2 min of global ischemia (P less than 0.01), was near maximally activated (greater than 10-fold) after only 5 min of ischemia, and remained activated throughout the entire ischemic interval examined (2-60 min). Activation of membrane-associated plasmalogen-selective phospholipase A2 after 5 min of myocardial ischemia was rapidly reversible during reperfusion of ischemic tissue. Both the activation of phospholipase A2 and its reversibility during reperfusion were temporally correlated to alterations in myocytic anaerobic metabolism. Furthermore, activation of membrane-associated phospholipase A2 was essentially complete before electron microscopic evidence of cellular damage. Collectively, these results identify dynamic alterations in calcium-independent plasmalogen-selective phospholipase A2 activity during myocardial ischemia which precede irreversible cellular injury and demonstrate that activation of plasmalogen-selective phospholipase A2 is amongst the earliest biochemical alterations in ischemic myocardium."
-What was the purpose of the study on thallium-201 scintigraphy and how reproducible were the quantitative measurements?,"Reproducibility of quantitative planar thallium-201 scintigraphy: quantitative criteria for reversibility of myocardial perfusion defects. Fifty-two paired stress/delayed planar 201TI studies (27 exercise studies, 25 dipyridamole studies) were processed twice by seven technologists to assess inter- and intraobserver variability. The reproducibility was inversely related to the size of 201TI perfusion abnormalities. Intraobserver variability was not different between exercise and dipyridamole studies for lesions of similar size. Based upon intraobserver variability, objective quantitative criteria for reversibility of perfusion abnormalities were defined. These objective criteria were tested prospectively in a separate group of 35 201TI studies and compared with the subjective interpretation of quantitative circumferential profiles. Overall, exact agreement existed in 78% of images (kappa statistic k = 0.66). We conclude that quantification of planar 201TI scans is highly reproducible, with acceptable inter- and intraobserver variability. Objective criteria for lesion reversibility correlated well with analysis by experienced observers."
-What are the main components of delay in treatment for acute myocardial infarction?,"Delays in the treatment of acute myocardial infarction: an overview. Delays in treatment of acute myocardial infarction prevent a substantial portion of patients from receiving maximal benefit from reperfusion therapy. Median delay between onset of symptoms and arrival at the hospital is 2 to 4 hours. Average time between arrival at the hospital and initiation of thrombolytic therapy is 84 minutes. Approximately 50% of patients hospitalized for suspected acute myocardial infarction do not use the emergency medical service system. Delay before treatment can be divided into several components: patient delay, emergency medical service delay, and hospital delay. Factors contributing to delay in each component and possible approaches to decreasing these delays are discussed. The effects of treatment delay on prognosis and future care-seeking behavior of patients hospitalized with suspected acute myocardial infarction are also discussed."
-"How does Na,K-ATPase activity change in different nephron segments in rats with moderate heart failure compared to the control group?","Na,K-ATPase in isolated nephron segments in rats with experimental heart failure. To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control)."
-What were the key findings regarding the prognosis of Hodgkin's disease in patients aged 60 to 79 years compared to patients aged 40 to 59 years?,"The prognosis of Hodgkin's disease in older adults. This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates."
-"How do the concentrations of somatostatin, gastrin-releasing peptide (GRP), and gastrin differ in the stomachs of rats with streptozotocin-induced diabetes and insulinoma compared to control rats?","Somatostatin, gastrin-releasing peptide and gastrin in the stomach of rats with streptozotocin-induced diabetes and insulinoma. Somatostatin, gastrin-releasing peptide (GRP) and gastrin were measured in the stomach of rats with streptozotocin-induced diabetes, insulinoma-bearing rats and their respective controls. Rats injected with streptozotocin exhibited hyperphagia, insulinopenia and severe hyperglycemia. Stomach weights, and the concentrations and total amounts of GRP and gastrin in the stomach, were similar to nondiabetic control rats. The concentration of somatostatin in the stomach of diabetic rats was 25% greater, but the total stomach content of somatostatin was similar to that of control rats. Insulinoma-bearing rats exhibited hyperphagia, hyperinsulinemia and hypoglycemia. Concentrations of GRP and gastrin in the stomach were 72% and 19% lower, respectively, than in control rats. Despite 45% greater stomach weight, the total stomach content of GRP was 61% lower. Stomach concentrations of somatostatin, and total stomach contents of somatostatin and gastrin, were similar in insulinoma-bearing and control rats. The results demonstrate abnormalities in the stomach concentrations of regulatory peptides in rats with diabetes and insulinoma. These abnormalities are not attributable to changes in food intake alone, suggesting specific effects of these metabolic diseases on gastric regulatory peptides and gastric function."
-"What rare condition was observed in the 4-year-old girl with sinusitis, and how was it diagnosed and treated?","Periorbital hematoma secondary to sinusitis in a child. Periorbital abscess secondary to sinusitis is a well-recognized entity in children. However, subperiosteal hematoma is extremely rare and has been reported in only four adult patients. This article presents the case of a 4-year-old girl with sinusitis, proptosis, and decreased visual acuity. Surgical exploration of the orbit revealed the presence of a large organizing subperiosteal hematoma that was drained. The presence of a periorbital hematoma should be suspected in patients with acute onset of proptosis and findings of a periorbital mass and sinusitis on computed tomographic scan."
-How does dopamine release in the nucleus tractus solitarii change during severe hypoxia in rabbits?,"Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits. A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures."
-What is gliomatosis peritonei and what unique transformation was observed in this case report?,"Gliomatosis peritonei with malignant transformation: a case report and review of the literature. Gliomatosis peritonei is the implantation of glial tissue within the peritoneal cavity associated with ovarian teratomas. Previous reports have emphasized improved outcomes when these implants are found to be mature, even if the ovarian component is immature. A 16-year-old female with grade 3 immature teratoma was found on two subsequent laparotomies to have extensive peritoneal implantation of mature glial tissue. More than 5 years after the original surgery she was found to have a malignant abdominal glial neoplasm. This case illustrates a rare finding of malignant transformation of previously mature gliomatosis peritonei."
-How does glucagon affect the serum total bile acid levels in patients with different stages of liver cirrhosis?,"Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis. Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver."
-How can PCR analysis of BCR-abl fusion transcripts help in detecting potential relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia patients after bone marrow transplantation?,"Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph-) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL."
-What was the hospital mortality rate for patients undergoing coronary bypass reoperation with bilateral internal mammary artery grafts compared to those receiving primary revascularization?,"Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups."
-What was the purpose of the Rheumatoid Arthritis Azathioprine Registry (RAAR) established in 1982?,"Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. The Rheumatoid Arthritis Azathioprine Registry (RAAR) was established in 1982 to examine the safety of azathioprine (AZA) and other disease modifying agents (DMARD) in the treatment of RA. In yearly followup over the past 7 years, 20 malignant conditions have been reported in 530 DMARD treated adult patients with RA. Incidence density ratios (IDR) and standardized morbidity ratios (SMR) were calculated to assess cancer risk. For all cancers the SMR was 1.52 (95% CI 0.90-2.60). For men the SMR was 1.71 (95% CI 0.84-3.52); for women the SMR was 1.52 (95% CI 0.89-2.60). Adjusted for age, the IDR was highest in the 70-79-year-old study population (3.41). The age and sex adjusted SMR for lymphoproliferative disorders and myeloma was 8.05 (95% CI 3.30-20.81). The SMR for lung cancer (n = 6) was also increased (3.37; 95% CI 1.58-7.34). Compared with the general population, patients with RA requiring DMARD therapy may be at increased risk of malignancy, particularly lymphoproliferative disorders. The RAAR is an important prospective technique which will ultimately permit assessment of neoplasia risk by type and duration of DMARD therapy."
-What advantages does adenosine have over dipyridamole as a pharmacologic stress agent in positron emission tomography (PET) imaging?,"Adenosine in myocardial perfusion imaging using positron emission tomography. Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction."
-What are the precipitating factors for colovesical fistula in the described diabetic patient?,Colovesical fistula secondary to vesical gangrene in a diabetic patient. We present a case of colovesical fistula secondary to vesical gangrene. Precipitating factors were diabetes and vesical distension caused by the obstruction of an indwelling catheter. This complication is an exceptional outcome in gangrenous cystitis and it requires emergency surgical treatment.
-How did the atrial natriuretic factor analog A68828 affect glomerular filtration rate (GFR) in a postischemic acute renal failure model?,"Beneficial effect of the atrial natriuretic factor analog A68828 in postischemic acute renal failure. Short-term administration of atrial peptides has been reported to improve renal function in several animal models of acute renal failure. We designed experiments that determined the effect of a 13-amino acid analog of atrial natriuretic factor (ANF), A68828, on renal function in the postischemic model of acute renal failure. Experiments were conducted using euvolemic, male Sprague-Dawley rats (200-250 g) under Inactin anesthesia. Acute renal failure was induced by complete occlusion of both renal arteries for 30 min. After release of the clamp, vehicle (0.1% bovine serum albumin in saline), A68828 (3, 10 or 30 micrograms/kg/min), dopamine (10 micrograms/kg/min), A68828 (10 micrograms/kg/min) plus dopamine (10 micrograms/kg/min) or ANF (1-28) (0.5 micrograms/kg/min) were infused i.v. for a 2-h period. A68828 at 10 micrograms/kg/min produced a significant increase in glomerular filtration rate (GFR) compared with vehicle controls (0.39 +/- 0.08 vs. 0.19 +/- 0.04 ml/min/100 g; P less than .05) despite a lower arterial pressure (87 +/- 5 vs. 101 +/- 5 mm Hg; P less than .05). A subpressor dose of dopamine had no effect on GFR during the postischemic period (0.25 +/- 0.11 ml/min/100 g). Dopamine in combination with A68828 prevented the decrease in arterial pressure seen with A68828 alone but did not potentiate the beneficial effects on GFR (0.28 +/- 0.05 ml/min/100 g). ANF (1-28) at 0.5 micrograms/kg/min increased GFR to levels nearly identical to those induced by A68828 (0.40 +/- 0.04 ml/min/100 g). These results indicate that infusion of a reduced-size analog of ANF improves renal function in the immediate postischemic period. Furthermore, prevention of the hypotensive effects of the analog with dopamine provides no additional beneficial effect."
-What is clear cell cribriform hyperplasia (CCCH) of the prostate and what were the key findings of this study?,"Clear cell cribriform hyperplasia of the prostate. Immunohistochemical and DNA flow cytometric study. Clear cell cribriform hyperplasia (CCCH) of the prostate is an unusual form of benign prostatic hyperplasia characterized by a nodular proliferation of clear cells with small, uniform nuclei. The authors studied 15 cases of CCCH by immunohistochemistry and 13 of them by DNA flow cytometry to establish the immunohistochemical and DNA profile of this lesion. Patients ranged in age from 58 to 88 years (mean, 68 years). Follow-up of a mean of 22 months showed all patients alive with no evidence of malignant prostatic disease. All 13 CCCHs showed diploid DNA content; in contrast, among 4 papillary/cribriform carcinomas of the prostate used for comparison, 3 were aneuploid and 1 was diploid. A basal cell layer was demonstrated in all 15 CCCHs by the use of the 34 beta E12 anti-high-molecular-weight keratin antibody (EAB-903) that reacts with the basal cells but not with the acinar cells of the prostate. A continuous basal cell layer was not evident in the carcinomas. The blandness of the epithelium, the well-defined nodular configuration, the presence of a basal cell layer demonstrable by immunocytochemistry, and the lack of aneuploidy as determined by DNA flow cytometry together lend support to the concept that CCCH is a benign lesion."
-What is cramp-fasciculation syndrome and how was it treated in the reported patients?,"Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder. We report nine patients with muscle aching, cramps, stiffness, exercise intolerance, and peripheral nerve hyperexcitability. Neurologic examination showed calf fasciculations in seven, quadriceps myokymia in two, and deltoid myokymia in one patient. Two patients had mild increase in serum creatine kinase. Muscle biopsy showed either no abnormality (three patients) or mild neurogenic changes (four patients). Fasciculations were the only abnormality on routine electrodiagnostic studies. Supramaximal stimulation of the median, ulnar, peroneal, and posterior tibial nerves at frequencies of 0.5, 1, 2, and 5 Hz produced showers of electrical potentials following the M response in at least one nerve. In three patients, the fasciculations and evoked electrical potentials were abolished by regional application of curare but not nerve block. Carbamazepine therapy caused moderate-to-marked reduction of symptoms and nerve hyperexcitability. We designate this hyperexcitable peripheral nerve disorder as the ""cramp-fasciculation syndrome.""."
-What diagnostic methods are recommended for identifying acid peptic disease in adolescents?,"Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment. Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life."
-How did the perceived beliefs of others and attitudes impact regimen compliance among myocardial infarction patients two years after the intervention?,"Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens."
-What was the incidence of allergic reactions in patients receiving long-term benzathine penicillin prophylaxis for rheumatic fever?,"Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group. 1790 patients from 11 countries were enrolled in a prospective international study to determine the incidence of allergic reactions to monthly intramuscular benzathine penicillin (penicillin G benzathine) injections to prevent recurrences of rheumatic fever. After 32,430 injections during 2736 patient years of observation, 57 of the 1790 patients (3.2%) had an allergic reaction. 4 had anaphylaxis, an incidence of 0.2% (1.2/10,000 injections), all in patients over 12 years of age, and 1 patient died, a fatality incidence of 0.05% (0.31/10,000 injections). These rates are similar to those described for patients without rheumatic fever who receive short-term treatment with parenteral penicillin. Rheumatic fever recurred in 8 of 1790 patients (0.45%) who received benzathine penicillin prophylaxis compared with 11 of 96 (11.5%) who did not comply with treatment. Life-threatening allergic reactions are rare in patients on long-term parenteral benzathine penicillin to prevent recurrences of rheumatic fever; the long-term benefits of such prophylaxis by far outweigh the risk of a serious allergic reaction."
-How does the degree of carotid arterial stenosis affect cerebral blood flow reactivity to hypercapnia?,"Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results. To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia."
-How does protein kinase C (PK-C) contribute to parathyroid hormone (PTH)-induced desensitization in UMR-106 osteosarcoma cells?,"Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells. We have investigated mechanisms of PTH-induced homologous desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced desensitization. Thus, PK-C seemed to play a major role in rPTH-induced desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced homologous desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells."
-How did the use of the Hemonetics cell saver apparatus impact blood transfusion requirements during coronary artery bypass graft surgery?,"The benefit of the Hemonetics cell saver apparatus during cardiac surgery. This retrospective chart review of 155 patients having coronary artery bypass graft surgery (CABG) over a two-month period determined whether the use of a cell saver apparatus (CSA) (1) reduced or increased the requirements for homologous blood; (2) increased the incidence of post-surgical bleeding; (3) was cost-effective. Two groups of patients were identified. Group 1 (n = 99) received both CSA processed red blood cells and homologous blood components. Requirement for homologous blood products was reduced in the first 24 hr after surgery (0.5 +/- 1.0 vs 1.3 +/- 1.8 units; P less than 0.05) when compared with Group 2 (n = 56) in whom only homologous blood products were utilized. More patients in Group 1 had no transfusion requirements (45 vs 8; P less than 0.05) and there was no increased risk of major haemorrhage. When the capital costs are included, utilization of the CSA was not cost-effective. We conclude that utilisation of a CSA was safe, with no increased risk of bleeding, reduced requirements for homologous blood transfusions, but added to the cost of the procedure."
-What percentage of patients in the study had syncope produced by orthostatic testing?,"Abnormal responses to orthostatic testing in children and adolescents with recurrent unexplained syncope. Syncope in the pediatric age group is a frequent event. Most often the cause is readily apparent--i.e., orthostatic hypotension or a vasovagal event. However, there are a large number of children with frequent recurrent unexplained syncope. Neither history, physical examination, nor standard testing reveals a cause. One hundred four consecutive patients were evaluated by orthostatic testing after standard methods found no cause for the recurrent syncope. Forty-seven (44%) of these 104 patients had syncope produced by orthostatic testing. Twenty-six of the 47 (55%) became syncopal within 5 minutes of testing initiation and 21 of the 47 (45%) after 5 to 11 minutes of testing. These patients had an average decrease of 81.5 mm Hg in blood pressure and a 25 beat/min decrease in heart rate. Of 12 control subjects, none lost consciousness with standing times as long as 14 minutes. Pacing was ineffective in preventing syncope, as two patients with a previously implanted normally functioning pacemaker had recurrent syncope clinically. Syncope was also induced by orthostatic testing, with the pacemaker showing a normal response with pacing as the patient became bradycardic. The syncopal event produced by orthostatic testing occurred with a downward blood pressure trend and a narrowing of the pulse pressure without a significant increase in heart rate. This was followed by a sudden drop in blood pressure and then by bradycardia. There is a group of children and adolescents with recurrent unexplained syncope due to abnormal orthostatic control mechanisms. Orthostatic testing appears helpful in identifying these patients."
-What were the two methods of epidural diamorphine administration compared in this study?,"Lumbar epidural diamorphine following thoracic surgery. A comparison of infusion and bolus administration. Twenty-two patients received a single dose of diamorphine 5 mg through a lumbar epidural catheter before thoracic surgery. The patients were transferred after surgery to a high dependency unit where they were allocated randomly to receive either an infusion of epidural diamorphine at a rate of 1 mg/hour (group 1) or bolus doses of epidural diamorphine 5 mg on demand (group 2). There was no statistically significant difference between the groups in visual analogue pain scores in the first 18 postoperative hours. Arterial carbon dioxide tension was elevated in both groups and was consistently higher in group 1 than in group 2, with a statistically significant intergroup difference 12 hours after operation. Respiratory rate was not a useful index of respiratory depression. The commonest nonrespiratory side effect was urinary retention, but the incidences of this and other minor side effects were similar in the two groups."
-How accurate is MR imaging with a body coil in estimating prostate tumor volumes?,"Carcinoma of the prostate: MR images obtained with body coils do not accurately reflect tumor volume. MR imaging with a body coil is unreliable in directly demonstrating tumor spread through the prostatic capsule. However, the likelihood of extracapsular spread of prostatic cancer rises with increasing tumor volume. The aim of our study was to assess the accuracy of MR with a body coil in diagnosing capsular penetration indirectly via an estimation of prostatic tumor volumes. Twenty-six patients with proved prostatic cancer that was clinically confined to the gland underwent MR imaging before radical prostatectomy and whole-mount pathologic sectioning of the specimen. Twenty of 31 lesions prospectively outlined on the MR images corresponded to cancers outlined on the pathology slides, and tumor volumes were calculated by using a voxel summation technique. On MR, tumor volume was underestimated in 11 of 20 cases and overestimated in nine of 20 cases. Only two of 20 size estimates based on MR findings were within 10% of actual tumor volume. Overlap in MR tumor volumes was significant between lesions with and without capsular penetration at microscopy. Factors contributing to inaccuracies in measurements of tumor volume on MR images included the variable histologic make-up of the tumors. Our results show that, although knowledge of the size of a prostatic lesion is important in predicting the behavior of the tumor, MR imaging with a body coil is not reliable for accurate estimation of tumor volume."
-What is Parathyroid Hypertensive Factor (PHF) and in what percentage of North American essential hypertensive patients is it found?,"Purification of parathyroid hypertensive factor from plasma of spontaneously hypertensive rats. Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor that may be related to elevation of blood pressure in 30-40% of North American essential hypertensive patients. PHF is also found in several animal models of hypertension, including spontaneously hypertensive rats, and deoxycorticosterone acetate salt hypertensive rats. Plasma collected from spontaneously hypertensive rats (SHR) was used in the present study for purification of PHF. Plasma was dialyzed at a molecular mass cutoff of 1 kDa, and then ultrafiltered at a molecular mass cutoff of 5 kDa. PHF activity, as determined by bioassay (characteristic delayed hypertensive response in normotensive rat) was retained in the fraction that was greater than 1 kDa and less than 5 kDa. Dialyzed and ultrafiltered SHR plasma was fractionated by molecular-exclusion chromatography, either with Bio-Gel P-6 liquid chromatography, or TSK 2000 SW HPLC. The biological activity was detected in a discrete region corresponding to a molecular mass of 2.5-3 kDa. When the molecular-exclusion fraction was subsequently fractionated by reverse-phase HPLC, biological activity was located in a single discrete peak, which did not occur in plasma from normotensive rats prepared in a similar manner. The biologically active fraction of PHF was inactivated by trypsin; this and its UV spectrum indicate the presence of a peptide structure."
-What is a nasal schwannoma and what is the recommended treatment approach?,Nasal schwannoma. A 36-year-old man with a nasal septal mass is presented. The diagnosis of a benign neoplasm arising from peripheral nerve Schwann cells was made by excisional biopsy. A benign nerve sheath tumor may be either a schwannoma or neurofibroma. Schwannomas may be distinguished from neurofibroma by clinical and histologic criteria. Malignant degeneration and intracranial extension may complicate the course of a nasal schwannoma. Complete excision is the preferred therapy.
-What signs of essential fatty acid deficiency were observed in infants receiving a medium-chain-triglyceride (MCT) infant formula?,"Essential fatty acid deficiency associated with the use of a medium-chain-triglyceride infant formula in pediatric hepatobiliary disease. Serum phospholipid fatty acid patterns were determined by gas chromatography in four infants with hepatobiliary disease receiving a formula with a high content of medium-chain-triglyceride (MCT) oil. All four infants demonstrated signs of essential fatty acid deficiency, characterized by decreased arachidonic acid and increased palmitoleic and oleic acids. All had substantial concentrations of the pathologic triene 5,8,11-eicosatrienoic acid. Three of four had decreased linoleic acid concentrations and abnormal ratios of triene to tetraene (5,8,11-eicosatrienoic acid: arachidonic acid), greater than 0.38. One patient may have experienced growth failure due to abnormal essential fatty acid status. Infants with the potential for fat malabsorption should only receive MCT-oil feedings with well above the generally recommended requirements for linoleic acid (3% of total caloric intake)."
-What is the main purpose of the postoperative infusional continuous regional analgesia (PICRA) technique described in the context?,"Postoperative infusional continuous regional analgesia. A technique for relief of postoperative pain following major extremity surgery. A new technique using postoperative infusional continuous regional analgesia (PICRA) for postoperative pain relief was investigated in 23 surgical patients treated by amputation (12 patients) or by limb-salvage resection operations (11 patients). Bupivacaine was delivered into peripheral nerve sheaths via catheters placed therein at the time of surgery. Only patients in whom the nerves were easily accessible were treated. Catheters were placed in the axillary sheath, the lumbosacral trunk, and the femoral nerve sheaths of patients treated with shoulder girdle and pelvic procedures (resections and amputations), and within the sciatic nerve sheath of those treated with lower extremity procedures. The anesthetic agent was delivered at controllable rates. Regional analgesia was obtained in the operative site with minimal motor or sensory decrease. To assess the efficacy of this technique, the results of this study group were compared with those of a matched group of 11 patients treated with similar surgical procedures but who received epidural morphine. Eleven of the 23 patients on PICRA required no supplemental narcotic agents. The mean level of the narcotic agents required by the remaining 13 PICRA patients was approximately one third of that required by the matched group of 11 patients receiving epidural morphine. Overall, the patients on PICRA had an 80% reduction of narcotic requirements when compared to the historical controls. The technique is reliable and can be performed by the surgeon, requiring about a ten-minute increase in operating time. It has potentially wide application in orthopedics in procedures in which the major nerves are easily accessible (e.g., pelvic fractures and revision hip surgery) and for patients with intractable pain of the extremities."
-What are the key findings of the immunoelectronmicroscopic study regarding the binding sites of jejunal antibodies (JAB) in patients with dermatitis herpetiformis?,"Extracellular binding sites of IgA anti-jejunal antibodies on normal small bowel detected by indirect immunoelectronmicroscopy. Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA."
-What are the key findings regarding amenorrhoea in women with non-alcoholic chronic liver disease?,"Amenorrhoea in women with non-alcoholic chronic liver disease. Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage."
-What is the purpose of computer-assisted superimposition of magnetic resonance and high-resolution SPECT images in this study?,"Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain. A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy."
-What are the typical 2-year survival rates for dementia patients in outpatient clinics and nursing homes?,"Survival of patients with dementia. The evidence on survival in dementia is summarized. There are no reliable data on survival after onset of dementia or after first contact with medical services. People with dementia in outpatient clinics and nursing homes have 2-year survival rates of 75% (range 60%-95%) and 50% (range 30%-65%), respectively. Differences in survival between patients with senile dementia of the Alzheimer's type (SDAT) and multi infarct dementia (MID) are small. Women in nursing homes have a better prognosis than men (2-year survival rates, 60% vs 40%). Dementia patients have a considerable excess mortality when compared to the vital statistics. There is no evidence for improvement of survival rates during recent decades. Recommendations for future studies are made."
-What percentage of patients in the study had lesions not ideal for balloon angioplasty?,"Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty BACKGROUND. Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates. METHODS AND RESULTS. In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively. CONCLUSIONS. In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients."
-What percentage of postmenopausal women with adnexal masses were found to have malignant tumors in this study?,"The postmenopausal adnexal mass: correlation between ultrasonic and pathologic findings. One hundred two postmenopausal women underwent ultrasonographic evaluation of adnexal masses before surgery. Twenty-nine (28%) had malignant tumors and 73 (72%) had benign tumors. Two of 33 patients with a ""simple cyst"" smaller than 5 cm in diameter by ultrasound had malignant ovarian tumors. Twenty-two of the 52 women (42%) with ""complex masses"" by ultrasound and five of the 17 (29%) with solid tumors had ovarian cancer. For predicting malignancy in ovarian tumors, abdominal ultrasonography had a positive predictive value of 39% and a negative predictive value of 94%. If a negative sonogram had been relied upon, 6% of malignant ovarian tumors in postmenopausal women might have been missed."
-What were the key findings of the study comparing enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure?,"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination."
-What treatment was used for Pneumocystis carinii pneumonia in heart transplant patients and how effective was it?,"Pneumocystis carinii pneumonia after heart transplantation. Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation."
-What novel technique was developed for detecting Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections?,"Detection of single copies of Epstein-Barr virus in paraffin wax sections by non-radioactive in situ hybridisation. A highly sensitive non-isotopic in situ hybridisation technique was developed for the localisation of Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections. The method uses a repeated sequence of the EBV genome as a probe, labelled with the novel reporter molecule, digoxigenin. The method can identify individual copies of EBV by detection of both EBV DNA and highly localised RNA transcripts. A combination of careful proteolytic digestion of tissue sections, high temperature denaturation of probe and target DNA, and sensitive immunocytochemical detection are used to attain single copy sensitivity. The technique is quicker and simpler to perform than some other methods used for the identification of EBV, and provides simultaneous morphological information which cannot be obtained by methods using tissue extracts. This method permits the investigation of the role of EBV in neoplastic conditions of lymphoid and epithelial cells, and may prove valuable in determining the sites of latent virus in healthy subjects."
-What imaging technique was used to locate the intrathoracic meningocele in the patient with neurofibromatosis?,"Intrathoracic meningocele associated with neurofibromatosis: case report. The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy."
-"What is cyclosporine, and how does it potentially cause hypertension in patients?",Mechanism of cyclosporine-induced hypertension. Cyclosporine is a common immunosuppressive agent used in solid organ and bone marrow transplants and the treatment of some immunological diseases. It has been established that treatment with cyclosporine can cause a patient to develop hypertension within a few weeks of treatment. This review will examine this effect and effective ways to treat it.
-"How do serum, salivary, and intestinal IgA anti-gliadin antibody levels differ in celiac disease patients compared to controls?","Mucosal and systemic IgA anti-gliadin antibody in celiac disease. Contrasting patterns of response in serum, saliva, and intestinal secretions. Serum IgA anti-gliadin antibody estimation is a recognized screening method for celiac disease. However, celiac disease is primarily a small intestinal mucosal disorder, and so we have examined the possibility that secreted, mucosal IgA anti-gliadin antibody might provide a more relevant measure of gluten sensitivity than that obtained from serum tests. Serum IgA anti-gliadin antibody and serum, salivary, and small intestinal aspirate IgA anti-gliadin antibody were measured by enzyme-linked immunosorbent assay. Serum IgA and IgG anti-gliadin antibody were markedly increased in untreated celiacs (N = 31) as compared to normals (N = 20) or disease controls (N = 39) (P less than 0.0001). Levels were lower in treated (N = 30) than untreated celiacs (P less than 0.001). In intestinal aspirates both untreated and treated patients had similar levels of IgA anti-gliadin antibody (P = 0.48), but both were significantly higher than in controls (P less than 0.01). Salivary IgA anti-gliadin antibody, by contrast, was not increased in celiac patients as compared to controls. Serum IgA anti-gliadin antibody was the most sensitive (84%) and specific (95%) test for detecting untreated celiac disease. It was also the most useful in patient follow-up where it provides an early objective indicator of adherence to a gluten-free diet. Mucosal IgA responses to gliadin in celiac disease appear to be compartmentalized, with different portions of the gastrointestinal tract functioning as separate immunological organs. Our results also demonstrate that serum and secretory IgA production are under independent control."
-How does intraaortic balloon pumping (IABP) affect reocclusion rates and left ventricular function in patients with acute myocardial infarction after successful percutaneous transluminal coronary angioplasty (PTCA)?,"Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction. To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 +/- 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p less than 0.05). An increase in ejection fraction in group II compared with group I was marginally significant (4.5 +/- 12.2% vs 9.2 +/- 13.0%, p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function."
-What were the five-year disease-free survival rates for different treatment stages of IIB osteosarcoma in this study?,"IIB osteosarcoma. Current management and survival statistics in the USSR. Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease-free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease-free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion."
-How did the jitter and blocking characteristics of motor end-plates differ between patients with myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) at different stimulation rates?,"Single motor end-plates in myasthenia gravis and LEMS at different firing rates. The jitter and frequency of blocking was studied at single motor end-plates in 10 patients with myasthenia gravis (MG) and in a patient with Lambert-Eaton myasthenic syndrome (LEMS), using single fiber EMG (SFEMG) with axonal microstimulation at rates varying from 0.5 Hz to 20 Hz. While some myasthenic motor end-plates showed lowest degrees of transmission disturbance at the lowest rates and most pronounced abnormality at the highest rates of stimulation, over one-half were most abnormal at intermediate rates and improved at higher rates. In 1 patient, all end-plates behaved in this way. On the other hand, all end-plates in the LEMS patient showed the expected improvement of the abnormal jitter and blocking on increasing the stimulation rate. It is argued that improvement of jitter and blocking at higher rates, unless dramatic, does not necessarily suggest a presynaptic abnormality."
-What was the main finding of the study comparing low and high doses of ethanolamine oleate in treating esophageal varices?,"Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant."
-"What were the key findings regarding proarrhythmia, cardiac arrest, and death in young patients receiving encainide and flecainide?","Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease."
-How does plasma glucose level affect infarct size in focal cerebral ischemia-reperfusion?,"Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious."
-How does hypoalbuminemia impact various physiological processes in the human body?,"The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted."
-How does blood pressure serve as a predictor of cardiovascular diseases according to the Framingham Study?,"Blood pressure as a risk factor for cardiovascular disease. The Framingham Study--30 years of follow-up Data from 30 years of follow-up of the original Framingham Study cohort of 5,070 men and women aged 30-62 years who were first examined during the period 1948-1952 and who were free of cardiovascular disease reveal that blood pressure is a strong and consistent predictor of the development of coronary heart disease, stroke, transient ischemic attack, and congestive heart failure. Other factors related to blood pressure like obesity, left ventricular hypertrophy as demonstrated on electrocardiograms, and heart enlargement as shown by x-ray radiography made several selective additional independent contributions to risk; heart enlargement by x-ray radiography was the best predictor of congestive heart failure."
-What challenges do physicians face in distinguishing between Crohn's colitis and amebic colitis?,"Crohn's colitis complicated by superimposed invasive amebic colitis. The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD."
-What was the proportion of melanomas diagnosed in patients under 30 years old during the study period?,"Malignant melanoma occurring in those aged under 30 in the west of Scotland 1979-1986: a study of incidence, clinical features, pathological features and survival. The study population consisted of the 95 patients who presented with cutaneous malignant melanoma in the west of Scotland between 1979 and 1986 and who were aged under 30 at the time of diagnosis. Over this 7-year period, 1299 melanomas were diagnosed in all age groups in this geographical area, increasing in incidence by 82% from 135 in 1979 to 246 in 1986. The proportion of melanomas diagnosed before the patients' thirtieth birthday remained constant at 6%. None were diagnosed in the under-15 age-group, and none developed on giant congenital naevi. Forty-two of the 95 melanomas (44%) in the under-30 group developed on a small naevus present either from birth or early childhood. These melanomas were thicker than those apparently developing on normal skin, but once controlled for tumour thickness and sex the presence of a pre-existing naevus did not affect 5-year survival. The overall 5-year survival was 76% with poorer survival associated with thicker tumours and male sex. This study suggests that small early onset naevi may have a higher potential for post-pubertal malignant change than has been previously recognized."
-What were the haemodynamic changes observed during the apnoea test for diagnosing brain death?,"Haemodynamic changes during the apnoea test for diagnosis of brain death. Haemodynamic responses to the apnoea test for the diagnosis of brain death were investigated in nine patients with severe head injury or cerebrovascular disease. To prove apnoea, the ventilator was disconnected for ten minutes and oxygen was insufflated to avoid hypoxaemia. No respiratory movement was seen in any patient. Ten minutes after disconnecting the ventilator, PaCO2 was increased to 78 +/- 3 mmHg and pH was reduced to 7.17 +/- 0.02. Adequate oxygenation was maintained in all patients. Cardiac output increased from 4.8 +/- 0.7 to 5.7 +/- 0.8 L.min-1 (P less than 0.05), and mean pulmonary artery pressure increased from 11 +/- 1 to 17 +/- 2 mmHg (P less than 0.01). However, mean arterial pressure, heart rate, pulmonary artery wedge pressure and right atrial pressure did not change. Plasma catecholamines were measured in three patients. Plasma norepinephrine concentrations increased in all three patients but the changes in plasma epinephrine were minimal. These circulatory responses to acute hypercapnia were less than those reported in awake volunteers and in patients during general anaesthesia. However, since plasma norepinephrine concentration increased during the test, some sympathoadrenal response, probably of spinal origin, was present, and may have prevented the direct depressant circulatory effects of acute hypercapnia. In conclusion, the apnoea test did not produce haemodynamic disturbances when respiratory acidosis was limited to a pH 7.17 +/- 0.02 and PaCO2 60-80 mmHg."
-How do energy-absorbing steering wheels compare to standard steering wheels in terms of facial injury severity?,"Traumatic facial injuries with steering wheel loading. This study was conducted to evaluate the biomechanics of facial fractures caused by steering wheel loading. Twelve intact fresh human cadaver heads were impacted onto standard or energy-absorbing steering wheels with a custom-designed and validated vertical-drop apparatus. Either zygoma was impacted once at a velocity of 2.0-6.9 m/s. The specimens were oriented to permit a direct comparison between pretest and posttest radiography, and two-dimensional and three-dimensional CT images. Bone mineral content was determined, and biomechanical forces, accelerations, and deformations were recorded. More severe fractures were associated with higher forces on the zygoma. With increasing velocities, fractures initiated at the zygomatic region propagated to other unilateral regions such as the mandible and orbit or to the contralateral side. Less facial trauma was observed with energy-absorbing steering wheels compared with standard wheels at similar impact velocities. Bone mineral content did not correlate well with specimen age or with fracture severity. Clinically significant fractures were identifiable on 3-D CT images. The flexibility of 3-D CT in evaluating the spatial extent of facial abnormalities in different orientations may have significant impact in planning surgical procedures."
-What was the relationship between nocturnal hypoxaemia and serum erythropoietin concentrations in patients with obstructive sleep apnoea?,Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
-What are the key components of the computer-assisted neurosurgical navigational system described in the context?,"A frameless, armless navigational system for computer-assisted neurosurgery. Technical note. A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures."
-How does diclofenac affect the healing of gastroduodenal mucosal lesions according to the study?,"Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions."
-What are the three main types of pharmacologic agents used in the treatment of congestive heart failure according to the context?,"Progressive congestive heart failure. Ways to approach office management. Treatment of congestive heart failure depends on the cause, precipitating factors, and symptoms of the disease in each patient. Dr Kahn outlines the use of the three main types of pharmacologic agents given for heart failure--diuretics, vasodilators, and digoxin. He describes a stepwise regimen, whereby agents are added as needed to improve symptoms and prolong life."
-What method was used to evaluate the main parameters of liver circulation in this study?,"Combined evaluation of total and functional liver plasma flows and intrahepatic shunting A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation."
-What is the primary treatment method described for superior vena cava thrombosis in this case report?,Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).
-What characterizes the subtype of global aphasia described in this study?,"The aphasic isolate. A clinical-CT scan study of a particularly severe subgroup of global aphasics. This paper outlines the clinical and CT scan features of a subtype of global aphasia, characterized by an extreme loss of communicative abilities, verbal as well as nonverbal. Three to four weeks after a left hemisphere stroke, 17 patients were completely unable to communicate with people addressing them. Though there were differences in their willingness to interact with the environment, they were characterized by complete loss of speech output and by inaccessibility to any kind of message, whether given verbally or through gestures. Patients who survived were reassessed 6 and 12 mos later and half of them were still found in a state of complete communicative isolation. The remainder had somewhat improved, but remained globally aphasic. The attempt to find a CT scan basis for this picture was disappointing. Only 35% of patients had a lesional pattern in agreement with the traditional view that ascribes global aphasia to the involvement of Broca's and Wernicke's areas. The location of lesion in the other cases spanned from anterior cortical damage, to posterior cortical damage, to deep nuclei damage and none of the lesions that have been proposed to account for subcortical global aphasia was consistently observed."
-What were the success and mortality rates for different clinical scenarios in PTCA for patients with unstable angina?,"Clinical factors affecting the immediate outcome of PTCA in patients with unstable angina and poor candidates for surgery. Percutaneous Transluminal Coronary Angioplasty (PTCA) has been successfully applied in unstable angina to carefully selected patients. In this study, PTCA was performed in 277 consecutive patients suffering from unstable angina and for whom bypass surgery was not a valid alternative because either of inoperable conditions or of emergency, or because surgery was not the best option. All patients were admitted first to the intensive care unit where an attempt was made to control unstable angina under conventional medical therapy using at least iv nitroderivative, heparin, and calcium blockers. After a standardized preparation PTCA was performed either as an emergency procedure in medically refractory unstable angina (107 cases) or as an elective procedure in controlled situations after a 7 to 10 days symptom-free period. Three hundred fifty-three coronary vessels were attempted. Results of this group are compared with those of a control group made of 670 consecutive stable patients recruited during the same period, and clinical characteristics are envisaged as potential predictive factors. Unstable angina is undoubtedly associated with a higher overall complication rate, but the immediate outcome is strongly affected by the clinical context. As an example, respective success and mortality rates are: 93% and 0% when a full revascularization is attempted; 91% and 0% in elective procedures in patients under 60; 87% and 1.2% in elective PTCA for multiple vessel disease; 80% and 6.5% in emergency PTCA; 80% and 11% in the overall triple vessel disease; 84% and 16% in patients with deeply altered ejection fraction; and 58% and 26% in triple vessel disease with 2 previously occluded coronary arteries."
-What are the hemodynamic effects of octreotide in patients with autonomic neuropathy?,"Hemodynamic effects of octreotide in patients with autonomic neuropathy. BACKGROUND. The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. METHODS AND RESULTS. Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. CONCLUSION. The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output."
-What is the difference between disease and illness according to the given context?,"Medical aspects of delayed convalescence. Disease and illness are not synonymous. In most instances, disease is demonstrable by anatomic, physiologic, biochemical, microbiologic, or immunologic abnormalities. Disease is a pathologic process. Not all persons with a disease are sick or ill. Symptoms of illness associated with a disease may be manifest or persist after the disease has disappeared. The absence of demonstrable disease, however, does not necessarily mean that symptoms of illness are unreal. Recovery from disease and recovery from illness are not always equated. Many factors, including personal characteristics and social circumstances, can be responsible for recovery from disease and illness. Chronic fatigue syndrome or symptoms of illness can persist in some patients but not in others after many different diseases."
-What are the six characteristic features that help identify psychogenic disorders of stance and gait?,"How to identify psychogenic disorders of stance and gait. A video study in 37 patients. Thirty-seven patients with psychogenic disorders of stance and gait were clinically evaluated, recorded on video, and analysed with regard to clinical phenomenology. Characteristic, suggestive and unspecific features were identified. Six characteristic features proved most valuable for diagnosis of psychogenesis, as they occurred alone or in combination in 97% of patients: (1) momentary fluctuations of stance and gait, often in response to suggestion; (2) excessive slowness or hesitation of locomotion incompatible with neurological disease; (3) ""psychogenic"" Romberg test with a build-up of sway amplitudes after a silent latency or with improvement by distraction; (4) uneconomic postures with wastage of muscular energy; (5) the ""walking on ice"" gait pattern, which is characterized by small cautious steps with fixed ankle joints; (6) sudden buckling of the knees, usually without falls. Seventy-three percent of patients had additional suggestive features. Classification into characteristic subtypes was not found useful because predominant features varied from patient to patient and occurred in various combinations. Factitious impairment of stance and gait was studied in 13 healthy drama students. Simulated gait dysfunction appeared less conspicuous and more difficult to diagnose than the clinical psychogenic disorders."
-What are the key management recommendations for orbital lymphangioma based on the analysis of thirty cases?,"An analysis of thirty cases of orbital lymphangioma. Pathophysiologic considerations and management recommendations. Thirty cases of orbital lymphangioma were reviewed. Clinical, imaging, and microscopic findings were integrated to develop a pathophysiologic construct and management guidelines. The basic lesion might be considered an abortive vascular system which arborizes among normal structures. Intrinsic hemorrhage expands portions of the small-caliber network into large blood cysts, prompting clinical recognition. While major hemorrhage led to early surgery in 12 cases, long pretreatment intervals could be analyzed in 17 others. Twelve patients had second hemorrhages of varied magnitude, from 2 weeks to 15 years after initial recognition; five patients did not in an average of 6.8 years. Some blood cysts contracted spontaneously. Among 23 operated cases, 12 patients had major new bleeds from 4 days to 12 years after initial surgery; 11 patients did not in an average of 4.2 years. Poor final visual acuity was associated with multiple surgeries. The authors advocate conservatism in surgical case selection and in operative dissection."
-What was the success rate of laser-assisted balloon angioplasty in this multicenter study?,"Percutaneous coronary excimer laser-assisted angioplasty: initial multicenter experience in 141 patients. Initial multicenter clinical experience with percutaneous coronary excimer laser-assisted angioplasty is described for 158 lesions in 141 patients. Using a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% improvement in luminal diameter) was achieved in 138 (87%) of 158 lesions, with a reduction to less than 50% stenosis noted in 77 lesions (49%). Overall, laser-assisted balloon angioplasty success (less than 50% residual stenosis without major complication) was observed in 129 (91%) of 141 patients. Procedural complications (abrupt closure 1.3%, side branch occlusion 1.9%, intimal dissection 6.3%, embolization 1.3%, filling defect 1.3%, perforation 1.9% and spasm 1.3% and major complications (non-Q wave myocardial infarction 4.8%, emergency coronary bypass surgery 3.5% and death 0%) were infrequent and predominantly related to subsequent balloon angioplasty. In the early follow-up period (range 1 to 10 months, mean 7), 111 (79%) of the 141 patients remain asymptomatic, whereas symptoms have recurred in 27 (19%) and 3 patients (2.1%) have died. Thus, percutaneous coronary excimer laser angioplasty appears to be a feasible and safe procedure. Assessment of the impact of this technology on the acute complications of and restenosis rates after angioplasty awaits further follow-up analysis."
-How does the frequency of Helicobacter pylori infection change with age according to the study?,"Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection."
-How did changes in carbon dioxide tension (PCO2) affect respiratory resistance in healthy and asthmatic subjects?,"Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented."
-What is a gliofibroma and why is it considered a rare type of tumor?,"Gliofibroma. Case report. The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature."
-What ultrasound findings can help sonologists suspect midgut malrotation complicated by volvulus in infants?,"Midgut volvulus in infants: diagnosis with US. Work in progress. The authors present findings from ultrasound (US) studies that can alert sonologists to the possibility of midgut malrotation complicated by volvulus in neonates and infants. A fluid-filled, distended duodenum seen at US examination in infants is a nonspecific sign of duodenal obstruction, as well as one of the signs of midgut malrotation. In addition, dilated, thick-walled bowel loops, mainly to the right of the spine, and peritoneal fluid were found at abdominal US examinations of three infants with midgut malrotation complicated by volvulus. In one infant with uncomplicated midgut malrotation, only signs of duodenal obstruction were present. The findings at US of duodenal obstruction associated with thickened bowel loops to the right of the spine and peritoneal fluid should lead the sonologist to suspect midgut malrotation complicated by volvulus, a potentially fatal condition, and an upper gastrointestinal series should then be performed to confirm the diagnosis."
-What was the impact of higher haloperidol doses compared to neuroleptic threshold (NT) doses on patients with schizophrenia in this study?,"Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects."
-What are the three different types of colonic contractions that achieve the basic motor functions of the colon?,"Physiology and pathophysiology of colonic motor activity (2). The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS)."
-How does food restriction affect the daily concentration pattern of plasma corticosterone in male Fischer 344 rats?,"Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes."
-How do calcium antagonists and agonists affect halothane-induced contracture in muscle bundles from patients susceptible to malignant hyperthermia?,"Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia. The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors."
-How does the effect of TNF-alpha on IFN-gamma-induced MHC class II expression vary depending on the cell's maturation and differentiation stage?,"Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. MHC class II induction by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. TNF-alpha has been found both to enhance and also to inhibit IFN-gamma-induced MHC class II expression. In the present studies, the effect of TNF-alpha on IFN-gamma induced MHC class II expression was tested in various cell lines. On the basis of the data, we propose that, depending on the stage of differentiation and maturation of the cells, TNF-alpha might synergize or antagonize the affects of IFN-gamma on the regulation of MHC class II expression. Thus, in immature cells such as HL-60 or THP-1, TNF-alpha enhances IFN-gamma-induced class II expression. However, when differentiation was induced in these cells by TPA or IFN-gamma, the additive effect of TNF-alpha on the IFN-gamma induced DR expression was eliminated. Furthermore, TNF-alpha down-regulates the IFN-gamma-induced class II expression in differentiated cells such as human skin fibroblasts or activated macrophages. In bone marrow cells induced to differentiate in vitro, TNF-alpha decreased the IFN-gamma-induced MHC class II expression in a maturation-dependent fashion. These results provide a rational explanation for the conflicting reports regarding the effect of TNF-alpha on IFN-gamma-induced class II expression. But more importantly they may be relevant to the biologic function of TNF-alpha. Thus, we show that TNF-alpha-treated mice have reduced level of Ia expression on peritoneal macrophages and in vivo treatment with TNF-alpha antagonizes the ability of IFN-gamma to induce class II expression on these macrophages."
-What were the key findings of the study comparing enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure?,"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination."
-What was the main purpose of comparing endoscopic injection sclerotherapy (EIS) with conservative treatment in patients with unresectable hepatocellular carcinoma and bleeding esophageal varices?,"Endoscopic injection sclerotherapy versus conservative treatment for patients with unresectable hepatocellular carcinoma and bleeding esophageal varices. We performed endoscopic injection sclerotherapy (EIS) in the treatment of 37 patients with bleeding esophageal varices due to unresectable hepatocellular carcinoma (HCC). The results were compared with those in another 33 HCC patients treated only conservatively, without EIS, during the same period. A majority of both groups died within 3 weeks after treatment. Comparing the two groups, there was no significant difference in fatal bleeding (66% vs 75%), but significantly fewer of the EIS patients died of the index hemorrhage (43% vs. 83%; p less than 0.01). Also, in the absence of portal vein thrombosis, EIS significantly reduced the risk of fatal bleeding (31% vs. 73%; p less than 0.25). The mean days of survival were 32 +/- 15 (range, 2 to 320) in the EIS group and 10 +/- 14 (range, 2 to 270) in the compared group (p less than 0.001). We conclude that EIS provides temporary control of acute esophageal variceal bleeding in patients with unresectable HCC. The major factors contributing to EIS failure are the lethal propensity of the underlying disease and portal vein thrombosis."
-What is the relationship between proteinuria and tubulointerstitial nephritis in experimental nephrosis in rats?,"A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis."
-What are the key categories of etiologic treatments for dizziness mentioned in the context?,"The dizzy patient: etiologic treatment. The basis for the vestibular complaint in dizzy patients should be viewed as having an etiology rather than a description of its clinical presentation. Effective treatment of vestibular disorders is based on the stabilization of the vestibular abnormality, to allow for central vestibular compensation. While not all of the etiologies for dizziness have been described, there are effective etiologic treatments available. These fit into categories of neurotransmitters, blood sugar and blood fat control, hormones, minerals, and treatments for autoimmune dizziness."
-How does the contractile response of aorta to alpha 1-adrenergic stimulation differ between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in a calcium-free medium?,"Contractile response of aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium is reduced in spontaneous hypertension. Vascular responses of aortic rings to alpha 1-adrenergic stimulation by phenylephrine (Phe) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied in Ca(2+)-containing medium and Ca(2+)-free medium plus 50 mumol/L EGTA. Although there was no difference in the sustained force development between SHR and WKY vessels in response to 100 mmol/L KCl or 10 mumol/L Phe in Ca(2+)-containing medium, the transient contractile response to 10 mumol/L Phe in Ca(2+)-free medium was substantially smaller in SHR compared to that in WKY. Subsequent addition of 2.5 mmol/L Ca2+ restored the sustained contractile response to a similar level in both SHR and WKY vessels. The transient contractile response to Phe in Ca(2+)-free medium containing EGTA, presumably due to the release of intracellular Ca2+, decreased progressively with preincubation time in Ca(2+)-free medium, indicating intracellular Ca2+ depletion. Such a temporal change of aortic response was more pronounced in SHR than in WKY. The subsequent response to Ca2+ repletion in the presence of Phe, on the other hand, increased progressively with Ca(2+)-depletion period and was higher in SHR than in WKY. The rate of relaxation after washout of Phe was slower in SHR aorta compared to WKY aorta. These results, together with our earlier findings, collectively suggest that the previous known deficiency in Ca2+ pumping mechanisms of vascular muscle microsomes leading to a reduced functional size of intracellular Ca2+ pool may account for the smaller contractile response of SHR aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium and the slower rate of relaxation."
-What did the twin study reveal about the genetic factors in epilepsy and febrile seizures?,"The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures."
-What unusual combination of neurological and vascular symptoms was observed in the patient with primary antiphospholipid antibody syndrome?,"Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome. We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome."
-What were the limitations of coronary flow reserve measurements in assessing the efficacy of coronary angioplasty within the first 24 hours?,"Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. To determine functional and anatomic changes in the first 24 hours after coronary angioplasty, we studied at random 15 patients (9 men, mean age 60 years) who underwent coronary angioplasty of 16 coronary arteries. Quantitative coronary angiography and coronary flow reserve measurements from digitized coronary angiograms were performed before, immediately after, and 24 hours after coronary angioplasty. Calculated were the minimal luminal diameter, obstruction area, and percentage diameter stenosis from two preferably orthogonal projections. Prior myocardial infarction in the myocardial region of interest was present in four patients. Seven patients had multivessel disease. Collateral vessels supplying the compromised flow region were observed in three patients. Six patients had refractory unstable angina pectoris. After coronary angioplasty, angiographically visible dissection was noted in six patients, whereas side branch occlusion was observed in one. Minimal luminal diameter before, immediately after, and 24 hours after was 0.93 +/- 0.18 mm, 1.53 +/- 28 mm, and 1.53 +/- 0.21 mm, respectively; obstruction area was 0.70 +/- 0.26 mm2, 1.92 +/- 0.69 mm2, and 1.87 +/- 0.51 mm2, respectively; diameter stenosis was 60.4 +/- 8.0%, 36.8 +/- 11.4%, and 37.6 +/- 5.3%, respectively. The coronary flow reserve (lower limit of normal with this technique 3.4) was essentially the same before and immediately after coronary angioplasty (1.26 +/- 0.59 vs 1.30 +/- 0.42, p = NS) with a slight improvement to 1.78 +/- 0.90 (p less than 0.05) 1 day later. Coronary artery dimensions correlated poorly with coronary blood flow reserve before and after angioplasty."
-What are the key clinical features of posterior cortical dementia as described in this case study?,"Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET."
-What was the overall 5-year actuarial disease-free survival rate after salvage surgery for patients with carcinoma of the buccal mucosa?,"Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05)."
-What is the significance of reactive astrogliosis in the subcortical white matter of amyotrophic lateral sclerosis (ALS) brains?,"Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown."
-What were the key findings of the serial echocardiographic study on HIV-infected individuals regarding cardiac abnormalities?,"Reversibility of cardiac abnormalities in human immunodeficiency virus (HIV)-infected individuals: a serial echocardiographic study. Seventy adults who tested positive for human immunodeficiency virus (HIV) were prospectively studied with serial echocardiography to better define the prevalence and progression of cardiac disease in such patients. Fifty outpatients (Group A), including 44 with acquired immunodeficiency syndrome (AIDS) and 6 with AIDS-related complex, and 20 additional patients (Group B) with asymptomatic HIV infection had baseline echocardiographic studies at a time when no patient had symptomatic heart disease. Follow-up studies were performed at 9 +/- 3 months in 52 patients (74%) and again at 15 +/- 3 months after baseline studies in 29 patients (41%). During the study, 22 patients (44%) in Group A and 1 patient (5%) in Group B died. Cardiac abnormalities were noted in 26 patients (52%) in Group A and 8 patients (40%) in Group B (p = NS) on initial or follow-up study. An abnormal left ventricular ejection fraction (less than 45%) or fractional shortening (less than 28%) was seen in seven patients in Group A; of these, three had normal left ventricular function on a later echocardiogram. One patient in Group B had persistent left ventricular dysfunction. All patients in Group A with left ventricular dysfunction on two serial studies died within 1 year after the initial echocardiogram. Ejection fraction did not change between baseline and two follow-up studies in either group (A: 52 +/- 9 vs. 56 +/- 9 vs. 55 +/- 5%, p = NS; B: 58 +/- 6 vs. 58 +/- 5 vs. 59 +/- 6%, p = NS). Right-sided cardiac enlargement resolved in 18 patients (44%), including 5 of 10 in Group A and 3 of 8 in Group B."
-How does a single gluten challenge affect intestinal permeability in patients with coeliac disease compared to healthy controls?,"Intestinal permeability after single dose gluten challenge in coeliac disease. The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood."
-What was the mortality rate associated with class IC antiarrhythmic drug overdose in this study?,"Clinical course and outcome in class IC antiarrhythmic overdose. 120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome."
-What were the key findings of the pilot study on sphincter-sparing management of rectal adenocarcinoma?,"A pilot study of sphincter-sparing management of adenocarcinoma of the rectum. After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy."
-How does transesophageal echocardiography compare to transthoracic echocardiography in detecting valvular vegetations in patients with suspected infectious endocarditis?,"Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography."
-How does native C5a (nC5a) differ from recombinant C5a (rC5a) in inducing histamine release from cutaneous mast cells in BALB/c mice?,"C5a, cutaneous mast cells, and inflammation: in vitro and in vivo studies in a murine model. To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin."
-How does elevated intravesical pressure affect blood perfusion in colocystoplasty according to the fluorometric study?,"Elevated intravesical pressure causes arterial hypoperfusion in canine colocystoplasty: a fluorometric assessment. Since 1988 there have been 15 reported cases of late, spontaneously ruptured intestinal cystoplasties at bowel sites remote from the anastomosis. Ischemic necrosis has been suggested as a possible etiology. We examined this hypothesis by quantifying the uptake of intravascular fluorescein in the augmented bowel of adult mongrel canines. There was a statistically significant decrease in fluorescein uptake at high intravesical pressures, which appeared to be most pronounced at the antimesenteric border. This laboratory study supports a recent clinical report of histological changes pathognomonic for chronic ischemia in the augmented bowel of patients with spontaneous rupture."
-What is the relationship between ventricular arrhythmias and the patency of the infarct-related coronary artery after thrombolytic therapy?,"Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy. In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen."
-What percentage of atypical hyperplasia cases showed a direct mammographic-histologic correlation in the study?,"Atypical hyperplasia of the breast: mammographic appearance and histologic correlation. The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found in 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographic-histologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a five- to tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly mammographic follow-up is suggested once AH is discovered."
-What was the main hypothesis tested in this randomized study of cesarean delivery?,"A randomized study of closure of the peritoneum at cesarean delivery. This study was conducted to test the hypothesis that nonclosure of the visceral and parietal peritoneum during low transverse cervical cesarean delivery is not associated with increased intraoperative or immediate postoperative complications. One hundred thirteen patients scheduled for low transverse cervical cesarean were randomized to either closure of both the visceral and parietal peritoneum with absorbable suture (N = 59) or no peritoneal closure (N = 54). Patients were cared for in the usual postoperative manner without reference to treatment group. There were no demographic differences between the groups and no differences in method(s) of anesthesia, operative indication(s), or use of peripartum epidural narcotics. The incidence of fever, endometritis, or wound infection was similar between groups. There were no differences in the number of patients requiring parenteral narcotic analgesia or in the number of doses per patient. The number of oral analgesic doses was significantly greater with closure than without (P = .014). The frequency with which postoperative ileus was diagnosed in each group was similar, and there was no difference regarding the day on which patients were advanced to liquid or select diets. Bowel stimulants were administered more frequently to the closure than to non-closure patients (P = .03). The average operating time was shorter for the open group than for the closure group (P less than .005). We conclude that non-closure of the visceral and parietal peritoneum at low transverse cervical cesarean delivery appears to have no adverse effect on immediate postoperative recovery, may decrease postoperative narcotic requirements, allows less complicated return of bowel function, and provides a simplified and shorter surgical procedure."
-What was the primary purpose of performing transcervical resection of the endometrium (TCRE) in this study?,"Experience with the first 250 endometrial resections for menorrhagia [published erratum appears in Lancet 1991 Jan 1;337(8753):1362] 234 patients with menorrhagia were treated hysteroscopically by transcervical resection of the endometrium (TCRE) instead of hysterectomy. 250 procedures were performed under general anaesthesia (63%) or under sedation plus local anaesthesia (38%). The endometrium was excised either totally (91%) or partially (9%) in all but one case, and 56 (22%) of the patients underwent simultaneous resection of submucous fibroids. Surgical time (range 10-100 min) varied with the gynaecologist's experience. 479 ml was the average volume of uterine irrigant absorbed by the patient. Blood loss was usually slight. Operative complications were uncommon, but 4 (2%) women sustained a uterine perforation (without serious sequelae), 7 (3%) absorbed more than 2 litres of fluid, and 1 required tamponade to control postoperative bleeding. Hospital stay was short and full recovery usual by 1-2 weeks. Menstrual symptoms improved in over 90% of the patients throughout the follow-up of up to 2 1/2 years; 27-42% of the women became amenorrhoeic at some time after total TCRE. Results were best in women greater than 35 years of age, but was not influenced by the presence of fibroids or pretreatment dysmenorrhoea. 10 (4%) women later underwent hysterectomy. Hysteroscopy 3 and 12 months after surgery revealed a small, fibrotic uterine cavity in the majority."
-How does the increased collagen content in hypertrophic cardiomyopathy affect heart function?,"Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in ""normal"" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease."
-What was the relationship between nocturnal hypoxaemia and serum erythropoietin concentrations in patients with obstructive sleep apnoea?,Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
-What suture technique and material were found to result in less stenosis when performing tracheal anastomosis in a growing animal model?,"Growth of tracheal anastomoses: advantage of absorbable interrupted sutures [published erratum appears in Ann Thorac Surg 1991 Jul;52(1):176] Growth of the trachea after complete transection and anastomosis was studied in four groups of 1-month-old New Zealand white rabbits. The trachea was transected at the fifth cartilaginous ring and then anastomosed with continuous 6-0 polypropylene (Prolene) (group 1), interrupted 6-0 polypropylene (group 2), continuous 6-0 polydioxanone (PDS) (group 3), or interrupted 6-0 PDS (group 4). The animals were followed up for 90 to 103 days (mean follow-up, 95 days). At the time the animals were killed, body weight had increased 125% (1.2 to 2.7 +/- 0.18 kg). Growth of the trachea was assessed at the time of death. Results from this study suggest that growth of a tracheal anastomosis is retarded in a growing animal model. The degree of resultant stenosis was significantly less when an absorbable suture material (PDS) and an interrupted suturing technique were used."
-What is the purpose of using impedance plethysmography in monitoring muscle perfusion after free tissue transfer?,"Impedance plethysmography: a new method for continuous muscle perfusion monitoring. Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion."
-What pathological features were observed in the small vessels of the nonelderly demented patients with sclerosing vasculopathy?,"Sclerosing vasculopathy of the central nervous system in nonelderly demented patients. Three nonelderly patients without hypertension whose clinical and radiologic features otherwise resembled Binswanger's subcortical arteriosclerotic encephalopathy underwent biopsy of the hyperintense periventricular lesions seen on magnetic resonance imaging. The pathologic findings of the periventricular lesions consisted of gliosis with mild rarefaction and edema of the white matter. All patients had a sclerosing vasculopathy of unknown cause, which involved numerous small vessels within the periventricular lesions. The vessels stained negatively for amyloid, amyloid precursors, desmin, vimentin, keratin, immunoglobulin, and complement. On electron microscopy, small arteries, arterioles, venules, and capillaries were characterized by swollen astrocytic foot processes surrounding the vessels; dense, perivascular collagen packing; crystalline arrays of filaments within basement membrane; giant lipid-laden lysosomes within perivascular cells; and narrowing of the vascular lumina. Similar changes were not seen in a control group of 19 patients. The pathologic features of the vessels in these cases are distinct from the vasculopathy associated with Binswanger's subcortical arteriosclerotic encephalopathy. We suggest that a spectrum of vasculopathies may be associated with dementia and periventricular hyperintense lesions on magnetic resonance imaging."
-What were the different management approaches used for treating pancreatic fluid collections in this study?,"Invasive treatment of pancreatic fluid collections with surgical and nonsurgical methods. Pancreatic fluid collections (PFC) can be drained surgically or nonsurgically with endoscopic or radiologic techniques. To define subgroups of patients with PFC who would benefit from the new modalities, we reviewed a period (1977 to 1990) during which both surgical and nonsurgical invasive techniques were available. Patients with phlegmon or necrosis at initial diagnosis were excluded. Sixty-five patients (35 male, 30 female) underwent 1 or more drainage procedures. A mean postprocedure follow-up of 10.2 months was available for 59 patients. Initial management was nonsurgical in 80% of patients. Procedures in patients with follow-up comprised invasive nonsurgical drainage (n = 25), invasive nonsurgical drainage plus surgery (n = 22), and surgery only (n = 12). Results for each group, respectively, were: morbidity, 20%, 20%, and 24%; mortality, 8%, 5%, and 0%; and successful drainage, 92%, 82%, and 83%. The choice of management appeared to be based on etiology and radiologic characteristics. Patients with nonalcohol- and nonbiliary-associated pancreatitis without a radiographically defined wall were more common in the invasive nonsurgical group and were successfully treated without surgery. Nonsurgical invasive techniques are efficacious in the treatment of PFC in this subgroup of patients."
-What was the primary objective of the seromuscular enterocystoplasty experiment in rats?,"Seromuscular enterocystoplasty in rats. Enterocystoplasty is commonly used in clinical practice. Many of its undesirable effects, that is infections, stones, mucus production, absorption of urinary components into the blood stream and risk of cancer, result from the intestinal mucosa lining the urinary tract. We report on the feasibility of creating an enterocytoplasty with a seromuscular colonic segment that acquires a transitional epithelial lining. Augmentation enterocystoplasty was performed in 51 male, 500 gm., Sprague-Dawley rats with a 1.82 cm.2 patch of left colon from which the mucosa had been stripped. The serosal surface was used as lining for the enterocystoplasty. The intestinal patch and the bladder capacity at known pressure were measured at operation and at sacrifice. The histology of the enterocystoplasty was studied in detail following sacrifice. Of the animals 40 survived without significant complications and were sacrificed at a mean postoperative time of 30 days (range 5 to 80 days). In the remaining 11 rats a bladder stone developed but it did not seem to affect the outcome of the experiment. The size of the patch could be measured in 22 rats: it was 1.82 cm.2 (standard deviation +/- 0.86) at operation and 2.30 cm.2 (standard deviation +/- 1.1) at sacrifice. In none of the rats did the patch decrease in size. The bladder capacity at a known pressure (mean 17 cm. water) could be measured in 26 animals: it was 2.35 ml. (standard deviation +/- 0.65) at operation and 5.18 ml. (standard deviation +/- 1.19) at sacrifice. Histological analysis was done in 40 rats. In all cases the serosal surface was lined with transitional epithelium, there was no fibrosis or inflammation and the structure of the muscular layer of the bowel remained intact. The earliest growth of uroepithelium in the serosal surface of the bowel was noted at 5 days. This model suggests that the seromuscular enterocystoplasty can be constructed successfully in the rat model. The seromuscular intestinal patch does not shrink. The bladder capacity increases and histology shows a uroepithelial lining of the augmentation."
-What are the key causes of obesity according to the given context?,"Obesity: types and treatments. Causes of obesity include a low resting metabolic rate, environmental factors, family behavior patterns, a poorly developed satiety response and reactive eating due to stress or anxiety. Morbid obesity is characterized by an increased number of adipocytes and a degree of irreversibility. Overeating increases the size of adipocytes; however, once adipocytes achieve their maximal size, proliferation is induced and massive, irreversible obesity may result. A syndrome of restrained eating produced by chronic dieting leads to hunger, frustration and rebound overeating. Treatment may be unsuccessful because of the failure to address specific causes of obesity in individual patients and the use of reducing regimens that are not designed to maintain weight loss. Recognition of the diverse clinical forms of obesity and their different etiologies permits treatment regimens to be more specific, increasing the likelihood of success. Even with this approach, treatment failure is common."
-What variations in transmembrane domain length were observed in the MHC class I genes of Peromyscus leucopus?,"Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes. The fifth exons of major histocompatibility complex (MHC) class I genes encode a transmembrane domain (TM) that is largely responsible for class I antigen cell-surface expression usually through conventional hydrophobic amino acid-membrane interactions or, less often, through phosphatidylinositol linkage. In this report we show that Peromyscus leucopus, a Cricetidae rodent, has MHC class I genes (Pele-A genes) encoding three distinct sizes of TMs. Increases in TM lengths were due to tandem duplications of sequences similar to human hypervariable minisatellite repeats and the lambda chi site. We discerned remnants of a similar duplication event in comparable rodent and primate MHC class I genes. Furthermore, several duplications and deletions appear to have occurred independently in H-2, RT1, Pele-A, and ChLA genes in near-identical positions. Accumulated data suggests that sequences in the fifth exon of MHC class I genes may, therefore, constitute a mutational or recombinational hot spot that is mediated by minisatellite- and chi-like sequences imbedded within the coding region. The MHC class I genes may thus have recruited ""selfish"" DNA in their evolution to encode cell surface proteins. Expression of Pele-A genes was examined by the polymerase chain reaction (PCR) using oligonucleotide primers specific for exon 4 and 5 sequences. The PCR product sizes indicated that genes encoding each TM domain length are ubiquitously transcribed."
-How does FDG-PET imaging help in detecting and assessing the prognosis of malignant lymphoma in the head and neck region?,"The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis. Twenty-one patients with untreated malignant lymphoma in the head and neck region were evaluated with positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) and gallium-67 SPECT imaging. Tumor-to-normal soft-tissue contrast ratios (TCRs) obtained 60 min after injection of FDG were higher than 2.6, and all malignant lymphomas were clearly visualized. In patients with poor prognosis, higher TCRs and glucose utilization rates (GURs) were observed, whereas low TCR and GUR were shown in a patient with low-grade malignancy. In comparison with 67Ga scintigraphy, patients with high TCRs and GURs were likely to show increased accumulation of gallium-67, but accumulation of gallium-67 was not increased as much as FDG in poor prognostic patients. FDG-PET may be useful in the detection and management of malignant lymphoma."
-Where and when did the Campylobacter enteritis outbreak occur in New Zealand?,"Campylobacter enteritis--New Zealand, 1990. In August-September 1990, an outbreak of Campylobacter enteritis occurred at a camp near Christchurch, New Zealand. This report provides a preliminary summary of the investigation of this outbreak by the New Zealand Communicable Disease Centre and the Canterbury Area Health Board."
-How effective was transesophageal echocardiography in diagnosing conditions in patients initially suspected of having aortic dissection?,"Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. Between September 1987 and April 1989, forty patients suspected to have aortic dissection were evaluated by transesophageal echocardiography. Aortic dissection was identified in 18 patients. This study evaluated the ability of transesophageal echocardiography in the assessment of the 22 patients in whom aortic dissection was not found. A range of pathologic conditions was diagnosed in these patients. Five patients had ischemic heart disease when they were initially seen. Among the remaining 17 only one patient had a normal aorta. Aortic disease was present in the other 16 patients with aortic dilatation in 10. Atheromas were detected in seven patients with concomitant aortic dilatation in five of them. An extrinsic aortic mass was present in two patients. Transesophageal echocardiography correctly identified an anastomotic leak at the site of left coronary artery implantation in a patient with a recent Bentall procedure, and a large mobile clot within the proximal descending aorta in a patient with blunt chest trauma. These findings obviated the need for other tests in 15 patients and led to surgery in four with no ancillary tests performed in three of them. Thus transesophageal echocardiography has an important role in assessing patients with suspected dissection. Aortic disease is common even in patients in whom aortic dissection is excluded, and some of the conditions can be just as life-threatening as dissection. Transesophageal echocardiography not only reliably identifies dissection but can also detect luminal and extraluminal diseases not adequately visualized by other modalities."
-How did the researchers measure local refractoriness during ventricular fibrillation in dogs?,"Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. In 18 dogs on total cardiopulmonary bypass, the average interval between local activations during artificially induced ventricular fibrillation (VF interval) was measured from extracellular electrograms, simultaneously recorded from up to 32 ventricular sites. VF intervals were used as an index of local refractoriness, based on the assumption that during ventricular fibrillation, cells are reexcited as soon as they have recovered their excitability. In support of this, microelectrode recordings in two hearts during ventricular fibrillation did not show a diastolic interval between successive action potentials. Refractory periods determined at a basic cycle length of 300 msec with the extrastimulus method correlated well with VF intervals measured at the same sites. Thus, this technique allows assessment of spatial dispersion of refractoriness during brief interventions such as sympathetic stimulation. The responses to left, right, and combined stellate ganglion stimulation varied substantially among individual hearts. This was observed both in dogs with an intact (n = 12) and decentralized (n = 6) autonomic nervous system. Individual ventricular sites could show effects of both left and right stellate ganglion stimulation (42% of tested sites) or show effects of left-sided stimulation only (31%) or right-sided stimulation only (14%). In 13% of sites, no effects of stellate stimulation were observed. Apart from these regional effects, the responses could be qualitatively different; that is, within the same heart, the VF interval prolonged at one site but shortened at another in response to the same intervention, although shortening was the general effect and prolongation the exception. Whenever sites responded to stellate ganglion stimulation with a shortening of VF interval, this shortening was approximately 10% for left, right, or combined stimulation, whether the autonomic nervous system was intact or decentralized. In six of 12 hearts in the intact group, there was a distinct regional effect of left stellate ganglion stimulation; in the other six hearts, the effects were distributed homogeneously over the ventricles. In three hearts, the effect of left stellate ganglion stimulation was strongest in the posterior wall, and in the other three hearts, in the anterior wall. The effects of right stellate ganglion stimulation were restricted to the anterior or lateral part of the left ventricle. Dispersion of VF intervals increased after left and combined stellate ganglion stimulation in the intact group and after right stellate ganglion stimulation in the decentralized group, but not significantly in every heart. This points to a marked individual variation with regard to the effects of sympathetic stimulation on electrophysiological properties of the heart."
-How does mitral valve replacement affect contractile function in a canine model of mitral regurgitation?,"Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload [published erratum appears in J Clin Invest 1991 Aug;88(2):723] It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload."
-What are the key hemodynamic characteristics of septic shock?,"Septic shock. Septic shock (SS) is the most common type of shock encountered by internists, and its prevalence appears to be increasing. SS complicates all types of infections. The hemodynamic characteristics of SS include a low systemic vascular resistance and an elevated, but relatively inadequate, cardiac output. A cardiomyopathy frequently occurs. The major endogenous mediator of SS is tumor necrosis factor, and interleukins-1 and -2 may also contribute. Important secondary phenomena include release of platelet activating factor, vasodilator prostaglandins, and upregulation of adhesion molecules on polymorphonuclear leukocytes and endothelial cells. Current therapy is often ineffectual, and potentially promising new therapeutic approaches are reviewed."
-What were the key findings of the study regarding cervical spine injuries in alert trauma patients?,"Clinical indications for cervical spine radiographs in alert trauma patients. Cervical spine fracture/dislocation is a potentially devastating injury that may be clinically difficult to diagnose. Therefore, a vast majority of trauma patients undergo cervical spine X rays when only a relatively small number of them will actually have a cervical spine injury. Because of the costly overuse of radiography, studies have been undertaken to define high yield criteria for evaluation of patients. This study examined the characteristics of acute cervical spine fracture/dislocation in alert trauma patients. Of 79 patients with this discharge diagnosis at St. Elizabeth Hospital Medical Center between 1982 and 1987, 47 met the criteria of Class I level of consciousness. All 47 patients complained of neck pain or demonstrated cervical tenderness to palpation. Other parameters (such as loss of consciousness, paresthesias, decreased sensation, weakness, cervical muscle spasm, decreased anal tone, and associated injuries) did not, individually or in combination with each other, consistently predict cervical spine injury. Although occult or painless cervical spine injuries have been reported in the literature, a careful review of these cases revealed that these injuries were not truly asymptomatic. Our study suggests that selected patients can be excluded from radiologic evaluation of the cervical spine. However, large prospective studies are needed to validate this finding."
-What precaution should be taken when using suxamethonium in a patient with a permanent pacemaker during anaesthesia?,"Pacemaker failure on induction of anaesthesia. A patient with a permanent pacemaker presented for repair of a strangulated hernia. During induction of anaesthesia, the pacemaker generator stopped discharging, thus causing cardiac arrest. The likely cause of the generator failure was inhibition by suxamethonium-induced muscle fasciculations. Following defibrillation, and increase in stimulation threshold necessitated urgent insertion of a transvenous pacing system. It is suggested that, when suxamethonium is to be used in a patient with a permanent pacemaker, consideration should be given to reprogramming the pacemaker to asynchronous mode before induction of anaesthesia. If a patient with a pacemaker requires defibrillation, an acute increase in stimulation threshold may result and cause loss of capture. Rapid insertion of a transvenous pacing system may be necessary."
-What potential complication can occur to the pancreas during extracorporeal shock wave lithotripsy (ESWL) for renal calculus fragmentation?,"Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed."
-What are the three different types of skew deviation described in the context?,"Different types of skew deviation. Although all manifest skew deviations appear the same for the clinician, skew deviation can result from different combinations of dysconjugate vertical ocular deviations. Evidence is presented for three different types of skew deviation when it occurs as a feature of an ocular tilt reaction. In type 1 (utricle) there is upward deviation of both eyes with different amplitudes, as described for otolith Tullio phenomenon in humans. In Type 2 (dorsolateral medulla oblongata) hypertropia of one eye occurs while the other eye remains in the primary position, the hypothetical mechanism of skew deviation in Wallenberg's syndrome. In Type 3 (midbrain tegmentum) there is simultaneous hypertropia of one eye and hypotropia of the other eye, as described for electrical stimulation of midbrain tegmentum in monkeys and observed in clinical cases with a paroxysmal ocular tilt reaction."
-What was the main objective of the study on P6 acupressure in children undergoing strabismus correction?,"Effect of P6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction. A prospective, double-blind study was conducted to compare the effect of pressure at the P6 (Neikuan) point with placebo as an antiemetic in children. Sixty-six patients, ages 3-12 yr, undergoing outpatient surgery for correction of strabismus, were allocated randomly to receive either bilateral P6 acupressure or placebo during the perioperative period. The study was designed to detect a 50% difference in the incidence of postoperative vomiting between the two groups, with a 90% power of achieving a statistically significant result at the 5% level (two-tailed). The incidence of postoperative vomiting for the placebo group was 58% before discharge from hospital, 73% at home and 82% in the first 24 h after surgery. The corresponding results for the acupressure group were 58% before discharge, 71% at home and 94% in the first 24 h. These differences were not significant; P6 acupressure did not reduce the incidence of postoperative vomiting in children undergoing strabismus surgery."
-What were the significant prognostic factors for recovery of awareness in patients with prolonged posttraumatic unawareness?,"Prognosis for recovery from prolonged posttraumatic unawareness: logistic analysis. This study reviews the course and outcome of 130 patients who remained in a state of prolonged unawareness 30 days after severe cranio-cerebral trauma. Prognostic indicators and outcome were fitted by a logistic model. The significant prognostic factors observable in the first week after trauma were found to be ventilatory status, motor reactivity and significant extraneural trauma. The significant prognostic factors after the first month of unawareness were early ventilatory status, early motor reactivity, late epilepsy and hydrocephalus. The estimated probability of recovery of awareness (that is, consciousness) ranged from 0.94 in patients with early decorticate posturing in the absence of both extraneural trauma and ventilatory disturbance to 0.06 in patients with flaccidity, extraneural trauma and ventilatory disturbance in the first week after injury."
-Which thrombolytic agent is most effective in restoring patency in coronary arteries according to clinical trials?,"Coronary artery thrombolysis: comparison of approved agents. Three agents approved for the lysis of thrombi in coronary arteries--alteplase, anistreplase and streptokinase--have undergone critical clinical experimental trials in Europe and the United States. Global comparison of their efficacy shows that alteplase is slightly more effective (71 percent) in restoring patency than anistreplase (60 percent) and streptokinase (58 percent). Streptokinase and anistreplase are allergenic, and repeat administration is not feasible in the short-term, a distinct advantage for alteplase. More accurate dosing of thrombolytic agents and skillful use of aspirin and heparin improve the efficacy of thrombolytic therapy but can also increase the risk of bleeding. A recanalization rate of 90 percent or more could be achieved if the thrombolytic agent is administered within the first hour after thrombosis. Administration this soon after the development of thrombosis may be possible if the agent is given outside the hospital by practicing physicians or, perhaps, paramedics."
-"What were the predictive values of digital rectal examination, transrectal ultrasound, and MRI for tumor confinement and extracapsular disease in prostate cancer?","Preoperative prediction of pathological tumor volume and stage in clinically localized prostate cancer: comparison of digital rectal examination, transrectal ultrasonography and magnetic resonance imaging. Accurate preoperative staging is important for proper selection of patients for radical retropubic prostatectomy. Preoperative staging by digital rectal examination, transrectal ultrasound, magnetic resonance imaging (MRI), Gleason grade and prostate specific antigen was compared to pathological stage for 25 patients who underwent radical retropubic prostatectomy. The predictive value for tumor confinement was 36% by rectal examination, 37% by ultrasound and 30% by MRI. The predictive value for extracapsular disease was 100% by rectal examination, 83% by ultrasound and 66% by MRI. Preoperative determinations of tumor volume by any modality did not correlate with pathological tumor volume. Digital rectal examination, ultrasound and MRI clinically understage the disease in most patients but they may be reliable to predict extracapsular disease."
-"What was the purpose of using sublaminar fixation in lumbosacral fusions, and what were the outcomes of the study?","Sublaminar fixation in lumbosacral fusions. Sublaminar fixation to stainless steel rectangles was employed in an effort to improve the fusion rate in lumbar and lumbosacral arthrodesis. Thirty-seven patients had spondylolisthesis, and 26 had other causes of pain secondary to lumbar mechanical instability. Of the 63 patients, 53 achieved fusion and 52 had relief of pain. No infections or neurologic complications were encountered. This fusion rate of 84% does not significantly differ from rates obtained with noninstrumented methods, and this construct is no longer used for lumbar fusions."
-What is the primary genetic mechanism behind Leber's hereditary optic neuropathy?,"Leber's hereditary optic neuropathy and Kearns-Sayre syndrome: mitochondrial DNA mutations. Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported."
-What was the main objective of the study on luteinizing hormone-releasing hormone agonist (LH-RH-a) treatment for uterine leiomyomata?,"Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women. OBJECTIVE: To evaluate the efficacy of luteinizing hormone-releasing hormone agonist (LH-RH-a) in the treatment of leiomyomata. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Twenty-five women, ages 36 to 54 years with symptomatic uterine leiomyomata, were divided into two groups according to the responsiveness to LH-RH-a: group A patients reached menopause after LH-RH-a, whereas resumption of menstruation occurred within 12 weeks after cessation of therapy in group B. INTERVENTIONS: Luteinizing hormone-releasing hormone agonist was administered intranasally three times a day with 150 micrograms insufflation of one spray in each nostril (total dose: 900 micrograms/d). MAIN OUTCOME MEASURES: Efficacies of treatment were assessed in terms of uterine volume, hemoglobin concentrations, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and bone density during and after treatment. RESULTS: In both groups, hemoglobin concentrations increased significantly after 16 weeks of treatment. A significant reduction in uterine volume was observed in both groups. After completing therapy, there was no further significant change in uterine volume in group A, whereas uterine volume in group B returned to pretreatment values. Serum LH and FSH concentrations were suppressed during treatment, but those gonadotropins in group A increased significantly up to the menopausal levels after treatment. Serum E2 concentrations in both groups showed consistent suppression by the end of the first treatment cycle. After cessation of therapy, serum E2 levels on group A remained in the castrate range, whereas E2 in group B returned to pretreatment levels, concomitant with the return of normal ovulation. CONCLUSIONS: Intranasal administration of LH-RH-a was successful in significantly decreasing uterine volume and increasing hemoglobin concentration in premenopausal women with leiomyomata."
-"What are the differences in the expression of Tn, sialosyl Tn, and T antigens across normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma?","Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis."
-What was the main finding of the study regarding epithelial migration in patients with unilateral cholesteatoma?,"Patterns of epithelial migration in the unaffected ear in patients with a history of unilateral cholesteatoma. Epithelial migration in a centrifugal manner is an established phenomenon in the normal human tympanic membrane. This pattern of migration is symmetrical in both ears of any one individual. We present a prospective study on the pattern of tympanic ink dot migration on the normal drum, in patients with a history of cholesteatoma in one ear. It was demonstrated that patients who develop cholesteatoma have a normal migratory pattern and rate in the unaffected ear. The conclusion from this study is that defective migration is not the initiating factor in the development of acquired cholesteatoma."
-Can CT scanning help determine which patients with minimal head injury can be safely discharged from the emergency department?,"The use of CT scanning to triage patients requiring admission following minimal head injury. Recent data have suggested that patients with both a normal cranial CT scan and normal neurologic examination following minimal head injury (MHI) have no risk of neurologic deterioration. This study prospectively examined the safety of discharging patients from the emergency department (ED) after MHI whether or not there was a responsible observer at home. MHI was defined as a history of loss of consciousness (LOC), a Glasgow Coma Scale (GCS) score of 14 or 15, and no focal neurologic findings. In a 4-month period 111 patients with MHI were evaluated. Fifteen (14%) patients had a CT scan which revealed an intracerebral injury; 96 patients had a normal CT scan; five patients with normal CT scans were admitted because of persistent lethargy; and one patient was admitted after his CT that demonstrated an old infarct; the remaining 90 patients were discharged. There were 71 men and 19 women with a mean age of 29 years. The mechanism of injury was assault in 55, MVA in 30, and falls in five. The initial GCS in was 15 in 79 and 14 in 11. Fifty-eight per cent of patients were intoxicated. Fifty-seven (63%) patients were successfully contacted by telephone; none had developed any neurologic symptoms. Thirty-one patients who could not be followed up gave fictitious phone numbers. These data suggest that CT can reliably triage patients who can be discharged from the ED following MHI, even in the absence of a responsible observer. Hospital admission can be avoided in more than 80% of patients sustaining MHI, better utilizing scarce hospital resources."
-How does the extent of coronary collateral circulation relate to the presence of viable myocardium in patients with recent myocardial infarction?,"Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction. The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area."
-What were the four radiological examinations investigated for acoustic neuromata in this study?,"Patient dose and associated risk due to radiological investigation of the internal auditory meatus. The radiation doses and associated somatic risks due to four radiological examinations for acoustic neuromata (AN) have been investigated. These examinations were (1) plain film radiography of the internal auditory meatus (IAM), (2) computed tomography (CT) of the IAM, (3) CT of the posterior fossa and (4) CT of the IAM with air contrast. Organ dose measurements were performed using lithium fluoride thermoluminescent dosemeters loaded in a patient equivalent phantom. Dose equivalents to various organs are presented, together with the effective dose equivalent and collective effective dose equivalent for each examination. Hypothetical fatal somatic risks for each examination studied here have been estimated from the effective dose equivalents. The estimated number of hypothetical fatal cancers induced by radiological examinations for AN is between approximately 110 and 820 times lower than the number of detected AN, depending on the method of assessing the radiation dose to the remainder organs. It is concluded that in this particular study the radiological examinations are of net benefit to this group of patients."
-What is the key finding regarding the origin of fetal tissue in the reported cases of repetitive hydatidiform mole?,"Hydatidiform mole and fetus with normal karyotype: support of a separate entity. Repetitive hydatidiform mole was observed in four pregnancies. The pregnancies presented with heavy bleeding and vomiting, but the post-evacuation courses were uncomplicated, with rapid regression of serum hCG levels. Cytogenetic investigations, analyses of restriction fragment length polymorphisms, and flow cytometry in three pregnancies were consistent with diploid, biparental conception as the origin of fetal tissue and molar and nonmolar villi. In one pregnancy, the analyses of cytogenetic markers suggested the coexistence of two different cell lines of dizygotic, biparental origin, whereas DNA analysis was consistent with a single conception. With incomplete genetic information, a hydatidiform mole with coexistent normal fetus is generally considered to result from dizygous twinning comprising an androgenetic complete mole and a normal conception. In the present gestations, the results based on several techniques applied on numerous samples from different tissues render this possibility unlikely. Some of the contradictions between histologic and cytogenetic classifications of hydatidiform mole may be explained by diploid, biparental partial mole, which seems to constitute a separate subgroup within hydatidiform mole. Following chorionic villus sampling or amniocentesis, continued pregnancy may be considered, depending on prenatal diagnosis including genetic marker analysis."
-What potential side effect did two siblings experience after receiving phenothiazine-containing medications?,"Phenothiazine-associated apnea in two siblings. A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed."
-What was the primary objective of using the miniaturized infrared end-tidal CO2 detector in this study?,"Confirmation of endotracheal tube placement: a miniaturized infrared qualitative CO2 detector. STUDY OBJECTIVES: A miniaturized, infrared, solid-state, end-tidal CO2 detector was used to confirm emergency endotracheal tube (ETT) placement. DESIGN: This prospective, clinical study used a miniature, infrared, solid-state end-tidal CO2 detector to confirm ETT placement in an acute setting. SETTING: The ICU, emergency department, and hospital floor. TYPE OF PARTICIPANTS: There were 88 consecutive adult patients requiring 100 emergency intubations. MEASUREMENTS AND MAIN RESULTS: The indication for airway intervention was considered urgent in 79% and under arrest conditions in 21%. The mean number of intubation attempts was 1.83 (range, one to five) with difficulty of intubation of 6.48 and confirmation of 7.75, on a linear scale from 0 (lowest) to 10 (highest). Determination of ETT position revealed intratracheal intubation in 96% and esophageal intubation in 4%. Placement was confirmed by direct visualization or radiography in all cases. Sensitivity and specificity for ETT localization was 100% (P less than .0001). CONCLUSION: This hand-held infrared capnometer reliably confirms ETT placement under emergency conditions."
-What is the primary aim of the modified lateral rhachotomy procedure for thoracic spinal lesions?,"Lateral rhachotomy for thoracic spinal lesions. Capener's ""Lateral Rhachotomy"" was modified by additional excision of the pedicle, articular facets, part of the lamina, and a posterior half of the vertebral bodies on one side through a transpleural approach to the thoracic spine, and a retroperitoneal approach to the lumbar spine. The aim was to excise a space-occupying lesion, which exists in front of the thoracic or lumbar spinal cord, safely. This modification enable the authors to expose more than 50% of the spinal canal, and decompress it from its anterior, lateral, and posterior compressing mass. The utmost important point of this procedure is the excision of the lesion under the direct visualization of the dura. In ossification of the posterior longitudinal ligament (OPLL), the dura is usually indented by the thick bony mass, and the lesion extends over a few segment with adhesion. Using ""Modified Lateral Rhachotomy,"" it was possible to explore three or four vertebral levels in continuity through the same skin incision. In the present report, the authors described their ""Modified Lateral Rhachotomy"" procedure, and reviewed the case material."
-How do Factor XIII subunits change in patients with ulcerative colitis during active and quiescent stages of the disease?,"Factor XIII subunits in relation to some other hemostatic parameters in ulcerative colitis. The hemostatic parameters, particularly with respect to F.XIII subunits, were examined in 48 untreated UC patients (22 at active and 26 at quiescent stage). UC active patients showed a significant decrease of F.XIII subunit ""a,"" compared with healthy subjects, as well as in UC patients in remission. In contrast, the level of F.XIII subunit ""b"" in each group was similar. Compared with normal subjects, UC active patients revealed a significant decrease in AT III concentration, prolonged ELT, and elevated fibrinogen level. In addition, the elevated titer of SDPS test for SFMC appeared in approximately 40% of those patients. However, no strict relationship was found between the presence of positive SDPS and diminution of AT III, as well as of F.XIIII subunit ""a"" in active UC state. In patients in remission, AT III level and ELT were similar to those as in the control group, but fibrinogen concentration was elevated. Such constellation of hemostatic parameters may indicate a tendency to blood hypercoagulability in UC active patients, whereas, in general, these changes are not associated with the stage of remission. The present data may also suggest that F.XIII behavior pattern should be taken into account in the clinical management of UC."
-What were the key differences in characteristics between palpable and mammographically detected breast lesions in this study?,"The prevalence of carcinoma in palpable vs impalpable, mammographically detected lesions. Concern over excessive numbers of false-positive mammograms, leading to unnecessary investigations and surgical interventions, has been cited as a barrier to mammographic screening for breast cancer. We compared the biopsy results from palpable vs impalpable, mammographically detected lesions from one experienced breast surgeon's practice from July 1980 through July 1989. Overall, there were 372 biopsies in 346 women. Of 143 biopsies for palpable abnormalities, 48 (34%) yielded a primary malignant lesion. The length of the palpable cancers averaged 3.7 cm (median, 2.8 cm). Sixteen (33%) of the 48 biopsies were in patients who had positive axillary lymph nodes, and five (10%) were in patients who had distant metastases at the time of biopsy. Of 229 biopsies for impalpable, mammographically detected lesions, 72 (31%) yielded a primary breast carcinoma. Excluding 34 carcinomas that had only calcifications, the length of the mammographically detected tumors averaged 2.0 cm (median, 1.5 cm). Eleven (15%) of the 72 biopsies were in patients who had positive axillary nodes, and none were in patients who had distant metastases at the time of biopsy. The positive predictive values (number of cancers detected divided by the number of biopsies recommended) were not significantly different when comparing biopsies indicated for palpable, clinically detected (34%) vs impalpable, mammographically detected (31%) abnormalities (p = .669). However, the mammographically detected cancers were smaller, more often noninvasive (32% vs 4%), less often associated with axillary metastases (15% vs 33%), and without distant metastases (0% vs 10%)."
-What is the significance of the modified endoscopic classification of burns in the management of corrosive ingestion?,"The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. We prospectively evaluated the role of fiberoptic esophagogastroduodenoscopy in the management of 81 patients with corrosive ingestion. A total of 381 endoscopic examinations were performed: 88 within 96 hours following corrosive ingestion, 108 between the third and ninth week, and 185 during the period of follow-up after bougie dilation of esophageal strictures. The customary endoscopic classification of burns (grades 0 to 3) was modified by subdividing grade 2 burns into 2a and 2b, and grade 3 burns into 3a and 3b for prognostic and therapeutic implications. There was no significant correlation between oropharyngeal and upper gastrointestinal tract injury. Early major complications and deaths were confined to patients with grade 3 burns. All patients with grade 0, 1, and 2a burns recovered without sequelae. The majority of patients (71.4%) with grade 2b injury and all survivors with grade 3 injury developed esophageal or gastric cicatrization, or both, which needed endoscopic or surgical treatment. There were no complications related to endoscopy. We conclude that early endoscopy is not only a safe, reliable, and accurate diagnostic tool in such patients, but also is of crucial importance in management and prognosis."
-How does corneal hypesthesia affect the duration of proparacaine anesthetic eyedrops?,"The effect of corneal hypesthesia on the duration of proparacaine anesthetic eyedrops. The duration of action of proparacaine is known in the normal cornea but not in the hypesthetic cornea. To determine this, we examined both eyes in seven patients with documented unilateral corneal hypesthesia associated with inactive herpetic disease. Cochet-Bonnet measurements were made in both eyes before and at two- to five-minute intervals after the instillation of one drop of 0.5% proparacaine until baseline corneal sensitivity levels were again achieved. Mean recovery time was 34.86 minutes in eyes with normal corneal sensitivity, compared to 45.43 minutes in hypesthetic corneas. In all patients, the recovery time was remarkably longer in the hypesthetic eye than it was in the normal fellow eye. These data demonstrate the need to wait up to one hour after the instillation of proparacaine in eyes suspected of having corneal hypesthesia if corneal sensitivity is to be determined accurately. Additionally, the duration of action of topically instilled anesthetic may be a useful method of discovering subtle differences in corneal sensitivity."
-What are the three hypotheses proposed to explain neurobehavioral impairments following cranial radiation therapy and intrathecal chemotherapy?,"Absence of synergistic effects of CNS treatments on neuropsychologic test performance among children. Three hypotheses are proposed to account for neurobehavioral impairments following treatment with cranial radiation therapy (CRT) and intrathecal (IT) chemotherapy: CNS treatments exert a synergistic effect (A x B), an additive effect (A + B), or a single-agent effect (A or B). Eighty-five long-term survivors of non-CNS cancers aged 6 to 16 years were classified into groups on the basis of CNS treatments: CRT-IT (n = 25), CRT-No IT (n = 11), No CRT-IT (n = 24), and No CRT-No IT (n = 25). Study I findings did not provide support for synergistic mechanisms; nonorthogonal analysis of variance showed interaction effects (CRT x IT) restricted to tactile-perceptual speed. However, main effects were significant for a single agent (CRT) across a wide range of measures. General intelligence, academic achievement, verbal knowledge and reasoning, and perceptual-motor abilities were found to be significantly lower among CRT-treated groups. Study II findings provided additional support for the role of CRT; Pearson correlations within the CRT-No IT group indicated significant negative associations between CRT dose estimates for cortical regions and perceptual-motor abilities."
-What percentage of lupus nephritis patients in the study were found to have renal vascular lesions (RVL)?,"Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the ""Gruppo Italiano per lo Studio della Nefrite Lupica"" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL."
-What is the significance of 99mTc-sestamibi in assessing myocardial area at risk during myocardial infarction?,"Perfusion imaging with 99mTc-sestamibi for the assessment of myocardial area at risk and the efficacy of acute treatment in myocardial infarction. There is a clear need to develop better measurement tools for assessment of the effect of acute therapy in myocardial infarction. Such tools must permit accurate measurement of the amount of myocardium that is initially at risk. 99mTc-sestamibi is a new radiopharmaceutical with unique properties that are well suited to the measurement of myocardium at risk without any delay in acute therapy. Tomographic imaging with this agent has been shown to provide accurate quantitative estimates of the myocardium at risk, which varies widely, even for patients with a similar coronary occlusion. For example, there is more than a threefold range in myocardium at risk for patients with a nonproximal occlusion of the left anterior descending coronary artery. The determination of the myocardium at risk before intervention and the change in this region after intervention constitute a promising measurement tool for the assessment of the effect of acute therapy. Initial studies with tomographic imaging have shown a significant improvement in a group of patients treated with thrombolysis, although the magnitude of improvement is highly variable in individual patients. Qualitatively similar results have been reported with planar imaging. Although it has a number of technical limitations, sequential imaging with 99mTc-sestamibi seems to have a clear advantage over those end points that have previously been used to assess acute therapy. This new measurement tool should facilitate future clinical trials of different treatments in acute myocardial infarction."
-What is the relationship between chronic pleural inflammatory disease and the development of soft tissue sarcoma in the pleural cavity?,"Soft tissue sarcoma of the pleural cavity. Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS."
-What changes in mucosal hemodynamics were observed in the canine model of gastric ulceration after ethanol injection?,"Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer. In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer."
-What are the two main clinical presentations of orbital lesions with granulomatous inflammation observed in the study?,"Orbital lesions with granulomatous inflammation. Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis)."
-What was the primary purpose of the clinical trial involving felbamate for complex partial seizures?,"Felbamate: a clinical trial for complex partial seizures. We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM."
-How do cytokines like interleukin-1 and tumor necrosis factor influence leukocyte-endothelial adhesion and contribute to inflammatory responses?,"Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. This paper reviews the evidence that cytokines induce a variety of functional and structural alterations in endothelium and that cytokine-endothelial interactions play important roles in the evolution of inflammatory and immune responses. The effect of cytokines, particularly interleukin-1 and tumor necrosis factor, on leukocyte-endothelial adhesion has led to the discovery of several endothelial adhesion molecules, and the molecular and biological characteristics of these are described. Finally, the review discusses the possible contribution of cytokine-induced activation to vascular injury in such pathological processes as septic shock, the Shwartzman reaction, delayed hypersensitivity, and immune-mediated vasculitis."
-What is central pontine myelinolysis and what causes it in burn patients?,Pontine myelinolysis after correction of hyponatremia during burn resuscitation. Central pontine myelinolysis is a neurologic disease produced by the rapid correction of hyponatremia. This report describes the occurrence of central pontine myelinolysis in a patient with burns. The natural history of this paralyzing condition and suggestions for its prevention are discussed. Severely burned and hyponatremic patients are at risk for this disorder because a large amount of sodium ion is typically required for the treatment of burn shock. Awareness of this phenomenon and avoidance of rapid correction of hyponatremia are essential to its prevention.
-What are the main endoscopic techniques used for palliation of tracheobronchial malignancies?,Endoscopic palliation of tracheobronchial malignancies. The prognosis for tracheobronchial tumours remains poor. Most patients can be offered only palliation. When the main symptom is breathlessness or refractory haemoptysis from a large airway tumour endoscopic treatment may be very effective. Over the last decade most attention has focused on the neodymium YAG laser. This often produces dramatic effects but has some important limitations. In the last few years better techniques for stenting and intrabronchial radiotherapy (brachytherapy) have also been developed. This article discusses the range of techniques now available and aims to help clinicians decide which patients may benefit from referral to centres providing these techniques.
-In how many primary brain lymphomas was Epstein-Barr virus (EBV) DNA detected?,"Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency. We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma."
-What factors are associated with increased delay in seeking treatment for acute myocardial infarction?,"Treatment-seeking behavior among those with signs and symptoms of acute myocardial infarction. Significant delays in seeking definitive treatment for the signs and symptoms of acute myocardial infarction increase morbidity and mortality. In most studies, delay times average more than 4 hours. The following variables are associated with increased delay: a medical history of angina, diabetes mellitus, or hypertension; older age; black race; seeking advice from a family member or a physician; symptom onset on a weekday; and attempts at self-treatment. Variables associated with reduced delay times are the following: pain recognized as cardiac in origin, hemodynamic instability, severe chest pain, younger age, and consultation with a coworker. Surprisingly, patients who have already experienced a myocardial infarction are just as likely to delay as patients who have not had this experience. These findings provide direction for developing and testing patient and family interventions, establishing community education programs, and reducing patient delay in response to the signs and symptoms of acute myocardial infarction."
-What are the characteristic features of nevoid basal cell carcinoma syndrome that pediatricians should be aware of?,"Cardiac tumors and the nevoid basal cell carcinoma syndrome. Nevoid basal cell carcinoma syndrome is a multisystem disease with a wide range of initial symptoms that can be seen at any age. The most characteristic features are vertebral or rib anomalies, intracranial falx calcification, multiple basal cell carcinomas, odontogenic keratocysts of the jaw, and palmar and/or plantar pits. Pediatricians need to be aware that if any one of these major anomalies is seen, this diagnosis should be considered. There now appears to be an established association between cardiac tumors and nevoid basal cell carcinoma syndrome. Primary cardiac tumors have been associated with cerebral tuberous sclerosis and neurofibromatosis, and evaluation of cardiac status is recommended when these genetically determined syndromes are diagnosed. This communication should serve to alert pediatricians to the need for complete cardiac evaluation and genetic counseling when a diagnosis of nevoid basal cell carcinoma is made."
-How rare is Hodgkin's disease involvement in the gastrointestinal tract according to the study?,"The surgical pathology of gastrointestinal Hodgkin's disease. The files of the National Cancer Institute were searched for all surgical specimens from the gastrointestinal (GI) tract with the diagnosis of Hodgkin's disease (HD) that were accessioned during the years 1953-1990; six patients with a histologically reconfirmed diagnosis were identified. Of these patients, four presented with GI HD and two had recurrent HD. Primary HD appeared in the stomach (three patients) and the duodenum (one patient); recurrent HD after diagnosis in a conventional nodal site appeared in the stomach (one patient) and the colon (one patient). One of the cases of primary gastric disease was a composite lymphoma consisting of HD and diffuse large cell lymphoma. In view of the rarity of GI tract involvement by HD, a diagnosis of primary GI HD should be viewed with skepticism; support for such a diagnosis may be provided by both classic histopathologic features of HD and immunostaining, but no single feature can be regarded as pathognomonic."
-What is the potential complication described in this medical case involving a saphenous vein graft and a native coronary artery?,Dislodgement of a vein graft thrombus by angiographic injection of native coronary artery. A case of retrograde dislodgement of thrombus in a saphenous vein graft during injection of the native right coronary artery is presented. Attention to this previously undescribed complication may allow for timely treatment with emergency surgery or thrombolysis.
-What is the recommended intervention for significantly increased plantar tissue pressure after a calcaneal fracture?,"Compartment syndrome of the foot after intraarticular calcaneal fracture. Seventeen patients with a total of 21 intraarticular calcaneal fractures were examined at up to 30 days after trauma for the development of tissue pressure in the central plantar muscle compartment. Twelve patients had a significant increase in tissue pressure with values greater than 30 mmHg because of primary fracture hematoma or interstitial fluid accumulation. This increase in pressure persisted for three to five days after trauma, so that ischemic damage to the short plantar foot muscles had to be suspected. Plantar muscle scarring and claw-toe formation were observed in seven patients with a total of 11 fractures during a mean observation period of 18 months. The plantar aponeurosis, which forms the constricting fascial envelope of the plantar muscles, is the anatomic structure responsible for the compartment syndrome that may develop after calcaneal fracture. Therefore, to avoid functional deficit, plantar compartmental pressures should be regularly measured after calcaneal fracture. Significantly increased plantar tissue pressure greater than 30 mmHg should be relieved by longitudinal incision of the plantar aponeurosis, preferably by a plantar incision as soon as the diagnosis is made."
-What percentage of patients with IgG antibody to hepatitis C virus also had IgM antibody to hepatitis C virus?,"IgM antibody to hepatitis C virus in acute and chronic hepatitis C. To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%)."
-What are the key challenges emergency physicians face when treating patients with headaches?,"Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache."
-How effective was desipramine in treating pain for patients with diabetic neuropathy in this clinical trial?,"Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect."
-"What is the treatment approach for cystoid macular edema in Coats' disease, and what potential side effects should patients be aware of?","Cystoid macular edema secondary to juxtafoveolar telangiectasis in Coats' disease. A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema."
-What were the key findings of the study on hypertonic saline resuscitation in burn patients?,"Hypertonic saline resuscitation: efficacy in a community-based burn unit. Many have discussed hypertonic saline for resuscitation in burned patients only to discourage its use or to emphasize it only as a research tool and not as standard resuscitation. We reviewed the records of 47 adults with burns over 20% or more of the total body surface area (TBSA) in whom hypertonic saline was used as standard resuscitation fluid in a large community burn unit. The solution consisted of sodium, 300 mEq/L, acetate, 200 mEq/L, and chloride, 100 mEq/L, with an osmolality of 600 mOsm/L. The mean TBSA burned was 37% and the mean patient age was 44.8 years. Eighteen patients (mean age 39.7 years, mean TBSA burned 27%) received hypertonic saline alone. They required an average of 75% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value over the first 48 hours was 44.2% and the mean serum sodium level was 141.6 mEq/L. Twenty-nine patients (mean age 51.8 years, mean TBSA burned 47.8%) received hypertonic saline plus colloid (albumin or fresh frozen plasma). Colloid was used in older patients with more serious burns. This group required 57% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value was 45.1% and mean sodium level was 143.8 mEq/L. The mean weight gain for both groups was 7.3% of the admission weight. None of the patients had changes in pH or renal function. All patients survived the resuscitation phase of their injury; the overall death rate was 49%. We conclude that hypertonic saline is a safe, effective means of resuscitation even in a community-based unit. It allows less fluid to be delivered for adequate resuscitation. The usual hyponatremia, hemoconcentration, and significant weight gain associated with administration of isotonic solutions was avoided. Colloid may further improve the resuscitation capabilities of hypertonic saline."
-What were the key findings of the TIMI II-B Study regarding the timing of beta-blocker therapy in patients with acute myocardial infarction?,"Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality."
-What was the effect of thoracic epidural analgesia on catecholamine levels during coronary artery bypass grafting in a patient with bilateral phaeochromocytoma?,"Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. A patient suffering from phaeochromocytoma and coronary artery stenoses needed coronary artery bypass grafting before adrenalectomy. High thoracic epidural analgesia (T1-T2) with bupivacaine and sufentanil in combination with general anaesthesia was used. Plasma adrenaline and noradrenaline concentrations decreased during the period before bypass grafting compared to the baseline value and no important haemodynamic changes were seen during this period. Thoracic epidural analgesia failed to suppress the release of catecholamine during the bypass period. After the operation, the plasma catecholamine concentrations returned to the baseline value. Excellent analgesia (visual analogue scale = 1-2) was achieved with a postoperative epidural, but the plasma catecholamine concentration increased considerably."
-What was the prevalence of antibodies to hepatitis C virus among patients with chronic hepatitis B virus infection in this study?,"The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection."
-How does amiodarone affect the mitochondrial beta-oxidation of fatty acids in mice?,"Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from [U-14C]palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of [14C]CO2 from [U-14C]palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of [U-14C]palmitic acid. One hour after 100 mg.kg-1, the exhalation of [14C]CO2 from [1-14C]palmitic acid, [1-14C]octanoic acid or [1-14C]butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of [14C]CO2 from [1-14C]palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice."
-How does DNA ploidy status and proliferative fraction correlate with the clinical behavior of atrial myxomas?,"DNA analysis of atrial myxomas. The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior."
-What psychological effects were observed in women undergoing different stages of breast screening?,"Assessment of the psychological impact of a breast screening programme. In order to assess the psychological effect of mammographic screening, questionnaires (which included psychometric tests) were sent to 750 women at invitation and, 6 weeks after screening, to 420 women normal after the first mammograph, to 240 women normal after special assessment, and to 68 women normal after open biopsy. Increasing degree of the investigation was associated both with increasing frequency of breast self examination (10% were practising breast self-examination at least once a week before screening compared with 24% for women after special assessment and 35% of women who had had an open biopsy (p less than 0.001)), and with greater confidence that any malignancy in the breast would have been found. Psychometric scores showed no increase of general levels of anxiety or depression in the screened groups. For anxiety, percentages abnormal were 5, 4, 2 and 6 for the four groups, respectively, and for depression the percentages abnormal were 5, 4, 4 and 6, respectively; 10% of screened women were more anxious about having breast cancer as a result of the screening. At least 10% of women proceeding to open biopsy of benign lesions require professional counselling and support. Psychological ill effects were not detected by the psychometric test among women who did not proceed to this final investigation. Behavioural changes did suggest a raised awareness or fear of potential cancer among the screened population."
-What percentage of infants with neonatal seizures experienced an unfavorable neurologic outcome in this study?,"Neurologic outcome after electroencephalographically proven neonatal seizures. Infants in whom neonatal seizures were confirmed by randomly recorded ictal electroencephalographic (EEG) tracings were retrospectively examined to determine their global neurologic outcome and the specific frequency of epilepsy, development delay, and cerebral palsy. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to the neurologic outcome. Forty infants with EEG documented seizures of diverse etiologies were studied. The 27 survivors were followed up at a mean of 31 months. The outcome was unfavorable in 70%. The rate of epilepsy was 56%, of developmental delay 67%, and of cerebral palsy 63%. The etiology of seizures was an important factor influencing the outcome. Other clinical factors that showed a significant relationship with global or specific aspects of the neurologic outcome included the age at the onset of seizures, birth weight, and neurologic examination results. The EEG parameters that significantly predicted the neurologic outcome were interictal EEG background, increased seizure frequency, and decreased seizure duration."
-What are the primary acute triggers for sudden cardiac death?,"Sudden cardiac death: management of high-risk patients Sudden cardiac death remains a leading cause of death in the United States, accounting for more than 350,000 deaths each year, and the survival rate of victims remains low. Most survivors face a significant risk for recurrence. The typical substrate is chronic--abnormal myocardium with fibrosis (often from previous myocardial infarction) and left ventricular dysfunction. Acute triggers for sudden cardiac death are primarily electrical, ischemic, metabolic, neurohormonal, and pharmacologic. In most electrocardiographically documented cases of sudden cardiac death, the trigger-substrate interaction appears to result in ventricular tachycardia and fibrillation. After initial resuscitation, survivors need a thorough cardiovascular evaluation, including definition of coronary anatomy, left ventricular function, and wall-motion abnormalities, as well as an electrophysiologic evaluation. An attempt must be made to determine what each survivor's correctable triggers are. Management should address all reversible triggers, such as acute ischemia and electrolyte abnormalities, and should include modifying or correcting the arrhythmogenic substrate. Empiric antiarrhythmic therapy offers no advantage in such modification. Pharmacologic therapy with antiarrhythmic drugs should be guided by an objective therapeutic endpoint, which is best accomplished through the use of programmed ventricular stimulation and serial electrophysiologic studies. Other therapeutic options include surgical suppression of ventricular tachycardia and implantation of a cardioverter defibrillator."
-What is the relationship between serum aminoterminal propeptide of type III procollagen levels and liver fibrosis in psoriasis patients?,"Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis. Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis."
-How did melatonin affect sleep onset and wake times in subjects with delayed sleep phase syndrome?,"Delayed sleep phase syndrome response to melatonin. The actions of melatonin on the sleep-wake cycle were investigated by means of a randomised, double-blind, placebo-controlled trial in 8 subjects with a delayed sleep phase syndrome attending a sleep disorders clinic. In randomised order the subjects received placebo or melatonin 5 mg daily for 4 weeks with a 1 week washout period between the treatments. Drug or placebo was given at 2200 h, 5 h before the mean time of sleep onset determined by pretrial sleep logs. In all 8 subjects sleep onset time (mean advance 82 [range 19-124] min; p less than 0.01) and wake time (117 [10-187] min; p less than 0.01) were significantly earlier during melatonin treatment than during placebo. Mean total sleep time was slightly less on melatonin (8 h 12 min) than on placebo (8 h 46 min). Alertness acrophase calculated from the subjects' ratings of alertness made every 2 h while awake was unaltered. Melatonin may act as a phase-setter for sleep-wake cycles in subjects with a delayed sleep phase syndrome."
-What were the two leading causes of overseas fatalities among US citizen travelers according to the study?,"Overseas fatalities of United States citizen travelers: an analysis of deaths related to international travel. STUDY OBJECTIVE: Studies of travel-related mortality and morbidity have been limited to nonfatal events. Causes of travel-related mortality may differ significantly from morbidity and thus have different prevention strategies. DESIGN: We examined the overseas fatalities of US citizen travelers for the years 1975 and 1984. The death certificates were abstracted; all deaths under age 60 and a 20% sample of deaths 60 and older were examined. SETTING AND TYPE OF PARTICIPANTS: All overseas travel fatalities of US citizens were examined excluding those occurring in Canada. INTERVENTIONS: None. RESULTS: Cardiovascular events (including myocardial infarctions and cerebrovascular accidents) and injuries accounted for 49% and 25% of the overseas deaths of US citizen travelers, respectively. Infectious diseases other than pneumonia accounted for only 1% of the deaths. Eighty percent of injury deaths occurred outside of hospitals. Injury death rates for male travelers were greater than US age-specific death rates. CONCLUSIONS: Greater emphasis on the prevention of fatal events, especially those resulting from injury, must be given by physicians and other individuals and organizations who advise travelers. Further studies are needed to explore the issues of preventable injury deaths, emergency medical services, and overseas travel."
-How did isradipine affect blood pressure control in patients with mild essential hypertension during a 24-hour period?,"Twenty-four-hour blood pressure control with isradipine in mild essential hypertension. The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine."
-What potential risks did the study find when using EMLA cream on wounds?,"Damage to tissue defenses by EMLA cream. EMLA is a new topical agent that safely anesthetizes intact skin. The purpose of this study was to determine if this cream could be safely used for anesthetizing wounds. This investigation evaluated the potential toxicity of EMLA cream in wounds by measuring its effect on host defenses and on the biology of wound repair. In contaminated wounds, EMLA cream elicited an exaggerated inflammatory response that damaged host defenses, inviting the development of infection. As a result of these investigations, we do not recommend the use of EMLA cream in wounds."
-What is a carotid cavernous fistula and how can it develop after minimal facial trauma?,"Carotid cavernous fistula after minimal facial trauma. Report of a case. The carotid cavernous fistula has historically been associated with extensive facial trauma as a result of direct or indirect forces. Most fistulas of traumatic origin develop as a result of a fracture through the base of the skull, which produces a force causing laceration of the internal carotid artery in the region where it approximates the cavernous sinus. We report a case in which apparently minimal head trauma resulted in the development of a carotid cavernous fistula. The rather innocuous presentation of this complication requires particular attention by the caregiver in assessing the patient sustaining maxillofacial trauma."
-What were the mortality rates for ischaemic heart disease and cerebrovascular disease among different ethnic groups in England and Wales during the 1970s and 1980s?,"Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade."
-What were the three protocols used to determine the effect of exercise supplementation on dipyridamole thallium image quality?,"Effect of exercise supplementation on dipyridamole thallium-201 image quality To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone."
-What is the connection between the patient's Creutzfeldt-Jakob disease and the cadaveric dural graft?,Creutzfeldt-Jakob disease in a patient with a cadaveric dural graft. We report a 26-year-old woman with Creutzfeldt-Jakob disease (CJD) who had received cadaveric dural material 33 months before the onset of neurologic symptoms. This is the fourth case in which a dural graft was the putative source of the CJD agent. All four cases had the grafting before changes in the sterilization procedure adopted in 1987 to inactivate the CJD agent.
-What was the main purpose of the retrospective study involving 498 women with 666 breast lesions?,"Mammographic follow-up of nonpalpable low-suspicion breast abnormalities: one versus two views. A retrospective study involving 498 women with a total of 666 breast lesions was undertaken to determine the relative efficacy of one- and two-view mammography in the follow-up evaluation of ""low-suspicion"" abnormal mammographic findings. These abnormalities consisted of well-defined masses (47.1%), well-defined punctate microcalcifications (20.9%), and parenchymal asymmetry (32.0%). Confidence in the adequacy of the single-view follow-up was high in 91% of cases. The addition of the second mammographic view changed the one-view interpretation in approximately 1% of all cases. Two cancers were detected during the initial follow-up period. Both cancers were detected with single-view and standard two-view follow-up examinations, with high confidence. In this controlled retrospective study, the single-view follow-up examination was adequate for follow-up of most low-suspicion mammographic abnormalities. Monitoring by physicians, however, would be necessary to prevent an unacceptable number of patient recalls, which could make the one-view follow-up study impractical to use in some practices."
-"What is the ""two week syndrome"" observed in patients receiving injection treatment for chronic pain?","The ""two week syndrome"" associated with injection treatment for chronic pain--fact or fiction? Many patients attending the pain clinic for regular injections of local anaesthetic state that the pain returned ""two weeks"" ago. This study demonstrates that 85% of these patients have a ""return of pain"" interval which coincides with the proximity of their next clinic appointment."
-What imaging techniques were used to diagnose choledochal cyst and biliary atresia in the neonates?,"Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management."
-How did the cardiac myocytes change in size and shape in rats with aortocaval fistulas at 1 week and 1 month after surgery?,"Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy. The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth."
-What is EXOSURF and how was it used in the clinical trials for treating hyaline membrane disease in neonates?,"Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease. EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial."
-What was the survival rate of patients who received defibrillation during the Heartstart Scotland initiative?,"""Heartstart Scotland""--initial experience of a national scheme for out of hospital defibrillation. OBJECTIVE--To determine the outcome of out of hospital defibrillation in Scotland during the year after the introduction of automated external defibrillators in October 1988. DESIGN--Retrospective analysis of ambulance service reports and hospital records. SETTING--Scottish Ambulance Service and acute receiving hospitals throughout Scotland. MAIN OUTCOME MEASURES--Delay from cardiac arrest to first defibrillator shock; vital state on arrival at hospital accident and emergency department; survival to hospital discharge. RESULTS--During the study period 268 defibrillators were purchased by public subscription and 96% of the 2000 ambulance crew underwent an eight hour training programme in cardiopulmonary resuscitation and defibrillation. A total of 1111 cardiac arrests were recorded, and defibrillation was indicated and undertaken in 602 (54%) patients, mean age 63 (range 14-92) years. A spontaneous pulse was present on arrival at hospital in 180 (30%) of the defibrillated patients, and 75 (12.5%) were subsequently discharged alive. As expected, the likelihood of survival was inversely related to the delay from the onset of cardiac arrest to the time of the first shock and was greater in the case of witnessed arrest. If ventricular fibrillation occurred after the arrival of the ambulance, survival to discharge was 33%. CONCLUSIONS--An effective scheme for out of hospital defibrillation can be introduced rapidly, and with limited training implications and costs, by the use of automated external defibrillators in ambulances."
-"What is the relationship between interleukin-2, interferon-alpha, and colonic ischemia in cancer patients?","Colonic ischemia complicating immunotherapy with interleukin-2 and interferon-alpha. Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI."
-What was the median patient survival time for patients with pancreatic cancer in this study?,"Carcinoma of the pancreas: a personal experience with 100 cases. One hundred patients with pancreatic cancer were evaluated between March 1981 and December 1989. This study showed that 61 were not candidates for definitive surgery because of nonoperability (28 patients) or nonresectability (33 patients). An additional 25 patients had cancers that were unresectable because of metastases (13 patients) or local spread of disease (12 patients) discovered at laparotomy. Fourteen patients had resectable cancers. Ten were treated by total pancreatectomy, three by distal pancreatectomy and one by pancreatoduodenectomy (Whipple). There were two operative mortalities. The median patient survival time was 20.5 months. Two patients survived 5 years. Five patients are alive at 3, 14, 18, and 47 months. Palliative surgical procedures performed in 18 patients included 10 biliary bypasses, 9 gastrojejunostomies, and 6 T-tube placements. This was associated with an operative mortality rate of 11%. The median survival time was 5 months. Other palliative measures included endoscopic placement of biliary and pancreatic stents (47 patients, 2.7% mortality rate), endoluminal radiation therapy, interstitial radiation therapy and external beam radiation therapy. The median survival time of patients so treated was 4.5 months."
-What treatment approach was used to successfully manage Candida endocarditis in the three critically ill infants described in the study?,"Successful medical treatment of presumed Candida endocarditis in critically ill infants. Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants."
-What clinical factors were independently associated with a positive response to esophageal balloon distension?,"Clinical correlates of abnormal sensitivity to intraesophageal balloon distension. Sixty-five patients with esophageal complaints were studied to determine clinical associations with abnormal sensitivity to intraesophageal balloon distension (esophageal sensory dysfunction). Associations were examined in four categories: motility, esophageal symptoms, recent psychological symptoms, and general clinical features. A positive response to balloon distension (pain with less than or equal to 8 ml volume) was found in 29 (45%) of the subjects. This response was associated with specific findings in each category except recent psychological symptoms. A multiple logistic regression analysis indicated that an increased frequency of multipeaked waves on motility testing, presence of dysphagia, and shorter height of the subject each had an independent association with positive response to balloon distension (P less than or equal to 0.05 for each). Further comparison of subjects with sensory dysfunction, motor dysfunction, or both (sensorimotor dysfunction) indicated that subjects with the combined disorder appeared more symptomatic than those with either finding alone. These observations indicate that: (1) esophageal motor and sensory dysfunction are partially associated, but both contribute to the symptomatic state; (2) dysphagia may be representative of sensory dysfunction in some cases; and (3) subject height should be taken into consideration when interpreting balloon distension results."
-How do smoking and oral contraceptive pills potentially contribute to the exacerbation of Crohn's disease?,"Smoking, the oral contraceptive pill, and Crohn's disease. Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease."
-What was the treatment approach and outcome for HIV-associated Kaposi's sarcoma patients using recombinant interferon alpha-2a?,"Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a. Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy."
-How can dual-energy CT help differentiate focal fatty infiltration of the liver from low-density masses?,"Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. Focal (irregular, partial) fatty infiltration of the liver may simulate neoplastic or other hypodense masses on CT. On the basis of previous observations of the phenomenon that differences in X-ray attenuation diminish with increasing energy of X-rays used, we performed a preliminary study to determine if dual-energy CT could be used to discriminate between fatty infiltration and hypodense liver masses. Dual-energy CT at 140 and 80 kVp was performed in 14 patients undergoing liver biopsy and in seven control subjects with presumedly normal liver. Attenuation measurements were taken, and the changes in attenuation between 140 and 80 kVp were calculated. The mean changes in attenuation were 3.5 H for normal liver (n = 7), 2.5 H for hypodense liver masses (n = 6), 13 H for fatty liver (n = 5), 0.3 H for fatty liver combined with hemochromatosis or hemosiderosis (n = 3), and 2 H for the spleen (n = 18). The change in attenuation increased as the fat content in the liver increased. Analysis of variance showed a statistically significant difference (p less than .001) between fatty liver and the other groups. A difference greater than 10 H was unique to fatty infiltration. These results suggest that dual-energy CT may help to differentiate focal fatty infiltration of the liver from low-density neoplastic or other lesions, but only if the iron content of the liver is not increased."
-What specific autoantibodies have been implicated in the pathogenesis of dilated cardiomyopathy (DCM)?,"Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy. Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM."
-What was the purpose of the randomized study involving nifedipine and nitroglycerin in patients undergoing coronary artery bypass grafting?,"Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS]."
-How does isradipine potentially protect the brain from damage in stroke models?,"Prevention of stroke and brain damage with calcium antagonists in animals. In a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery [MCAO]), various 1,4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isradipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addition, also protect the brain from damage engendered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antagonist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isradipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, appears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy."
-What was the relationship between inflammatory cells and metaplasia in asbestos workers?,"The relationship between large airway inflammation and airway metaplasia. To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers."
-What is the main finding of the study regarding the management of gallbladder in elderly patients after endoscopic sphincterotomy for bile duct stones?,"Risks of leaving the gallbladder in situ after endoscopic sphincterotomy for bile duct stones. There is controversy concerning the subsequent clinical course of patients whose gallbladder is left in situ following successful endoscopic removal of stones from their common bile ducts. A total of 191 patients (median age 76 years) were reviewed between 12 and 100 months (mean 38 months) after endoscopic sphincterotomy. Ten patients (5.2 per cent) had symptoms requiring cholecystectomy which was uneventful, nine in the first year. Cholangitis at presentation or failure to fill the gallbladder by endoscopic retrograde cholangiography were not helpful in identifying these patients. Forty-nine (25.6 per cent) patients died during the review period from non-biliary pathology (usually cardiovascular). Elective cholecystectomy is not required in elderly patients with symptomatic bile duct stones if the common bile duct can be cleared of stones after endoscopic sphincterotomy."
-What factors were found to be significantly associated with progression-free interval in the multi-variate analysis of cervical carcinoma patients treated with radiation therapy?,"Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant."
-What diagnostic techniques were used to identify and confirm the intrahepatic arterioportal fistula in this patient?,"Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed."
-What is the significance of the changing appearance of the cephalocele during transvaginal sonographic follow-up between 13-19 weeks of gestation?,"Transvaginal sonographic follow-up on the formation of fetal cephalocele at 13-19 weeks' gestation. An occipital meningocele was detected by transvaginal sonography in a fetus of 13 weeks' gestation. This changed at 14 weeks to a cephalocele, which disappeared at 15-16 weeks and was detected again at 19 weeks. It is possible that sliding backward and forward of the herniated brain tissue caused this sequence of events."
-How do anesthesiologists help prevent respiratory complications during and after surgery?,"Respiratory problems in emergence from anesthesia. In conclusion, anesthesia and mechanical ventilation have major effects on respiratory function, both intraoperatively and postoperatively. Recognition that mechanical ventilation represents a major departure from spontaneous ventilation should enable anesthesiologists to compensate for the increases in dead space ventilation and the propensity for alveolar collapse that accompany low volume mechanical ventilation. The use of postoperative regional analgesic techniques to alleviate respiratory compromise constitutes both current clinical practice and an area of active, ongoing investigation. Gone are the days when the anesthesiologist's responsibility stopped at the recovery room door. Today, anesthesiologists with expertise in postoperative pain management, cardiovascular physiology, and intensive ventilatory care are able to provide patients an improved likelihood of avoiding postoperative respiratory complications."
-How can red blood cell deformability index (DI) be used as an early indicator of infection in trauma patients?,"Red cell deformability is an early indicator of infection. Red blood cells (RBC) have been shown to become less deformable during infection. The RBC deformability index (DI) was measured within 24 hours of admission in 37 patients who had suffered trauma and every 48 to 72 hours thereafter while they were in the surgical intensive care unit to assess whether DI could be used as an early indicator of infection after injury. Infection was defined as a temperature of 101 degrees F or more and a white blood cell count of more than 12,000/cm3 associated with a positive culture. Eighteen patients developed an infection, and 19 patients did not. On day 1, both groups showed a significant decrease in DI, compared to controls (0.33 +/- 0.18 and 0.34 +/- 0.25 for patients with infection and patients with no infection vs 1.52 +/- 0.12 for control volunteers; p less than 0.05). In the group with no infection, the DI improved in 16 of 19 patients after injury; the DI in patients with infection continued to decrease in 17 of 18 patients. The decrease in DI occurred 4 +/- 2 days (range, 2 to 8 days) before the diagnosis of infection. No significant differences were apparent in the absolute white blood cell count between the group with infection and the group with no infection at any time after injury. Differences in maximal temperature were noted on day 3 and beyond; however, 30% of patients with no infection had a temperature of more than 101 degrees F for 7 days. These data show that trauma results in a significant decrease in RBC deformability and that serial changes in DI appeared to predict which patients would develop an infection and which patients would recover uneventfully. RBC deformability may be helpful in early detection of infection in patients who have suffered trauma."
-What was the main finding of the study regarding the sensitivity of the gastric mucosa in patients with nonulcer dyspepsia?,"Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents."
-What was the mean maximum temperature during an infection in the nursing home residents studied?,"Fever response in elderly nursing home residents: are the older truly colder? OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a ""blunted"" fever response (Tmax less than 101 degrees F). Of the 25 ""blunted"" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections."
-What percentage of primary neurogenous tumors arise from peripheral nerves in the head and neck region?,"Primary tumors of the facial (extracranial) nerve. Nearly 25% of all primary neurogenous tumors arise from peripheral nerves in the head and neck. The extracranial parts of the facial nerve, however, rank low as potential sites. Their tumors nonetheless pose diagnostic and management problems. In the intraparotid location the neurogenous tumors most often present as mass lesions, accompanied, in one third of patients, by various degrees of facial weakness. With the exception of a peculiar predilection of childhood plexiform neurofibromas to afflict the facial nerve, the majority of the tumors are neurilemomas. Recurrences are unusual after surgical removal of either neurilemomas or neurofibromas. The rare facial nerve sarcoma is a high-grade malignancy."
-What diagnostic challenges are associated with mucinous pancreatic tumors according to the ERCP findings?,"Mucinous pancreatic tumors: ERCP findings Mucin-producing tumors of the pancreas are rare and difficult to diagnose neoplasms. To further characterize the nature of these lesions, four such cases are described here in which the diagnosis was suspected at endoscopic retrograde cholangiopancreatography by the presence of ampullary or intraductal mucus. In one patient, pancreatoscopy directly visualized the tumor. Ultrasound and computed tomography failed to suggest the presence of a neoplasm in the majority of these cases, but endoscopic ultrasound was performed in one and correctly identified the multi-cystic tumor. A high incidence of acute pancreatitis was seen in these cases and was felt to be secondary to intermittent ductal obstruction by mucus. The characteristic appearance of intra-ductal mucus provides an important clue to the presence of this type of pancreatic neoplasia."
-What was the main purpose of the study on hepatitis C virus antibodies in blood donors?,"Antibody to hepatitis C virus and liver disease in volunteer blood donors. OBJECTIVE: To evaluate the specificity of antibodies to hepatitis C virus (anti-HCV) and their relation to liver disease in blood donors. DESIGN: Case series of consecutive blood donors found positive for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Patients were evaluated for antibody specificity using a recombinant immunoblotting assay (RIBA) and were evaluated for biochemical evidence of liver disease. Patients showing increased alanine aminotransferase (ALT) levels had a liver biopsy. SETTING: University hospital. PARTICIPANTS: Fifty consecutive blood donors found to be anti-HCV positive on both an initial and repeat ELISA. Inclusion criteria were as follows: an absence of hepatitis B surface antigens and non-organ-specific autoantibodies; a daily alcohol intake of less than 50 g; no history of recent hepatotoxic drug use; and normal serum levels of alpha 1 antitrypsin, ceruloplasmin, and copper. MAIN RESULTS: Anti-HCV positivity was confirmed by RIBA in only 13 of 50 donors (26%) who had positive ELISA results. These 13 donors had an elevated ALT level and histologic evidence of chronic hepatitis, which was active in 8 patients (62%) and had already produced cirrhosis in 2 patients (15%). In contrast, the 17 donors with an intermediate RIBA pattern had only mild and often nonspecific histologic liver abnormalities. The 20 patients with a negative RIBA result had normal ALT levels. CONCLUSION: In blood donors, the anti-HCV RIBA is not only more specific than the anti-HCV ELISA, but is also useful in identifying patients who have an underlying chronic liver disease."
-How does gadopentetate dimeglumine-enhanced magnetic resonance imaging improve the detection and staging of uterine carcinomas?,"Carcinoma of the uterus: use of gadopentetate dimeglumine in MR imaging. This prospective study assessed the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging in the detection and staging of carcinomas of the endometrium and cervix. Surgical-pathologic findings were used as the standard of reference. In the evaluation of endometrial carcinoma, contrast-enhanced imaging improved tumor detection and differentiation between viable tumor and retained debris. Use of contrast material significantly improved the staging accuracy. The ability to assess the depth of myometrial invasion was also improved. In the evaluation of cervical carcinoma, assessment of tumor location and size did not improve following contrast enhancement. Use of gadopentetate dimeglumine resulted in overestimation of stromal, parametrial, vaginal, and/or bladder wall invasion in eight patients. However, evaluation of intratumoral architecture and large lesions was easier with contrast-enhanced imaging. When only stage II and higher disease was analyzed, use of contrast material improved the evaluation of disease extent. The authors conclude that gadolinium enhancement adds to the accuracy of evaluation of endometrial carcinoma but is useful in only advanced cases of cervical carcinoma."
-What rare combination of tumors is described in this case report?,Osteogenic sarcoma arising adjacent to a long-standing ameloblastoma. A case report. Ameloblastoma is an uncommon odontogenic tumor usually occurring in the mandible. Rarely do other primary tumors occur with or arise from ameloblastoma. We describe a patient with simultaneous osteogenic sarcoma of the maxilla and recurrent ameloblastoma.
-What is the relationship between radiation therapy and the development of monomelic amyotrophy in the described cases?,"Postradiation lower motor neuron syndrome presenting as monomelic amyotrophy. Monomelic amyotrophy developed 16 months, nine and 12 years after irradiation of the lumbosacral spinal cord for seminoma in one patient and for Hodgkin's disease in two others. In two patients, involvement was clinically limited to one leg, with a subacute course followed by plateau in the first case and with progressive worsening in the second one. In the third patient, the course was progressive with involvement of the other lower limb occurring five years later. From clinical and electrophysiological data, it seems probable that the disease process was a result of a selective injury to the lower motor neuron in the lower spinal cord."
-How can transesophageal echocardiography help in diagnosing and managing cardiac tamponade with a patent foramen ovale?,"Right-to-left shunt across a patent foramen ovale caused by cardiac tamponade: diagnosis by transesophageal echocardiography. Cardiac tamponade can manifest as profound hypoxemia from intracardiac shunting across a patent foramen ovale. As a consequence, pulmonary embolus can be erroneously diagnosed. As demonstrated in the case described herein, transesophageal echocardiography can be useful in determining the correct diagnosis, especially if transthoracic echocardiography is technically limited. In our patient, the findings on transesophageal echocardiography also helped determine the appropriate treatment. The relative inaccessibility of the pericardial effusion to needle drainage prompted open surgical drainage."
-What was the primary finding regarding EMG activity in patients with chronic tension-type headache compared to healthy volunteers?,"EMG activity in pericranial muscles during postural variation and mental activity in healthy volunteers and patients with chronic tension type headache. EMG activity was recorded over frontalis, temporalis and trapezius muscles in a supine position, a standing position and during a mental task in 32 female patients suffering from chronic tension-type headache and in 20 healthy volunteers. Measurements in patients were made before and after biofeedback therapy. All EMG levels were on average significantly higher in patients than in controls. 62.5% of patients had at least one abnormal EMG level, but only 34% were beyond the normal range, if 1 muscle and 1 recording condition was considered. EMG levels were not correlated with headache severity, anxiety or response to biofeedback treatment. It is therefore suggested that pericranial EMG activity is not pathogenetic in chronic tension type headache, but merely one of several pathophysiologic changes, that are produced by a central dysfunction."
-What is the relationship between HLA B27 and the incidence of hypopyon in anterior uveitis?,"Anterior uveitis and hypopyon. We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective-tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis."
-What is the relationship between eosinophilic fasciitis and cutaneous T-cell lymphoma in this case study?,"Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms? Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms."
-What was the rate of adhesion formation after ovarian electrocauterization in the selective and unselective groups of patients with polycystic ovarian syndrome?,"Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. The rate of adhesion formation after ovarian electrocauterization has been described in two selective and unselective groups of patients with PCOS. The rate of this complication in the selective group was 0 from 16 ovaries and in the unselective group (5/25). However, the rate of major adnexal adhesion in the unselective group was 1 from 25 ovaries."
-How did the diagnosis of Asperger's syndrome impact the understanding of the children's emotional needs and their relationships with their parents?,"Asperger's syndrome: who is being abused? Six case histories of children referred and admitted to a psychiatric inpatient unit at a tertiary referral centre because of concerns about poor functioning and possible emotional abuse are presented. On initial assessment the children appeared to be well functioning and the impression was confirmed that their emotional needs were not being met by their parents. After detailed inpatient appraisal the diagnosis of Asperger's syndrome was made in all six cases, exemplified mainly by a formal concrete way of thinking and an inability to identify and understand human emotions and relationships. The impact of the diagnosis on the parents and their consequent relationships with their child and their willingness to work with professionals is discussed."
-How does the proportion of large molecular form of HBeAg relate to the severity of liver damage in chronic hepatitis B?,"Large molecular form of serum HBeAg in chronic hepatitis B virus infection: relation to liver cell damage. We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% +/- 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% +/- 27.8% in 32 patients with chronic persistent hepatitis and 65.6% +/- 23.3% in 21 patients with chronic active hepatitis (p less than 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B."
-"What neurological condition did the 39-year-old AIDS patient develop, and what was the underlying cause of his myelopathy?","Ischaemic myelopathy secondary to disseminated intravascular coagulation in AIDS. A 39-year-old patient with AIDS presented with a rapidly progressive myelopathy with a partial Brown-Sequard syndrome. He died, 9 weeks after onset of the first neurological signs, from diffuse encephalopathy. Neuropathological examination revealed multiple, usually small, frequently haemorrhagic, infarcts or various ages and numerous fibrin thrombi in medium and small penetrating vessels and capillaries of the brain and spinal cord, characteristic of disseminated intravascular coagulation. There were no inflammatory changes. Immunohistochemical studies for human immunodeficiency virus, cytomegalovirus, varicella zoster virus, herpes simplex virus type 1 and type 2 were negative. Ischaemic spinal cord lesions due to disseminated intravascular coagulation may represent an unusual cause of focal, non-inflammatory, non-tumoral, myelopathic syndrome in AIDS."
-How do mink cell focus-forming (MCF) viruses affect the interleukin-2 (IL-2) dependence of a rat T-cell lymphoma line?,"Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line. The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor."
-What are the key characteristics of pulmonary angiitis and granulomatosis syndromes in terms of clinical presentation and radiologic features?,"Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions."
-What is Acanthoma fissuratum and what is its primary cause according to the given context?,Acanthoma fissuratum. Acanthoma fissuratum secondary to the use of spectacles is a rare clinical finding associated with an ill-fitting frame. An interesting case is presented to highlight such a problem. Surgical excision of such lesions is recommended with advice to the patient regarding the suitable fitting of spectacles.
-What percentage of patients in the study had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex?,"Electrophysiologic and anatomic characteristics of ventricular tachycardia induced at the right ventricular outflow tract but not at the apex. The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex."
-How does sphincterotomy prevent gallstone formation in prairie dogs fed a high-cholesterol diet?,"Effect of bile diversion and sphincterotomy on gallbladder muscle contractility and gallstone formation. Feeding prairie dogs a diet rich in cholesterol induces gallstone formation that is preceded by a sustained decrease in gallbladder smooth muscle contractility. Sphincterotomy is known to prevent gallstone formation in cholesterol-fed prairie dogs. Experiments were designed to determine whether the effect of sphincterotomy is a consequence of hepatic bile diversion, and whether bile diversion prevents the altered contractility. Following sham operation, surgical biliary enteric bypass, or sphincterotomy, prairie dogs were fed a high-cholesterol or a regular diet. Gallbladder muscle contractility and the presence of crystals and stones were determined. In sham-operated animals, the cholesterol diet induced a decrease in gallbladder muscle contractility and caused the formation of cholesterol gallstones. In animals with bile diversion and sphincterotomy, the effects of cholesterol feeding were reduced or prevented. Thus, these procedures may prevent stone formation by preventing a reduction in gallbladder contractility. Contractility was depressed in animals with bile diversion fed a regular diet, compared with animals with a sham operation fed a regular diet. The mechanism for this depression may differ from that induced by the cholesterol diet. Diversion, and perhaps sphincterotomy, impairs gallbladder filling. Thus, gallbladder muscle is not stretched and does not contract against a load. This could result in a ""disuse atrophy."" If the results from our study apply to humans, sphincterotomy may reduce stone formation by preventing the effects of lithogenic bile on gallbladder muscle contractility and by enhancing the ability of the muscle to empty the lithogenic bile."
-What was the prevalence of hepatitis C antibodies among patients with alcoholic liver disease in this study?,"Antibody to hepatitis C is common among patients with alcoholic liver disease with and without risk factors. Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity."
-How did site-directed mutagenesis of the region around Cys-241 in human C2 affect its hemolytic activity?,"Site-directed mutagenesis of the region around Cys-241 of complement component C2. Evidence for a C4b binding site. We probed the functional significance of the region around Cys-241 in human C2 by testing the hemolytic activity of a series of mutant rC2. Mutant C2 cDNA were constructed by oligonucleotide-directed site-specific mutagenesis and expressed transiently in COS cells. Wild-type rC2 had threefold higher specific hemolytic activity than native serum C2. Substitution of Gly, Ala, or Ser for Cys-241 resulted in a slightly, but significantly, increased activity. In addition, I2 had no effect on the activity of these mutant C2. Substitution of Lys for Gln-243 increased the hemolytic activity by more than two-fold. Increased activity in all cases was due to slower decay rates of the C3 convertase. Finally, substitution of Leu or Ala for Asp-240 or Ser-244, respectively, resulted in more than 100-fold decrease of hemolytic activity. The results suggest that residues 240 to 244 of human C2 represent an important structural determinant of the C4b binding site of C2a. They also confirm that Cys-241 is the residue responsible for the increased activity of C2 reacted with I2."
-What is the main hypothesis tested in this study about Wolfram syndrome and psychiatric disorders?,"Psychiatric disorders in 36 families with Wolfram syndrome. OBJECTIVE: The purpose of this study was to test the hypothesis that heterozygous carriers of the gene for the Wolfram syndrome, who constitute about 1% of the population, are predisposed to significant psychiatric illness. The Wolfram syndrome is an autosomal recessive neurodegenerative syndrome in which 25% of the individuals who are homozygous for the condition have severe psychiatric symptoms that lead to suicide attempts or psychiatric hospitalizations. METHOD: The authors collected questionnaires, death certificates, and hospital records for blood relatives and their spouses in 36 families of individuals with the Wolfram syndrome and compared the proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness to the proportion of spouses with the same manifestations. RESULTS: The proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness significantly exceeded the proportion of spouses with the same manifestations. CONCLUSIONS: Since heterozygous carriers of the gene for the Wolfram syndrome are 50-fold more common among the blood relatives than among the spouses, the larger proportion among blood relatives is evidence that heterozygous carriers of the gene for the Wolfram syndrome are predisposed to significant psychiatric illness."
-How does sonography compare to chest radiography and CT in monitoring the therapeutic response of mediastinal lymphomas?,"Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT. The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas."
-"How does pyruvate kinase activity differ between normal fibrous tissue, benign proliferations, and malignant tumors?","Pyruvate kinase activity and isozyme composition in normal fibrous tissue and fibroblastic proliferations. Pyruvate kinase (PK) was studied in 57 fibroblastic and fibrohistiocytic proliferations and normal fibrous tissue (n = 10). The specific activity was significantly increased in malignant tumors (1.67 +/- 0.25) compared with normal tissue (0.26 +/- 0.04; P less than 0.001) and benign proliferations (0.52 +/- 0.05; P less than 0.005). Although an overlap exists between aggressive fibromatosis and the benign group, high values of PK activity are indicative of Grade 2 and 3 malignancy. Significant shifts in isozyme pattern, favoring the expression of K-type subunits were found in tumors with a metastasizing potential and aggressive fibromatosis. These changes in the isozyme pattern of PK in aggressive fibromatosis may act as another argument to place them in the category of malignant fibroblastic tumors."
-What method did the researchers use to detect mixed hematopoietic chimerism after allogeneic bone marrow transplantation?,"Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction. The influence of mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation remains unknown. Increasingly sensitive detection methods have shown that MC occurs frequently. We report a highly sensitive novel method to assess MC based on the polymerase chain reaction (PCR). Simple dinucleotide repeat sequences called microsatellites have been found to vary in their repeat number between individuals. We use this variation to type donor-recipient pairs following allogeneic BMT. A panel of seven microsatellites was used to distinguish between donor and recipient cells of 32 transplants. Informative microsatellites were subsequently used to assess MC after BMT in this group of patients. Seventeen of the 32 transplants involved a donor of opposite sex; hence, cytogenetics and Y chromosome-specific PCR were also used as an index of chimerism in these patients. MC was detected in bone marrow aspirates and peripheral blood in 18 of 32 patients (56%) by PCR. In several cases, only stored slide material was available for analysis but PCR of microsatellites or Y chromosomal material could be used successfully to assess the origin of cells in this archival material. Cytogenetic analysis was possible in 17 patients and MC was detected in three patients. Twelve patients received T-cell-depleted marrow and showed a high incidence of MC as revealed by PCR (greater than 80%). Twenty patients received unmanipulated marrow, and while the incidence of MC was lower (44%), this was a high percentage when compared with other studies. Once MC was detected, the percentages of recipient cells tended to increase. However, in patients exhibiting MC who subsequently relapsed, this increase was relatively sudden. The overall level of recipient cells in the group of MC patients who subsequently relapsed was higher than in those who exhibited stable MC. Thus, while the occurrence of MC was not indicative of a poor prognosis per se, sudden increases in the proportions of recipient cells may be a prelude to graft rejection or relapse."
-What was the impact of omentectomy on postoperative sepsis in patients undergoing proctocolectomy and ileoanal anastomosis?,"Let sleeping dogs lie: role of the omentum in the ileal pouch-anal anastomosis procedure. A surgical aphorism has long held that the omentum is the ""watchdog of the abdomen."" However, detractors believe that leaving the omentum behind after colectomy precipitates later small bowel obstruction. A retrospective comparison was made between a group of 406 patients (Group I) having omentectomy with proctocolectomy and ileoanal anastomosis and a group of 239 patients (Group II) having a similar procedure without omentectomy. Follow-up in this series of 645 patients was 4.3 +/- 2.1 years (mean +/- SEM). No difference was present in the rate of partial small bowel obstruction or complete small bowel obstruction between Group I patients (32 percent partial, 12 percent complete) and Group II patients (29 percent partial, 12 percent complete; P greater than 0.1). However, a better outcome with regard to postoperative sepsis and sepsis requiring operation was apparent in Group II patients retaining the omentum (4 percent and 3 percent, respectively) than in Group I patients (10 percent and 8 percent, respectively), in whom the omentum was removed (P less than 0.01). As this experience would support, we urge surgeons to ""let sleeping dogs lie"" and, when possible, retain the omentum when performing colectomy or proctocolectomy."
-What was the effectiveness of fluconazole in treating hepatosplenic candidiasis in patients who did not respond to previous antifungal treatments?,"Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy."
-How did colchicine affect renal function and fibrosis in a rabbit model of anti-glomerular basement membrane disease?,"Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit. A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis."
-What age groups were most affected by diarrheal deaths in the United States between 1979 and 1987?,"Diarrheal deaths in the United States, 1979 through 1987. A special problem for the elderly. OBJECTIVE.--Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal death among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States. DESIGN/SETTING/PARTICIPANTS.--We reviewed national mortality data complied by the National Center for Health Statistics, Hyattsville, Md, which consists of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a ""diarrheal death"" and included in the analysis. RESULTS.--We found that 28,538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children (younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin. CONCLUSION.--For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population."
-What are the acute and chronic hemodynamic effects of xamoterol in patients with mild to moderate congestive heart failure?,"Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure. Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment."
-What is the significance of using interphase cytogenetics with in situ hybridization in studying trisomy 12 in chronic lymphocytic leukemia?,"Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study. Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cells of conventional cytogenetic preparations from eight patients and on morphologically and immunologically classified cells of cytospin preparations from seven patients. The results show that trisomy 12 is more common than assumed on the basis of karyotype analysis of metaphase chromosomes: 2 of 13 patients with a normal karyotype in G-banding analysis were shown to have trisomy 12 by interphase cytogenetics. Immunophenotyping of the cells of one patient showed that the trisomy was restricted to cells with Ig light chain clonality. For the evaluation of the prognostic, therapeutic, and biologic significance of trisomy 12, in situ hybridization should be used in parallel with karyotype analysis because it allows the study of all cell populations of both interphase and mitotic cells, whether neoplastic or normal."
-What was the primary aim of the 10-year prospective screening study on multiple endocrine neoplasia type 1 (MEN 1)?,"Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified."
-What is the relationship between neurosurgical intervention and the risk of cerebral hemorrhage in patients with cerebral amyloid angiopathy?,"Surgical risk of hemorrhage in cerebral amyloid angiopathy. Cerebral amyloid angiopathy is increasingly recognized as a cause of lobar cerebral hemorrhage in normotensive elderly individuals. Isolated reports have suggested that neurosurgical intervention entails a high risk of precipitated hemorrhage. We identified 16 pathologically confirmed cases of cerebral amyloid angiopathy. Fourteen of these patients presented with lobar cerebral hemorrhage. Fifteen neurosurgical procedures in eight patients included eight clot evacuations, three abscess drainage procedures, two ventriculoperitoneal shunts, one biopsy, and one lobectomy. Recurrent postoperative cerebral hemorrhage was seen in four patients at 2 days, 9 days, 6 weeks, and 10 months, but surgery was thought to have precipitated the cerebral hemorrhage in only one patient. Recurrent cerebral hemorrhage also was seen in two of the eight nonoperated cases. Recurrent cerebral hemorrhage is characteristic of cerebral amyloid angiopathy, but we conclude that neurosurgical intervention, particularly evacuation of hematomas, is not associated with major risk of precipitated hemorrhage."
-What is the primary purpose of transvenous endomyocardial biopsy in cardiac transplant recipients?,"Ventricular fibrillation complicating endomyocardial biopsy of a cardiac allograft. Transvenous endomyocardial biopsy remains the most useful diagnostic aid in assessing rejection in the transplanted heart. Although invasive, the complications associated with endomyocardial biopsy are few, and the procedure is generally regarded as safe. We report a case of apparent ventricular fibrillation complicating transvenous endomyocardial biopsy. Histologic section revealed evidence of moderate acute rejection. This case represents the first report of a life threatening ventricular dysrhythmia following routine endomyocardial biopsy in a cardiac transplant recipient."
-What percentage of patients had an excellent result after catheter-less suprapubic cystolithotomy in children?,"Catheter-less suprapubic cystolithotomy in children. Bladder stones in children are common in developing countries and the procedure of choice for their removal is suprapubic cystolithotomy. It is standard practice to drain the bladder for a few days post-operatively to prevent urinary leakage. We have observed that, if the bladder is closed meticulously in 2 layers, bladder drainage by means of a catheter is not required. We have analysed 86 children treated by suprapubic cystolithotomy without a catheter. Size of the stones and intra-operative findings were noted and it was found that 85% of the patients had an excellent result; 10% had a satisfactory result and 4.7% were unsatisfactory. The advantages of the procedure and selection of the patients are discussed."
-What evidence suggests a potential link between HTLV-I and mycosis fungoides in the study?,"Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides."
-How does the pre-treatment PSA level correlate with treatment outcomes in prostate cancer patients receiving primary radiation therapy?,"Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy. The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures. Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence."
-What were the effects of DuP 753 and captopril on left ventricular end-diastolic pressure and volume in rats with heart failure?,"Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction."
-What are the major risk factors for coronary heart disease in the elderly?,"Preventive maintenance of the aging heart. Coronary heart disease (CHD) is the major cause of mortality in the elderly. Important risk factors include hypercholesterolemia, systolic and diastolic hypertension, cigarette smoking, hyperglycemia, and obesity. Elderly patients with existing CHD should be treated aggressively to control these risk factors, along with other medical therapies to treat myocardial ischemia. For elderly patients without recognized CHD, however, a more conservative approach is recommended and includes behavioral interventions when appropriate and pharmacologic therapy for higher risk patients with persistent, uncontrolled risk factors."
-"How many American women are expected to be affected by ovarian cancer this year, and what is the estimated mortality rate?","Screening in ovarian cancer. Ovarian cancer will affect 20,000 American women this year and some 13,500 will die of the disease. Most patients will have stage III or IV disease at the time of diagnosis. Because ovarian cancer may be initially without symptoms, attempts have been made to develop screening tests that would lead to an early diagnosis. Two tests, serum CA 125 and pelvic ultrasonography, have been suggested by some to be accurate enough to be included in yearly screening for ovarian cancer. Although further testing of these techniques is encouraged, data to date do not justify yearly screening with CA 125 or pelvic ultrasonography in all women."
-What factors were associated with less favorable crude survival in patients undergoing hepatic resection for colorectal secondaries?,"Indicators of prognosis after hepatic resection for colorectal secondaries. From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding ""high risk"" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control."
-What was the effectiveness of palliative radiation therapy in treating epidural compression caused by metastatic malignant melanoma?,"The effect of palliative radiation therapy on epidural compression due to metastatic malignant melanoma. The efficacy of palliative radiation therapy in the treatment of spinal cord and cauda equina compression due to metastatic malignant melanoma was evaluated in 38 sites in 35 patients treated between 1970 and 1990. All patients had radiographic documentation of epidural compression. The median dose of radiation therapy was 2850 cGy (range, 500 to 4000 cGy), with daily fractions ranging from 200 to 800 cGy. Twenty-eight sites in 26 patients were evaluable 1 month after completion of radiation therapy, and symptoms responded completely in 11 of 28 (39%) sites. Fourteen sites (46%) showed a partial response of symptoms. Response lasting until death was documented in 21 of 26 patients (81%). Patients receiving a total dose of 3000 cGy or greater were more likely to achieve a complete response than those receiving less than 3000 cGy (62% versus 20%) by univariate (P = 0.025) and multivariate (P = 0.048) analyses. A treatment program of radiation therapy and corticosteroids is effective in palliating the symptoms of epidural compression due to metastatic malignant melanoma. It is recommended to deliver an accelerated course of radiation therapy to a dose of 3000 cGy or greater without exceeding spinal cord tolerance (e.g., 3000 cGy in ten fractions at 300 cGy per fraction)."
-"What behavioral modification technique was used to help a patient with adipsia, diabetes insipidus, and memory impairment achieve independent drinking and be discharged from the hospital?","Management of adipsia by a behavioural modification technique. Adipsia combined with diabetes insipidus after hypothalamic damage may produce major difficulties in clinical management. If there is an associated memory impairment it may be impossible to teach self-regulation of fluid balance, necessitating long-term hospital supervision. The successful use of a behaviour modification technique to achieve independent drinking and allow discharge from hospital into the community is described in a patient with adipsia, diabetes insipidus and memory impairment resulting from the removal of a craniopharyngioma."
-What was the primary objective of the study involving thermal ablation of the gallbladder in dogs?,"Thermal ablation of the gallbladder. Gallbladder ablation by means of injection of hot contrast medium was attempted in 13 dogs. Room temperature contrast medium was injected into the gallbladders of two additional dogs (controls). After midline laparotomy was performed to expose the gallbladder, temperature probes were placed in the liver adjacent to the gallbladder, and on the surface and in the lumen of the gallbladder. A 7-F catheter with multiple side holes was placed into the gallbladder. The cystic duct was clamped during the procedure. After injection of boiling contrast medium, the mean temperature in the gallbladder lumen was 80 degrees C; in the adjacent liver, 43.5 degrees C; and on the gallbladder surface, 45.8 degrees C. After the procedure, the cystic duct was unclamped, temperature probes and catheter were removed, and the laparotomy was closed in standard fashion. In the hot contrast medium group, one dog each was sacrificed at 2, 4, 8, and 12 weeks, and at 6 months. Six animals were sacrificed at 1 year. The gallbladder was completely ablated in 11 of 13 animals in the hot contrast medium group. One dog was sacrificed at 8 days because of bile leakage, and another was sacrificed at 17 days because of gallbladder rupture. The two control animals were sacrificed at 12 and 13 weeks, and their gallbladders were normal at that time."
-What were the key predictors of breast cancer screening among women aged 40 and older in the Rhode Island study?,"A study guided by the Health Belief Model of the predictors of breast cancer screening of women ages 40 and older. In late 1987, a total of 852 Rhode Island women ages 40 and older were interviewed by telephone (78 percent response rate) to measure their use of breast cancer screening and to investigate potential predictors of use. Predictors included the women's socioeconomic status, use of medical care, a provider's reported recommendations for screening, and the women's health beliefs about breast cancer and mammography. The Health Belief Model guided the construction of the interview questions and data analysis. Logistic regression was used to identify leading independent predictors of breast cancer screening according to contemporary recommendations: reporting that a medical provider had ever recommended a screening mammogram (odds ratio [OR] = 18.77), having received gynecological care in the previous year (OR = 4.92), having a regular source of gynecological care (OR = 2.63), having ever had a diagnostic mammogram (OR = 2.32), and perceiving mammography as safe enough to have annually (OR = 1.93). The findings suggest that programs intended to increase the use of breast cancer screening should include ""inreach"" and ""outreach"" elements; inreach to patients with established patient-provider relationships, by assuring that physicians recommend screening to all eligible patients, and outreach to all eligible women, by helping them overcome barriers to effective primary care, and by promoting mammography, emphasizing its effectiveness and safety. The findings also suggest that socioeconomically disadvantaged women, who are less likely to be screened than other women, should become special targets of inreach and outreach interventions."
-What was the effectiveness of percutaneous drainage for traumatic pancreatic pseudocysts in children according to this study?,"Percutaneous drainage of traumatic pancreatic pseudocysts in children. To determine the effectiveness of percutaneous drainage of traumatic pancreatic pseudocysts, we reviewed the courses of 13 children. Six pseudocysts resolved on complete bowel rest and total parenteral nutrition. Seven required further therapy. Two pseudocysts were treated operatively; five were drained percutaneously with fluoroscopic guidance. These five ranged from 5 to 15 cm in diameter and were present for 10 to 42 days (mean, 26 days). In all cases, the cyst fluid was clear, had an amylase level of greater than 40,000 IU/L, and grew no organisms. The pigtail catheters left in place in four of the five children were removed when drainage stopped. Patients were followed by ultrasound while still in the hospital and 1 month after discharge. There were no complications nor any pseudocyst recurrence. Percutaneous drainage of traumatic pancreatic pseudocysts in children is an effective alternative to the standard operative therapy of pseudocystenteric anastomosis."
-What was the efficacy of continuous intravenous diltiazem infusion in controlling heart rate during atrial fibrillation and atrial flutter?,"A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem. Of the 47 patients, 44 responded to the bolus injection and were randomized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem (10 to 15 mg/h) (23 patients) or placebo (21 patients) for up to 24 h. Seventeen (74%) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h (p less than 0.001). Over 24 h, patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion (p less than 0.001). Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion. The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83% (34 of 41). Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients, those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg. However, intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter. No significant untoward effects were noted."
-What are histamine H2-receptor antagonists and how do they work to reduce gastric acid secretion?,"Histamine H2-receptor antagonists. In summary, histamine initiates acid secretion by stimulating the H2 subtype histamine receptor on parietal cells. Cimetidine, rantidine, famotidine, and nizantidine are histamine H2-receptor antagonists that block this action of histamine, reducing gastric acid output and concentration under both basal and stimulated conditions. These agents are used for treatment and prevention of peptic and stress ulcers as well as for hypersecretory states. Because of their effectiveness and low incidence of side effects, H2-antagonists have largely replaced more traditional antiulcer regimens."
-"What percentage of patients with parenchymal brain hemorrhage experience seizures, and in what stages do these seizures typically occur?","Seizures caused by nontraumatic parenchymal brain hemorrhages. Seizures occurred in 15% of patients with parenchymal brain hemorrhage (early in 12% and delayed in 3%). Seizures were most frequent with lobar hemorrhages and uncommon with deep subcortical hemorrhages. Lobar hemorrhages in the frontal, parietal, or temporal region were more commonly associated with seizures, whereas occipital hemorrhages were not. Seizures were most common if the hemorrhage was due to an aneurysm, angioma, or neoplasm and less common if hypertensive or spontaneous. If the patient had recurrent seizures or developed delayed seizures, CT showed that the hemorrhage evolved to a hypodense appearance; if the seizure did not recur, CT showed that the hemorrhage evolved to an isodense appearance."
-What diagnostic technique was found to be more sensitive in identifying patent ductus arteriosus in an infant with atrioventricular septal defect?,Patent ductus arteriosus in an infant with atrioventricular septal defect and pulmonary hypertension: diagnosis by transesophageal color flow echocardiography. An infant with complete atrioventricular septal defect (atrioventricular canal) was examined by standard transthoracic two-dimensional pulsed Doppler and color Doppler echocardiography. No evidence of ductus arteriosus was present. Preoperative transesophageal echocardiography identified a patent ductus: the left-to-right shunt seen by color Doppler echocardiography was enhanced by pharmacologic maneuvers aimed at decreasing pulmonary vascular resistance and increasing systemic vascular resistance. Transesophageal echocardiography was found to be more sensitive than transthoracic echocardiography even in a small infant.
-How did the study use ADL dependencies to determine long-term care eligibility for individuals with dementia in the Oregon Medicaid program?,"Using ADLs to establish eligibility for long-term care among the cognitively impaired. Using a database from the Oregon Medicaid program, we examined the differences in the potential insurance coverage of demented persons by using different formulations of ADL (activities of daily living) dependencies in which the definition of dependency did or did not include the need for supervision. For those with clear dementia, 81-88% of the persons with significant behavioral problems were correctly identified when a cut score of three or more ADLs was used; this percentage was even higher for two or more ADLs. This approach was not as effective in correctly discriminating those who had no behavioral problems."
-What neurological and musculoskeletal complications were observed in a 75-year-old woman with untreated primary hypothyroidism?,"Neuropathy, myopathy and destructive arthropathy in primary hypothyroidism. A 75-year-old woman with untreated primary hypothyroidism was found with peripheral neuropathy (including carpal tunnel syndrome), severe myopathy (high levels of creatine phosphokinase) and destructive arthropathy, affecting fingers, toes and the left knee. Radiographs of her knee showed destructive lesions of the tibial plateau similar to a pathologic compression fracture, while the joints of the fingers and toes showed all signs of severe erosive osteoarthritis (OA), radiographically documented over a period of 7 years. It is suggested that hypothyroidism is causally related to the development of erosive OA."
-What evidence suggests an autoimmune mechanism in the patient's neuromyotonia?,"Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome). Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases."
-What was the most common symptom among patients with lower esophageal mucosal rings in this study?,"Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring."
-What rare ictal phenomenon was investigated in two patients with epilepsy?,"Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions."
-What are the most common CT findings in patients with malignant pleural mesothelioma?,"Malignant pleural mesothelioma: CT manifestations in 50 cases. Malignant pleural mesothelioma, a rare and usually fatal neoplasm that is associated with asbestos exposure, is being encountered with increasing frequency. Pretreatment CT findings from 50 patients with malignant pleural mesothelioma are illustrated. Pleural thickening was found in 46 (92%) of the 50 patients, thickening of the pleural surfaces of the interlobar fissures in 43 (86%), pleural calcifications in 10 (20%), and pleural effusions in 37 (74%). The volume of the involved hemithorax varied appreciably. Contractions of the involved hemithorax was noted in 21 (42%) of 50 patients and contralateral mediastinal shift in seven (14%). Disease beyond the parietal pleura was found in the chest wall (nine patients), mediastinum, lymph nodes, and diaphragm."
-What was the clinical presentation and treatment of the 22-year-old patient with a prostatic mass?,"Pseudosarcomatous fibromyxoid tumor of the prostate. A case report with immunohistochemical, electron microscopic, and DNA flow cytometric analysis. A 22-year-old man presented with symptoms of urinary obstruction and was found to have a 5-cm mass protruding from the left side of the prostate into the prostatic urethra. The lesion was partially removed by transurethral resection (TURP). The patient's symptoms recurred, so he required another TURP four months later; at latest follow-up (four years later), there waas no evidence of disease. Light microscopy revealed a myxoid lesion characterized by an atypical fibroblastic proliferation associated with a prominent inflammatory component and granulation tissue-type vasculature. The lesion nearly replaced the prostatic parenchyma and invaded the bladder wall. Immunohistochemistry and electron microscopy showed a predominance of fibroblasts with occasional myofibroblasts. DNA flow cytometric analysis showed that the tumor cells had a diploid DNA content. Given these findings and the indolent clinical course, the authors think that this lesion represents a benign, reactive process consistent with a pseudosarcomatous fibromyxoid tumor, a recently described rare lesion of the genitourinary tract."
-What molecular weight of macrophage colony-stimulating factor (hM-CSF) was detected in serum and urine samples using immunoblot analysis?,"Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis. We characterized the molecular species of human macrophage colony-stimulating factor (hM-CSF) found in serum and urine, using immunoblot analysis after partial purification on an antibody-bound affinity column. Although antibodies were prepared using the recombinant product of the large form of hM-CSF with a molecular weight (MW) of 85 Kd as the antigen, this immunoblot system was also capable of detecting the small form of hM-CSF with a MW of 40 to 60 Kd. A single band with a MW of 43 Kd, which reacted with anti-recombinant hM-CSF IgG but not with control IgG, was found when serum and urine from normal adults underwent electrophoresis on reduced sodium dodecyl sulfate-polyacrylamide gel and subsequent immunoblotting. This band represented a subunit of the large form of hM-CSF, because the large form of hM-CSF is a homodimer of a subunit with a MW of 43 Kd and the small form of hM-CSF is a homodimer of a subunit with a MW of 20 to 30 Kd. Analysis of serum and urine from leukemic patients and pregnant women, who had higher serum levels of hM-CSF than normal adults, showed only a single band with a MW of 43 Kd as a hM-CSF-specific molecule. These results suggest that the large form of hM-CSF is the major species in human body fluids."
-What is the significance of a positive direct antiglobulin test (DAT) in multiple myeloma patients?,"Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance. Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis."
-What is the diagnostic value of mouse rosettes (M-rosette) and surface immunoglobulin (SIg) in differentiating B-chronic lymphocytic leukemia (B-CLL) from reactive lymphocytosis (RLC)?,"The importance of surface immunoglobulin, mouse rosettes, and CD5 in the immunophenotyping of chronic lymphocytic leukemia and reactive lymphocytosis. Peripheral blood from 167 B-chronic lymphocytic leukemia (B-CLL) and 119 reactive lymphocytosis (RLC) patients were analyzed to evaluate the immunophenotypic diagnostic value of mouse rosettes (M-rosette), and weak expression of monoclonal surface immunoglobulin (SIg). In B-CLL, 145 cases were M-rosette+ (86.83%), 135 surface immunoglobulin (SIg)+ (80.84%), and 117 M-rosette+ SIg+ (70.06%). Of 32 SIg- cases, 28 were M-rosette+; and of 22 M-rosette-cases, 18 were SIg+. By combining results of the two assays and accepting positivity of either one or both as sufficient for diagnosis, B-CLL was diagnosed in 163 cases (97.60%). CD5 was performed in 49 cases of the 167 with paired data for SIg and M-rosettes. By combining the results of the three assays and accepting positivity of any two or all three as sufficient for diagnosis, all 49 cases (100%) were diagnosed. Correlation analysis showed no significant association between M-rosette, SIg, and CD5 expression. The results demonstrate the independent expression of the three markers, and their complementary role in immunophenotyping B-CLL. In RLC, all 119 cases were T-lineage and SIg-, and 115 were M-rosette-, indicating the role of the two markers in differentiating B-CLL from RLC. Three of the four M-rosette+ T-RLC were subsequently diagnosed as B-CLL, suggesting the necessity of follow-up of such cases."
-How do different structural forms of hen egg lysozyme (HEL) affect its presentation by MHC class II molecules?,"Class II-restricted presentation of an endogenously derived immunodominant T-cell determinant of hen egg lysozyme. An in vitro model was used to investigate the potential for different structural forms of endogenous antigen to be processed and presented by major histocompatibility complex class II molecules. For this purpose the class II-restricted presentation of an immunodominant epitope of hen egg lysozyme [HEL-(46-61)] was studied in class II-positive B-lymphoma cells (M12.C3) transfected with genes encoding HEL molecules either (i) secreted in high (hi) or low (lo) amounts as soluble antigen [sHEL(hi/lo)], (ii) localized within the endoplasmic reticulum (ER)/salvage compartment (ER-HEL), or (iii) anchored on the cell surface as an integral membrane protein (mHEL). The corresponding sHEL, ER-HEL, and mHEL gene products were expressed as predicted except that HEL determinants accumulated in the culture supernatant as well as on the cell membrane of mHEL-transfected cells. Class II-positive cells endogenously expressing all three forms of HEL antigen constitutively presented the immunodominant HEL-(46-61) determinant with differential efficiency (mHEL, sHEL greater than ERHEL) to a class II-restricted T hybridoma. A second T hybridoma recognized endogenous HEL-(46-61) determinants constitutively presented on sHEL(hi) and mHEL transfectants but not on sHEL(lo) or ERHEL transfectants. The formation of HEL-(46-61)/I-Ak complexes in the ERHEL and sHEL(lo) transfectants was therefore limiting. Mixing experiments with different antigen-presenting cells indicated that the HEL-(46-61) determinant was derived from endogenous antigen rather than by reuptake of shed or secreted HEL determinants. We conclude that MHC class II molecules can present some antigenic determinants derived from endogenous proteins that are sequestered in the ER/salvage compartment as well as distally transported in the form of secretory or membrane antigens."
-What minimally invasive technique was used to successfully treat chylothorax after pneumonectomy when conservative therapy failed?,"Thoracoscopic diagnosis and treatment of chylothorax after pneumonectomy. Chylothorax after pneumonectomy was treated successfully by selective application of fibrin glue through a thoracoscope. Conservative therapy for 18 days failed to close the fistula. The site of leakage was identified during thoracoscopy, and fibrin glue was applied under direct vision. Leakage decreased immediately and eventually stopped completely. This technique is less invasive than standard surgical treatment and should be considered in all patients with postoperative chylothorax."
-What was the main strategy used for managing distal ileal Crohn's disease in this study?,"Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy."
-What modifications were made to the original T-shaped musculomucosal buccal flap method to improve cleft palate surgery outcomes?,"The modified buccal musculomucosal flap method for cleft palate surgery. We have reported previously on a palatoplasty method, called the T-shaped musculomucosal buccal flap method, for the primary repair of a cleft palate. This method has been used on more than 90 patients, and satisfactory outcomes have resulted in terms of maxillar development, the prevention of fistulation, and verbal functions. However, 14.3 percent of these patients exhibited a velopharyngeal incompetence that showed no potential improvement through training. In the majority of these patients, the entire raw surface of the oral cavity side could not be covered with a buccal musculomucosal flap, and as a result, postoperative contraction of the soft palate occurred. Thus a new surgical method has proven effective in which both buccal musculomucosal flaps are used as an oral lining, the nasal mucosa having been extended by Z-plasty. We have performed 25 operations using this new method and have observed no postoperative contractions of the soft palate, notwithstanding two cases (8.0 percent) of postoperative fistulation."
-What were the complete fragmentation rates and 3-month stone-free rates for the three different lithotripsy devices studied?,"Comparative studies of extracorporeal shock wave lithotripsy by Dornier HM3, EDAP LT 01 and Sonolith 2000 devices. During a 2-year period extracorporeal shock wave lithotripsy (ESWL) was done at our institution in 70 patients with the Dornier HM3, 113 with the EDAP LT 01 and 104 with the Sonolith 2000 lithotriptors. The size and location of stones were comparable in all 3 series, and all treatments were done by the same team of urologists. Complete fragmentation occurred in 79% of the patients treated by the Dornier, 82% treated by the EDAP and 79% treated by the Sonolith devices, with 3-month stone-free rates of 66, 67 and 58%, respectively. Auxiliary procedures were needed in 12% of the patients in the Dornier, 13% in the EDAP and 9% in the Sonolith groups. Repeat treatment was necessary in 4% of the Dornier group, 42% of the EDAP group and 26% of the Sonolith group. Therefore, all 3 lithotriptors are effective in stone disintegration and produce satisfactory results when selection criteria for ESWL are observed. The most significant difference among the 3 lithotriptors is the number of repeat treatments, which reflects the power and energy output of the lithotriptors. In conclusion, the Dornier HM3 device has the advantage of low repeat treatment rate and easier stone localization. The EDAP LT 01 unit has the advantage of lower treatment costs and anesthesia-free treatment with no irradiation. The Sonolith 2000 device has features of the other 2 lithotriptors with a superior ultrasound image."
-What were the key findings from linking the Illinois AIDS and Cancer Registries regarding neoplasia in people with AIDS?,"A systematic consideration of the neoplastic spectrum of AIDS: registry linkage in Illinois. To examine unexplored aspects of the association between AIDS and neoplasia, the Illinois AIDS and Cancer Registries were linked. The method integrated use of a personal computer to find exact matches on names and dates of birth with manual review to assure satisfaction of a match definition. Of the factors examined, white race and homosexuality predicted Kaposi's sarcoma (KS) among people with AIDS (PWAs), and white race predicted non-Hodgkin's lymphoma (NHL). Earlier reports of a declining proportion of PWAs with KS were confirmed. Lymphoma (mixed lymphocytic/histiocytic type), while not currently diagnostic of AIDS, occurred more frequently among PWAs than in the Illinois population. For the first time, rates of cancers other than KS and NHL were demonstrated to be significantly increased among PWAs compared with general populations. In the light of these findings, reconsideration of current neoplastic definitions may be useful."
-What treatment was used for children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and what were its outcomes?,"Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin. We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients."
-What were the two-year clinical success rates for the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups?,"Experience with laser-assisted balloon angioplasty and a rotary angioplasty instrument: lessons learned. Favorable early results with mechanical angioplasty devices and laser-assisted balloon angioplasty have resulted in aggressive marketing and a rapid increase in the use of these devices for the treatment of femoropopliteal occlusive disease. Recent reports, however, have questioned the durability of these less invasive procedures. Since 1986 we have been involved in the clinical investigation of the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty. One hundred two balloon angioplasty procedures assisted by the Nd:YAG laser (n = 56) and the Kensey dynamic angioplasty instrument (n = 46) were performed for the treatment of femoropopliteal occlusive lesions. Both Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups were similar with regard to age, operative indication, preoperative ankle-brachial index, lesion length, and distal runoff. Mean follow-up was 19 months in the Kensey dynamic angioplasty instrument group and 15 months in the laser-assisted balloon angioplasty group. Technically successful recanalization was achieved in 67% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 82% of laser-assisted balloon angioplasty procedures. Early hemodynamic and clinical improvement was obtained in 59% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 57% of laser-assisted balloon angioplasty procedures. Two-year clinical success by life-table analysis was 37% in the Kensey dynamic angioplasty instrument group and 19% in the laser-assisted balloon angioplasty group. The level of subsequent surgical revascularization was not altered in any patient by Kensey dynamic angioplasty instrument-assisted balloon angioplasty or laser-assisted balloon angioplasty."
-What was the impact of long-term passive anti-HBV immunoprophylaxis on HBV reinfection and survival in liver transplant patients?,"Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. 110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation."
-How does the diaphragmatic activity differ between slow-wave sleep and rapid-eye-movement (REM) sleep in cats?,"Differential activation within costal diaphragm during rapid-eye-movement sleep in cats. Simultaneous recordings of the diaphragmatic electromyogram (EMG) were made from two separate regions of the costal diaphragm in six normal cats. The diaphragmatic activities were always synchronous and the amplitudes and rates of rise were similar during slow-wave sleep. In contrast, during natural rapid-eye-movement (REM) sleep, different activity was often present in the two leads. These differences were in the time of onset and offset, as well as in the amplitude and spike patterns, and occurred in approximately 5-20% of the diaphragmatic bursts averaged over the entire REM sleep period. With respect to eye movement density, the rate of differential activation was higher during periods of high density (26%) than in the absence of eye movements (1%) in the four animals for which these data were available. Differential activation of portions of the costal diaphragm is apparently a normal event of REM sleep. This could result from descending state-specific phasic neuronal activity that bypasses the medullary respiratory generator. Differential activation of portions of the diaphragm could contribute to disordered ventilation during REM sleep."
-What symptoms are commonly associated with posttraumatic headache as part of the postconcussion syndrome?,"Posttraumatic headache and the postconcussion syndrome. Although headache is the most common sequelae of head injury, the posttraumatic headache is associated frequently with dizziness, irritability, lack of concentration, and intolerance to alcohol ingestion as a part of a symptom complex known as the postconcussion syndrome. This article clarifies the definitions of acute traumatic headache, posttraumatic headache, and the postconcussion syndrome and improves diagnostic ability, making the assessment and treatment of patients with these three conditions more accurate and effective."
-What are the two bacterial factors identified as important in enteropathogenic Escherichia coli (EPEC) infection?,"Characterization of interactions of enteropathogenic Escherichia coli O127:H6 with mammalian cells in vitro. Previous studies have identified two bacterial factors involved in enteropathogenic Escherichia coli (EPEC) infection. A plasmid-mediated EPEC adherence factor (EAF) is responsible for initial and localized adherence. A chromosomally encoded E. coli attachment and effacement factor (eae) is involved in effacement of the eukaryotic cell surface and characteristic ""pedestal"" formation. By using isogenic strains deficient in either EAF, eae, or both, the process of EPEC adherence and entry in vitro was examined. While EAF proved necessary and sufficient for efficient bacterial association with HEp-2 cells, both EAF and eae were required for efficient effacement of and entry into these cells and other cultured cell lines. Invasion mediated by eae was markedly inhibited by cytochalasin D and colchicine. Afimbrial adhesion or type I pili from uropathogenic strains of E. coli substituted for EAF in EAF-Eae+ strains to provide initial adherence to HEp-2 cells and to facilitate actin condensation."
-What are the key initiatives proposed to address the shortage of trained eye care professionals in sub-Saharan Africa?,"Who will operate on Africa's 3 million curably blind people? About half the 6 million blind people in sub-Saharan Africa have surgically curable cataract. The available manpower and resources can only provide services for less than 10% of the new blind cataract patients each year, and little is being done for the estimated 3 million ""cataract backlog"". A serious limiting factor to the development of prevention of blindness programmes is lack of trained manpower. Despite an increase in the number of ophthalmologists trained in cataract surgery (which varies greatly from country to country), this number is not keeping pace with increased demand for eye-care services, especially in large rural populations. Initiatives that will help to overcome this dilemma are specific post-graduate courses in community ophthalmology in Africa, plans to develop a one-year diploma in ophthalmology course for English-speaking West African countries, and a proposal to upgrade a similar course in Zimbabwe. Additionally there is a need for the training of more ophthalmic assistants, cataract surgeons, and nurses in the diagnosis and management of common ophthalmic disorders. Experienced expatriate ophthalmologists also have an important role in the teaching of doctors and ophthalmic assistants how to select patients and carry out successful inexpensive cataract surgery with appropriate technology and limited facilities."
-What unique characteristics were observed in this case report of a pituitary adenoma?,"Ectopic pituitary adenoma in the suprasellar cistern: case report. The case of a 56-year-old man with an ectopic pituitary adenoma is reported. Neurological examinations, neurodiagnostic imaging, surgical observation, endocrinological evaluation, histological examination, and immunohistological study demonstrated evidence of ectopic prolactinoma in the suprasellar cistern and the presence of a normal pituitary in the sella turcica. The patient underwent total removal of the suprasellar mass by a pterional approach, leading to a surgical and endocrinological cure."
-What is neoplastic angioendotheliomatosis (NAE) and how did it manifest in the two described cases?,"Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months."
-What was the main finding of the study comparing low and high doses of ethanolamine oleate in treating esophageal varices?,"Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant."
-How do the responses of pial arterioles to bradykinin differ between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive (WKY) rats?,"Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP."
-What rare condition was reported in this medical case involving the gasserian ganglion?,Primary malignant melanoma of the gasserian ganglion associated with neurofibromatosis. A case of primary intracranial malignant melanoma of the left gasserian ganglion associated with temporal lobe gliosis in a patient suffering from von Recklinghausen's disease is reported. The association of primary malignant melanoma of the trigeminal nerve and neurofibromatosis is discussed.
-What was the average number of lymph nodes found in stations 1-11 and 1-16 in the cadaveric study?,"Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma."
-How does gamma-interferon influence astrocyte proliferation and reactive gliosis?,"Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to gamma-interferon (IFN). Recombinant IFN alone can induce proliferation of human adult astrocytes in vitro and increase the extent of trauma-initiated gliosis in the adult mouse brain. The astrocyte proliferation-inducing activity of supernatants of glial cultures treated with IFN can be completely blocked with IFN-neutralizing antibody, suggesting that the proliferative effect does not require intermediary cytokines or cells. These results implicate IFN as an important mediator of the gliosis observed in pathologic conditions of the adult central nervous system associated with infiltrating lymphocytes."
-What was the incidence of clinically significant pneumatosis intestinalis in patients who underwent abdominal operations or bariatric procedures with needle catheter jejunostomy?,"Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication. We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics."
-What are the typical symptoms and clinical presentation of medially invasive petrous bone cholesteatoma?,"Facial nerve and medially invasive petrous bone cholesteatomas. Eight patients with extensive petrous bone cholesteatomas that invaded the labyrinth and fallopian canal are presented. The eight cases are added to a tabulation of prior literature reports to elucidate concepts of routes of extension of medially invasive temporal bone cholesteatoma. Medially invasive petrous bone cholesteatoma develops insidiously, often without symptoms other than facial palsy and/or unilateral deafness. Typically, a history of chronic ear disease can be obtained. While hearing is unlikely to be preserved in this group of patients, facial nerve function can usually be preserved, and a facial nerve graft was not necessary in our series. Acute facial nerve palsy or facial nerve paresis progressing to palsy in patients with a history of chronic ear disease should be studied radiographically for petrous bone cholesteatoma, even if there is no physical evidence of cholesteatoma."
-What were the four different 6-month chemotherapy regimens used in this study for treating pulmonary tuberculosis?,"Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Hong Kong Chest Service/British Medical Research Council In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at random to four 6-month regimens of chemotherapy, all given three times weekly from the start and all containing isoniazid (H) and rifampin (R) throughout. Three contained streptomycin (S) for the first 4 months and pyrazinamide (Z) for 2 months (Z2), 4 months (Z4), or 6 months (Z6); the fourth contained pyrazinamide for 6 months but no streptomycin (Z6noS). Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis. During the later part of the intake patients were allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide, or as the three drugs separately. Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment, bacteriologic failure during chemotherapy occurred in 4, all Z6noS (2% of 224; p less than 0.005 for the comparison with the S-containing regimens). During 30 months of follow-up after the end of chemotherapy, bacteriologic relapse occurred in 2 (3%) of 71 Z2, 2 (3%) of 72 Z4, 4 (6%) of 66 Z6, and 6 (9%) of 64 Z6noS patients allocated to Rifater, and in 4 (3%) of 149 Z2, 8 (6%) of 133 Z4, 2 (1%) of 142 Z6, and 6 (4%) of 135 Z6noS patients allocated to separate drugs. In the relapse rates there were no significant differences between the Rifater and separate drug regimens, the different durations of pyrazinamide, or the regimens with and without streptomycin."
-Does 24-hour esophageal pH monitoring predict the response of reflux esophagitis to standard medical therapy?,"Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis. Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy."
-What were the key findings of the morphometric study on gastric endocrine cells after 6 months of omeprazole treatment in duodenal ulcer patients?,"Ultrastructural morphometry of gastric endocrine cells before and after omeprazole. A study in the oxyntic mucosa of duodenal ulcer patients. Long-term toxicological experiments with inhibitors of acid secretion were found to induce hyperplasia and eventually carcinoid tumors of the enterochromaffin-like cells of the oxyntic mucosa. To evaluate the effects of 6 months' treatment with omeprazole in humans, the oxyntic endocrine cells were morphometrically investigated at the ultrastructural level in five patients with active duodenal ulcer. No omeprazole-induced changes were found in the volume density of the total endocrine cell population and specific cell types (including the enterochromaffin-like cell) as well as in the other cytological parameters investigated (number of cell profiles per unit area, mean cross-sectional area of cell profiles, nuclear-cytoplasmic ratio, and density of cytoplasmic secretory granules). Both pretreatment and post-treatment values in our patients with duodenal ulcer significantly differed from those of a previous investigation of healthy volunteers with regard to the volume density of enterochromaffin-like cells and non-granulated cells, which increased, and of D cells, which markedly decreased. The latter result may provide a cellular basis for impairment in the paracrine release of fundic somatostatin in peptic ulcer disease. Finally, morphometric data on endocrine cell volume density provided by electron microscopy were found to correlate with those obtained in the same patients using light microscopy techniques (Grimelius silver impregnation and chromogranin A immunostaining). It is concluded that 6 months' treatment with pharmacological doses of omeprazole is devoid of appreciable trophic effect on endocrine cells of human oxyntic mucosa."
-What were the key differences in outcomes between patients with thrombolysis-mediated patency and those with patency achieved by angioplasty in acute myocardial infarction?,"Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy."
-How do deletions in different domains of the dystrophin gene affect the clinical presentation of Becker muscular dystrophy?,"Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels."
-What are the typical symptoms associated with anterior urethral polyps in male patients?,"Anterior urethral polyp associated with hematuria in six-year-old child. Anterior urethral polyps are rare, occur only in male patients, and have been associated with obstruction, terminal hematuria, and enuresis. We believe this is the fifth reported case of anterior urethral polyp associated with terminal hematuria. The radiographic findings, treatment, and pathology are reviewed."
-What is the purpose of the study on percutaneous stimulation of the cauda equina?,"Percutaneous stimulation of the cauda equina. A new diagnostic method in spinal stenosis. A study to determine the feasibility of measurement of conduction velocities through the lumbosacral nerve roots by direct percutaneous stimulation of the cauda equina is reported. The technique was applied to a series of normal volunteers and its reliability and reproducibility confirmed. An electrophysiologic defect was demonstrated in most patients with surgically proven lateral recess stenosis. Electrophysiologic recovery was shown in patients examined after surgery. Although the technique can be refined, these early results are encouraging."
-What are the key noninvasive strategies to reduce stroke risk in elderly patients?,"Reducing the risk of stroke: identifying patients to refer for carotid endarterectomy. The most common causes of stroke are two diseases of aging: hypertension and atherosclerosis. Therefore, although stroke may occur at any age, the incidence is highest among the elderly population. Noninvasive efforts to reduce the risk of stroke in the elderly include control of hypertension and diabetes, smoking cessation, low-cholesterol dietary habits, and moderate exercise. Routine low-dose aspirin also provides some protective effect. High-risk patients (with asymptomatic high-grade stenosis, TIAs, or prior stroke) should be considered candidates for carotid endarterectomy in the absence of contraindications to surgery."
-"What was the effect of different doses of interferon alfa-2b on alanine aminotransferase levels in patients with chronic non-A, non-B hepatitis?","Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond."
-What is the primary medical intervention discussed for managing retroperitoneal hemorrhage from renal angiomyolipoma in a patient with polycystic kidney disease?,"Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited."
-"What medical condition caused paraplegia in the pregnant thalassemic woman, and how was she successfully treated?","Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions. The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed."
-What percentage of hemodialysis patients in the study developed hypertension after receiving recombinant human erythropoietin (rHuEpo) therapy?,"Hypertension following erythropoietin therapy in anemic hemodialysis patients. Recombinant human erythropoietin (rHuEpo) corrects the anemia of end-stage renal disease. However, hypertension has been observed as an adverse effect of increasing red cell mass. In our study, 44 of 63 patients (70%) treated with rHuEpo had an increase in mean arterial pressure greater than 10 mm Hg or required new or additional hypertensive medications. Retrospective analysis disclosed that increasing blood pressure was associated with pretreatment hematocrit level less than or equal to 0.20 (P = .05) and dependency on red cell transfusions (P less than .01). Factors not associated with hypertension included the rate of rise of the hematocrit, the net rise in hematocrit, age, sex, the number of years on dialysis, the presence or absence of kidneys, smoking, or the presence of pretreatment hypertension. Noninvasive hemodynamic studies in eight normotensive patients before and after improvement of the anemia demonstrated a normalization of the decreased peripheral vascular resistance and a reduction toward normal in the elevated cardiac output. In three of these patients, clinical hypertension subsequently evolved. Follow-up hemodynamic studies in nine other patients receiving new or additional antihypertensive medications were difficult to interpret. Although the hypertension can be controlled with routine medication, hypertensive encephalopathy may occur if the blood pressure increases rapidly when the hematocrit increases with rHuEpo therapy."
-What were the survival rates for children with malignant intracranial ependymomas based on different radiation treatment approaches?,"Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas? Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory."
-How can the measurement of free light chains in urine potentially help in monitoring multiple sclerosis disease activity?,"Increased free light chains in the urine from patients with multiple sclerosis. We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity."
-How do monoclonal antibodies help identify interaction sites of Plasminogen Activator Inhibitor 1 (PAI-1) with tissue-type plasminogen activator (t-PA) and fibrin?,"The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: localization of interaction sites and physiologic relevance. Plasminogen activator inhibitor 1 (PAI-1), an essential regulatory protein of the fibrinolytic system, harbors interaction sites for plasminogen activators (tissue-type [t-PA] and urokinase-type [u-PA]) and for fibrin. In this study, anti-PAI-1 monoclonal antibodies (MoAbs) were used to identify interaction sites of PAI-1 with these components. The binding sites of 18 different MoAbs were established and are located on five distinct ""linear"" areas of PAI-1. MoAbs, binding to two distinct areas of PAI-1, are able to prevent the inhibition of t-PA by PAI-1. In addition, two interaction sites for fibrin were identified on PAI-1. The area located between amino acids 110 and 145 of PAI-1 contains a binding site for both components and its significance is discussed in the context of the t-PA inhibition by fibrin-bound PAI-1. Subsequently, the MoAbs were used to assess the role of platelet-PAI-1 in clot-lysis. An in vitro clot-lysis system was used to demonstrate that clot-lysis resistance is dependent on the presence of activated platelets and that PAI-1 is a major determinant for lysis-resistance. We propose that, upon activation of platelets, PAI-1 is fixed within the clot by binding to fibrin and retains its full capacity to inhibit t-PA and u-PA."
-What is unique about the reported case of pulmonary zygomycosis in this medical report?,Granulomatous pulmonary zygomycosis in a patient without underlying illness. Computed tomographic appearances and treatment by pneumonectomy. Pulmonary zygomycosis rarely occurs in the absence of underlying disease. We report a patient with granulomatous pulmonary zygomycosis without underlying disease who presented with a pulmonary mass. We present the computed tomographic findings that we believe have not been described previously. We also report the successful treatment by pneumonectomy.
-What was the main finding regarding dysplasia and carcinoma in ulcerative colitis patients who underwent ileorectal anastomosis (IRA) in this follow-up study?,"Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a defined patient group. In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955-1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n = 22, one postoperative death) or owing to dysplasia (n = 3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low."
-What did the study suggest about the relationship between erythrokeratoderma variabilis (EKV) and progressive symmetrical erythrokeratoderma (PSEK)?,"Is erythrokeratoderma one disorder? A clinical and ultrastructural study of two siblings. Two sisters with erythrokeratoderma are described. In the younger sister the clinical appearance corresponded to erythrokeratoderma variabilis (EKV), whereas in the older sister it corresponded to progressive symmetrical erythrokeratoderma (PSEK). Ultrastructural findings in both cases were identical. We suggest that EKV and PSEK are different manifestations of a single condition."
-How do oral contraceptive pills affect insulin-like growth factor binding protein-1 (IGFBP-1) concentration in women with polycystic ovarian disease (PCOD)?,"Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease. Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD."
-What is the significance of CD23 expression on lymphocytes in chronic inflammatory conditions?,"Immunohistochemical demonstration of CD23 expression on lymphocytes in rheumatoid synovitis. The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate."
-What unique medical condition did the patient develop in her surgically reconstructed neovagina?,"Ulcerative colitis in the autotransplanted neovagina. A 33-year-old woman had undergone a radical surgical excision for carcinoma of the vagina at age 11. Vaginal reconstruction using a pedicled transplant of the sigmoid colon was successfully accomplished at age 19. Fourteen years later she developed vaginal bleeding, and a biopsy of the neovagina revealed changes consistent with ulcerative colitis. Within 2 weeks the patient developed bleeding per ano, and a rectal biopsy also revealed changes consistent with ulcerative colitis. Symptoms responded to sulfasalazine. This is believed to be the first case report of ulcerative colitis developing in colonic tissue used for a neovagina. The etiology, natural history, and surveillance of ulcerative colitis in relation to this unique case are reviewed. This case argues against the hypothesis that chronic ulcerative colitis is causally related to direct exposure to alimentary antigens."
-How did the administration of atrial natriuretic factor (ANF) affect the vasoconstrictor response during lower body negative pressure in patients with hypertension?,"An atrial natriuretic factor analogue at low doses attenuates forearm reflex vasoconstriction to cardiopulmonary receptor deactivation in patients with hypertension. Contrasting data exist about a possible modulation of the autonomic function by atrial natriuretic factor (ANF) in human beings, particularly at low, biologically, significant concentrations. We have evaluated that possibility by increasing plasma ANF levels through the infusion of a synthetic analogue (WY-47,663, anaritide) in five male patients with mild to moderate uncomplicated hypertension. Nonhypotensive lower body negative pressure (-10 mm Hg x 5 min) was used to selectively deactivate cardiopulmonary receptors and to stimulate sympathetic efferent tone reflexogenically. ANF was given at either a low rate (0.005 micrograms/kg/min x 60 min, which was previously shown to increase plasma ANF in a range compatible with physiologic stimuli) or at a high rate (0.05 micrograms/kg/min x 60 min, each). Administration of ANF was preceded and followed by vehicle infusion (Haemacell x 30 min). Forearm blood flow (venous plethysmography), intraarterial blood pressure, and heart rate were monitored continuously, and venous immunoreactive ANF, plasma renin activity, aldosterone level, and venous hematocrit were measured at the end of both control and infusion periods. Arterial norepinephrine values, an indirect index of sympathetic discharge, were measured at rest and during lower body negative pressure conditions. Graded systemic ANF infusion increased immunoreactive ANF and venous hematocrit, decreased aldosterone level and plasma renin activity, whereas resting norepinephrine levels, blood pressure, and heart rate did not change. Lower body negative pressure decreased forearm blood flow during vehicle infusion, but it lost its vasoconstrictor effect during infusion of ANF. To identify the site of that inhibitory action, ANF was also infused into the brachial artery at rates that raised local but not systemic levels of immunoreactive ANF."
-What immunological evidence suggests the co-existence of Lambert-Eaton myasthenic syndrome and myasthenia gravis in the two patients described?,"Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. Two patients are described in whom a clinical and electromyographic diagnosis of the Lambert-Eaton myasthenic syndrome (LEMS) was made. Serum antibodies to voltage-gated calcium channels (VGCCs), the antigenic target in LEMS and to acetylcholine receptors (AChRs), the antigen in myasthenia gravis, were detected at raised titres in both cases, using radioimmunoassays based on 125I-omega-Conotoxin labelled VGCCs and 125I-alpha-Bungarotoxin labelled AChRs. These data provide immunological evidence for the coexistence of the two disorders in these patients."
-What was the sensitivity and specificity of fine-needle aspiration biopsy in this pediatric head and neck masses study?,"Fine-needle aspiration biopsy: application to pediatric head and neck masses. Fine-needle aspiration biopsy cytology is widely used to screen masses in adults. The authors present a series of 89 fine-needle aspiration biopsies performed between January 1973 and December 1988 on 86 pediatric patients with clinically significant head and neck masses. All fine-needle aspiration diagnoses were confirmed by subsequent surgical biopsy, autopsy, or clinical follow-up for a minimum of 18 months. Of 21 tumors identified, 19 were malignant. Of the 89 aspirations performed, 67 required no subsequent surgical biopsy. In 11 of these cases, metastatic or recurrent tumor was diagnosed and appropriate therapy instituted. Fifteen of the 89 aspirates revealed previously undiagnosed tumors requiring surgical intervention. One false-negative and two false-positive results were obtained. No radical treatment resulted from the false-positive diagnoses, and no patient delay in treatment occurred because of the false-negative result. The sensitivity was 94.4%, and the specificity was 97.1%. The usefulness and cost-effectiveness of fine-needle aspiration is stressed."
-What medical procedure did the two patients with previous malignancy undergo to treat their congestive cardiomyopathy?,Orthotopic cardiac transplantation in two patients with previous malignancy. This report presents 2 patients with previous malignancy in whom congestive cardiomyopathy developed secondary to doxorubicin toxicity. Both patients underwent orthotopic cardiac transplantation 3 and 5 years ago and are now in functional class I with no evidence of malignant recurrence.
-What is priapism and how can it be related to vasculitis?,"Priapism as a manifestation of isolated genital vasculitis. Vasculitis may affect virtually any organ system in the body. We describe a patient who presented with priapism due to isolated genital vasculitis. This responded promptly to oral corticosteroids. In patients presenting with priapism, a possible underlying vasculitis should be considered in the differential diagnosis; the treatment for this may be nonsurgical."
-What symptoms were significantly more common in patients with infectious mononucleosis during the acute phase of illness?,"Acute and chronic symptoms of mononucleosis. BACKGROUND. The clinical symptoms and durations of illness of patients with infectious mononucleosis (IM) are variable and are poorly documented in the scientific literature. METHODS. Patients who presented for care at the Student Health Service of a Canadian university between September 1985 and May 1988 and had been diagnosed as having IM were surveyed. Health experience during the acute and convalescent phases of IM was compared with that of a group of patients matched for age, sex, date of diagnosis, and year of study, who had suffered acute upper respiratory tract infections (URI), other than Epstein-Barr virus (EBV)-induced, during the same period. RESULTS. Students were sicker for longer after IM than after non-EBV-induced URI. During the acute phase of illness, the symptoms of fatigue (P = less than .000001), night sweats (P = .000001), and painful neck swelling (P = .00003) were seen significantly more often in the IM group. The severity and duration of these symptoms were also significantly worse in IM patients. Getting tired easily (P = .002), diurnal somnolence (P = .002), and depression (P = .002) were significantly more common postacute symptoms. Eleven percent of IM patients reported persistence of symptoms longer than 100 days, and in 6% of patients the symptoms had persisted after 1 year. Convalescent cases showed a trend toward reduced alcohol intake and, perhaps, reduced alcohol tolerance. CONCLUSIONS. IM involves excessive morbidity in a student community compared with URI that was other than EBV-induced, during both the acute and the postacute phases of infection."
-How do plasma atrial natriuretic peptide (ANP) levels change during dynamic exercise in patients with effort angina pectoris?,"Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris. We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise."
-How does acute appendicitis present differently in patients with AIDS/HIV infection compared to immunocompetent patients?,"Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality."
-How has the use of antihypertensive agents changed in different age groups in the United States?,"Changes in hypertension treatment and in congestive heart failure mortality in the United States. The use of antihypertensive agents has increased in recent years and has been more marked among individuals in older age groups (65-74 years) than in middle-aged groups (45-54 years). Because hypertension is a strong risk factor for the development of congestive heart failure, more common use of antihypertensive agents would be expected to reduce the incidence of congestive heart failure. Examination of the national death statistics reveals decreases in congestive heart failure mortality at younger ages with mortality increases at older ages. The reasons for these divergent trends in congestive heart failure mortality in different ages and the apparent inconsistency with respect to the changes in the use of antihypertensive drugs are explored. We speculate that antihypertensive treatment does not completely prevent congestive heart failure but merely postpones its development by several decades."
-What was the most common cause of death among patients with tuberous sclerosis complex (TSC) in the Mayo Clinic study?,"Causes of death in patients with tuberous sclerosis. Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications."
-What imaging technique is recommended for diagnosing sigmoid sinus thrombosis?,"Sigmoid sinus thrombosis diagnosis by contrasted MRI scanning. Septic thrombosis of the transverse-sigmoid sinuses and the jugular bulb is a highly lethal condition. The presenting signs and symptoms of this disease entity are subtle and not in proportion to the magnitude of the problem. Later in the disease course, sudden fulminant findings appear. A high index of suspicion, combined with scanning techniques of either enhanced MRI or CT, allows prompt diagnosis and treatment. MRI enhanced with gadolinium-DTPA (Gd) is a valuable adjunct that confirms the diagnosis and delineates the extent of suspected pathology."
-What is the prevalence of transverse aortic arch hypoplasia in infants undergoing coarctation repair?,"Coarctation and hypoplasia of the aortic arch: will the arch grow? Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to-end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25."
-"How does the left atrial pump function differ between normal subjects, patients with essential hypertension, and patients with healed myocardial infarction?","Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation. To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 +/- 3 mm) and in those with myocardial infarction (32 +/- 4 mm) than in normal subjects (28 +/- 3 mm) (p less than 0.01, p less than 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 +/- 3 mm Hg.mm, p less than 0.01) and in subjects with myocardial infarction (29 +/- 10 mm Hg.mm, p less than 0.05), compared with normal subjects (20 +/- 8 mm Hg.mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p less than 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p less than 0.01, p less than 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p less than 0.01)."
-What are the potential benefits and complications of using small-diameter flexible fiberscopes for visual diagnosis of spinal canal diseases?,"Observation of spinal canal and cisternae with the newly developed small-diameter, flexible fiberscopes. Small-diameter (0.5-, 0.9-, and 1.4-mm) flexible fiberscopes were developed for visual diagnosis of spinal canal diseases. The fiberscopes were introduced via a Tuohy needle into the subarachnoid and epidural spaces of ten patients with various pain syndromes. Clear visualization of the subarachnoid space was achieved using the fiberscopes. The epidural space could be visualized only during withdrawal of the fiberscope. In five cases, the fiberscope could be advanced up to the level of the cisternae without causing the patient any discomfort. A slight headache and transient fever were noted after the examination in five and two cases, respectively, but no other complications occurred. Interestingly, preexisting pain diminished (two cases) or disappeared (one case) after the myeloscopy in three of five cases in which the myeloscopy revealed aseptic adhesive arachnoiditis. Further studies should be carried out to evaluate the usefulness of this technique."
-"What is the ""cuff sign"" in the context of sonographic evaluation of pancreatic cancer and superior mesenteric artery involvement?","Thickening at the root of the superior mesenteric artery on sonography: evidence of vascular involvement in patients with cancer of the pancreas. Thickening of the root of the superior mesenteric artery (SMA) was studied by using preoperative sonography in 23 patients with pancreatic cancer and in 10 healthy control subjects. Of the 23 with cancer, 11 had neoplastic involvement of the SMA and 12 did not. Prominent thickening of the area around the SMA with (six patients) or without (five patients) decreased echogenicity compared with the adjacent retropancreatic connective tissue was observed in patients with involvement of the SMA, a finding called the ""cuff sign."" Mean thickness of the periarterial area in the cancer patients with and without involvement of the SMA and in control subjects were 8.5 mm, 4.0 mm, and 2.9 mm, respectively. With an upper limit of normal of 7.0 mm for the thickness of the SMA, the sensitivity, specificity, and overall accuracy of this sign in the evaluation of involvement of the SMA were 91%, 100%, and 96%, respectively. Decreased echogenicity of the periarterial area was not observed in patients without involvement of the SMA or in control subjects. Our results show that sonographic evidence of periarterial thickening of the root of the SMA (cuff sign), especially with decreased echogenicity, is a reliable finding of tumor infiltration of the SMA in patients with pancreatic carcinoma."
-What is the incidence of masseter muscle spasm (MMS) in children during anesthesia with succinylcholine?,"Masseter muscle spasm in children: implications of continuing the triggering anesthetic. This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique."
-How does unilateral brain damage in the left hemisphere affect decision-making accuracy compared to right hemisphere damage?,"Hemisphere asymmetry in decision making abilities. An experimental study in unilateral brain damage. Thirty control subjects and 60 unilateral brain-damaged patients, 30 with left hemisphere (LH) damage and 30 with right hemisphere (RH) disease, underwent a disjunctive 4-choice reaction time study. Speed of reaction (as defined by the reciprocal of reaction time (RT), movement time (MT) and total response time (TRT] and accuracy of response (as represented by the sum of errors in selecting the correct response key) were investigated comparatively as a function of side of lesion and of performance on Raven's Coloured Progressive Matrices (PM47). In contrast to movement speed (1/MT), reaction speed (1/RT) as well as total response speed (1/TRT) showed a lesion effect independent of side of damage. Conversely, accuracy was differentially impaired, LH damage being associated with a significantly higher number of errors. Speed and accuracy had different relationships with the performance on the PM47 in the two hemisphere groups. Speed was affected in parallel with changes in PM47 performance both in the LH and in RH groups, whereas accuracy was altered only in LH patients. It was concluded that speed of motor reaction is affected by unilateral brain lesions irrespective of their side, whereas decision making processes, as expressed by accuracy of response, seem to be specifically impaired by LH damage."
-"What were the key findings of the study comparing cisplatin and etoposide (PE) with cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for metastatic breast carcinoma?","Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research. In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research."
-What is idiopathic colonic perforation in a neonate and how is it typically diagnosed?,"Idiopathic colonic perforation in the neonate. We describe a premature infant in whom spontaneous perforation of the colon was initially detected on routine abdominal films. There was no clinical evidence of necrotizing enterocolitis, peritonitis, or bowel obstruction. Surgical and pathologic findings confirmed the diagnosis of idiopathic bowel perforation. Since spontaneous gastrointestinal perforation in the neonate is often difficult to diagnose clinically, radiographic evaluation may allow earlier diagnosis and prompt surgical treatment of this life-threatening condition."
-What were the key determinants of outcome in the cervical cerclage study?,"Prognostic factors and complication rates for cervical cerclage: a review of 482 cases. Charts from 482 singleton pregnancies undergoing cerclage placement in patients over a 6-year period were reviewed. Cervical dilatation at time of surgery, number of previous spontaneous losses, and gestational age at placement were key determinants of outcome. The most frequent complication, premature rupture of the membranes, ultimately occurred in 38% of patients. The 6.6% infection rate was increased in patients undergoing emergent versus elective surgery (12.7% vs 4.7%, p less than 0.005) and in patients at increased dilatation at time of surgery (5.7% for less than or equal to 2 cm vs 41.7% for greater than 2 cm, p less than 0.005). McDonald and Shirodkar procedures had similar obstetric outcomes in patients undergoing their first cerclage. The subgroup of patients with prior cerclage surgery showed improved birth weight when the Shirodkar procedure was performed instead of the McDonald cerclage (mean birth weight 3020 vs 2470 gm, p less than 0.005). An increased rate of primary cesarean section was found in the Shirodkar group (31% vs 17%, p less than 0.005). Complication rates and pregnancy outcome appear to reflect cervical dilatation more than gestational age at time of surgery."
-What diagnostic tests were found to be most useful in identifying extraspinal causes of lumbosacral radiculopathy in this study?,"Extraspinal causes of lumbosacral radiculopathy. Twelve of 12,125 patients who had been referred during a seven-year period to a specialist in spinal disorders were found to have an extraspinal cause of radiculopathy or neuropathy of the lower extremity. The records of these twelve patients were reviewed retrospectively. The average age of the twelve patients was sixty-five years (range, forty-two to seventy-seven years). The cause of the symptoms was an occult malignant tumor in nine patients and a hematoma, an aneurysm of the obturator artery, or a neurilemoma of the sciatic nerve in the others. The average time from the onset of symptoms to the final diagnosis was eight months (range, one month to two years). The most useful test for determination of the correct diagnosis was computed tomography or magnetic resonance imaging of the abdomen and pelvis. Computed tomography or magnetic resonance imaging of the spine and bone-scanning of the whole body were of little help in localizing the disease. In four of the twelve patients, an operation was performed on the basis of an incorrect diagnosis. In dealing with elderly patients who have radiculopathy, one should be suspicious that the cause is outside the spine."
-What percentage of patients in the study were confirmed to have hepatitis A and hepatitis B through IgM antibody testing?,"Hepatotoxicity of rifampin and isoniazid. Is it all drug-induced hepatitis? Serologic markers for hepatitis viruses were studied in 40 children who developed acute hepatitis during antituberculosis therapy with rifampin and isoniazid, with the aim of assessing the contributory role of these viruses toward producing hepatic injury. Hepatitis A and B were confirmed in 7.5 and 35% patients, respectively, by IgM antibodies. Epidemiologic evidence suggested the possibility of non-A, non-B hepatitis in at least a few of the remaining 23 children. Hepatitis B was seen more often in children with severe tubercular disease (72%) and was largely (92.8%) parenterally transmitted. The study highlights that the endemicity of viral hepatitis in developing countries, among other factors, could also be responsible for the reported higher incidence of hepatotoxicity from developing countries and also for the increased risk of hepatotoxicity seen in severe tubercular disease."
-What are the key differences observed between women with single and multiple admissions for hyperemesis gravidarum in this study?,"Hyperemesis gravidarum. A comparison of single and multiple admissions. Recurrent hyperemesis gravidarum is a frustrating and poorly studied complication of early pregnancy. Between 1979 and 1987, 140 women with emesis severe enough to require parenteral fluid and electrolyte replacement were admitted to the Medical University of South Carolina Hospital, Charleston, on 220 occasions. Thirty-nine of the 140 women were admitted on multiple occasions. A comparison of clinical characteristics of women with single and multiple admissions revealed no significant differences except that women admitted repeatedly for hyperemesis gravidarum were more likely to be nulliparous (P less than .05). Ptyalism (59% vs. 9%) and persistent vomiting for greater than 24 hours after admission (69% vs. 23%) were significantly more common among women who were admitted repeatedly (P less than .05). Despite published reports that hyperemesis gravidarum has no impact on ultimate perinatal outcome, this study indicated that women admitted repeatedly have a more severe nutritional disturbance, associated with significantly reduced maternal weight gain and neonatal birth weight. These risks argue for more aggressive antenatal treatment and increased fetal surveillance in pregnancies complicated by recurrent hyperemesis gravidarum."
-What was the main finding of the study regarding the use of vancomycin in empirical antibiotic therapy for febrile granulocytopenic cancer patients?,"Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group [published erratum appears in J Infect Dis 1991 Oct;164(4):832] A total of 747 febrile granulocytopenic patients with cancer were randomized to receive ceftazidime plus amikacin (CA) with or without vancomycin (V) as initial empirical therapy. Single gram-positive bacteremias responded in 29 (43%) of 68 patients treated with CA and in 48 (72%) of 67 treated with CAV (P = .001). For single gram-negative bacteremias and clinically documented and possible infections the response rates of CA and CAV were 80% and 63% (P = .17), 55% and 75% (P = .009), and 74% and 81% (P = .16), respectively. However, for patients with gram-positive bacteremia and for all other patients, there were no differences by treatment regimens in the proportion of febrile patients on each trial day (P = .85, P = .82, respectively) or in the duration of fever (P = .22, P = .93, respectively). Moreover, no patient with gram-positive bacteremia died during the first 3 days of true empirical therapy. Antibiotic-associated nephrotoxicity was more frequent in patients treated with vancomycin (6% vs. 2%, P = .02). These results do not support the empirical addition of vancomycin to initial antibiotic therapy in cancer patients with fever and granulocytopenia."
-What are the key enzymes involved in the bioconversion of primaquine's side chain?,"The conversion of primaquine into primaquine-aldehyde, primaquine-alcohol, and carboxyprimaquine, a major plasma metabolite. Although efficacy and toxicity of primaquine (PQ) depend on bioconversion, the process is poorly understood, even for carboxyprimaquine (CPQ), the major plasma metabolite. Earlier work to clarify drug metabolism showed that PQ could be converted quantitatively into CPQ, in vitro, with human erythroleukemic K562 cells or nonleukemic bone marrow supplemented with calf serum. We have now found--using systems with serum only, as well as with K562, bone marrow, and adult or embryonic liver cells--that the bioconversion of the side chain of PQ involves a branched pathway with at least three separate enzymes and two derivatives other than CPQ. An oxidase activity in serum converted PQ first into a novel side chain aldehyde (Y). Aldehyde dehydrogenase transformed PQ-aldehyde into CPQ in cell-free systems and in K562, bone marrow, and adult liver cells. Embryonic hepatocytes or bone marrow treated with 1,3-bis(2-chloroethyl)-1-nitrosourea did not produce CPQ; instead, they made a metabolite (Xc) that we could synthetize via PQ-aldehyde and identify as PQ-alcohol. PQ-alcohol replaced CPQ as the final product whenever alcohol-dehydrogenase prevailed over aldehyde dehydrogenase. These enzymes operated in intact cells and controlled the biotransformation of PQ absolutely. Unless both dehydrogenase were absent, inhibited, or deprived of coenzyme, potentially cytotoxic PQ-aldehyde intermediate did not accumulate. Some of the unique tissues schizonticidal and gametocidal effects of PQ may depend on the distribution pattern and relative activities of PQ oxidase, aldehyde dehydrogenase, and alcohol dehydrogenase in human subjects and in parasites."
-What is an inflammatory pseudotumor of the liver and how was it treated in this case report?,"Inflammatory pseudotumor of the liver causing biliary obstruction. Treatment by biliary stenting with 5-year follow-up. Inflammatory pseudotumors of the liver are rare lesions that are becoming increasingly recognized, possibly because of frequent use of abdominal computed tomography (CT) and ultrasonography. Most previously reported cases have been treated by hepatic resection. For this reason, we describe a patient with obstructive jaundice secondary to an inflammatory hepatic pseudotumor in the porta hepatis. Bilateral internal biliary stents were inserted, and the patient remains well 5 years later. The clinicopathologic features of inflammatory pseudotumors of the liver are described, as are the implications of accurate diagnosis. There have been no previous reports of biliary stenting in management of inflammatory hepatic pseudotumors."
-What percentage of patients with syncope were found to have orthostatic hypotension in this study?,"Syncope and orthostatic hypotension. PURPOSE: The purpose of this study was to determine the postural blood pressure response over time, the prevalence of orthostatic hypotension in patients with syncope, and the relationship of orthostatic hypotension to recurrence of symptoms. PATIENTS AND METHODS: We prospectively evaluated 223 patients with syncope in a standardized manner. Orthostatic responses were measured in a standardized fashion at 0, 1, 2, 3, 5, and 10 minutes or until symptoms occurred. Follow-up was obtained at 3-month intervals. Causes of syncope were assigned by predetermined criteria. RESULTS: Orthostatic hypotension (20 mm Hg or greater systolic blood pressure decline) was found in 69 patients (31%). The median time to reach minimal standing systolic blood pressure was 1 minute for all subjects. In patients with orthostatic hypotension (20 mm Hg or greater), mean time to reach minimum blood pressure was 2.4 minutes. The vast majority of patients with significant orthostatic hypotension had this finding within 2 minutes of standing. Orthostatic hypotension was common in patients for whom other probable causes of syncope were assigned. The recurrence of syncope was not related to the degree of orthostatic hypotension; however, the recurrence of dizziness and syncope as end-points was lower in patients with 20 mm Hg or greater systolic blood pressure reductions as compared with patients with lesser degrees of orthostatic blood pressure declines. CONCLUSION: Orthostatic hypotension is common in patients with syncope and is detected in the vast majority of patients by 2 minutes. Although symptom recurrence on follow-up was lower in patients with more severe orthostatic hypotension, the clinical significance of this finding needs to be further defined by future studies."
-What did the meta-analysis reveal about the effectiveness of prophylactic antibiotics in head and neck surgery?,"A meta-analysis of prophylactic antibiotics in head and neck surgery. Although it is generally agreed that prophylactic antibiotics are necessary for the prevention of postoperative wound infection, the choice of antibiotic regimen is controversial. In an attempt to determine the most effective antibiotic regimen, a meta-analysis of published clinical trials of prophylactic antibiotics for head and neck surgery was undertaken. The meta-analysis revealed a relative difference in infection rates of 43.7 percent in favor of the use of antibiotics versus placebo, of 8.3 percent in favor of multiple antibiotics versus a single antibiotic, of 13.7 percent in favor of multiple antibiotics versus cefazolin, and of 4.1 percent in favor of multiple-day prophylaxis versus single-day prophylaxis. This meta-analysis suggests that a 1-day course of clindamycin may be the most effective prophylactic antibiotic regimen for head and neck surgery."
-What are the key immunohistochemical and electron microscopic findings of the ossifying fibromyxoid tumor of soft parts?,"Ossifying fibromyxoid tumor of soft parts. Additional observations of a distinctive soft tissue tumor. The author studied four subcutaneous soft tissue tumors, similar to those recently described by Enzinger and associates (Am J Surg Pathol 1989;13:817) by the name ""ossifying fibromyxoid tumor,"" by immunohistochemistry and electron microscopy to further understand the cellular nature of this lesion. The four tumors were composed of uniform round cells often surrounded by a lacunar space. The tumors often contained a peripheral zone of metaplastic bone. The cellularity was high, but the mitotic rate was low, suggesting a benign or borderline nature of the lesion. Longer follow-up was available for three cases, showing recurrence-free survival times of 11, 8, and 3 years. Immunohistochemistry studies revealed that all tumors were strongly positive for S-100 protein and focally positive for Leu-7, whereas melanoma-specific marker HMB45 was negative. Vimentin was the main type of intermediate filament protein, and one case also contained scattered glial fibrillary acidic protein-positive cells. Epithelial markers (keratins, epithelial membrane antigen), desmin, and muscle actins were negative. Electron microscopic examination showed partial, sometimes reduplicated, basal lamina surrounding many cells. Complex cell processes were also present. No myofilaments were found. The immunohistochemical and electron microscopic results may suggest that this tumor has Schwann's cell differentiation."
-What changes in colonic mucosal blood flow were observed after exposure to 10% acetic acid in the rat study?,"Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. The hypothesis that a significant reduction in colonic mucosal perfusion, and hence ischemic injury, precedes the development of mucosal ulceration and inflammation is tested in this report. The microcirculatory changes in the rat colonic mucosa within 1 hr of topical exposure to 10% acetic acid were assessed. Colonic mucosal blood flow signals measured by laser Doppler flowmetry were significantly reduced to 61 +/- 8, 52 +/- 10, and 37 +/- 13% (mean +/- SEM) of baseline values at 1 min, 4 min, and 10 min after the colonic mucosa was exposed to 10% acetic acid, respectively, but not in controls exposed to saline. After the start of application of 10% acetic acid (for 4 min), in vivo microscopy studies demonstrated that colonic mucosal ischemia (stasis of the red blood cells in the mucosal capillaries) occurred at 9 +/- 5 min (mean +/- SEM). Evidence of endothelial cell death (failure to exclude a fluorescent dye, propidium iodide, by endothelial cells) developed at 25 +/- 10 min (mean +/- SEM). These findings indicate that within minutes after contact of the colonic mucosa with 10% acetic acid, colonic mucosal ischemia develops, followed shortly by death of endothelial cells. The data do not establish a cause-and-effect relationship between the reductions in mucosal blood flow and loss of endothelial cell viability in response to acetic acid. Nevertheless, because these events occur at such an early time point, they may play a pathogenetic role in the development of the subsequent inflammatory and ulcerative changes in this animal model of colitis. Further studies to define the potential causal relationships between these parameters are warranted."
-What alternative agents were used in epidural infusions for patients with intractable non-cancer pain?,"Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or vertebral body compression fracture were treated with alternative solutions in an epidural route. For maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used, and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5% bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache, nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also advantageous for programmable pumps because it is 100 times more potent than morphine and therefore allows longer pump refill times and higher infusion doses. Although this study was done on a limited number of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for non-cancer patients provide significant alternative drug combinations and routes."
-How does the HIV-1 protease affect the processing of the NF-kappa B precursor (p105) during infection?,"Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. Transcription of the human immunodeficiency virus type-1 (HIV-1) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells. T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat. This factor consists of two DNA-binding subunits of relative molecular mass 50,000 (50K) associated with two 65K subunits. It is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex. External stimuli, including those that activate T cells, result in nuclear translocation of active NF-kappa B. The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor (p105) (V.B., P.K. and A.I., manuscript submitted). The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105. Because HIV-1 requires active NF-kappa B for efficient transcription, we tested the effect of HIV-1 infection on the processing of the human 105K precursor. We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex."
-How does Trichinella spiralis infection affect small intestinal motor activity and transit time?,"Trichinella spiralis infection alters small bowel motor activity in the fed state. The effect of Trichinella spiralis infection on small intestinal transit and motor activity in the fed state during the intestinal phase of infection was studied. Contractions were recorded by strain gauge transducers, and mean transit time was measured by marker dilution technique. The mean amplitude and area of individual phasic contractions decreased, but no change occurred in their mean duration during trichinosis. The total amplitude and area of phasic contractions also decreased; this was caused by a decrease in the frequency of contractions as well as a decrease in the mean parameters. The reduction in the total duration was entirely caused by the decrease in frequency. The reduction in the total parameters of all contractions was the result of a reduction in the same parameters for both propagating and nonpropagating contractions. However, the decrease in the parameters of propagating contractions was much greater. Also, there was a decrease in the distance of propagation of phasic contractions. The transit time as a result of phasic contractions increased during T. spiralis infection. Additionally, T. spiralis infection induced giant migrating contractions in the fed state that were never observed during control. Chyme was propelled very rapidly and effectively by giant migrating contractions. The findings of the present study suggest that during diarrhea induced by T. spiralis infection, the phasic contractions may act to decrease transit and, hence, allow more contact time for absorption of water and nutrients. However, this response may be counter-balanced by giant migrating contractions that rapidly propel chyme into the colon and compound the diarrhea associated with T. spiralis infection."
-What is the significance of the STRO-1 monoclonal antibody in identifying stromal cell precursors in human bone marrow?,"Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM], erythroid bursts [BFU-E], and mixed colonies [CFU-Mix]). Fibroblast colony-forming cells (CFU-F) are present exclusively in the STRO-1+ population. Dual-color cell sorting using STRO-1 in combination with antibody to glycophorin A yields a population approximately 100-fold enriched in CFU-F in the STRO-1+/glycophorin A+ population. When plated under long-term BM culture (LTBMC) conditions, STRO-1+ cells generate adherent cell layers containing multiple stromal cell types, including adipocytes, smooth muscle cells, and fibroblastic elements. STRO-1+ cells isolated from LTBMC at later times retain the capacity to generate adherent layers with a cellular composition identical to that of the parent cultures. The STRO-1-selected adherent layers are able to support the generation of clonogenic cells and mature hematopoietic cells from a population of CD34+ cells highly enriched in so-called long-term culture-initiating cells. We conclude that antibody STRO-1 binds to BM stromal elements with the capacity to transfer the hematopoietic microenvironment in vitro."
-What was the success rate of the percutaneous posterolateral lumbar discectomy procedure in this study?,"Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise."
-What factors contribute to the varying prevalence of obesity across different population groups?,"Obesity in minority populations: policy implications of research. Obesity is a major health problem for many Americans, with an overall prevalence for adults of approximately 25% and a range for specific subgroups of 24-75%. This range is striking and reflects many factors shown to influence the development and maintenance of obesity, including physical activity, diet, ethnicity, income, education, and genetic susceptibility. Many minority populations have higher prevalences of obesity and, thus, experience its adverse health consequences disproportionately. Research in diverse populations indicates that the relative importance of risk factors for cardiovascular disease varies in many populations. Data characterizing the profile of risk factors, including obesity and physical activity, for various special populations are limited and some, such as obesity, are based on standards developed in the general population. For public health policy and interventions to succeed, they must address the needs of special populations and of the overall population. This paper discusses some of the relevant broader social and research issues."
-What method was used to evaluate body composition in alcohol-induced migraine patients?,"Bioelectrical impedance assay (BIA) of total body composition in alcohol-induced migraine patients. Preliminary report. ""Whole body composition"" was investigated in 30 people subject to alcohol-induced migraine. The control group was 30 people matched for age, sex, height and weight, who were not subject to migraine and who consumed moderate amounts of alcohol. The following were evaluated: anthropometric data, alcohol intake in grams per day, total body water, fat-free mass, fat mass, and body mass index (kg/m2). Two methods of measurement were used: skin fold thickness evaluation, and bioelectric impedance assay (BIA). BIA is a non-invasive method based on the principle that lean tissues conduct a low frequency alternating current of electricity better than do fatty tissues. Body mass index was increased in the alcohol-induced migraine patients (p less than 0.04), as was fat mass, (p less than 0.03) as evaluated by skin fold measurements. Bioelectric impedance assay demonstrated a slight total body water increase in alcohol-induced migraine patients (p less than 0.07). Possibly, if this total body water increase was reflected at the neuronal level, the bioelectric properties of the migrainous brain may be altered, thus creating a hypothetical link with the phenomenon of spreading depression."
-What percentage of families with alcohol-related problems were identified by physicians in the study?,"Detection of alcoholism in hospitalized children and their families The study sought to measure provider recognition of family alcohol-related problems among hospitalized children and to identify characteristics distinguishing ""positive"" families. The study sample (N = 147) was drawn from admissions to the general pediatric medical service of a metropolitan teaching hospital. Positivity was assessed through parent and patient interviews that included standard alcohol abuse screening instruments. Provider recognition was assessed through record review and physician interview. Of the 22 families screened positive, only one was so identified by the child's attending or resident physician. Positive and ""negative"" families were similar in most respects, although parents in positive families were more likely to report stress and sleeping problems and adolescents were more likely to report being troubled by a parent's drinking. The similarity of positive and negative families and the low pediatrician recognition rate suggest that alcohol problems are likely to go unnoticed without a conscious screening effort."
-What is Generalized Resistance to Thyroid Hormone (GRTH) and how was it detected in this case study?,"Neonatal detection of generalized resistance to thyroid hormone [published erratum appears in JAMA 1991 Feb 20;265(7):869] Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. We detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L (normal, 84 to 232 nmol/L). Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels (liothyronine sodium, 21 micrograms/kg per day, and levothyroxine sodium, 44 micrograms/kg per day) were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH."
-What were the clinical results and Harris hip ratings for different types of hip prostheses in this study?,"Total hip replacement with cemented, uncemented, and hybrid prostheses. A comparison of clinical and radiographic results at two to four years. One hundred and thirty-one patients who had 144 cemented or uncemented hip prostheses were followed prospectively for two to four years. A cemented or a hybrid prosthesis (consisting of a cemented femoral component and an uncemented acetabular component) was used in men older than seventy years, in women older than sixty years, and in younger patients in whom adequate initial fixation could not be obtained without cement. Uncemented, porous-surfaced implants were used in all other patients. The over-all clinical results were similar for the three groups. For the fifty-two hips that had a cemented prosthesis, the mean total Harris hip rating was 91 points and the score for pain, 42 points; for the twenty-seven hips that had a hybrid prosthesis, 90 and 43 points; and for the sixty-five hips that had an implant allowing ingrowth of bone in both the acetabulum and the femur, 95 and 43 points. Two prosthetic stems that were designed to allow ingrowth of bone had aseptic loosening; one was revised. Pain in the thigh, usually slight and not disabling, occurred at one year in 24 per cent of the patients in whom a femoral component allowing ingrowth had been used; the prevalence of pain then declined. The incidences of migration of the components and of radiolucent lines were greater in the acetabula that had a cemented component than in those that had a cup allowing ingrowth of bone."
-What was the effect of oral nitroglycerin on portal blood velocity in cirrhotic patients according to this study?,"The effect of oral nitroglycerin on portal blood velocity as measured by ultrasonic Doppler. A double blind, placebo controlled study. We studied the effect of oral nitroglycerin on portal blood velocity (PBV) in 20 cirrhotic patients by a double blind, placebo controlled method using noninvasive Doppler sonography. After we obtained baseline Doppler in the fasting state, 0.6 mg nitroglycerin or placebo was given orally and the mean of 3 s averaged mean PBVs was repeated at 5 min intervals for 60 min. Ten patients each received nitroglycerin or placebo. Portal vein flows were antegrade in all. Of the 10 patients receiving nitroglycerin, seven (P = 0.002) showed a greater than 10% fall in the mean PBVs for at least 15 min. Of these seven ""responders,"" five patients had a 10% decrease in mean systemic blood pressure for at least 15 min. None of the ""nonresponders"" had systemic hypotension. Our study suggests that the PBV-reducing effect of nitroglycerin in cirrhotics may be explained in part by systemic hypotension."
-What factors were considered in determining the safety of vaginal delivery for the second twin?,"Twin delivery: influence of the presentation and method of delivery on the second twin. To ascertain the perinatal mortality and morbidity in the second twin as related to its presentation and method of delivery, we reviewed the data on 578 sets of twins delivered from 1980 to 1987 and included 397 sets in whom both twins were greater than or equal to 1000 gm, without lethal anomalies, and in whom the first twin presented as a vertex. The perinatal outcome comparing twin A (all vertex) with twin B (vertex or nonvertex) with cesarean section or vaginal delivery was analyzed. No statistically significant difference in perinatal mortality or morbidity was found in comparing the nonvertex second twin delivered vaginally or by cesarean section. The one perinatal death and significant perinatal morbidity occurred in infants weighing less than 1500 gm or at less than 32 weeks' gestational age. It is concluded that vaginal delivery, irrespective of the position of the second twin, is valid in selected cases as long as fetal weight is greater than 1500 gm and the gestational age is greater than or equal to 32 weeks."
-What was the objective response rate of menogaril in patients with cisplatin-refractory advanced ovarian carcinoma?,"A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic. Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment."
-What were the key findings of the study comparing calcium channel receptors in normal and myelodysplastic bladders?,"The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders. The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function."
-What did the study reveal about the relationship between IgA2 allotypes and IgA nephropathy in Black patients?,"IgA nephropathy in blacks: studies of IgA2 allotypes and clinical course. The prevalence of IgA nephropathy (IgAN) varies among racial groups, being most common among Caucasians and Orientals and rare in Blacks. Other investigators have hypothesized that the risk for IgAN may be influenced by the IgA2 allotype. It has been suggested that the rare Black patients with IgAN may be homozygous for the A2m(1) allele which predominates in Whites, but is less common in Blacks. In a multicenter study, 27 Black IgAN patients were enrolled to investigate this hypothesis and analyze the clinical course of disease in Blacks. The IgA2 allotypes of 18 Black patients and 14 controls were determined using restriction fragment length polymorphism analysis. Three patients were homozygous for the A2m(1) allele, four were homozygous for A2m(2) and 11 were heterozygous. The respective allelic frequencies of A2m(1) and A2m(2) were 0.47 and 0.53 and did not differ significantly from Black controls. Most clinical manifestations of disease did not significantly differ with respect to distribution of the two alleles, although the gender ratio differed between the homozygous A2m(1) and heterozygous patients. The presence of the A2m(1) allele did not increase the risk for IgAN, and the presence of the A2m(2) allele or homozygosity for this allele did not protect Blacks from the development of IgAN."
-What diagnostic tests were performed on patients with angina pectoris-like pain and normal coronary angiograms?,"Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms. Twenty patients with angina pectoris-like pain, normal coronary angiography and abnormal exercise 201Tl scans were investigated by means of haemodynamic, coronary sinus blood flow and lactate determinations before and after cold provocation, pacing and dipyridamole infusion. Radionuclide angiography, a new exercise 201Tl scan and noninvasive hyperventilation and ergonovine tests were performed. Intracoronary infusions of acetylcholine were given in increasing doses and a second coronary angiogram in combination with a 201Tl scintigram was performed. Despite a previously pathological 201Tl scintigram, with reversible perfusion defects, only ten of the patients had reversible perfusion defects at the second investigation. Hyperventilation and ergonovine tests did not result in ECG signs indicative of coronary spasm. Intracoronary infusion of acetylcholine resulted in a diffuse coronary constriction in 3 of 14 patients, and in one patient a perfusion defect was observed on thallium scintigram. In conclusion, although most of the common methods for inducing coronary vasospasm were used, no consistent pattern of reaction was found to explain the chest pains experienced in this group of patients."
-What are the key pathological characteristics of Erdheim-Chester disease?,"Erdheim-Chester disease. Case report with autopsy findings. Erdheim-Chester disease is a rare pathologic entity characterized by symmetrical radiodensities in the metaphyseal and the diaphyseal portions of the long bones. Fibrosis, osteoblastic cortical bone deposition, and fibroxanthomatous granulomas with lipid-laden macrophages and multinucleated giant cells, which have a particular tropism for connective and adipose tissues, are the pathologic hallmarks. To our knowledge, 27 cases have been reported in the literature since the entity was first described in 1930. Protean clinical features range from a focal and asymptomatic process to a multisystemic infiltrative disease. We describe the clinical course of a new case and review the extensive pathologic findings at autopsy, including those demonstrated by light and electron microscopy and cytochemical and immunocytochemical studies."
-What were the minor complication rates for different trocar insertion methods in this laparoscopic study?,"Comparison of direct insertion of disposable and standard reusable laparoscopic trocars and previous pneumoperitoneum with Veress needle. A randomized prospective study was conducted to evaluate the ease of use and safety of direct insertion of laparoscopic trocars. Comparison of previous pneumoperitoneum by Veress needle insertion with direct insertion of the reusable conventional laparoscopic trocar and direct insertion of the disposable shielded trocar revealed minor complication rates of 22, 6 and 0%, respectively. No major complications occurred in this series of 200 patients."
-What percentage of acoustic tumors showed no detectable growth or apparent regression in this conservative treatment study?,"Conservative treatment of patients with acoustic tumors. Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy."
-What is the rare medical condition described in this case report involving a plasmacytoma and superior vena cava syndrome?,"Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described."
-How does hypoxic ventilation affect the pulmonary arterial pressure-flow relationship in a canine preparation?,"Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation. We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure."
-What is the significance of detecting antineutrophil cytoplasmic antibodies (ANCA) in classifying patients with necrotizing arteritis?,"Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. PURPOSE: Assessment of the value of determination of antineutrophil cytoplasmic antibodies (ANCA) and its specificities for classification of patients with biopsy-proven necrotizing arteritis. PATIENTS AND METHODS: The serum samples of 28 consecutive patients with biopsy-proven vasculitis involving medium- and/or small-sized arteries were tested for ANCA by an indirect immunofluorescence technique, by neutrophil extract enzyme-linked immunosorbent assay (ELISA), and by catching ELISA. RESULTS: Eight patients had Churg-Strauss syndrome; six had myeloperoxidase (MPO) antibodies, and in the other two patients, ANCA were not detected. Six patients had polyarteritis nodosa (PAN) limited to the skin and the musculoskeletal system; ANCA were not detected in these patients. Two patients had systemic PAN and both had MPO antibodies. The remaining 12 patients had overlapping clinical features of the different forms of vasculitis. Five patients had polyarteritis in combination with chronic nasal inflammation and glomerulonephritis compatible with Wegener's granulomatosis (WG) but without granulomas in the respiratory tract. All five patients had 29-kd serine protease antibodies. Two patients had polyarteritis in combination with nasal polyposis and asthma compatible with Churg-Strauss syndrome, but eosinophilia was not detected. Both patients had MPO antibodies. Three patients with unclassified granulomatous arteritis had either elastase antibodies or ANCA of unknown specificity. One patient with unclassified systemic vasculitis had 29-kd serine protease antibodies, and one patient with necrotizing arteritis of the bowel in combination with Schonlein-Henoch purpura was negative for ANCA. CONCLUSION: Determination of ANCA and its specificities is a useful adjunct to the classification of patients with biopsy-proven necrotizing arteritis. Within the spectrum of idiopathic vasculitides, 29-kd serine protease antibodies are associated with WG, MPO antibodies are associated with Churg-Strauss syndrome and systemic PAN, and PAN limited to the skin and the musculoskeletal system is not associated with ANCA."
-What are the current challenges in lung transplantation despite its improved success rates?,"Current status of lung transplantation. Techniques and indications for single and bilateral lung transplantation have evolved significantly in the past several years. Lung transplantation has entered a new era in which transplantation can be achieved with the same degree of success as that achieved with other major organ transplants. Many problems, common to organ transplantation remain to be solved including availability of suitable donor organs, improved immunosuppressive regimens, and the ability to properly diagnose and effectively treat organ rejection."
-What percentage of patients experienced complications in this five-year vascular audit?,"Five-year vascular audit from a district hospital. Vascular patients under the care of one surgeon over a 5-year period have been reviewed, from computer-based discharge records, with regard to in-hospital measures of outcome to determine whether or not surgery was being performed to an acceptable standard. Out of 466 procedures, 30 per cent of patients had at least one complication, 14 per cent had further surgery and 9 per cent died. Outcome was examined within the following treatment groups: aorto/iliac aneurysm, aortofemoral bypass, femoroproximal popliteal bypass, femorodistal popliteal bypass, femorocrural bypass, embolectomy and percutaneous transluminal angioplasty. Patients having below-knee bypass surgery were found to have an unacceptably high rate of complications, reoperations and amputations. An overall rate of reoperation for postoperative bleeding of 5 per cent was also considered to be high. With these exceptions, it was concluded that the surgery was being performed to an acceptable standard, but that comparative audit of this type remained difficult while there was a deficiency of national statistics against which the work of individual surgeons could be judged."
-What were the most common causes of persistent vegetative state (PVS) among the patients in this study?,"Clinical characteristics of patients in the persistent vegetative state Little is known concerning the specific clinical characteristics of patients in persistent vegetative states (PVS). Fifty-one patients from four nursing homes, approximately 3% of the total patients, were identified as being in a PVS. The mean age of the patients was 64.8 +/- 3.2 years (range, 19 to 96 years) and the mean duration of the PVS was 3.3 +/- 5.0 years (range, 1 to 16.8 years), with 13 patients' PVS being longer than 5 years. Cerebrovascular accidents and dementia were the most common causes of the PVS, accounting for 32 of the cases (63%). In the younger patients cerebral trauma secondary to motor vehicle accidents was the most common cause. All 51 patients were fed via tube feeding and 35 patients had urinary catheters (75%). All patients were receiving daily medications, with greater than 50% taking daily vitamins. Over 30% were taking digitalis and/or diuretics and over 32% were taking H2 blockers. Transfer of patients to an acute care hospital was not uncommon, with 31 patients (61%) requiring 63 acute care hospitalizations during their stay in the nursing home. As expected, infections were the most common reason for acute care hospitalization, although 15 of the patients were hospitalized for surgical procedures. Another common problem encountered by the patients was pressure sores, with 78% of patients requiring specific therapy for at least one pressure sore. Surprisingly, only 27 (53%) of 51 patients had a specific resuscitation status designation in the medical chart, and neither presence of a chart designation nor specific resuscitation order was related to the patient's age or the cause or duration of PVS. From these data it would appear that clinical characteristics of patients in PVS are variable. Some patients are young, others are old. The cause varies from cerebrovascular accidents to cerebral trauma. Survival may be prolonged; complications are not uncommon, with some patients requiring acute care hospitalization."
-What was the distribution of ischemic episodes in patients with stable angina pectoris during a 24-hour period?,"Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia. The circadian variation of total ischemic activity was examined during 3289 hours of ambulatory ECG monitoring in 101 patients with stable angina pectoris and proved coronary artery disease, who were not receiving any prophylactic antianginal therapy. The 101 patients displayed 411 episodes of ischemia, 312 (76%) of which were silent; a circadian rhythm was noted for the occurrence of total and silent ischemia. Thirty-eight percent of the ischemic episodes occurred between 6 AM and 12 noon, and total and silent ischemia were significantly more frequent during this period compared with the other three 6-hour periods (p less than 0.01); a lesser peak was noted in the evening. The effects of metoprolol and combined therapy with metoprolol and nifedipine on the circadian variation of ischemic activity were studied in two subgroups of patients in a random, double-blind study design (31 patients receiving metoprolol and 42 receiving combined therapy). During therapy with metoprolol the morning increase in ischemic activity was attenuated, and the highest frequency of ischemia was then noted in the evening (6 AM to 12 noon compared with 6 PM to 12 midnight; p less than 0.05). Combined therapy abolished the morning peak as did metoprolol monotherapy, but even the evening increase in ischemic activity was attenuated (p less than 0.05). The diurnal distribution of the mean heart rate at the onset of ischemia, when patients were off therapy, showed a morning increase similar to the increase in ischemic activity but no second peak in the evening."
-What is lymphedema-distichiasis syndrome and why is it important for ophthalmologists to be aware of it?,Hereditary lymphedema and distichiasis. Two patients with lymphedema-distichiasis syndrome illustrate that both Milroy's disease and late-onset hereditary lymphedema are sometimes associated with distichiasis. It is important for ophthalmologists to be aware of the lymphedema-distichiasis syndrome because of its ophthalmic manifestations and the associated systemic abnormalities that can be potentially life threatening.
-What is the primary goal of rapidly controlling severe hypertension?,"Management of hypertensive emergencies: changing therapeutic options. Rapid lowering of severe hypertension is essential to prevent irreversible damage to vital organs. The patient's clinical status should be evaluated, noting particularly cardiac, neurologic, and renal functions. Choice of treatment should be based on speed and efficacy of action and on hemodynamic, vascular, and renal consequences. It is also important to preserve circulatory homeostasis and vital organ function. Sodium nitroprusside, labetalol, diazoxide, and hydralazine have been used parenterally for rapid control of severe hypertension, but they do not always produce optimal, balanced hemodynamic effects. Calcium antagonists have been advocated because of their beneficial circulatory effects. Nicardipine, a new dihydropyridine calcium antagonist, produces significant antihypertensive effects, and when given intravenously, results in a rapid fall in blood pressure. Studies have confirmed that nicardipine is effective and safe in the management of severe hypertension and hypertensive crises. Because the aim of rapidly controlling severe hypertension is to prevent target organ dysfunction, nicardipine therapy offers a useful additional option in the clinical management of severe hypertension and hypertensive crises."
-How did the picture book help children cope with venous blood sampling in the study?,"Preparing children for venous blood sampling. A convenience sample of 100 children, aged 6-12 years, attending Kuwait government hospital laboratories for venous blood sampling was studied. A picture book was used to prepare half of the children for the procedure. Preparation was carried out just prior to sampling and took less than 5 min. The story provided a simple description of venous blood sampling, and why it is carried out; it stressed that the pain is noticeable but not unbearable, and that children will experience less pain if they relax their arm and cooperate with the technician. Prepared children reported significantly less pain, and radial pulse rates confirmed that they were less distressed by the procedure. Observers' and parents' evaluations also indicated that prepared children coped better. Various explanations for the benefits observed are discussed, together with requirements for managing the pain, fear and stress experienced by children during medical treatment."
-How does outlet obstruction constipation affect urinary flow parameters in women?,Relationship between outlet obstruction constipation and obstructed urinary flow. Ten women with symptoms and radiological features of outlet obstruction constipation underwent urodynamic bladder studies. The results were compared with ten age- and sex-matched controls. The mean (s.e.m.) peak flow rate for patients was 19.4 (6.4) ml/s compared with 32.1 (7.2) ml/s for controls (P less than 0.05). The mean (s.e.m.) voiding time for patients was 62.9 (23.7) s against a corresponding value of 15.6 (6) for controls (P less than 0.05). The mean (s.e.m.) bladder volume in patients was 482 (80) ml compared with a control value of 254 (112) ml (P less than 0.03). The mean (s.e.m.) detrusor pressure during the voiding phase was 53.3 (12) cmH2O. These results demonstrate that patients with outlet obstruction constipation have a generalized pelvic floor disorder resulting in obstructed urinary flow.
-What are the key characteristics of peritoneal cystic mesothelioma based on the three reported cases?,"Cystic mesothelioma of the peritoneum. A report of three cases. Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis."
-"What were the three surgical techniques used for treating chronic ear disease in this study, and how did their post-operative outcomes compare?","Surgery for chronic ear disease in a non-university hospital: open cavity, obliteration and intact canal wall techniques. The long-term results of surgery for chronic suppurative middle ear disease at a non-university ENT-clinic (Vasa Central Hospital, Finland) are reported. The material consisted of 273 ears, 65 of which had been operated on by open cavity techniques, 178 by the original Palva obliteration method, and 30 by the intact canal wall method. Post-operative cholesteatoma occurred equally frequently with the two canal wall down methods (7.7 and 7.3%, respectively) but was more frequent after intact canal wall surgery (23.3%). Hearing was better and the infection rate lower with obliteration than with open cavity techniques. Post-operative infection was the least frequent and the hearing result best in the intact canal wall ears, but compared to the other two groups the extent of disease found at surgery was considerably less in this group. The obliteration operation proved to be a safe method in the hands of a practising otologist outside university clinics."
-What unique technique was used to establish the DuPro-1 human prostate adenocarcinoma cell line?,"Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer."
-How does induced hypertension affect neuronal injury and edema formation after temporary middle cerebral artery occlusion in rats?,"Induced hypertension during restoration of flow after temporary middle cerebral artery occlusion in the rat: effect on neuronal injury and edema. The effect of hypertension instituted during restoration of flow after focal ischemia was studied. After the middle cerebral artery (MCA) of 12 rats was occluded for 2 hours, the ligatures were released and flow was restored for a period of 2 hours. In the control group, mean arterial pressure (MAP) was not manipulated. In the hypertensive group, the MAP was elevated by 25-30 mm Hg immediately after reestablishment of MCA patency. The area of neuronal injury, determined by 2,3,5-triphenyltetrazolium staining, was significantly smaller in the hypertensive group. Specific gravity, determined by microgravimetry, did not differ between groups. The data demonstrate that modest hypertension, when induced during reperfusion after 2 hours of MCA occlusion, reduces neuronal injury and does not exacerbate edema formation."
-What percentage of breast reconstructions performed at the University of Texas M.D. Anderson Cancer Center experienced some degree of flap necrosis?,"The early management of flap necrosis in breast reconstruction. Flap necrosis is a potential complication of any type of breast reconstruction. Of 302 breast reconstructions performed by the author at the University of Texas M.D. Anderson Cancer Center, some degree of flap necrosis occurred in 59 (19.5 percent). Small areas of flap necrosis can be managed with simple observation, but secondary healing may not be complete for months. Early and aggressive excision of the ischemic tissue with immediate primary closure often can achieve rapid primary healing. In addition, early revision and reshaping of the breast may, in selected patients, permit achievement of a significantly better final result. This is true not only for TRAM and latissimus dorsi flaps, but also for the mastectomy flap necrosis sometimes encountered in immediate reconstruction with simple implants or tissue expanders."
-How did monthly pulses of vincristine and prednisone impact the relapse-free survival of children with low-risk acute lymphoblastic leukemia in the CCG-161 study?,"Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group. On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX."
-How did the researchers find that IGFBP-3 gene expression is increased in renal adenocarcinoma tissues?,"Expression of the insulin like growth factor-binding protein 3 (IGFBP-3) gene is increased in human renal carcinomas. After we had established that the IGFBP-3 gene is expressed in normal human kidney we examined renal adenocarcinoma tissue for alterations of the expression of this gene. For this purpose we prepared poly(A)+ RNA from normal kidney tissue and adjacent renal adenocarcinoma of 18 adult patients and compared the levels of IGFBP-3 mRNA by Northern analysis in both samples. The mean content by densitometry was markedly increased in the carcinoma tissues; in 17 of 18 patients the carcinoma contained significantly more IGFBP-3 mRNA than the normal kidney sample. The highest mRNA levels were found in patients with N2 and N3 lymph node extensions. Comparative Southern analysis of paired samples of four of these patients did not reveal amplification of the gene as the cause of these increased mRNA levels. In one patient, however, we identified a restriction fragment length polymorphism (RFLP) present in normal and malignant cellular DNA. This suggests a participation of the IGFBP-3 gene in the development of human renal cell cancer."
-What differences in mortality and kernicterus were observed between the jaundiced RHA/N-j and ACI/N-j rat strains?,"A difference in mortality between two strains of jaundiced rats. Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. Two new, inbred rat strains that carry the Gunn mutation are described. These were developed by breeding the mutant Gunn gene (j) into the RHA/N and ACI/N strains, producing the new lines, which were designated RHA/N-j and ACI/N-j. Liver assay confirmed the absence of transferase activity in jaundiced rats from both of the new strains, but marked differences in mortality between the strains were observed. The mortality of jaundiced RHA/N-j rats through 8 weeks was the same as that of their nonjaundiced littermates (20%). In contrast, mortality of jaundiced ACI/N-j rats was distinctly greater than that of their nonjaundiced littermates (81% vs 34%, P less than .001). Signs of kernicterus such as ataxia were much more frequent in jaundiced ACI/N-j rats than in jaundiced RHA/N-j rats (73% vs 11%, P less than .001). Both strains had comparable albumin concentrations through 8 weeks of age. Serum bilirubin concentrations were also comparable, except for a small but significant difference at 20 days of age (ACI/N-j = 294 mumols/L, RHA/N-j = 248 mumols/L, P less than .01). Similarly, the bilirubin-to-albumin ratios were comparable except for a significantly higher ratio at 20 days of age in the ACI/N-j rats (ACI/N-j = 0.70, RHA/N-j = 0.51, P less than .01). Thus, the RHA/N-j strain is unusual in that the jaundiced animals remain healthy. Conversely, the ACI/N-j animals demonstrate a high incidence of kernicterus with mortality."
-What is asymptomatic bacterascites and how does it differ from spontaneous bacterial peritonitis?,"Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required."
-What was the primary objective of the study on fetal sheep?,"Fetal hypertension induced by norepinephrine infusion and umbilical artery flow velocity waveforms in fetal sheep. This study was designed to examine the effects of fetal hypertension on the umbilical artery pulsatility index. Fetal arterial blood pressure and umbilical venous pressure were measured in eight sheep, 3 to 5 days after surgery. Umbilical blood flow was measured with an electromagnetic flowmeter around the common umbilical vein. Umbilical artery flow velocity waveforms were obtained either by an indwelling 5 MHz pulsed Doppler device (n = 4) or transcutaneously by a 4 MHz continuous-wave Doppler device (n = 4). Fetal blood pressure was raised by intravenous infusion of norepinephrine 10 micrograms/min during 5 minutes. Norepinephrine infusion resulted in elevated arterial and umbilical venous pressures, accompanied by a bradycardia during the first 3 minutes. Umbilical blood flow, calculated placental vascular resistance, and umbilical artery pulsatility index did not change. After atropine administration, the norepinephrine-induced elevated arterial and umbilical venous pressures were accompanied by tachycardia, increased umbilical blood flow, and no change in placental vascular resistance and umbilical artery pulsatility index. It is concluded that fetal arterial hypertension provoked by norepinephrine infusion has no effect on placental vascular resistance, umbilical blood flow, and umbilical artery pulsatility index."
-What makes this case of prolactin-producing pituitary carcinoma unique in medical literature?,"Prolactin-producing pituitary carcinoma with pulmonary metastases. Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34-year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed."
-What potential complication occurred during the ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma?,Renal pelvic explosion during conservative management of upper tract urothelial cancer. Ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma is a relatively new and limited procedure. We present a case of intrarenal explosion during ureteroscopic fulguration.
-What are the five response subtypes observed in the cutaneous test examining the flushing response to ethanol and acetaldehyde among Chinese of Han ethnicity?,"Cutaneous vasomotor sensitivity to ethanol and acetaldehyde: subtypes of alcohol-flushing response among Chinese. A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol-induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers."
-What were the key findings regarding parental occupational exposures and childhood leukaemia risk in this study?,"Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead OBJECTIVE--To determine whether parental occupations and chemical and other specific exposures are risk factors for childhood leukaemia. DESIGN--Case-control study. Information on parents was obtained by home interview. SETTING--Three areas in north England: Copeland and South Lakeland (west Cumbria); Kingston upon Hull, Beverley, East Yorkshire, and Holderness (north Humberside), and Gateshead. SUBJECTS--109 children aged 0-14 born and diagnosed as having leukaemia or non-Hodgkin's lymphoma in study areas during 1974-88. Two controls matched for sex and date and district of birth were obtained for each child. MAIN OUTCOME MEASURES--Occupations of parents and specific exposure of parents before the children's conception, during gestation, and after birth. Other adults living with the children were included in the postnatal analysis. RESULTS--Few risk factors were identified for mothers, although preconceptional association with the food industry was significantly increased in case mothers (odds ratio 2.56; 95% confidence interval 1.32 to 5.00). Significant associations were found between childhood leukaemia and reported preconceptional exposure of fathers to wood dust (2.73, 1.44 to 5.16), radiation (3.23, 1.36 to 7.72), and benzene (5.81, 1.67 to 26.44); ionising radiation alone gave an odds ratio of 2.35 (0.92 to 6.22). Raised odds ratios were found for paternal exposure during gestation, but no independent postnatal effect was evident. CONCLUSION--These results should be interpreted cautiously because of the small numbers, overlap with another study, and multiple exposure of some parents. It is important to distinguish periods of parental exposures; identified risk factors were almost exclusively restricted to the time before the child's birth."
-What is L-tryptophan-induced eosinophilia-myalgia syndrome and what symptoms did the patients in this study experience?,"L-tryptophan-induced eosinophilia-myalgia syndrome. This report describes three Belgian cases of the eosinophilia-myalgia syndrome associated with the use of L-tryptophan-containing products. Three women, aged 51, 53 and 73 years, were taking L-tryptophan for 2 months to 2 years, at 500, 1500, and 2250 mg d-1, respectively. All developed disabling myalgias, fatigue, and a variable skin rash, in association with marked eosinophilia. In one patient, symptoms and eosinophilia reappeared after rechallenge with L-tryptophan. Discontinuation of the drug resulted in gradual disappearance of the symptoms, signs and laboratory abnormalities in two patients. One patient was treated with corticosteroids because of persisting myalgias. Because of the non-specific clinical manifestations, clinicians from all subspecialties of internal medicine might be confronted with such patients and should be aware of this new entity."
-What are the common symptoms shared by mitral valve prolapse and panic disorder?,"Mitral valve prolapse, panic disorder, and chest pain. Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS)."
-How do nitrone free-radical spin traps affect c-fos induction and ATP recovery in a rat model of hepatic ischemia and reperfusion?,"Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents. Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction."
-Where is the translocation breakpoint located in the patient with Menkes syndrome?,"Localization of the translocation breakpoint in a female with Menkes syndrome to Xq13.2-q13.3 proximal to PGK-1. Menkes syndrome is a rare X-linked recessive disorder characterized by an inability to metabolize copper. A female patient with both this disease and an X; autosome translocation with karyotype 46,X,t(X;2)(q13;q32.2) has previously been described. The translocation breakpoint in Xq13 coincides with a previous assignment of the Menkes gene at Xq13 by linkage data in humans and by analogy to the mottled mutations which are models for Menkes disease in the mouse. Therefore, this translocation probably interrupts the gene for Menkes syndrome in band Xq13. We describe here experiments to precisely map the translocation breakpoint within this chromosomal band. We have established a lymphoblastoid cell line from this patient and have used it to isolate the der(2) translocation chromosome (2pter----2q32::Xq13----Xqter) in human/hamster somatic cell hybrids. Southern blot analyses using a number of probes specific for chromosomes X and 2 have been studied to define precisely the location of the translocation breakpoint. Our results show that the breakpoint in this patient--and, therefore, likely the Menkes gene--maps to a small subregion of band Xq13.2-q13.3 proximal to the PGK1 locus and distal to all other Xq13 loci tested."
-What are the key findings from the report of five cases of solitary extradural cavernous hemangiomas in the spinal canal?,"Solitary extradural cavernous hemangiomas in the spinal canal. Report of five cases. Five cases of solitary extrathecal cavernous hemangioma in the spinal canal are reported. In one case, two coexistent massive cerebral venous medullary malformations were found. The symptomatology and prognosis of extrathecal spinal cavernous hemangiomas are discussed, as is the significance of various diagnostic measures. The patient material further permitted a rough calculation of the incidence of symptomatic extrathecal cavernous hemangiomas in the spinal canal."
-What is the accuracy of transesophageal echocardiography in evaluating the patency of ventriculoatrial shunts?,"Transesophageal echocardiography: a simple method for monitoring the patency of ventriculoatrial shunts. Technical note. A new method for evaluating the patency of a ventriculoatrial shunt is described, and early experience with it is reported. Transesophageal echocardiography can demonstrate a cerebrospinal fluid leak in the right atrium through the atrial tip of a shunting device. This capability was an incidental discovery, and since then the accuracy of the technique in evaluating the patency of a ventriculoatrial shunt has been prospectively studied in 20 observations of 16 patients. The method proved to be accurate in 90% to 100% of cases. It is concluded that transesophageal echocardiography offers a rapid and accurate assessment of ventriculoatrial shunt function, is well tolerated, and is easy to perform."
-What is heterotopic ossification and how can it potentially impact peripheral nerves?,"Heterotopic ossification and peripheral nerve entrapment: early diagnosis and excision. Heterotopic ossification can occur in neurologic disorders, burns, musculoskeletal trauma, and metabolic disorders. In addition to producing the complications of contracture, skin breakdown, and pain, it can cause peripheral nerve entrapment. Nerve entrapment due to heterotopic ossification may be misdiagnosed, and it is difficult to evaluate and treat without recurrence. Computed tomography is especially useful in localization before surgical release of the entrapped nerve. Resection of heterotopic ossification can be successful using disodium etidronate to decrease the risk of recurrence, and resection can improve range of motion and nerve function. Two case studies of nerve entrapment due to heterotopic ossification are presented with the results of computed tomography localization, successful resection, and long-term follow-up. Clinicians should be aware of this complication and the potential for rapid nerve injury. If heterotopic ossification is causing clinically significant peripheral nerve entrapment, early surgical treatment may be indicated, and may be successful."
-How does a multidisciplinary approach help in managing chronic orthopedic infections?,"The effect of chronic orthopedic infection on quality of life. The patient with chronic orthopedic infection presents a unique challenge to the orthopedic surgeon. The orthopedic surgeon must not only possess an expertise in constantly evolving diagnostic and treatment techniques but also be able to identify numerous related problems and direct the patient in receiving the most appropriate treatment. This demands a commitment of time by the treating surgeon to the individual patient to properly assess the need for support, the extent of psychologic distress, the intensity of pain, and the requirement for medication management. The effective utilization of a multidisciplinary team of health care providers (e.g., specialists in infectious disease, physical medicine and rehabilitation, psychiatry, nursing, pharmacology) can provide an optimal treatment program for this multifaceted problem and maximize the potential for a favorable outcome."
-How do cells generate ATP during hypoxic conditions when aerobic metabolism is compromised?,"Cellular energy metabolism during hypoxia. Tissue hypoxia is frequently seen in critically ill patients and it perhaps predisposes these patients to development of multiple system organ failure. In cellular terms, hypoxia is characterized by decreases in the intracellular concentration of oxygen, leading to a decline in aerobically produced adenosine triphosphate (ATP). The deficit arising from unequal levels of cellular ATP requirements and aerobic ATP production is partially satisfied by anaerobic sources of ATP, including glycolysis, the creatine kinase reaction, and the adenylate kinase reaction. These reactions can set in motion cellular mechanisms that ultimately may lead to cellular dysfunction and death. A clear understanding of the relative importance of these reactions is impossible to acquire from global measures of oxygen delivery and oxygen consumption; therefore, the clinical monitoring of tissue oxygenation also should include the measurement of metabolically relevant, organ-specific variables."
-What was the perioperative mortality rate in the acoustic neuroma surgery series from Manchester Royal Infirmary between 1978 and 1990?,"Acoustic neuroma (schwannoma) surgery 1978-1990. A series of 151 patients with 154 acoustic schwannomas have been operated upon in Manchester Royal Infirmary by a joint Otological and Neurosurgical team, employing either the translabyrinthine or the suboccipital approach. The perioperative mortality rate was 3 per cent. Anatomical preservation of the facial nerve was achieved in 89 per cent of tumour removals and a good to normal functional result in 79 per cent of cases. Attempts at hearing preservation have been unsuccessful, largely because of the small number of patients in the series in whom useful hearing was present preoperatively. Complications included major brain stem ischaemia (1.2 per cent), CSF fistula (5 per cent) and facial dysaesthesia (7 per cent). The incidence of mortality and morbidity is directly related to tumour size and to the experience of the surgeons. A number of patients experienced an unusual type of post-operative dreamlike state which appeared to be a form of hypnagogic hallucination, and the possible neurophysiological mechanism responsible for this phenomenon is discussed. The continuing failure to attain the ideal of early diagnosis is lamented, and the importance of a flexible bidisciplinary surgical approach emphasized."
-What are the main syndromes of mitochondrial encephalopathies observed in children during the 1984-1988 study?,"Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders."
-What medical condition did the 2-year-old boy have that led to difficulty swallowing and spasticity due to compression of the medulla and cervical spine?,Cervicomedullary junction decompression in a case of Marshall-Smith syndrome. Case report. The case is reported of a 2-year-old boy born with Marshall-Smith syndrome who had difficulty in swallowing and who exhibited spasticity and quadriparesis due to compression of the medulla and cervical spine. This is the first child with this rare condition reported to have brain-stem compression from bone abnormalities at the craniovertebral junction and who has required surgery.
-"What morphometrical parameters were found to be most useful in distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis?","Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma. Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well-differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid-sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well-differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue."
-What is pure akinesia and how does it relate to progressive supranuclear palsy (PSP)?,"Pure akinesia: an atypical manifestation of progressive supranuclear palsy. Two patients with ""pure akinesia"" who showed the characteristic changes of progressive supranuclear palsy (PSP) at necropsy are described. They had akinesia but no rigidity or tremor, and ophthalmoplegia was not observed during the course of illness. The symptoms of ""pure akinesia"" was not improved by levodopa therapy but was considerably improved by L-threo-3,4-dihydroxy-phenylserine. At necropsy, pathological findings were not different from those reported for PSP. It is suggested that ""pure akinesia"" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP."
-What unusual characteristic was observed in the Listeria monocytogenes isolate from the patient's cerebrospinal fluid culture?,"Catalase-negative listeria monocytogenes causing meningitis in an adult. Clinical and laboratory features. A 63-year-old previously healthy woman presented with acute meningitis. Cultures of the cerebrospinal fluid yielded a serotype 1/2a isolate of Listeria monocytogenes that was biochemically typical in all respects, other than the reproducible lack of catalase production. During therapy, the patient developed oculomotor dysfunction that was attributed to an abscess in the internal capsule. This case report documents the existence of catalase-negative L. monocytogenes indicating that catalase production should not be a strict criterion for identification of Listeria. Furthermore, this clinical experience extends in vitro and experimental animal studies indicating that catalase production is not a necessary virulence factor for invasion by Listeria."
-What percentage of patients achieved complete thrombolysis based on the duration of their limb ischaemia symptoms?,"Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected."
-What were the key selection criteria for surgical resection in cirrhotic patients with liver cancer in this study?,"Limited hepatic resection for selected cirrhotic patients with hepatocellular or cholangiocellular carcinoma: a prospective study. From 1 January 1983 to 1 January 1989 123 cirrhotic patients with hepatocellular cancer (n = 122) or cholangiocarcinoma (n = 1) were screened using liver function tests, alpha-fetoprotein determination, ultrasonography with biopsy (and in selected cases computed tomography or nuclear magnetic resonance), laparoscopy and angiography, Child-Pugh classification and urea-nitrogen synthesis rate. Twenty-three patients were selected for surgical resection because the tumour was smaller than 5 cm, not centrally located and at least 1 cm away from main structures; there was no evidence of multicentricity or metastatic disease; and the Child-Pugh classification was A or B and the urea-nitrogen synthesis rate at least 6 g/day. Upper gastrointestinal endoscopy was used routinely to identify oesophageal varices which were present in 17 cases; ten patients with a history of variceal haemorrhage (43 per cent) had preoperative endoscopic sclerotherapy. In cases with recurrent haemorrhage, surgery was used to prevent intraoperative and postoperative bleeding. Tumour resection was carried out using controlled hypotension and hepatoduodenal ligament clamping. Twelve bisegmentectomies, ten segmentectomies and one atypical resection were performed. The operative mortality rate was 13 per cent with liver failure and sepsis as the causes of death. The 'recurrence rate' was 26 per cent and the late mortality rate for the whole group up to 1 January 1990 was 30 per cent; 13 patients were still alive. The 12-month survival rate was 77 per cent and after 5 years it was 49 per cent. Thus, surgical resection of small liver tumours is the treatment of choice in this selected group of patients."
-What are the key clinical features associated with T-cell ALL cases having the t(11;14) translocation?,"Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations."
-What imaging technique was found to accurately demonstrate the spread of disease in a case of spinal leptomeningeal metastasis from cerebral glioblastoma?,"Spinal leptomeningeal metastasis from cerebral glioblastoma. Appearance on magnetic resonance imaging. A case of circumferential leptomeningeal metastasis to the spinal cord from an intracranial glioblastoma multiforme (spinal meningeal gliomatosis) is presented. The clinical, radiographic, and pathological features are described. Spinal magnetic resonance imaging with gadolinium-diethylenetriaminepentaacetic acid accurately demonstrated the spread of disease when compared with autopsy findings. The value of spinal magnetic resonance imaging in patients with symptoms attributable to cerebrospinal fluid metastases is discussed."
-What surgical approaches were used to treat localized and diffuse supravalvar aortic stenosis (SVAS) in this study?,"Supravalvar aortic stenosis: a 29-year review of surgical experience Between February 1960 and August 1989, 73 consecutive patients underwent surgical correction for supravalvar aortic stenosis (SVAS) at the Texas Heart Institute. There were 43 male (59%) and 30 female patients (41%) ranging in age from 5 days to 27 years (mean age, 12 years). Preoperatively, 8 patients were in New York Heart Association functional class I, 43 in class II, 18 in class III, and 4 in class IV. Of the 73 patients, 62 had localized SVAS and 11 (15%), diffuse SVAS. For all procedures, patients were placed on cardiopulmonary bypass. Those with localized SVAS were successfully treated with patch aortoplasty, whereas those with diffuse SVAS required either an apicoaortic conduit or extensive end-arterectomy with extended patch aortoplasty. There were eight early deaths (less than or equal to 30 days postoperatively) (11%) and four late deaths (greater than 30 days postoperatively) (6%) in a follow-up period ranging from 2 months to 28 years. Sixteen patients (25%) underwent one or more additional operations in the follow-up period. Postoperatively, there were 44 patients in New York Heart Association functional class I and 17 in class II. Preoperative functional class III and class IV (p less than 0.0005), diffuse SVAS (p = 0.05), and the presence of associated congenital defects (p less than 0.01) were important determinants of death."
-How did the visual evoked potentials change in patients after transurethral resection of the prostate using glycine as an irrigating fluid?,"Visual evoked potentials and visual acuity after transurethral resection of the prostate. Changes in visual evoked potentials, visual acuity, blood ammonia levels and serum electrolytes (Na+ and K+) after transurethral resection of the prostate using glycine as an irrigating fluid performed under subarachnoid block were studied in 12 patients, in the pre-operative and immediate postoperative periods. Visual evoked potentials (p100 latency), recorded by shift of a checkerboard pattern, increased significantly from a pre-operative value of mean (SEM) 101.18 (1.63) msec in the right eye, and 102.5 (1.47) msec in the left eye to 108.91 (1.8) msec (p less than 0.01) and 108.08 (2.53) msec (p less than 0.01) respectively in the postoperative phase. There were no changes in visual acuity as assessed by a Snellen's chart, blood ammonia levels and serum electrolyte concentrations. The amount of glycine used intra-operatively for irrigation ranged from 3 to 31 litres."
-How do delusions and hallucinations impact the progression and neuropsychological characteristics of Alzheimer's disease patients?,"Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates. We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality."
-What is the specific anesthesia-related complication observed in the 4-year-old boy with Williams syndrome?,Williams syndrome: masseter spasm during anaesthesia. A 4-year-old boy with Williams syndrome developed masseter spasm after halothane and suxamethonium. He did not develop malignant hyperthermia; the surgery was accomplished with a nontriggering anaesthetic and no further problems.
-What was the concern regarding the use of transillumination for breast cancer screening in Wisconsin in 1990?,"Inappropriate use of transillumination for breast cancer screening--Wisconsin, 1990. The overall effectiveness of early breast cancer detection efforts requires the appropriate use and maintenance of dedicated radiographic mammography systems. However, the effectiveness of early detection efforts can be compromised if proven technology is improperly used and/or maintained or if ineffective technology is successfully marketed as an equivalent or superior alternative to mammography. This report summarizes state and federal responses to the inappropriate use of a nonradiographic imaging technique in a breast cancer screening service advertised and used in Wisconsin in 1990."
-What was the purpose of the study on thallium stress testing in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation?,"Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. PURPOSE: This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. PATIENTS AND METHODS: The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressions on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). RESULTS: Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test (10 of 64 versus 27 of 77, chi 2 = 6.66, p less than or equal to 0.025). Forty-three percent (26 of 61 in Group B) of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients (p less than 0.001). Thallium stress testing was less expensive than cardiac catheterization ($1,000 versus $4,000 to $5,000). CONCLUSIONS: Thallium stress testing allowed 45% of patients to avoid cardiac catheterization before renal transplantation. Discontinuing beta-blockers before thallium stress tests may improve exercise performance. The risk of perioperative cardiac events after transplantation was low and not different among patient groups. The relatively low predictive value of thallium stress testing for significant coronary artery disease and perioperative cardiac events in diabetic patients with end-stage renal disease suggests the need for the development of a more cost-effective, noninvasive screening test for this patient population."
-What is the sensitivity and specificity of color Doppler imaging in detecting portal vein thrombosis according to this study?,"Diagnosis of portal vein thrombosis: value of color Doppler imaging. This study was undertaken to determine the accuracy of color Doppler imaging in the diagnosis of portal vein thrombosis. Two hundred fifteen patients were studied with color Doppler imaging to determine patency of the main portal vein. Sonographic findings were confirmed in 75 patients, aged 19 to 66 years. Correlation with angiography was obtained in 13 patients, and surgical correlation was obtained in the remaining 62. Nine patients had portal vein thrombosis on the basis of these gold standards. Sonograms were classified as showing either patency or thrombosis, depending on the ability to show color flow within the main portal vein. Agreement between sonography and angiography or surgery was found in 69 patients (61 patent, eight thrombosed). One patient with a patent portal vein at sonography was found to have a thrombosed vessel at surgery, whereas five patients without portal venous flow at sonography had patent vessels at angiography (one patient) or surgery (four patients). Overall sensitivity and specificity for detection of portal vein thrombosis were 89% and 92%, with an accuracy of 92%, a false-negative rate of 0.11, a negative predictive value of 0.98, and a positive predictive value of 0.62. We postulate that the majority of errors in our study occurred in vessels that, although patent, had only sluggish flow, which could not be resolved because of technical limitations. We conclude that color Doppler imaging is a valuable screening procedure for the assessment of portal vein patency. If the sonogram shows a patent portal vein, no further studies are required. However, a lack of demonstrable flow does not always indicate thrombosis, and other imaging studies should be performed for confirmation."
-How has aggressive chemotherapy impacted the cure rate and treatment of osteosarcoma?,"Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable."
-What was the incidence rate of posterior wall left ventricular rupture during mitral valve replacement surgeries between 1970 and 1989?,"Rupture of the posterior wall of the left ventricle after mitral valve replacement. During a 20 year period from 1970 to 1989, 1100 patients underwent mitral valve replacement. Rupture of the posterior wall of the left ventricle occurred in seven patients (0.6%); four in the operating room and three in the postoperative room. It was possible to institute CP bypass in six patients and in all of them bleeding was controlled successfully, with repair by an external approach. Only one patient survived. We believe that institution of CP bypass and reinfusion of cardioplegic solution is a major determinant of the outcome."
-What technique was used to detect and differentiate heat-labile enterotoxins from enterotoxigenic Escherichia coli strains of human origin?,"Heterogeneity of immunotypes of heat-labile enterotoxins of enterotoxigenic Escherichia coli of human origin. A new technique, checkerboard immunoblotting (CBIB), has been applied to detect and to differentiate heat-labile enterotoxins, (LTs), from enterotoxigenic strains of Escherichia coli of human origin using polyclonal and monoclonal antibodies. Optimal conditions of production and release of LTs were defined using CBIB. LT release was enhanced when E. coli cells were treated with 8 M urea. LT production was highest when E. coli strains were incubated with shaking (200 rpm) at 37 degrees C for 12 h in CAYE-2 medium. Two hundred and five strains of E. coli, isolated from patients with diarrhea in Japan, Thailand, the United States, Mexico, and Brazil, were examined for LT. Of 133 LT-positive strains, 4 (3%) produced an LT that reacted like H-LT-1 (originally isolated from E. coli strain H-74-114) while 126 strains (94.7%) produced LT that reacted like H-LT-2 (originally isolated from strain H-10407) or H-LT-3 (from strain H-240-3). Three strains of human origin (2.3%) produced an LT that reacted like P-LT (produced by E. coli strains of porcine origin). This study shows that CBIB, a simple, efficient, and practical assay, might be useful for epidemiologic surveys and for evaluation of serologic responses to LTs and antitoxic vaccines."
-How does von Willebrand factor (vWF) influence platelet activation and occlusive arterial thrombosis in normal and von Willebrand disease pigs?,"Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs. With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis. Two methods of arterial injury have been used to determine the thrombotic response of flowing blood in vivo. The first involves balloon catheter injury. After superficial denudation of endothelium from coronary intima, platelets adhere to the subendothelium in a monolayer. Similar numbers of adherent platelets are found in both phenotypes, but platelets in vWD pigs have impaired pseudopod formation and are less well spread morphological indexes of limited platelet activation. Deeper injury, which involves the media, produces nonocclusive platelet-fibrin microthrombi. The second injury method involves pinching the artery at a site of superimposed stenosis, a procedure that almost always exposes media. This procedure induces platelet-fibrin microthrombi in normal and vWD pigs, but only normal pigs develop occlusive thrombosis. Both methods of arterial injury have also been performed in normal and vWD pigs with diet-induced hypercholesterolemia and atherosclerosis. Atherosclerosis promotes platelet spread in vWD pigs but does not abolish the protection from stenosis and injury-induced occlusive thrombosis. In addition, neutralization of vWF activity in normal pigs by a monoclonal antibody prevents the induction of occlusive thrombosis by the stenosis and pinch-injury procedure. This monoclonal antibody also causes performed platelet aggregates to break up. These experimental models of inducing arterial thrombosis have been used in normal and vWD pigs to demonstrate interactions between normal and atherosclerotic vessel wall constituents, circulating platelets and vWF that are fundamental in the process of arterial thrombosis."
-How do serum zinc levels differ between patients with active inflammatory bowel disease and healthy controls?,"Serum zinc, copper, and selenium levels in inflammatory bowel disease: effect of total enteral nutrition on trace element status. Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed."
-How did tranexamic acid help in treating hemothorax in patients with malignant mesothelioma?,Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma. Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of transfusion requirements.
-What was the most commonly involved nerve in peripheral nerve lesions among hemophilia patients at the Nuffield Orthopaedic Centre?,"Peripheral nerve lesions in hemophilia. Between 1962 and 1986, eighty-one of the 1351 admissions of patients who had hemophilia to the Nuffield Orthopaedic Centre were for peripheral nerve lesions. Eighty-eight such lesions were identified in fifty-four patients, and thirty-nine of these patients (sixty-one lesions) had adequate follow-up (mean, 8.4 years; range, four months to eighteen years). The femoral nerve was most commonly involved, but involvement of other peripheral nerves also occurred. In thirty (49 per cent) of the sixty-one lesions, the nerve had full motor and sensory recovery; in twenty-one (34 per cent), a residual sensory deficit; and in ten (16 per cent), both a persistent motor and sensory deficit. Patients who had antibodies to factor VIII were significantly less likely to recover full motor or sensory function than were those who did not have such antibodies, and the time to full motor recovery in these patients was significantly longer."
-How did mammography impact the treatment approach for patients with small breast cancers in this study?,"Mammography in the management of patients with small breast cancers. Findings on mammography resulted in a change of treatment policy in 17 of 200 patients with small breast cancers (T1/T2 less than 4 cm, N0/N1, M0). Twelve patients were considered unsuitable for conservation therapy because of mammographic evidence of either extensive in situ carcinoma or more than one focus of invasive carcinoma. These patients were treated by mastectomy and histology confirmed widespread in situ carcinoma or multifocal/multicentric invasive carcinoma. Seven patients were found to have unsuspected contralateral lesions on mammography, of which five were subsequently shown to be malignant. Routine preoperative mammography is essential in the management of patients with small breast cancers."
-"How does metformin treatment affect insulin resistance and metabolic risk factors in non-obese, non-diabetic men with hypertension?","Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease."
-What are the key neuropathologic features of generalized cortical dysplasia observed in the three children studied?,"Generalized cortical dysplasia. Clinical and pathologic aspects. Three children with profound mental retardation and intractable seizures died at ages 10 months, 3 years, and 7 years, respectively. Complete examination of their brains showed generalized cortical dysplasia, without any major malformation of the external gyral pattern. The neuropathologic features of cortical dysplasia include abnormally thickened cortex with indistinct demarcation of the gray-white matter junction. In many areas, the cortex contained increased numbers of large neurons with disordered cortical lamination. Heterotopic neurons were scattered throughout the white matter with decreased myelination of the underlying white matter. To our knowledge, these cases represent the first fully detailed neuropathologic study of diffuse cortical dysplasia--a newly recognized entity of abnormal neuronal migration."
-How does alcohol affect ferritin expression in the HepG2 human hepatoblastoma cell line?,"Alcohol induction of ferritin expression in a human hepatoblastoma cell line (HEP G2). Hyperferritinemia, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression."
-What was the relationship between preoperative dipyridamole perfusion scintigraphy findings and intraoperative transesophageal echocardiography in identifying myocardial ischemic risk?,"Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk. The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed."
-What diagnostic method is recommended for identifying Clostridium septicum abscesses in immunosuppressed patients?,"Recognition, management, and prevention of Clostridium septicum abscess in immunosuppressed patients. Spontaneous gas gangrene due to Clostridium septicum is a rapidly progressing disease that usually ends in fatal toxemia. We report three cases of asymptomatic C septicum abscesses to document the clinical course of this entity and to establish guidelines for its prevention and treatment. In contrast to previously reported data, C septicum infections can produce abscesses in solid organs, the retroperitoneum, and the extremities. These lesions often occur in patients with cancer, producing liver abscesses without gas formation that may be misinterpreted as metastatic carcinoma. Symptoms may be minimal or nonspecific before fulminant toxemia. Asymptomatic bacteremia should prompt a search for unsuspected cancer and an abscess. Computed tomography is the diagnostic modality of choice. The treatment consists of surgical debridement of necrotic tissue in concert with an appropriate course of antibiotics. We have found recurrences after adequate debridement and short-term antibiotic therapy, suggesting that prolonged and even lifelong prophylactic oral penicillin G potassium may be necessary to prevent further recurrences."
-How does endotoxin (LPS) infusion affect hypoxic pulmonary vasoconstriction in unanesthetized sheep?,"Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep. Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS."
-How did damage to the fornix affect memory function in the two patients after colloid cyst removal?,"Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans."
-How do nasal and pharyngeal resistances change during progressive normocapnic hypoxia in normal men?,"Changes in upper airway resistance during progressive normocapnic hypoxia in normal men. The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia."
-What were the predictive factors for thrombotic complications in venous coronary bypass graft angioplasty?,"Long-term angiographic follow-up after angioplasty of venous coronary bypass grafts. From April 1981 to June 1987, 57 patients underwent venous coronary bypass graft percutaneous angioplasty and had a minimal follow-up of 18 months. The procedure was elective for 28 patients, urgent for 19, and was considered as an emergency for 10. A total of 64 grafts were dilated that had been bypassed 58 +/- 48 months previously (range 2 to 184 months); lesions were located on the aortic anastomosis in 12 grafts, on the body in 38, and on the coronary anastomosis in 14. Technical success was 95.3% (61 of 64) per lesion; clinical success was 84.4% (54 of 64) per lesion and 82.5% (47 of 57) per patient. Thrombotic complications with images of a lacunar defect occurred in 11 grafts (17.2%). Predictive factors for these complications were: age of grafts 38.5% for greater than 60 month grafts versus 2.6% for less than 60 month grafts (p less than 0.01); site of lesion, body lesion 28.9% versus anastomosis none (p less than 0.01); type of lesion, concentric and short 6% versus other 29% (p less than 0.05); and recent fibrinolysis in 66% versus 10.6% (p less than 0.05). Long-term follow-up is available in the 47 successful patients and the three limited non-Q wave myocardial infarction patients. Two patients died at 13 and 17 months. Long-term angiographic follow-up is available in 45 of 48 patients or 94%. At the end of the study, 35 of 57 (61.4%) venous bypass grafts in 32 patients (64%) were patent after one or more percutaneous transluminal angioplasties."
-What differences were observed in the expression of primary response genes between renal compensatory hypertrophy (uninephrectomy) and renal hyperplasia (folic acid injection)?,"Differences in ""primary response"" gene expression in renal compensatory hypertrophy and hyperplasia. The induction of a family of primary response genes (ie, genes whose transcription is not dependent on new protein synthesis) occurs within minutes after stimulation of quiescent 3T3 cells by phorbol esters and growth factors. A similar pattern of gene expression is seen in PC-12 pheochromocytoma cells induced to differentiate by nerve growth factor (NGF), suggesting that a common set of activating signals occur in different forms of cell growth. To determine whether the same ""activation"" process occurs in renal hypertrophy, we measured mRNA levels in mice subjected to uninephrectomy (UNX) or sham operation. Regenerative renal hyperplasia was induced by intraperitoneal folic acid (FA) injection with vehicle as control. Northern blots showed induction of these genes by FA with elevated mRNA levels persisting for up to 24 to 48 hours. UNX and sham operation demonstrated a slight and transient elevation of mRNA levels, with a prompt return to basal levels by 60 minutes."
-How did the long-term psychological stress of patients with congenital heart disease compare to normative data in this 25-year follow-up study?,"Long-term psychologic implications of congenital heart disease: a 25-year follow-up. Patients with various types of congenital heart disease were contacted 25 years after their original examination at the Mayo Clinic. In addition to providing their current health status, level of education achieved, and current occupation, they were asked to complete a detailed standardized questionnaire to assess their degree of psychologic stress. Of the original 463 patients, 168 completed and returned the psychologic questionnaires. These patients had evidence of psychologic stress in excess of that expected on the basis of normative data. Furthermore, the degree of stress was unrelated to the clinical severity of the original cardiac defect. In addition, the psychologic stress occurred despite ""success"" as defined by educational achievement and occupational level. One can speculate that as children these patients were exposed to environmental stresses that may well have been colored by parental attitudes and perceptions."
-What is the most serious complication of thrombolytic therapy that can limit its usefulness?,"Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy. Bleeding is the most serious complication of thrombolytic therapy and limits its usefulness. We have reported a case of epidural hematoma, a rare occurrence after combined therapy with tissue plasminogen activator (TPA) and heparin. We emphasize that in patients treated with thrombolytic agents, any trauma may increase the risk of bleeding. The sudden onset of back pain and neurologic deficits should alert the clinician to the possibility of spinal hematoma with cord compression."
-What is the primary cause of death in children with maple syrup urine disease (MSUD) as described in this context?,"Cerebral edema causing death in children with maple syrup urine disease. Four children with the classic form of maple syrup urine disease (MSUD) died of cerebral edema during an intercurrent infection that caused severe dehydration and acidosis. The diagnosis of MSUD had been established during the neonatal period in all four patients, on day 1 of life in three of them. All were in satisfactory control before the intercurrent illness. Two patients underwent peritoneal dialysis. Signs of brain-stem compression occurred after treatment, when biochemical abnormalities were improving. Computed tomography of the head, which was done in two patients, revealed cerebral edema; one of these patients also had subarachnoid hemorrhage. Autopsy in one case revealed cerebral edema with herniation. Our experience documents that cerebral edema may occur in the older child with MSUD as well as in the neonate. The pathogenesis of cerebral edema in MSUD remains unclear. Early treatment of dehydration and acidosis may prevent the catastrophic consequences that we have observed."
-How do personality traits and life events relate to the frequency of headaches in adults?,"The association of frequent headaches with personality and life events. The associations between personality traits, life events and frequent headaches were studied in a sample of 5766 adult subjects between 20 and 65 years of age from the general population. Subjects with at least weekly headaches had more life events and higher inadequacy, social inadequacy, rigidity and injuredness than subjects with less frequent headaches. These relationships were not observed in subjects of 50 years of age and older, with the exception of the association with inadequacy. From the traits measured, inadequacy had the highest odds ratios for frequent headaches and showed a modest interaction with the presence of a life event. These findings are in agreement with Sarason's interactional model."
-What inflammatory changes were observed at the neuromuscular junction in patients with myasthenia gravis?,"Inflammation at the neuromuscular junction in myasthenia gravis. To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG."
-What is the significance of lowering cholesterol levels in patients with coronary heart disease (CHD)?,"On lowering lipids in the post-infarction patient. In patients with coronary heart disease (CHD) elevated serum cholesterol levels, like other classical risk factors, remain predictive of further coronary events. The excess risk attributable to raised cholesterol levels is considerable, and greater than that in subjects without CHD. A recent meta-analysis of all eight qualifying trials of secondary prevention of CHD by cholesterol lowering is reviewed. There were significant reductions in recurrent non-fatal and fatal CHD, with a downward trend in total mortality. Mechanisms underlying the relationship between cholesterol lowering and secondary prevention are reviewed. The implication of this analysis of trials for clinical practice is that hypercholesterolaemia should be sought and effectively treated in patients with CHD, unless contraindications are present."
-What was the clinical outcome for children with glutathione peroxidase deficiency after discontinuing anticonvulsant medication and receiving selenium substitution?,"Glutathione peroxidase deficiency and childhood seizures. 4 children with intractable seizures, repeated infections, and intolerance to anticonvulsants had evidence of glutathione peroxidase deficiency. 2 had low intracellular enzyme activity but normal blood selenium and high plasma glutathione peroxidase concentrations. The other 2 had low intracellular glutathione peroxidase activity with low circulating glutathione peroxidase and selenium concentrations. The clinical state of the children improved after discontinuation of anticonvulsant medication and selenium substitution."
-How does polysialic acid help distinguish small cell lung carcinoma from carcinoids?,"Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. The neural cell adhesion molecule (NCAM) exists in various types of neuroendocrine cells and their tumors. A typical feature of NCAM is polysialic acid, of which the chain length is developmentally regulated. The authors have performed a comparative immunohistochemical study on small cell lung carcinomas and bronchial as well as gastrointestinal carcinoids with the monoclonal antibody (MAb) 735 reactive with the long-chain form of polysialic acid. The small cell lung carcinomas, irrespective of their histological type, were positive for polysialic acid. Metastatic tumor cell complexes also exhibited immunostaining. The tumor cell-surface-associated immunostaining for polysialic acid was sensitive to endoneuraminidase. The mature and atypical bronchial and gastrointestinal carcinoids were not immunoreactive for polysialic acid. Cytoplasmic staining in groups of cells of carcinoids (2 of 28 cases) was due to nonspecific antibody binding, which could be prevented by increased ion strength. These data indicate that neuroendocrine tumors of the lung can be distinguished by their content of highly sialylated NCAM."
-What are the potential consequences of malignant eye tumors in geriatric patients?,"Malignant tumors of the eye in geriatric patients. The ocular tissues can be the site of a number of malignant tumors in adults and geriatric patients. In addition to posing a threat to the patient's life, these tumors can cause severe visual loss or blindness. Therefore, the primary care clinician should be capable of prompt diagnosis of the various malignant ocular tumors and be prepared to refer the patient for appropriate management. This article provides a photographic guide to the most common primary and secondary malignancies that can affect the eyelid, conjunctiva, intraocular structures, and orbit in the geriatric patient."
-What factors were found to have the strongest univariate relations to the restenosis rate in this study?,"Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators. The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and ""optimal"" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis."
-What diagnostic techniques were used to identify the left ventricular aneurysm in the fetus?,"Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review. Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented."
-What was the main objective of the study on community obstetric care in West Berkshire?,"Community obstetric care in West Berkshire OBJECTIVE--To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN--Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING--West Berkshire Health District. SUBJECTS--All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES--Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS--Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION--Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife."
-How do the outcomes of psychogenic seizures differ between children/adolescents and adults according to the study?,"Outcome of psychogenic seizures in children and adolescents compared with adults. We compared outcome of psychogenic seizures documented by video-EEG in 18 nonepileptic children and adolescents (ages 8 to 18; median, 14.5 years old) and 20 adults (ages 25 to 56; median, 34.0 years old). Outcome was significantly better for the younger patients at 1 year, 2 years, and 3 years after diagnosis. At these follow-up times, the percentages of children and adolescents free of psychogenic attacks were 73%, 75%, and 81%; at the same follow-up times, the percentages of adults free of psychogenic attacks were only 25%, 25%, and 40%. Factors leading to better outcome for younger patients may have been different psychological mechanisms at different ages of onset and greater effectiveness with earlier intervention."
-What are the proposed criteria for diagnosing migraine without aura in clinical practice?,"Criteria for the diagnosis of migraine in clinical practice. Criteria for the diagnosis of migraine have evolved from generalized descriptions to specific rules designed to ensure the selection of homogenous groups of patients for research studies. For clinical practice, the former are insufficiently specific and the latter are too complex. For care of headache patients by primary care physicians, we propose that the diagnosis of migraine without aura (common migraine) is warranted if any two of the following symptoms are present: unilateral site, throbbing quality, nausea, photophobia or phonophobia. These criteria are derived from a study comparing the features of 100 patients with migraine without aura and 100 patients with chronic daily headache. The proposed criteria for the diagnosis of migraine without aura were highly sensitive and adequately specific in discriminating groups. These simple criteria should facilitate the diagnosis of migraine by primary care physicians."
-What was the main finding regarding secondary prophylactic drug use for patients after myocardial infarction in the study?,"Use of secondary prophylaxis against myocardial infarction in the north of England OBJECTIVE--To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. DESIGN--Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. SETTING--The nine family practitioner committee areas within the Northern Regional Health Authority. PATIENTS--Patients who had had a myocardial infarction and were discharged to their general practitioner. MAIN OUTCOME MEASURE--Whether beta blockers or aspirin, or both, were given on discharge. RESULTS--Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. CONCLUSIONS--Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary."
-How does the MELAS mutation affect mitochondrial RNA transcription termination?,"Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products."
-How do thromboxane A2 synthase inhibition and thromboxane A2/prostaglandin endoperoxide receptor antagonism differently affect occlusive thrombosis in canine coronary arteries with varying degrees of vascular damage?,"Differential effects of thromboxane A2 synthase inhibition, singly or combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on occlusive thrombosis elicited by endothelial cell injury or by deep vascular damage in canine coronary arteries. In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n = 24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16 +/- 0.16/hr; n = 6; p less than 0.05) or by a comparatively modest degree of TXA2/prostaglandin endoperoxide receptor antagonism on top of TXA2 synthase inhibition (5 mg/kg i.v. ridogrel; CFR, 0.22 +/- 0.1/hr; n = 10; p less than 0.05). By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-microA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1 +/- 13.9 minutes; n = 7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n = 7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n = 7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg + 10 mg/kg/hr i.v. sulotroban for 300 minutes; n = 5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion greater than 300 minutes, n = 7; incidence of occlusion within 300 minutes, one of seven experiments; p less than 0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel."
-What were the main outcome measures in comparing dual chamber pacing (DDD) and ventricular rate adaptive pacing (VVIR) in patients with complete heart block?,"Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block. OBJECTIVE--To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block. DESIGN--Double blind crossover comparison with one month in each pacing mode. PATIENTS--10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers. MAIN OUTCOME MEASURES--Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline. RESULTS--No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes. CONCLUSIONS--In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing."
-How does Epstein-Barr virus infection impact liver transplant patients and their graft function?,"Epstein-Barr virus and persistent graft dysfunction after liver transplantation. Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection."
-What surgical procedure was used to treat scaphoid pseudarthrosis in this long-term review study?,"Pseudarthrosis of the scaphoid treated by the Matti-Russe operation. A long-term review of 77 cases. We report the long-term results of the Matti-Russe operation for pseudarthrosis of the scaphoid in 100 cases, reported previously by Mulder in 1968. Clinical results for 77 patients and radiographic data for 74 were reviewed at 22 to 34.8 years after surgery. In general, there was satisfactory relief of pain and stiffness but some patients had limitation of motion and reduced grip-strength, with usually slight osteoarthritic changes. There was poor correlation between subjective, objective, and radiographic results but 88% of the patients were satisfied with their results."
-What is the significance of the reported case of hydroureteronephrosis secondary to perforated Meckel's diverticulum?,"Hydroureteronephrosis secondary to perforated Meckel's diverticulum. Complications related to Meckel's diverticulum are not unusual. However, involvement of the urinary tract is extremely rare. To our knowledge this is the first reported case of ureteral obstruction due to perforation of Meckel's diverticulum."
-What are the key risk factors that contribute to excess morbidity and mortality from influenza infections in children in developing countries?,"Pathogenesis of respiratory infections due to influenza virus: implications for developing countries. The influenza viruses have an important and distinctive place among respiratory viruses: they change antigenic character at irregular intervals, infect individuals of all ages, cause illnesses characterized by constitutional symptoms and tracheobronchitis, produce yearly epidemics associated frequently with excess morbidity and mortality, and predispose the host to bacterial superinfections. Much is known about influenza viruses, but their role in respiratory infections among children in developing countries is poorly understood, and the risk factors that lead to the excess morbidity and mortality have not been identified clearly. Among the many risk factors that may be important are alterations in host immunity, malnutrition, prior or coincident infections with other microorganisms, inhaled pollutants, and lack of access to medical care. There is a great need for research that can establish more precisely the role these and other unidentified factors play in the pathogenesis of influenza infections in children in the developing world."
-What did the study reveal about the presence of atrial natriuretic factor in the human ventricle in relation to ventricular dilation?,"Expression of atrial natriuretic factor in the human ventricle is independent of chamber dilation This study investigated the presence of atrial natriuretic factor in ventricular tissue obtained from humans with dilated or restrictive heart disease. In 17 patients with ventricular dilation and impaired systolic function and in 8 patients with restrictive heart disease and preserved systolic function, the presence of ventricular atrial natriuretic factor was investigated in tissue obtained by ventricular endomyocardial biopsy. The objective of the study was to determine if the ventricular presence of atrial natriuretic factor is dependent on ventricular dilation. Left ventricular end-diastolic volume index was greater in the group with dilated cardiomyopathy than in the group with restrictive cardiomyopathy (134 +/- 13 versus 78 +/- 5 ml/m2, p less than 0.05); end-diastolic pressure was elevated in the two groups (20 +/- 2 versus 25 +/- 4 mm Hg, p = NS). With the use of immunohistochemical techniques, ventricular atrial natriuretic factor was clearly detected in 15 of the 17 patients with dilated cardiomyopathy and in 6 of the 8 patients with restrictive cardiomyopathy. This study demonstrates the high prevalence of ventricular atrial natriuretic factor in living patients with either systolic or diastolic dysfunction. Whereas in the atria, stretch or dilation may be an important stimulus, atrial natriuretic factor in the ventricular chamber occurs independent of dilation."
-What is the primary purpose of the knowledge-based computer system described in the context?,"Knowledge-based computer system to aid in the histopathological diagnosis of breast disease. A knowledge-based computer system, designed to assist pathologists in the histological diagnosis of breast disease, is described. This system represents knowledge in the form of ""disease profiles"" and uses a novel inference model based on the mathematical technique of hypergraphs. Its design overcomes many of the limitations of existing expert system technologies when applied to breast disease. In particular, the system can quickly focus on a differential problem and thus reduce the amount of data necessary to reach a conclusion. The system was tested on two sets of samples, consisting of 14 retrospective cases and five hypothetical cases of breast disease. Its recommendations were judged ""correct"" by the evaluating pathologist in 15 cases. This study shows the feasibility of providing ""decision support"" in histopathology."
-What changes were observed in the high-frequency peak power of heart rate variability in patients not taking beta blockers during the 24-hour period after acute myocardial infarction?,"Diurnal variations of neurocardiac rhythms in acute myocardial infarction. To determine the diurnal pattern of cardiac autonomic tone in acute myocardial infarction (AMI), this study examined the power spectrum of heart rate (HR) variability in 24 patients during a single 24-hour segment within 4 days of AMI. Patients were nonrandomly allocated to a group (n = 14) without autonomic drugs and to a group (n = 10) already receiving beta blockers at the time of AMI. With use of autoregressive modeling, the power spectrum of HR variability was computed from continuous 1-hour electrocardiographic segments recorded at equally spaced intervals; 7 to 8 A.M., 3 to 4 P.M., and 11 to 12 P.M. All patients were supine, awake and pain free during recordings. There were no differences in HR, HR variance or the low-frequency peak power (0.06 to 0.1 Hz) from one temporal sequence to another. For the patients not taking beta blockers, the high-frequency peak power (0.2 to 0.36 Hz) or vagal component increased significantly from 3 P.M. to 11 P.M. (28 +/- 11 to 45 +/- 20 beats/min2.Hz-1, p less than 0.01). There was a significant decrease in the low- to high-frequency peak power and area ratios from 3 P.M. to 11 P.M. All power spectral parameters in the patients taking beta blockers remained unchanged over 24 hours. There was significantly heightened vagal modulation of sinus node activity in those receiving beta blockers, especially at 7 A.M. and 3 P.M. The data suggest that under steady-state wakeful conditions in the early recovery phase after an AMI, vagal tone is more pronounced during the late evening hours with a possible shift to relative sympathetic dominance during early morning and midafternoon hours."
-What are the three types of adenomatous hyperplasia (AH) identified in the study?,"Argyrophilic nucleolar organizer regions and alpha-fetoprotein in adenomatous hyperplasia in human cirrhotic livers. Recently, adenomatous hyperplasia (AH) of the liver has been suspected as a precancerous lesion in human hepatocarcinogenesis. The authors examined 75 cases of AH from 42 cirrhotic livers, using staining of argyrophilic nucleolar organizer regions (AgNORs). These reflect proliferative cell activity. Findings in AH were compared with those seen in hepatocellular carcinoma (HCC) and other chronic liver diseases. Expression of alpha-fetoprotein (AFP) was also examined immunohistochemically. The authors classified AH into three types: ordinary (OAH), atypical (AAH), and AH with focal malignancy (FM). OAH implies a lack of atypia; AAH represents AH with structural and cellular atypia but without the features of overt carcinoma; and FM denotes AH with foci of overt HCC. Forty of the 75 cases of AH were categorized as OAH, 19 as AAH, and 16 as FM. The noncancerous areas of FM had features of AAH. The mean number of AgNORs in AH was intermediate between that seen in cirrhosis (2.93) and HCC (6.18) and showed a step-wise increase in the following order: OAH (2.95), AAH (3.89), noncancerous areas in FM (4.58), and malignant foci in FM (5.71). There was no significant difference in AgNOR counts between OAH and cirrhosis. AgNOR counts in AAH and FM were significantly higher than those of OAH, and lower than those of HCC. AFP was positive in 12 of 25 HCCs and in malignant foci of 3 FM lesions, but it was absent in OAH and AAH. These data suggest that OAH has a limited capacity for proliferation but that AAH and FM are much more replicative. The latter two conditions are probably preneoplastic lesions or early forms of HCC."
-How does repetition priming differ from explicit memory in patients with depression?,"Explicit memory and repetition priming in depression. Preliminary findings. Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia."
-How does Lupron affect the cell cycle of the ovarian cancer cell line 2774?,"Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment."
-How effective was zidovudine (ZDV) treatment in preventing Friend virus (FV) progression in mice?,"Early-initiated zidovudine therapy prevents disease but not low levels of persistent retrovirus in mice. An F1 hybrid mouse strain containing the Rfv-3r/s genotype was inoculated with Friend virus complex (FV) and treated with zidovudine (ZDV) intraperitoneally three times daily for 20 days beginning as early as 10 min after initial viral exposure. This strain of mice develops FV-specific neutralizing antibodies that aid in reducing viremia and splenic virus titers but do not prevent splenomegaly and eventual FV-associated death. The virally exposed mice treated with ZDV did not develop splenomegaly or have detectable viremia after the last drug treatment. On day 21, a single animal had demonstrable virus in the spleen as determined by a focal immunoenzyme assay; 57% had detectable virus at 5 weeks, but non displayed splenic virus after 35 weeks. None of the animals died after the 35-week holding period, compared to 38% dying in placebo-treated mice. To detect low levels of the virus, or potentially latent virus, splenocytes were cocultivated with a cell line known to readily propagate FV, and the cells were subsequently passaged four times to amplify replication of the virus. After amplification, a significant increase was seen in the number of mice testing positive for virus. Thus, ZDV treatment initiated early after virus exposure was effective in preventing FV-induced splenomegaly and death, but did not prevent low levels of persistent retrovirus in the mice."
-What diagnostic technique was used to detect minute lesions in patients with Crohn's disease during the sigmoidoscopy procedure?,"Minute lesions of the rectum and sigmoid colon in patients with Crohn's disease. Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease."
-How did cardiac myocyte size and volume change in different heart regions of rats with aortocaval fistulas after 5 months?,"Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects. Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass."
-What were the main findings of the study regarding the effects of microsurgical DREZ-otomy (MDT) on somatosensory function?,"Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity. The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a ""retuning"" of the dorsal horn as the mode of action of MDT is presented."
-"How do neutrophils, PAF, and thromboxane contribute to the decrease in local blood flow during pulmonary inflammation?","Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane. The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response."
-What role does echocardiography play in diagnosing and evaluating mitral and tricuspid stenosis?,"Role of echocardiography in the diagnosis and evaluation of severity of mitral and tricuspid stenosis. The presence, severity, and hemodynamic consequences of mitral and tricuspid stenosis can be determined by echocardiographic techniques. In mitral stenosis two-dimensional echocardiographic imaging allows definition of leaflet anatomy and dynamics, subvalvular disease, ventricular function, and involvement of other valves. Spectral and color Doppler echocardiographic techniques permit accurate measurement of transvalvular gradient, determination of functional orifice area, evaluation of associated valvular regurgitation, and assessment of pulmonary artery pressures. These approaches are of recognized clinical value, and they provide additional diagnostic information that is unavailable from clinical assessment alone in a significant number of patients. Compared with available invasive diagnostic standards of reference, echocardiographic data have been found to be comparable in accuracy. In tricuspid stenosis echocardiographic imaging and Doppler techniques provide an assessment of valve morphology and function that should be similarly useful in clinical management decisions, although rigorous comparative studies have not been performed. Currently, carefully done echocardiographic studies are a definitive means of establishing the presence and significance of mitral stenosis and tricuspid stenosis, thereby obviating the need for invasive evaluation in many patients, reducing risk, and potentially decreasing the cost of diagnostic assessment."
-What was the impact of graft diameter on patency in this study of Dacron aortobifemoral bypass grafts?,"Lack of diameter effect on short-term patency of size-matched Dacron aortobifemoral grafts. This study examined the relationship between graft diameter and subsequent patency in 79 patients who received Dacron aortobifemoral bypass grafts for aortoiliac occlusive disease between 1985 and 1989. Sixty-five percent of these patients were men, 25% were diabetic, and 94% were smokers, with an average age of 62 years. Patients were followed for a mean interval of 24 months. Life-table survival was 92% at 3 years. All surviving patients showed ""significant"" postoperative improvement by use of Society for Vascular Surgery/International Society for Cardiovascular Surgery combined clinical and vascular laboratory criteria. There were three early and five late graft thromboses. Primary and secondary life-table patencies were 85% and 92%, respectively, at 3 years. Dacron bifurcation grafts were selected to match the size of native arteries. Patients receiving small diameter grafts, defined as 12 mm (n = 9) and 14 mm (n = 39), were compared with patients receiving large diameter grafts of 16 mm (n = 26) and 18 mm (n = 5). Small diameter grafts were more likely to be used in women (p less than 0.01), but patient groups were otherwise comparable with respect to age, smoking history, diabetes, outflow status, operative indications, type of proximal anastomosis (end-to-end or end-to-side), location of distal anastomosis (common femoral vs deep femoral), type of graft construction (knitted vs woven), and functional result. Graft diameter did not influence life-table patency, which was 84% for small and 87% for large diameter grafts at 3 years (p = 0.74). Furthermore, none of the other variables listed above influenced graft patency."
-How did patients with fornix damage perform on nonverbal memory tests compared to patients with other brain lesions?,"Amnesia following damage to the left fornix and to other sites. A comparative study. Two memory-impaired patients, who had suffered damage to the left or both fornix columns during removal of a ventricular cyst, were compared with 3 others having left-sided hippocampal or thalamic lesions, and with normal controls. The tests used were nonverbal--scene recognition, delayed matching-to-sample and concurrent pattern and object discrimination learning. The last two are differentially sensitive to fornix transection and to hippocampal or thalamic ablations in monkeys; however, the patients with fornix damage did not show a distinctive pattern of impairment. The reasons for this discrepancy are discussed. The study adds to the evidence that fornix transection can cause wide-ranging memory disturbances in man."
-"How did the DNA ploidy status of cervical carcinoma tumors change after radiation therapy, and what was its relationship to tumor response?","DNA ploidy analysis of effectiveness of radiation therapy for cervical carcinoma. Cellular DNA content from 30 patients with cervical carcinoma was determined using flow cytometry before and after radiation therapy (RT). The authors attempted to correlate changes in DNA content, tumor response to RT, and post-RT pathologic findings. Before RT, tumors from eight of 30 patients (26.7%) were diploid or near-diploid; tumors from 22 patients (73.3%) were aneuploid. After RT, diploid or near-diploid tumors were found in 23 patients (76.7%), and aneuploid tumors were observed in seven patients (23.3%). Aneuploidy disappeared in 15 of the patient tumors, and complete tumor response (CR) was observed in 13 of these 15 patients (86.7%). Pathologic examinations were negative in 12 of 15 cases and suspicious in one of 15 cases. Of the seven patients whose tumor aneuploidy did not change after RT, CR was observed in only two (28.7%). Pathologic examinations were positive in five of seven cases and suspicious in one of seven cases. The CR for the 22 patients with pre-RT aneuploid tumors was 15 of 22 (68.2%); the CR for the eight patients with pre-RT diploid tumors was two of eight (25%, P less than 0.01). From these data the authors conclude there is a direct correlation between DNA content and radiosensitivity in cervical carcinoma. Aneuploid tumors from these patients were more radiosensitive than diploid tumors, and they patients had a better clinical tumor response and improved pathologic findings."
-How does enhanced GABAergic inhibition impact neuronal death and cognitive function in an epilepsy model?,"Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy. The excitotoxic hypothesis of epileptic cell death [Olney, J. W. (1978) in Kainic Acid as a Tool in Neurobiology, eds. McGeer, E., Olney, J. W. & McGeer, P. (Raven, New York), pp. 95-121; Olney, J. W. (1983) in Excitotoxins, eds. Fuxe, K., Roberts, P. J. & Schwartch, R. (Wenner-Gren International Symposium Series, Macmillan, London), Vol. 39, pp. 82-96; and Rothman, S. M. & Olney, J. W. (1986) Ann. Neurol. 19, 105-111] predicts an imbalance between excitation and inhibition, which occurs probably as a result of hyperactivity in afferent pathways or impaired inhibition. In the present study, we investigated whether the enhancement of gamma-aminobutyric acid (GABA)-mediated (GABAergic) inhibition of neurotransmission by blocking the GABA-metabolizing enzyme, GABA transaminase, could influence the histopathological and/or the behavioral outcome in this epilepsy model. We demonstrate that the loss of pyramidal cells and hilar somatostatin-containing neurons can be abolished by enhancing the level of synaptically released GABA, and that the preservation of hippocampal structure is accompanied by a significant sparing of spatial memory as compared with placebo-treated controls. These results suggest that enhanced GABAergic inhibition can effectively block the pathophysiological processes that lead to excitotoxic cell death and, as a result, protect the brain from seizure-induced cognitive impairment."
-What percentage of children with acquired cortical blindness had a poor visual outcome in the study?,"Cortical blindness in children: a study of etiology and prognosis. Thirty-four children (20 boys, 14 girls) with congenital and acquired cortical blindness were analyzed for visual outcome in relation to etiology, visual evoked potentials, electroencephalography, and cranial computed tomography. All 7 children with congenital cortical blindness remained blind on subsequent examination. Of the 27 children with acquired blindness, 16 (59%) had poor visual outcome. Poor visual outcome occurred in those with cardiac arrest, hypoxia, status epilepticus, intracranial hemorrhage, cerebral thrombosis, and head trauma. Good visual outcome occurred in children with hypotensive episodes after cardiac surgery. Of the 12 children with recovery of vision, the interval from acute loss of vision to partial or total recovery was 2 weeks to 5 months. Seven children had complete recovery of vision with no residual visual field defect. The majority of children (87%) had focal or multifocal spike-and-waves and slow sharp-wave discharges on electroencephalography. None had photic recruitment response or occipital spike-and-wave discharges. Flash visual evoked potential studies performed during acute episodes of cortical blindness documented 11 with absent response, 10 with bilateral increases in latency, and 6 with normal responses. There was no correlation between normal visual evoked potentials and a good visual outcome. Only 2 of 6 children with normal responses had normal vision. Abnormal or absent responses are more predictive of a poor recovery of vision because only 3 of 21 (14%) had normal vision on subsequent examination. Abnormal electroencephalographic findings with focal or multifocal spike-and-wave discharges or cerebral atrophy on cranial computed tomography are also poor prognostic signs."
-What factors beyond physical swallowing ability influence a patient's capacity to resume oral nutrition in oropharyngeal dysphagia?,"Factors affecting ability to resume oral nutrition in the oropharyngeal dysphagic individual. Successful oral intake of nutrition depends not only on the patient's ability to swallow efficiently and safely but also a number of cognitive, neurolinguistic, and behavioral variables. This paper reviews these competencies as they are integrated into the act of oral feeding and describes the types of disorders that affect these abilities. Methods of evaluating and treating the abilities needed for successful oral intake are described."
-What is the significance of screening for Wilson disease in cases of unexplained recurrent abortion?,"Recurrent abortion and the diagnosis of Wilson disease. We describe the first patient with Wilson disease and recurrent abortion who was effectively treated with oral zinc for both conditions. Between the ages of 21-26, this patient experienced seven successive unexplained abortions. At age 27, neurologic signs and liver function disturbances appeared. Wilson disease was diagnosed when Kayser-Fleischer rings were detected in the cornea. Decoppering therapy was instituted with zinc sulfate per os. By the age of 31, hepatic and neurologic signs had vanished. The patient conceived, and after an uncomplicated eighth pregnancy she delivered her first healthy child. Two years later, a ninth pregnancy was equally successful. The chance that Wilson disease may be the cause of recurrent abortion is small. However, because the disease is fatal if left untreated and because it is an underdiagnosed disease, we recommend screening for Wilson disease in cases of unexplained recurrent abortion when family history demonstrates consanguinity or neurologic, psychiatric, and/or liver disorders. A strategy to this end is proposed."
-How does Ki-67 immunostaining correlate with nuclear grade and clinical outcome in node-negative breast carcinoma?,"Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity."
-How was DNA typing used to determine paternity in the case of a putrefied fetus during a forensic investigation?,"A forensic application of DNA typing. Paternity determination in a putrefied fetus. Using minisatellite DNA probes that hybridize to a variable number of tandemly repeated loci, an individual-specific DNA fingerprint can be determined. In the case reported here, we succeeded in extracting high-molecular-weight DNA from a 3-month-old fetus discovered during the autopsy of a murdered 28-year-old pregnant woman reported missing 10 days earlier. The results of analysis of restriction-fragment-length polymorphisms showed that all bands present in the fetus's pattern, but absent in the mother's, matched only those of the putative father. Thus, the paternity of the victim's husband was ruled out."
-What drugs showed the greatest influence on clinical outcomes in the treatment of metastatic neuroblastoma?,"Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma."
-What was the primary purpose of performing palliative amputations in this study?,"Major amputations done with palliative intent in the treatment of local bony complications associated with advanced cancer. Palliative amputations were performed on 11 patients (7 men, 4 women) with disseminated disease to control local bony complications. The average patient age was 54 years (range 14-78 years). The primary diseases were melanoma/sarcoma (seven patients) and carcinoma (four patients). All had pain; eight had intractable pain that could not be controlled by analgesics. All 11 patients had additional severe local complications, which included recurrent pathological fracture (4), sepsis (2), hemorrhage (2), radiation necrosis (2), and iliofemoral thrombosis secondary to tumor (1). Previous attempts of palliation had been made in all 11 patients, and 8 had undergone previous operative procedures (5 had undergone two or more) prior to amputation. Three anterior hemipelvectomies, five posterior hemipelvectomies, two hip disarticulations, and one forequarter amputation were performed. All patients survived the surgery, and there were no intraoperative complications. All patients received dramatic relief of pain. Postoperative complications included two cases of flap necrosis and two infections; all resolved satisfactorily. The six patients who were nonambulatory before surgery ambulated postoperatively, and two eventually ambulated with a prosthesis. Six of 11 patients survived 1 year or longer, with a median postoperative survival period of 13 months (average 16 months). Although major amputations are viewed at times as offering little to already-compromised patients, they can improve dramatically the quality of life in selected patients."
-What did the confirmatory factor analysis reveal about the theoretical structure of the McGill Pain Questionnaire in acute pain scenarios?,"Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain. Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain."
-What specific areas of medical knowledge must cardiologists possess when treating adults with congenital heart disease?,"The physician's responsibilities: residua and sequelae. Cardiologists assuming responsibility for adults with congenital heart disease must have knowledge of electrophysiologic, valvular (native valves), prosthetic (valves, patches and conduits), ventricular (especially chamber function), vascular (especially elevated pulmonary vascular resistance) and noncardiovascular residua and sequelae. Acquired cardiac and noncardiac diseases coexist in older adults with postoperative congenital heart disease and add to the physician's responsibilities."
-"How did the Mini Shah grommet compare to the conventional Shah grommet in terms of extrusion, effusion recurrence, and tympanosclerosis?","The mini-grommet and tympanosclerosis. One hundred and sixteen children with otitis media with effusion underwent myringotomy and insertion of a conventional pattern of Shah grommet in one ear and the much smaller Mini Shah grommet in the other. Close observation post-operatively determined the comparative rate of extrusion, recurrence of effusion, and of onset and degree of tympanosclerosis. At one year review, the Mini Shah shows a significantly earlier extrusion and a greater tendency to recurrence of otitis media with effusion. However, this is compensated by a decreased incidence of tympanosclerosis and reduced severity in those affected. This tends to support the view that shear forces produced by heavier patterns of ventilation tube promote tympanosclerosis."
-What is the rare complication observed in this patient with mixed connective tissue disease?,Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease.
-What unique medical findings were discovered in the autopsy of this 62-year-old world record marathon runner?,"A world record marathon runner with silent ischemia without coronary atherosclerosis. A 62-year-old world record marathon runner was found to have silent ischemia manifested by a very abnormal stress test, whereas at autopsy nine months later, there was virtually no coronary atherosclerosis nor other disease of the coronary microvasculature. However, there was focal fibrosis of the papillary muscles consistent with remote ischemia secondary to possible CV. It is postulated that endurance-related high catecholamine levels might have been responsible."
-What were the findings of the study regarding the potential ototoxic effects of ciprofloxacin when applied ototopically?,Lack of ciprofloxacin ototoxicity after repeated ototopical application. The possible side effects of ototopically applied ciprofloxacin on inner ear function were investigated. The hearing function of pigmented guinea pigs was evaluated by daily frequency-specific evoked response audiometry after repeated application of the drug to both ears. Ciprofloxacin appeared to have no statistically significant effect on the hearing thresholds of the experimental animals.
-What are the key risk factors for tunnel infections in continuous peritoneal dialysis?,"Risk factors for tunnel infections in continuous peritoneal dialysis. Little data are available about risk factors for peritoneal catheter subcutaneous tunnel infection. Therefore, we analyzed tunnel infections occurring in our program over a 10.5-year period. One hundred twenty-nine tunnel infections occurred in 92 of 411 patients (22%) on peritoneal dialysis for a mean of 19 +/- 19 months. Tunnel infection rate was 0.19 per year. By 1 year, 15% of patients had a tunnel infection, and by 2 years, 23%. Tunnel infection rates decreased with increasing time on peritoneal dialysis: 2.4 per year for patients on peritoneal dialysis less than 1 year, 0.8 per year for patients on dialysis 1 to 2 years, and 0.4 per year for patients on dialysis greater than 2 years (all different at P less than 0.01). Organisms were cultured in 109 tunnel infections: gram-positive cocci in 77 episodes (71%) [Staphylococcus aureus 57, 52%], and gram-negative bacilli in 24 episodes (22%). Tunnel infection rates were higher in diabetics than in nondiabetics (0.27 per year v 0.16 per year, respectively; P less than 0.001 by life-table analysis of time to first infection) and also higher in women than in men (0.23 per year v 0.17 per year, P less than 0.001). Tunnel infection rates were 0.35 per year for diabetic women, 0.20 per year for diabetic men, 0.18 per year for nondiabetic women, and 0.15 per year for nondiabetic men (groups different, P less than 0.001). Race and age were similar in patients with and without tunnel infections. Catheter loss was 80% when tunnel infection was associated with peritonitis and 40% when tunnel infection alone was present (P less than 0.001). We conclude that the risk of tunnel infection is highest early in the course of peritoneal dialysis and that diabetic women, for unclear reasons, are at the highest risk."
-How does color Doppler flow sonography help in assessing erectile function in normal and abnormal cases?,"Assessment of normal and abnormal erectile function: color Doppler flow sonography versus conventional techniques. The penile arteries were studied with color Doppler flow sonography in 10 subjects with normal and 39 patients with abnormal erectile function. The relationships of systolic and diastolic velocities to spectral waveform changes in the penile arteries in response to tumescence were studied before and after intracorporal injection of vasoactive medications that induce erection. In normal subjects, a characteristic spectral waveform pattern corresponded to increasing intracorporal pressure. Patients with abnormal arterial inflow and/or abnormal venous sinusoidal leakage demonstrated deviation from the patterns noted in normal subjects. Patients with abnormal arterial inflow had lower mean peak systolic velocities than normal subjects. Patients with severe venous sinusoidal incompetence had an arrest of waveform progression with evolution to but not beyond phases 1 or 2 (diastolic flow remained positive). Patients with abnormal arterial inflow and abnormal venous sinusoidal outflow had waveform changes that reflected both processes. Systolic/diastolic velocity and waveform relationships can be used to define the integrity of both the cavernosal artery inflow and venous sinusoidal outflow occlusion mechanisms."
-What percentage of women with metastatic breast cancer develop eye metastases?,"Breast cancer metastatic to the eye is a common entity. Breast cancer metastatic to the eye is a common entity occurring in up to 30% of women with metastatic disease. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs. The diagnosis should be suspected in any women with a history of breast cancer and any visual symptoms, particularly metamorphopsia and scotomata. A thorough ophthalmologic evaluation, aided by ultrasonography, computed tomography, or magnetic resonance scanning, usually confirms the diagnosis. Early treatment with radiation therapy can alleviate symptoms and control local disease. The recognition and treatment of this disorder is important in maximizing the quality of life in patients with metastatic breast cancer, especially because newer treatment regimens prolong survival and thereby increase the chances for ocular metastasis."
-What are the two major types of cystic pancreatic neoplasms mentioned in the context?,"Incidental detection of a microcystic adenoma of the pancreas. Cystic neoplasms of the pancreas are uncommon. The two major types of cystic pancreatic neoplasms are microcystic (serous) cystadenoma and mucinous cystic lesions (mucinous cystadenoma and mucinous cystadenocarcinoma). The two types differ substantially in the long-term mortality. Symptoms and signs do not distinguish between the two types, and small lesions are often asymptomatic. The neoplasms may be discovered during imaging procedures for unrelated complaints. Computerized tomography may suggest the diagnosis of microcystic adenoma or mucinous cystic neoplasm when the features are typical, but the final diagnosis must be established by surgical biopsy. Characteristic gross findings, light microscopic findings, and immunohistochemical staining patterns distinguish between the two types. When preliminary open biopsy confirms microcystic adenoma, extensive unnecessary surgery can be avoided."
-How does dobutamine affect left ventricular isovolumic relaxation in patients with congestive heart failure compared to normal subjects?,"Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle. BACKGROUND. We tested the hypothesis that beta-adrenergic receptor-stimulated acceleration of left ventricular (LV) isovolumic relaxation (i.e., positive lusitropic response) is attenuated in patients with severe congestive heart failure (CHF) compared with patients without LV dysfunction or CHF. METHODS AND RESULTS. The beta-adrenergic agonist dobutamine was infused by the intracoronary route in 14 subjects (normal group, six; CHF patients, eight) and by the intravenous route in a second group of 14 subjects (normal group, four; CHF patients, 10). The positive inotropic response to intracoronary or intravenous dobutamine was substantially and significantly reduced in the patients with CHF. LV isovolumic relaxation rate was determined by the methods of Weiss (TL), Mirsky (T1/2), and by a nonlinear regression technique (TNL). LV isovolumic relaxation assessed by all three methods was significantly prolonged in CHF patients compared with normal subjects. Intracoronary and intravenous infusions of dobutamine caused significant acceleration of LV isovolumic relaxation in both normal subjects and patients with CHF. The magnitude of the dobutamine-stimulated acceleration of isovolumic relaxation in patients with CHF was comparable with that in normal subjects. CONCLUSIONS. These data demonstrate that beta-adrenergic receptor stimulation causes significant acceleration of LV isovolumic relaxation in both normal subjects and patients with severe CHF. Coronary to our hypothesis, the lusitropic response to beta-adrenergic stimulation is well preserved in patients with severe CHF despite substantial attenuation of the beta-adrenergic positive inotropic response. These findings have potentially important implications regarding the physiology and pharmacology of adrenergically mediated LV relaxation in humans."
-What is the significance of dystrophin-positive fibers (revertants) in Duchenne muscular dystrophy patients?,"Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group. The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript."
-What is the relationship between dimethylformamide (DMF) exposure and liver enzyme levels among synthetic leather workers?,"Dimethylformamide-induced liver damage among synthetic leather workers. Prevalence of liver injury associated with dimethylformamide (DMF) exposure was determined. Medical examinations, liver function tests, and creatine phosphokinase (CPK) determinations were performed on 183 of 204 (76%) employees of a synthetic leather factory. Air concentrations of solvents were measured with personal samplers and gas chromatography. The concentration of DMF in air to which each worker was exposed was categorized. High exposure concentrations of DMF (i.e., 25-60 ppm) were significantly associated with elevated alanine aminotransferase (ALT) levels (ALT greater than or equal to 35 IU/l), a result that did not change even after stratification by hepatitis B carrier status. Modeling by logistic regression demonstrated that exposure to high concentrations of DMF was associated with an elevated ALT (p = .01), whereas hepatitis B surface antigen (HBsAg) was slightly but independently associated with an elevated ALT (p = .07). In those workers who had normal ALT values, there occurred still significantly higher mean ALT and aspartate aminotransferase (AST) activities, especially among those who were not HBsAg carriers. A significant association existed between elevated CPK levels and exposure to DMF. However, an analysis of the CPK isoenzyme among 143 workers did not reveal any specific damage to muscles. This outbreak of liver injury among synthetic leather workers is ascribed to DMF. It is recommended that the occupational standard for DMF and its toxicity among HBsAg carriers be evaluated further."
-What is Parathyroid Hypertensive Factor (PHF) and how does it contribute to hypertension?,"Parathyroid hypertensive factor, a circulating factor in animal and human hypertension. A new circulating hypertensive factor (parathyroid hypertensive factor; PHF) was shown to exist in the plasma of spontaneously hypertensive rats (SHR) but not in that of normotensive rats. PHF produced a delayed increase in blood pressure with a peak response at 45 min (bolus injection) or 60 to 90 min (continuous infusion). This increase in blood pressure was coupled with an in vitro increase in calcium uptake in rat tail artery with a similar time course. The involvement of calcium in the mechanism of action was supported by the inhibitory effect of calcium antagonists on the vascular action of PHF. Furthermore, PHF increased the intracellular free calcium concentration in cultured smooth muscle cells from rat tail artery. Parathyroidectomy and parathyroid transplant experiments indicated the parathyroid origin of PHF. A culture of parathyroid glands from SHR, but not from normotensive rats, produced in the medium a factor which has the same biological property and HPLC retention time as plasma PHF. A novel cell type was described in the parathyroid gland of SHR, but not normotensive rats, and the percent of these cells correlated significantly with plasma PHF level and blood pressure. In some hyperparathyroid patients, plasma PHF and hypertension were found, both of which disappeared after surgical removal of the parathyroid gland. In both animal models and human studies, PHF seems to be associated with low or normal plasma renin and salt-sensitive type of hypertension."
-How accurately can radiographers triage x-ray films in accident and emergency departments?,"How well can radiographers triage x ray films in accident and emergency departments? [published erratum appears in BMJ 1991 Mar 23;302(6778):696] OBJECTIVE--To assess the ability of radiographers to identify abnormal radiographs of patients attending accident and emergency departments. DESIGN--Prospective study over six weeks. SETTING--Teaching hospital casualty x ray department. PATIENTS--3394 consecutive patients referred for radiography. INTERVENTIONS--Radiographs were assessed by radiographers who were offered a four point triage scheme: normal, abnormal, insignificantly abnormal, or further advice required. MAIN OUTCOME MEASURES--Comparison of radiographers' assessments with an assessment made independently by the reporting radiologists. RESULTS--Overall disagreement between the radiographers and radiologists was 9.4%. There were 7% false positives and 14% false negatives. Most errors occurred in assessing radiographs of the skull, facial bones, chest, abdomen, and soft tissues. CONCLUSION--Unselected radiographers can offer useful advice on radiographs to casualty officers, but their high rate of false positive diagnoses indicates that they cannot triage casualty radiographs sufficiently accurately to allow them to extend their current reporting role."
-What was the primary objective of the nicardipine study in ischemic stroke patients?,"Early treatment of ischemic stroke with a calcium antagonist. We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified."
-Is intravenous immunoglobulin G recommended as a first-line treatment for acute thrombotic thrombocytopenic purpura?,"Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature. Acute thrombotic thrombocytopenic purpura (TTP) is a rare and serious disease. Treatment with prednisone, anticoagulation, antiplatelet drugs, splenectomy, exchange transfusions, vincristine, and plasmapheresis may be effective in some patients, but the response to these therapies is inconsistent and all carry the potential for serious side effects. We, and others, have recently seen dramatic responses to intravenous (IV) immunoglobulin G (IgG) when other treatments have failed. Although IV IgG is expensive, its costs are low compared with those extended plasmapheresis regimens. Since the response to treatment can usually be evaluated within a few days and the side effects appear less than with other treatments, we believe a strong case can be made for the use of IV IgG as first-line therapy for acute TTP. Continued multicenter studies are necessary to finally solve the problem of competing and confusing treatment attempts and synergism of treatment in acute TTP."
-What were the key findings regarding the prognostic value of tumor grade and DNA ploidy status in stage D2 prostate cancer patients?,"The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma. This study was designed to compare the prognostic potential of tumor grade and ploidy status in patients with stage D2 prostate cancer. Two outcome groups were selected on the basis of survival after orchiectomy: a bad outcome group consisting of 66 patients who died of the disease within 12 months and a good outcome group comprising 37 patients who survived beyond 5 years. Tumors were classified histologically as well (17%), moderately (17%) or poorly (66%) differentiated. Tumor grade was a significant predictor of outcome, with 76% of poorly differentiated tumors in the bad outcome group and 65% of well differentiated tumors in the good outcome group (p less than 0.005). Deoxyribonucleic acid (DNA) ploidy analysis was performed on formalin fixed, paraffin embedded samples of the primary tumor to yield 97 final tracings that were classified using set criteria for DNA ploidy status. Over-all, 54% of the tumors were nondiploid (33% aneuploid and 21% tetraploid) and the remaining 46% were diploid. DNA ploidy status was a significant indicator of outcome (p less than 0.001), with 64% of diploid tumors in the good outcome group and 88% of the nondiploid tumors in the poor outcome group. Tetraploid tumors behaved no differently from other nondiploid tumors. We conclude that DNA ploidy status and tumor grading are significant independent predictors of outcome after orchiectomy and when combined yield important additional prognostic information."
-How does milrinone affect left ventricular remodeling after an acute myocardial infarction in rats?,"Effects of milrinone on left ventricular remodeling after acute myocardial infarction. BACKGROUND. Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS. Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION. Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation."
-What percentage of women with chronic pelvic pain were found to have occult somatic pathology after a negative laparoscopy?,"Nongynecologic somatic pathology in women with chronic pelvic pain and negative laparoscopy. One hundred eighty-three women with chronic pelvic pain were referred to a multidisciplinary chronic pelvic pain clinic after negative laparoscopy. One hundred twenty-two of them completed a thorough medical and psychologic evaluation and were followed for a minimum of six months after completion of therapy. Occult somatic pathology was diagnosed in 57 women (47%), including 19 in whom coexistent psychopathology was diagnosed. Myofascial pain was the most common somatic diagnosis, followed by atypical cyclic pain (dysmenorrhea or mittelschmerz); gastroenterologic, urologic and infectious diseases; and pelvic vascular congestion. No plausible somatic etiology was apparent in the remaining 65 (53%) of the 122 referrals. Nongynecologic somatic pathology accounted for 34 (29%) and gynecologic pathology for 23 (19%) of the referrals, only 6 (5%) of whom ultimately required hysterectomy. Women with a somatic diagnosis were found to be significantly older than the remainder of the referral population. Long-term symptomatic improvement or resolution of pain was obtained in 43 (75%) of the 57 patients with somatic diagnoses. Coexistent psychopathology was found to correlate with a poorer long-term prognosis. Our findings underscore the importance of a multidisciplinary approach to evaluating and treating chronic pelvic pain in women and confirm that hysterectomy is indicated in this setting only rarely."
-What was the efficacy of teicoplanin in treating osteomyelitis and vascular-access-associated bacteremias in this study?,"Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin. Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed."
-"How did nicardipine affect glucose tolerance, insulin secretion, and blood lipid levels in the study?","Effect of the calcium antagonist nicardipine hydrochloride on glucose tolerance and insulin secretion. The calcium antagonist nicardipine was administered to 42 patients at a dose of 60 or 120 mg/day for an average of 7.8 weeks to determine its effects on glucose tolerance and insulin secretion. Glucose tolerance and immunoreactive insulin levels were essentially unchanged by nicardipine regardless of the preexisting level of glucose tolerance. Mean systolic and diastolic blood pressures decreased in all patients. Concentrations of triglycerides decreased and high-density lipoprotein cholesterol levels increased significantly (p less than 0.05) in association with nicardipine administration. Therefore it is concluded that, regardless of the preexisting level of glucose tolerance, nicardipine exerted hypotensive effects without significant adverse effects on glucose tolerance or insulin secretion."
-How did the monitoring of somatosensory evoked potentials (SEPs) help predict and potentially prevent neurological deficits during middle cerebral artery aneurysm surgeries?,"Monitoring of somatosensory evoked potentials during surgery for middle cerebral artery aneurysms. Somatosensory evoked potentials (SEPs) were monitored during 53 procedures for aneurysms of the middle cerebral artery (MCA). ""Significant"" changes were reported to the surgeon, who took corrective action when possible. Changes in the SEPs were categorized as follows: Type I, no change; Type II, significant change with complete return to baseline; Type III, significant change with incomplete return to baseline; Type IV, complete loss with no return; and Type V, no response at baseline. Only 1 of 37 patients with a Type I SEP had a new neurological deficit, and this was a patient who could not be examined for several days after surgery because he was in a pentobarbital coma. All 4 patients with Type III and IV changes had new postoperative neurological deficits. Perhaps of greater importance, 4 of 5 patients with Type II changes had no new deficit. These patients all had changes in SEPs that were completely reversible by clip adjustment (2), prompt removal of temporary clips (1), and inducing hypertension after aneurysm trapping (1). These cases may, therefore, represent instances in which SEP monitoring allowed the clinicians to prevent a neurological deficit. The MCA supplies the area of the somatosensory cortex that controls the hand. Median nerve SEPs are, therefore, a theoretically ideal monitor during surgery for MCA aneurysms. This study suggests that the results of MCA aneurysm surgery may be accurately predicted and improved with SEP monitoring."
-What diagnostic values were studied in patients with spinal metastasis from adenocarcinoma of unknown origin?,"Clinical diagnosis for metastatic adenocarcinoma of spine of unknown origin. A comparative study. The diagnostic values of the presence of Virchow's node (VN) or rectal shelf (RS) in spinal metastasis from adenocarcinoma of unknown origin were studied prospectively in 60 patients during 1986-1988. These were compared with 14 cases with other malignancies of the spine and 37 controls with nonneoplastic spinal lesions. The diagnosis was confirmed by histologic study in all malignant cases. The results were analyzed by diagnostic test analysis and McNemar chi 2 testing. This yields 18.3-21.6%, 97.2-100%, and 92.8-100% sensitivity, specificity, and predictive value, respectively, for a positive test for VN and RS to differentiate significantly adenocarcinoma from other malignancies and control patients (P less than 0.005). These findings may thus be considered as a simple and economic guide for physicians to determine the proper approach to patients with a spinal lesion suspected to be malignant."
-What is the primary purpose of using botulinum toxin in the treatment of spasmodic dysphonia?,"Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia. Spasmodic dysphonia is a focal dystonia that causes a loss of the fine control of intrinsic laryngeal muscles and produces a strained staccato voice. Temporary relief from symptoms has been reported in patients treated with botulinum toxin percutaneously injected into the thyroarytenoid muscle. A newly developed method of treatment differs from reported methods by increasing the accuracy of botulinum toxin placement, reducing soft tissue trauma, and applying basic scientific information about the functional histology of intrinsic laryngeal musculature. Sixteen patients with primarily adductor spasmodic dysphonia were treated. Initial assessment included laryngeal examination by indirect laryngoscopy, videoendoscopy, and stroboscopy, neurology examination (including laryngeal EMG), and vocal function studies with acoustic analysis and aerodynamic studies. A device originally designed for collagen injection allowed the precise microdelivery of toxin to the thyroarytenoid muscle. Indirect laryngoscopy was used to direct the needle, in an attempt to cover a broad area of motor end plates. The minimally effective dose was titrated for each patient, to avoid paralysis and preserve laryngeal function. All patients showed improved voices after treatment. There were no major complications. The basic technique can be performed in the otolaryngologist's office and does not require electromyography equipment or expertise."
-What is the main purpose of the new approach described in the study for differentiating between supraventricular tachycardia with aberrant conduction and ventricular tachycardia?,"A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. BACKGROUND. In the differential diagnosis of a tachycardia with a wide QRS complex (greater than or equal to 0.12 second) diagnostic mistakes are frequent. Therefore, we investigated the reasons for failure of presently available criteria, and we identified new, simpler criteria and incorporated them in a stepwise approach that provides better sensitivity and specificity for making a correct diagnosis. METHODS AND RESULTS. A prospective analysis revealed that current criteria had a poor specificity for the differential diagnosis. The value of four new criteria incorporated in a stepwise approach was prospectively analyzed in a total of 554 tachycardias with a widened QRS complex (384 ventricular and 170 supraventricular). The sensitivity of the four consecutive steps was 0.987, and the specificity was 0.965. CONCLUSIONS. Current criteria for the differential diagnosis between supraventricular tachycardia with aberrant conduction and ventricular tachycardia are frequently absent or suggest the wrong diagnosis. The absence of an RS complex in all precordial leads is easily recognizable and highly specific for the diagnosis of ventricular tachycardia. When an RS complex is present in one or more precordial leads, an RS interval of more than 100 msec is highly specific for ventricular tachycardia. This new stepwise approach may prevent diagnostic mistakes."
-What percentage of patients in the study experienced otolaryngic complications during cancer chemotherapy?,"The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed."
-How did rice bran treatment affect stone formation rates in hypercalciuric patients?,"Results of long-term rice bran treatment on stone recurrence in hypercalciuric patients. A series of 182 calcium stone formers with idiopathic hypercalciuria underwent treatment with rice bran for 1 to 94 months. Urinary calcium excretion was considerably reduced, but there was some increase in urinary phosphate and oxalate. Urinary excretion of magnesium and uric acid, serum calcium, magnesium, phosphate, uric acid, parathyroid hormone (PTH) and ALP was unaffected. There were no obvious changes in serum iron, zinc and copper even when patients were treated for long periods. Rice bran was well tolerated in almost all cases and there were no serious side effects; 49 patients have undergone treatment for more than 3 years (average duration of administration 5.09 years). The frequency of new stone formation was drastically reduced (individual stone formation rate (no./year) from 0.720 +/- 0.533 to 0.125 +/- 0.204; group stone formation rate (no./patient-year) from 0.721 to 0.120) compared with the 3-year period before treatment. During treatment, 61.2% of patients remained in remission. Although rice bran therapy should be effective in correcting absorptive hypercalciuria, there may be limits to the overall ability of rice bran monotherapy to prevent recurrence."
-What was the primary objective of this Phase II trial involving intraperitoneal mitoxantrone in epithelial ovarian cancer?,"Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer. Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation)."
-How does the presence of the S-allele in Dahl rats affect their alcohol consumption?,"The influence of the renin gene on alcohol consumption in Dahl rats. A rat renin allele (the S-allele) has been identified in Dahl rats which cosegregates with increases in blood pressure. Rats with a double dose of the allele--the salt-sensitive hypertensive rats--have low renin activity compared with the salt-resistant hypertensive rat that does not have this S-allele. Alcohol consumption in rats has also been shown to vary with renin activity, and the possible involvement of renin activity in the genetics of alcohol consumption was suggested by previous work showing that the alcohol-preferring P line of selected rats had low renin levels. In the present study we examined alcohol consumption in a group of inbred Dahl rats, which have a double dose of the S renin allele, and in a group of selected Dahl rats, which have only a single dose of this S-allele. After an initial acclimation period, these two groups were first given daily 1-hr access to ascending concentrations of alcohol (3%, 6%, 8% w/v) over a 34-day period followed by continuous access to alcohol for a further 10 days. Water and food were always available. Regardless of whether alcohol was rationed or continuously available, the rats with the double dose of the S-allele drank significantly more alcohol than the rats that had only a single dose of this allele. These findings suggest that genetically mediated alterations in the renin gene may exert a significant influence on alcohol consumption and may be a component in the etiology of alcoholism."
-What was the clinical outcome of treating 15 patients with high-risk intracranial saccular aneurysms using electrolytically detachable coils?,"Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. Fifteen patients with high-risk intracranial saccular aneurysms were treated using electrolytically detachable coils introduced via an endovascular approach. The patients ranged in age from 21 to 69 years. The most frequent clinical presentation was subarachnoid hemorrhage (eight cases). Considerable thrombosis of the aneurysm (70% to 100%) was achieved in all 15 patients, and preservation of the parent artery was obtained in 14. Although temporary neurological deterioration due to the technique was recorded in one patient, no permanent neurological deficit was observed in this series and there were no deaths. It is believed that this new technology is a viable alternative in the management of patients with high-risk intracranial saccular aneurysms. It may also play an important role in the occlusion of aneurysms in the acute phase of subarachnoid hemorrhage."
-"How did the National Health Service Corps physicians contribute to reducing perinatal mortality rates in Dade County, Florida between 1987 and 1989?","The impact of National Health Service Corps physicians in the lowering perinatal mortality rate in Dade County, Florida. In some parts of Dade County, Florida, perinatal mortality rates have revealed serious problems in the delivery of health care to poor pregnant women. From 1982-1985, the reported perinatal mortality rates varied from 32-36 per 1000 live births, more than double the national average. Under the leadership of the Primary Health Care Consortium of Dade County (a federation of community health centers and other primary care providers), National Health Service Corps obstetricians and pediatricians served inner-city, medically needy patients as part of a coordinated perinatal plan from 1987-1989. Data on fetal and neonatal deaths, collected from census tracts adjacent to the community health centers, were used to study the impact of Corps obstetrician and pediatrician placement. The respective perinatal mortality rates were compared with those of 1986 as historic controls. Within a year, the overall perinatal mortality rate was reduced by 45%. As a result, an estimated 320 lives were saved between 1987-1989. This public health achievement represents a measurable impact due to assignment of National Health Service Corps physicians and can be used as a working model to reduce perinatal mortality in medically underserved communities in the United States."
-How does smoking affect ambulatory systolic blood pressure in hypertensive patients over 50 years old?,"Elevation of ambulatory systolic blood pressure in hypertensive smokers. A case-control study. Although smoking raises blood pressure, the office blood pressure measurements of smokers are the same as, or lower than, those of nonsmokers. To resolve this paradox, we compared the office and 24-hour ambulatory blood pressures of 59 untreated hypertensive smokers with 118 nonsmoking hypertensives matched for age, sex, and race. The office blood pressures of the smoking and nonsmoking groups were 141/93 and 142/93 mm Hg, respectively. The awake ambulatory systolic blood pressure was significantly higher in the smokers (145 vs 140 mm Hg). This difference was greater among patients over the age of 50 years (153 vs 142 mmHg), and absent among patients under 50 years (140 vs 139 mm Hg). Blood pressures during sleep did not differ between the two groups (121/76 vs 123/77 mm Hg). We conclude that, among white hypertensives above the age of 50 years, smokers maintain a higher daytime ambulatory systolic blood pressure than nonsmokers even though blood pressure measured in the office is similar."
-What rare underlying condition was found in a 46-year-old obese and mildly hypertensive patient with bilateral central retinal vein occlusions?,"Bilateral central retinal vein occlusion as an initial manifestation of pseudotumor cerebri. Pseudotumor cerebri, or benign intracranial hypertension, is known to produce visual symptoms. Central retinal vein occlusion has been linked with pseudotumor cerebri but rarely as an initial manifestation. We describe a 46-year-old patient--who was obese and mildly hypertensive with bilateral central retinal vein occlusions--who was subsequently diagnosed as having pseudotumor cerebri. In patients with simultaneous bilateral central retinal vein occlusions, unusual underlying systemic conditions such as pseudotumor cerebri should be considered in the diagnostic evaluation."
-What were the outcomes of laser laparoscopic management for patients with endometriomas in terms of fertility and pelvic pain?,"Laser laparoscopic management of large endometriomas. Forty-seven patients underwent laser laparoscopic management of endometriomas from 3 to 12 cm in diameter. Eighteen patients had infertility, 15 had pelvic pain, and 14 had both. The types of laser used were the carbon dioxide, argon, and potassium-titanyl-phosphate. There were no surgical complications. Twelve of 32 patients with infertility achieved pregnancy after the initial procedure. Subsequently, 2 patients conceived after a second-look procedure. Twenty-three of 30 patients with pelvic pain reported improvement or resolution. We confirm the efficacy of operative laparoscopy using lasers in the management of large ovarian endometriomas."
-What were the key findings regarding family practice residents' attitudes and behaviors towards serum cholesterol screening and management?,"Serum cholesterol: attitudes and behavior of family practice residents BACKGROUND. Given the current health promotion efforts regarding coronary artery disease, more information is needed about residents' attitudes and behaviors that relate to identification and management of patients with elevated serum cholesterol levels. METHODS. Family practice residents from eight US programs (N = 128) were surveyed in 1989 to assess their attitudes and reported practice patterns. Resident survey data were compared, when feasible, to published data from 1986 and 1990 surveys of practicing physicians performed by the National Heart, Lung, and Blood Institute. RESULTS. The use of faculty ""key contacts"" resulted in a 90% response rate (N = 115). Both residents and practicing physicians attributed a high degree of importance to cholesterol as a risk factor. Residents reported more frequent routine screening of middle-aged men than the routine screening rate of practicing physicians in 1986 (P less than .01). Residents reported less frequent screening of younger and older adults than of middle-aged men (P less than .001). Residents' threshold for the use of cholesterol-lowering medication was lower than that of practicing physicians surveyed in 1986, but higher than that of physicians surveyed in 1990. Compared with practicing physicians, residents did not believe they were as well prepared to counsel patients about dietary change or as successful when they tried to help patients make changes; residents reported a significantly higher rate of referral to dietitians (P less than .01). CONCLUSIONS. Residents may need more education regarding screening guidelines for children and young adults. A health promotion skills gap may exist that explains reported discrepancies between self-report and actual behavior and indicates that residency educators may need to pay more attention to fostering dietary assessment and counseling skills in their residents."
-What were the key findings regarding the relationship between calcitonin gene-related peptide (CGRP) concentrations and blood pressure in patients with mild to moderate essential hypertension?,"Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension. Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease."
-How does interleukin-1 (IL-1) contribute to the autocrine growth regulation of the B1 leukemic cell line?,"Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line. A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation."
-"How do cephalometric measurements differ between patients with sleep apnoea, non-apnoeic snorers, and non-snoring control subjects?","Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age."
-What were the four major sources of artifactual staining identified in the study of intermediate filament antibodies in human brain and brain tumors?,"Unexpected immunoreactivities of intermediate filament antibodies in human brain and brain tumors. Immunoreactivities of 35 different monoclonal antibodies (MAbs) that detect intermediate filaments were studied systematically on serial cryostat sections of 14 well-defined human gliomas (five astrocytomas, three oligodendrogliomas, six glioblastomas) and on normal brain. Glial fibrillary acidic protein (GFAP), vimentin, desmin, neurofilaments, and broad-specificity keratin MAbs, as well as MAbs that recognize several or only single keratin polypeptides, were used. Unexpected reactivities were surprisingly frequent. As these may lead to diagnostic confusion and misinterpretation on this material, the authors investigated these phenomena more thoroughly. Four major sources of artifactual staining were found: 1) positive staining attributable to the rabbit gamma G immunoglobulins used in the alkaline phosphatase anti-alkaline phosphatase technique; 2) certain desmin and keratin MAbs cross-reacted with astrocytic glia and with other brain-specific epitopes; 3) technical difficulties; 4) some MAbs directed against neurofilaments and keratins showed unexpected reactivities only on individual anaplastic gliomas. The implications of these findings for intermediate filament typing of neuropathologic material are discussed."
-What behavioral and sensory changes were observed in rats after partial sciatic nerve injury?,"A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Partial nerve injury is the main cause of causalgiform pain disorders in humans. We present here a novel animal model of this condition. In rats we unilaterally ligated about half of the sciatic nerve high in the thigh. Within a few hours after the operation, and for several months thereafter, the rats developed guarding behavior of the ipsilateral hind paw and licked it often, suggesting the possibility of spontaneous pain. The plantar surface of the foot was evenly hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized. There was a sharp decrease in the withdrawal thresholds bilaterally in response to repetitive Von Frey hair stimulation at the plantar side. After a series of such stimuli in the operated side, light touch elicited aversive responses, suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a companion report, we show that these abnormalities critically depend on the sympathetic outflow. Based on the immediate onset and long-lasting perpetuation of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the resemblance of the contralateral phenomena to 'mirror image' pains in some humans with causalgia, we suggest that this preparation may serve as a model for syndromes of the causalgiform variety that are triggered by partial nerve injury and maintained by sympathetic activity."
-Which viruses demonstrated the most significant ability to infect and persist in human joint tissue according to the research?,"Susceptibility of normal human joint tissue to viruses. A model system has been developed to investigate the comparative ability of different viruses to replicate and persist intraarticularly. The viruses chosen for study were rubella, mumps, Coxsackie B4, adenovirus and varicella zoster, a selection of viruses with different degrees of association with joint symptoms in clinical studies. Our results showed that these viruses demonstrated a range of abilities to infect and persist in human joint tissue cultured in vitro. The most arthritogenic viruses, rubella, and to a lesser extent mumps, replicated and penetrated deeply into the synovial membrane. In contrast, the other 3 viruses were much less arthrotropic, and may only induce arthritis by immunopathological mechanisms."
-What is the relationship between intermittent claudication and silent myocardial ischemia in the study?,"Intermittent claudication as a manifestation of silent myocardial ischemia: a pilot study. One hundred consecutive patients with intermittent claudication were screened noninvasively with electrocardiography chest wall mapping stress test and transcutaneous aortovelography during bicycle ergometry. Electrocardiographic chest wall stress testing indicated three-vessel coronary disease in 25 patients and left anterior descending plus circumflex (left main stem equivalent) disease in seven. In these 32 patients transcutaneous aortovelography demonstrated a decrease in stroke distance (an index of cardiac stroke volume) (median, -28%; 90% range, +5% to -48%), and coronary angiography confirmed the presence and severity of the disease. The claudication distance ranged between 50 and 250 meters. After myocardial revascularization or medical therapy a significant increase occurred in the stroke distance after exercise (median, +20; 90% range, +40% to -25%); also a significant increase in the postexercise pressure index and a reduction in the recovery time (p less than 0.01). No change occurred in the ankle/pressure index at rest. Twelve patients were able to walk without being limited by claudication; 15 reported improvement with a two to tenfold increase in claudication distance. No change occurred in three. The results indicate that silent myocardial ischemia is a common finding in patients with intermittent claudication. It produces left ventricular dysfunction and a decrease in stroke volume leading to a large fall in ankle pressure and early onset of claudication during exercise. Niltrates and myocardial revascularization tend to reverse this."
-What unique characteristics were observed in the five children with intractable ulcerating enterocolitis of infancy?,"Intractable ulcerating enterocolitis of infancy. Five children (three boys, two girls) presenting in the first year of life with intractable diarrhoea had a number of features in common. All had ulcerating stomatitis, four had partial villous atrophy on small intestinal biopsy, all had colitis characterised by large ulcers with overhanging edges, and four had severe perianal disease; no stool pathogens were detected. Treatment with steroids, sulphasalazine, and azathioprine was unsuccessful. All five required subtotal colectomy. Four were children of consanguinous marriages, two were siblings of Pakistani origin, two were cousins of Arab origin, and the fifth was Portuguese. Although the diagnoses of Behcet's disease and Crohn's disease were considered, it appears that these children represent a distinct inherited condition affecting the whole gastrointestinal tract, particularly the colon."
-What trend was observed in operative mortality rates for gastric cancer surgery from 1970 to 1990?,"Improving survival in gastric cancer: review of operative mortality in English language publications from 1970. In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner."
-What evidence suggests a potential link between anal cancer and cervical cancer in this study?,"Aetiological parallel between anal cancer and cervical cancer. It has been postulated that an infectious agent and/or specific sexual behaviour is involved in the aetiology of anal cancer, in analogy with the aetiology established for cancer of the cervix. A case-control study of 29,648 women with cancers registered in the Danish Cancer Registry during 1968-87 tested the hypothesis that anal cancer patients were more likely than patients with colon, stomach, or vulva cancer to have had a previous diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cervical cancer. The odds ratio of CIN, adjusted for age and year of diagnosis, for anal vs colon cancer was 5.2 (95% confidence interval [CI] 3.3-8.3), that for anal vs stomach cancer 3.6 (2.1-6.0), and that for anal vs vulva cancer 1.6 (0.9-2.9). The median time from diagnosis of CIN to diagnosis of the registered cancer was 151 months for anal, 112 months for vulva, 114 months for colon, and 126 months for stomach cancer. The association with previous invasive cervical cancer was also investigated; no patient with cervical cancer in this second analysis had been included in the CIN analysis. The odds ratios were similar. In addition, anal cancer patients were significantly more likely to have had cervical cancer than were patients with vulva cancer (odds ratio 1.8 [1.0-3.9]). The strong association between anal cancer and CIN/invasive cervical cancer suggests that these cancers share common risk factors. The association is at least as strong as that between cervical and vulva cancer."
-How did two-dimensional echocardiography and continuous-wave Doppler help diagnose the pseudo-tricuspid stenosis in this case?,Reversible tricuspid stenosis. Demonstration with two-dimensional echocardiography and continuous-wave Doppler. We report a case of pseudo-tricuspid stenosis as a result of extrinsic compression of the tricuspid valve by a large right-sided pericardial effusion. Two-dimensional echocardiography and continuous-wave Doppler enabled accurate noninvasive diagnosis and hemodynamic assessment.
-What did the study reveal about the relationship between Helicobacter pylori antibodies and tissue staining in subjects with atrophic body gastritis?,"Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Helicobacter pylori is rarely found in gastric biopsy specimens from individuals with atrophic gastritis of the body mucosa. To determine if subjects with atrophic body gastritis have evidence of previous infection with H. pylori, immunoglobulin G antibody to H. pylori was measured by enzyme-linked immunosorbent assay in sera of 399 Finnish subjects. In 124 subjects, multiple biopsy specimens from body and antrum had been evaluated for the presence of H. pylori by Giemsa staining. Antibody correlated well with H. pylori staining except in the subgroup with atrophic body gastritis, in whom the prevalence of seropositivity (86%) was significantly greater than the prevalence of positive staining (33%) (P less than 0.001). Twenty-five subjects had positive antibody and negative staining. This group had a significantly higher prevalence of atrophic body gastritis (80%), lower maximal acid output, lower serum pepsinogen I levels, and higher serum gastrin concentrations than did seropositive subjects with H. pylori. These data suggest that most patients with atrophic body gastritis, despite having a low incidence of current overt infection, have been infected with H. pylori at some point in their lives."
-How does the superoxide anion production of neutrophils in Crohn's disease patients differ from that of healthy subjects when stimulated by PMA1 and PMA2?,"Superoxide production by Crohn's disease neutrophils. Neutrophil superoxide anion production was measured in healthy subjects and in patients with quiescent and active Crohn's disease using superoxide dismutase inhibitable cytochrome C reduction. Three stimuli were used: phorbol 12-myristate 13-acetate (PMA1), phorbol 20-oxo-20-deoxy 12-myristate 13-acetate (PMA2), and Candida albicans in serum. Normal neutrophils produced significantly more superoxide anion than Crohn's disease neutrophils with both PMA1 (mean (SD) 9.6 (2.2) v 8.6 (1.8) nmol/10(6) cells/5 minutes, p = 0.04) and PMA2 (1.8 (0.8) v 0.8 (0.77) nmol/10(6) cells/5 minutes, p = 0.00004). With C albicans in serum, normal and Crohn's disease neutrophils produced similar amounts of superoxide anion (4.4 (1.5) v 4.3 (1.7) nmol/10(6) cells/30 minutes, not significant). Results were independent of disease activity. Superoxide anion production by PMA-stimulated Crohn's disease neutrophils is significantly lower than by normal neutrophils."
-What changes were observed in the circulating levels of the N-terminus of the atrial natriuretic factor (ANF) prohormone in patients with pheochromocytomas?,"Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas. To investigate the possible relationship of hypertension and the N-terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas."
-What is the purpose of using human recombinant erythropoietin in the preoperative setting described in this case report?,"Use of human recombinant erythropoietin to correct severe preoperative anemia. The risks of homologous blood transfusion are well known. Herein, we describe the successful preoperative use of human recombinant erythropoietin to correct severe anemia in a patient refusing transfusion. This case report emphasizes the important perioperative role human recombinant erythropoietin may play in the future."
-How do staging procedures and tumor stage differ between academic and community hospitals for lung cancer patients?,"Cancer staging may have different meanings in academic and community hospitals. We investigated differences in lung cancer care and outcome between academic and community settings for all lung cancer patients diagnosed during 1973-1976 in New Hampshire and Vermont. Trained abstracters reviewed hospital charts to record personal, diagnostic, and clinical information, and survival was determined for all patients through the end of 1979. Patients diagnosed in university hospital cancer centers underwent more staging procedures and tended to be assigned to a higher stage than similar patients diagnosed in community hospitals. When tumor stage was considered as a covariable in a survival analysis, these patients appeared to have a lower mortality rate both for non-small cell tumors (mortality rate ratio, 95% confidence interval = 0.81, 0.71-0.91) and for small cell tumors (0.71, 0.55-0.91). When functional status rather than tumor stage was used to adjust for disease severity, there was no apparent survival advantage for university patients with non-small cell cancer (0.96, 0.85-1.09) and the lower mortality for small cell cancers (0.76, 0.59-0.97) was attenuated, although still statistically significant. We conclude that inconsistently-collected data on clinical stage can complicate comparisons of prognosis between cancer patients from different types of hospitals and that measures of performance status may be more useful indicators of disease severity in population based studies."
-How does lumbar puncture affect intracranial cerebrospinal fluid (CSF) volume and its relationship to post-lumbar puncture headache?,"Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. Post-lumbar puncture (LP) headache may be due to ""low CSF pressure"", leading to stretching of pain sensitive intracranial structures. The low intracranial pressure is secondary to net loss of intracranial CSF. It has, however, not been possible to measure intracranial CSF volume accurately during life until recently. Intracranial CSF volume can now be measured non-invasively by a MRI technique. The changes in intracranial CSF volume were studied in 20 patients who had LP. Total intracranial CSF volume was reduced in 19 of the 20 patients 24 hours after LP (range -1.8 mls to -158.6 mls). Most of the CSF was lost from the cortical sulci. Very large reductions in intracranial CSF volume were frequently related to post-LP headache but some patients developed headache with relatively little alteration in the intracranial CSF volume. There was not a measurable change in position of the intracranial structures following LP."
-What is the prognostic significance of proliferating cell nuclear antigen (PCNA) in gastric carcinoma according to the study?,"Prognostic value of proliferating cell nuclear antigen in gastric carcinoma. A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising."
-What is the recommended approach for treating renal oncocytomas based on the Australian experience described in the context?,"Renal oncocytomas--an Australian experience. A review was made of 24 cases of renal oncocytoma seen between 1978 and 1989. There was considerable overlap between the clinical presentation of renal oncocytomas and renal carcinomas. Although pre-operative radiological, cytological and pathological investigations may suggest the presence of an oncocytoma, these studies cannot make a definitive diagnosis. We recommend that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise."
-What were the key findings of the study comparing the effectiveness of metoprolol and nifedipine in patients with mixed angina?,"Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine. The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve."
-What are the primary indications for liver transplantation according to the context?,"Liver transplantation for alcoholic liver disease, viral hepatitis, and hepatic neoplasms. In closing, it is important to note that the indications for liver transplantation are not static but rather are remarkably dynamic and capable of change over time. Thus yesterday's major indications can become relative contraindications, while yesterday's absolute contraindications have become today's nuisances. The goal for physicians who care for individuals with problems such as alcoholic liver disease, viral hepatitis, and hepatic cancer should be to develop new strategies of care that will ultimately eliminate these diseases as problems, rather than eliminating individuals with such health problems from currently available health options. In other words, physicians who accept the responsibility for a patient's life should be searching for the best form of therapy available for their patient rather than examining the reasons that exist for limiting one's choice in health care."
-Which drug was more effective in converting paroxysmal atrial fibrillation to sinus rhythm: propafenone or flecainide?,"The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainide (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p less than 0.02). If atrial fibrillation was present less than or equal to 24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p less than 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS). Mean time to conversion was 16 +/- 10 min in the propafenone group versus 18 +/- 13 min in the flecainide group (p = NS). QRS lengthening (83 +/- 15 to 99 +/- 20 ms) was observed only in the patients treated with flecainide (p less than 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p less than 0.01). In conclusion, at a dose of 2 mg/kg in 10 min, flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter."
-What potential complication can tissue plasminogen activator (t-PA) cause during treatment of acute myocardial infarction?,"Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable."
-What are the primary early mechanical features observed in cemented femoral components of hip arthroplasties?,"The initiation of failure in cemented femoral components of hip arthroplasties. We studied 16 femora retrieved at post-mortem from symptomless patients who had a satisfactory cemented total hip arthroplasty from two weeks to 17 years earlier, with the aim of delineating the initial mechanisms involved in loosening. Only one specimen showed radiographic evidence of loosening; the other 15 were stable to mechanical testing at 17.0 Nm of torque. In all 16 specimens, the cement-bone interface was intact with little fibrous tissue formation. By contrast, separation at the cement-prosthesis interface and fractures in the cement mantle were frequent. The most common early feature was debonding of the cement from the metal, seen at the proximal and distal ends of the prosthesis. Specimens which had been in place for longer also showed circumferential fractures in the cement, near the cement-metal interface, and radial fractures extending from this interface into the cement and sometimes to the bony interface. The most extensive cement fractures appeared to have started at or near sharp corners in the metal, or where the cement mantle was thin or incomplete. Fractures were also related to voids in the cement. The time relationship in this series suggested that long-term failure of the fixation of cemented femoral components was primarily mechanical, starting with debonding at the interface between the cement and the prosthesis, and continuing as slowly developing fractures in the cement mantle."
-"What was the purpose of studying the vasomotor response of coronary artery segments in patients with syndrome X, chronic stable angina, and control subjects?","Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X) The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments."
-What is Henoch-Schonlein purpura and how does it affect children according to the surgical evaluation in this study?,"Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived."
-What were the key findings of the study regarding peritoneal factors in rabbits with surgically induced endometriosis?,"Surgically induced endometriosis does not alter peritoneal factors in the rabbit model. OBJECTIVE: It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN: Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS: There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS: These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue."
-What are the two distinct patterns of venous pulse observed in patients with dilated cardiomyopathy?,"Jugular venous 'a' wave in dilated cardiomyopathy: sign of abbreviated right ventricular filling time. OBJECTIVE--To study the mechanisms underlying the high venous pressure often seen in patients with dilated cardiomyopathy. DESIGN--Retrospective and prospective examination of the pattern of flow in the superior vena cava, cardiac echo-Doppler studies, and recordings of the jugular venous pulse. SETTING--A tertiary referral cardiac centre. PATIENTS PARTICIPANTS--23 patients with dilated cardiomyopathy, all with functional mitral and tricuspid regurgitation. RESULTS--Two patterns of venous pulse were seen: a dominant 'a' wave and 'x' descent, with systolic flow in the superior vena cava (group 1, n = 11), and a dominant 'v' wave with 'y' descent and diastolic flow in the superior vena cava (group 2, n = 12). A comparison of group 1 and group 2 showed: age (mean (SD] 58 (12) v 61 (6) years, left ventricular end diastolic dimension 7.0 (0.7) cm in both groups, right ventricular short axis 3.3 (0.6) v 3.6 (0.5) cm and long axis 7.3 (0.5) v 7.1 (0.7) cm, and duration of tricuspid regurgitation 350 (65) v 370 (50) ms. The RR interval (550 (100) v 680 (80) ms) and right ventricular filling time (150 (30) v 290 (50) ms) were significantly shorter in group 1. In all patients in group 2 right ventricular filling time was more than 200 ms with separate E and A waves on the tricuspid Doppler echocardiogram, while in all group 1 patients it was less than 200 ms with a single summation peak. In nine patients in group 1, the right ventricular filling time was limited by prolonged tricuspid regurgitation and in the remaining two by prolonged isovolumic relaxation time (215 (80) ms), so that it was consistently significantly less than that of the left ventricle. CONCLUSION--In patients with dilated cardiomyopathy, right ventricular filling time may be so short that it limits stroke volume. Such patients can be recognised by a dominant 'a' wave on the jugular venous pulse. Patients in whom the right ventricular filling time was longer showed a dominant 'v' wave. Both groups can present as ""congestive heart failure""."
-How does the response of atrial natriuretic factor (ANF) differ between patients with and without right ventricular (RV) infarction after volume expansion?,"Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction. To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction."
-Which virulence characteristics were independently associated with Escherichia coli strains causing acute pyelonephritis according to the multivariate statistical analysis?,"Relative importance of eight virulence characteristics of pyelonephritogenic Escherichia coli strains assessed by multivariate statistical analysis. We have previously reported univariate statistical analysis of the prevalences of putative virulence determinants in Escherichia coli isolated from children and adults with acute pyelonephritis. The expression of P-fimbriae, cell surface hydrophobicity, mannose resistant haemagglutination, haemolysin synthesis, cytotoxic necrotizing factor production and aerobactin mediated iron uptake occurred more often in a collection of 115 Escherichia coli strains isolated from children and women with acute non-obstructive pyelonephritis compared to 96 strains isolated from the commensal fecal flora. With the aim to study which of these virulence markers were independently associated with strains causing infection we performed a multivariate statistical analysis with the data from these strains. The previously proposed virulence factors, expression of type 1 fimbriae and adhesion to HeLa cells were also included in the analysis. P-fimbriae, mannose resistant haemagglutination and the production of haemolysin were, in the multivariate analysis, associated with strains isolated from patients with acute pyelonephritis."
-What was the mean time to sensation of warmth in the spinal and extradural groups during the study?,"Sensitivity, specificity and predictive value of the sensation of warmth as a method of detecting inadvertent subarachnoid injection of local anaesthetic when performing extradural blocks. In order to test if the rate of onset of sensation of warmth in the legs after the injection of 0.5% bupivacaine might discriminate between subarachnoid and extradural injection, 150 urological patients were allocated randomly to receive either spinal anaesthesia with isobaric (IS) or hyperbaric (HS) 0.5% bupivacaine, or extradural anaesthesia with isobaric 0.5% bupivacaine. The volume of the local anaesthetic for spinal anaesthesia and for the extradural test dose was 3-4 ml. The patients were asked to report at once if they had a sensation of warmth in the legs during or after injection of local anaesthetic. The mean time to the sensation of warmth was significantly shorter in the spinal groups (80 (SEM 10) s in IS and 76 (8.0) s in HS) than in the extradural group (558 (38) s). However, six patients in the IS and two in the HS group had no sensation of warmth."
-What is the purpose of the document developed by the Centers for Disease Control (CDC) regarding HIV and hepatitis B virus transmission?,Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. This document has been developed by the Centers for Disease Control (CDC) to update recommendations for prevention of transmission of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in the health-care setting. Current data suggest that the risk for such transmission from a health-care worker (HCW) to a patient during an invasive procedure is small; a precise assessment of the risk is not yet available. This document contains recommendations to provide guidance for prevention of HIV and HBV transmission during those invasive procedures that are considered exposure-prone.
-What was the main purpose of the study regarding pancreatic pseudocyst amylase concentration?,"The value of pancreatic pseudocyst amylase concentration in the detection of pseudocyst communication with the pancreatic duct. The aims of the study were to compare the results of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous cystopancreatography (PCP) in the detection of the communication between the pancreatic pseudocyst and the pancreatic duct, and to assess the reliability of the increased amylase concentration in the pseudocyst content as an indicator of the existence of communication between the pancreatic pseudocyst and the pancreatic duct system. Forty-three patients were included in the study. Pseudocystic fluid content was obtained by percutaneous aspiration. Twenty-four patients had pseudocyst amylase concentrations above 64 Wolgemuth units (WU), and 19 patients had less than 64 WU. The communication between pseudocyst and the pancreatic duct was determined in 22 patients by ERCP and in 13 patients by PCP, all in the group with increased pseudocyst amylase concentration. Due to high sensitivity and specificity of pseudocyst amylase concentration for the existence of pseudocyst communication with the pancreatic duct, we conclude that guided percutaneous aspiration of the pancreatic pseudocyst with the determination of amylase concentration in the fluid can replace ERCP as a method of choice for the detection of pseudocyst communication with the pancreatic duct."
-What are the key findings from the review of lumbar discectomies regarding intestinal injury?,"Intestinal injury after lumbar discectomy. In a review of 5,200 lumbar discectomies performed from 1974 to 1989, two patients sustained a ventral perforation of the disc space followed by isolated small intestinal injury. Both patients underwent lumbar discectomy at the lumbosacral junction and presented with signs and symptoms of acute abdominal distress within three days after the operation. At surgical laparotomy, small tears were noted in the ileum, which were closed primarily. The patients had an uneventful recovery. The results of a review of 11 instances reported in the literature suggest that isolated intestinal injuries usually occur postoperatively at the lumbosacral junction and involve the small intestine. Factors, such as body habitus, surgical experience, patient positioning and types of instruments, as well as the use of a surgical microscope, do not appear to modify the risk of intestinal injury. After discectomy, patients may present with acute abdominal signs and symptoms or chronic wound infections. Work-up studies include evaluation of vascular structures and ureters either roentgenographically or at abdominal exploration. A high index of suspicion and adequate disc space visualization during discectomy may reduce the incidence of this complication."
-What percentage of patients achieved union in the salvage operations for nonunion following total ankle arthrodesis?,"Salvage of nonunion following ankle arthrodesis for failed total ankle arthroplasty. Revision operations for nonunion following total ankle arthrodesis for total ankle arthroplasty (TAA) were reviewed in ten patients. Operations averaged 2.0 years after prior arthrodesis attempts and featured external fixation in seven, internal fixation in one, percutaneous pin fixation in one, and cast immobilization only in one. Bone graft was used in seven. Union was achieved in 78%. The one complication was an infection in a patient with prior sepsis. The results were considered excellent in three, good in one, fair in three, and poor in two of the nine patients with adequate follow-up evaluation (average, 7 years). Despite successful arthrodesis, residual symptoms were common because of factors such as hindfoot degenerative arthritis and malalignment."
-What was the main finding of the study regarding the effects of low to moderate lead exposure on vitamin D metabolism and bone mineral content in young children?,"Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure. One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure."
-What was the overall response rate and median survival time in this Phase II pilot study of weekly cisplatin-based induction regimen for extensive non-small cell lung cancer?,"A weekly cisplatin-based induction regimen for extensive non-small cell lung cancer. A Southwest Oncology Group study. The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach."
-What is the significance of intercellular adhesion molecule 1 expression in primary biliary cirrhosis and primary sclerosing cholangitis?,"Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis. It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis."
-What technique is described for salvaging thrombosed forearm polytetrafluoroethylene (PTFE) vascular access grafts?,"Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting. A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction."
-How did dopexamine compare to dopamine in preventing renal impairment in patients undergoing orthotopic liver transplantation?,"A comparison of dopexamine and dopamine to prevent renal impairment in patients undergoing orthotopic liver transplantation. The efficacy of low-dose dopamine as a renal protective agent was compared with that of dopexamine in patients who underwent orthotopic liver transplantation. Twelve patients who received a continuous infusion of dopexamine (1-3 micrograms/kg/minute) were matched for age, diagnosis, pre-operative creatinine clearance and blood loss with 12 patients who received a low-dose infusion of dopamine (2 micrograms/kg/minute). The catecholamine infusion was started after induction of anaesthesia and continued for 48 hours after surgery. Patients in the dopexamine group had less evidence of renal impairment and failure than those in the dopamine group during 7 days after the operation, although the differences between groups did not achieve statistical significance. Similarly there were no significant differences between the two groups in peri-operative urine output, urine/plasma osmolality ratio or creatine clearance. Dopexamine is at least as effective as dopamine for renal protection in patients who undergo liver transplantation."
-How does sodium benzoate administration affect the urinary carnitine profile?,"Alteration of urinary carnitine profile induced by benzoate administration. To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia."
-What are the key findings of magnetic resonance imaging (MRI) in patients with spinal trauma within 3 weeks and more than 3 weeks after injury?,"Magnetic resonance imaging of spinal trauma. A retrospective series of 118 magnetic resonance examinations of 110 patients who had sustained previous spinal trauma is reported. Examinations performed within 3 weeks of trauma showed extraspinal soft tissue (including ligamentous) injury in 48% and intraspinal lesions in 61% (mostly consisting of extradural haematoma and spinal cord contusion). In examinations performed more than 3 weeks after injury intraspinal abnormalities were shown in 51% and these represented spinal cord compression, atrophy, myelomalacia and syringohydromyelia. Magnetic resonance imaging has the unique capability of displaying non-invasively the late sequelae of spinal trauma permitting simultaneous evaluation of the extra-spinal soft tissues, vertebral column and spinal cord. It is therefore recommended as the technique of choice in the investigation of patients who have sustained previous spinal injury, particularly those with neurological deficit. In the acute phase potentially remediable causes of neurological impairment such as disc herniation or extradural haematoma can be identified. Signal changes in the cord may allow the prognosis for neurological recovery to be established. In the later stages sequelae such as cord atrophy, myelomalacia and syringohydromyelia are accurately identified and surgical therapy may be guided, where appropriate."
-What changes were observed in the density of glomerular atrial natriuretic factor binding sites in bile duct-ligated rats with ascites?,"Altered density of glomerular binding sites for atrial natriuretic factor in bile duct-ligated rats with ascites. The renal response to atrial natriuretic factor is blunted in cirrhosis with ascites. This might be due to alterations of renal receptors for atrial natriuretic factor. Therefore density and affinity of glomerular atrial natriuretic factor binding sites of bile duct-ligated rats with ascites (n = 10) and of sham-operated controls (n = 10) were determined. Glomerular atrial natriuretic factor binding sites were identified to be of the B-(""biologically active"") and C-(""clearance"") receptor type. Discrimination and quantitative determination of B and C receptors for atrial natriuretic factor were achieved by displacement experiments with atrial natriuretic factor(99-126) or des(18-22)atrial natriuretic factor(4-23), an analogue binding to C receptors only. Density of total glomerular atrial natriuretic factor binding sites was significantly increased in bile duct-ligated rats (3,518 +/- 864 vs. 1,648 +/- 358 fmol/mg protein; p less than 0.05). This was due to a significant increase of C-receptor density (3,460 +/- 866 vs. 1,486 +/- 363 fmol/mg protein; p less than 0.05), whereas density of B receptors was not significantly different in bile duct-ligated rats (58 +/- 11 vs. 162 +/- 63 fmol/mg protein). Affinity of atrial natriuretic factor to its glomerular binding sites did not differ significantly between both groups. These data suggest that an altered glomerular atrial natriuretic factor receptor density could be involved in the renal resistance to atrial natriuretic factor in cirrhosis with ascites."
-"How did the treatment approach for medulloblastoma change between 1970-1983 and 1984, and what impact did this change have on patient outcomes?","The change in patterns of relapse in medulloblastoma. The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases."
-What type of graft was used for venous reconstruction in the superior vena cava replacement during mediastinal and pulmonary tumor resections?,"Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors. The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease."
-"What is the purpose of using a free gastric mucosal flap with microvascular transfer in the reconstruction of malignant lesions in the oral cavity, base of tongue, and oropharynx?","Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered."
-What was the purpose of the study on intravenous heme-albumin in acute intermittent porphyria?,"Intravenous heme-albumin in acute intermittent porphyria: evidence for repletion of hepatic hemoproteins and regulatory heme pools. The purpose of this study was to assess effects of heme administered intravenously, complexed to human serum albumin, on activities of the hepatic hemoproteins, cytochrome(s) P-450, and tryptophan pyrrolase, and on the size of the heme pool that regulates activity of 5-aminolevulinate synthase. Effects were compared in six normal women and four women with acute intermittent porphyria. All porphyric subjects over-excreted heme precursors and had histories of acute neurovisceral porphyric attacks. All subjects were placed on a constant daily diet that included at least 3 g carbohydrate/kg body weight and sufficient total intake to provide 1.4 times the estimated resting energy expenditure. Urinary excretions of 5-aminolevulinate, porphobilinogen, porphyrins, and metabolites of tryptophan were measured daily before, during, and after infusions of heme-albumin. In the porphyric subjects, intravenous heme [4 mg (6.1 mumol)/kg body weight (BWt) with equimolar albumin], given daily for 4 days, markedly reduced overexcretion of 5-aminolevulinate, porphobilinogen, and porphyrins, indicating repletion of the regulatory heme pool. The heme infusions also decreased mean urinary excretion of 5-hydroxyindoleacetic acid from 4.9 to 2.9 mg/g creatinine per day, suggesting increased activity of hepatic tryptophan pyrrolase, the rate-controlling enzyme for metabolism of tryptophan to products not in the serotonin-5-hydroxyindoleacetic acid pathway. Heme-albumin infusions were without detectable effects on excretions of heme precursors or tryptophan metabolites in normal subjects. In contrast, in both normals and porphyrics, heme-albumin infusions significantly increased rates of antipyrine metabolism (by 159% and 330%, respectively), suggesting increased activities of cytochrome(s) P-450 were produced by the infusions. The infusions were well tolerated; no subject developed thrombophlebitis or bleeding. We conclude that such infusions are safe and effective in repleting deficient heme pools and hemoproteins in patients with acute porphyria, and that activities of cytochrome(s) P-450 in normal subjects may also be increased by heme administration. The therapeutic effect of heme in acute porphyria probably relates to its ability to decrease overproduction of precursors of heme or serotonin, as the result of its increasing critical cellular heme pools."
-How did the researchers use anti-V region antibodies to study cutaneous T cell lymphomas and leukemias?,"Anti-V region antibodies as ""almost clonotypic"" reagents for the study of cutaneous T cell lymphomas and leukemias. Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an ""almost clonotypic"" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL."
-What was the effect of recombinant human erythropoietin (rHuEPO) on anemia correction in predialysis patients with chronic renal failure?,"Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group [published erratum appears in Am J Kidney Dis 1991 Sep;18(3):420] One hundred seventeen patients with anemia related to chronic renal failure not severe enough to require maintenance dialysis were randomly assigned to receive recombinant human erythropoietin (rHuEPO; 50, 100, or 150 U/kg body weight) or placebo intravenously (IV) three times a week for 8 weeks or until their anemia was corrected. Correction of anemia (hematocrit of 40% for males, 35% for females) occurred in 87% of those given 150 U/kg, 64% of those given 100 U/kg, 46% of those given 50 U/kg rHuEPO and in 3% of the placebo group. Energy levels and work capacity improved significantly in the group with corrected anemia compared with the group with uncorrected anemia. rHuEPO appeared to be well tolerated. There was no evidence that rHuEPO therapy accelerated the deterioration of renal function as measured by serum creatinine and reciprocal of serum creatinine compared with placebo treatment. However, it is essential that blood pressure and hematocrit be carefully monitored, particularly in hypertensive patients, to prevent the development of complications associated with hypertension."
-How has the understanding and diagnosis of preeclampsia changed over time according to the given context?,"Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased."
-What is the relationship between non-cirrhotic portal hypertension and IgA nephropathy in the reported case?,IgA nephropathy in non-cirrhotic portal hypertension. Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease.
-What are the four types of diarrheal illnesses identified in rural Bangladesh according to folk terminology?,"Folk terminology for diarrhea in rural Bangladesh. Diarrhea, a descriptive term used in medical science for a variety of clinical diseases, denotes an illness that is categorized differently and known by numerous terms in various cultures. These diversified classifications and terminologies are based on the symptoms of diarrheal disorders, their perceived etiology, and their treatment. In Bangladesh, four types of illnesses with names derived from folk terminology have been identified for which the clinical symptoms resemble those of diarrhea. These include dud haga, which is due to ingestion of breast milk by infants; ajirno, which is due to overeating; amasha, a mucoid diarrhea; and daeria, which is severe watery diarrhea or cholera. Use of the word diarrhea in epidemiologic evaluations was discovered to be problematic; people confused this term with daeria, which accounted for only 5% of all episodes of diarrhea. The implications of such epidemiologic information for a large-scale program of oral rehydration therapy are also discussed."
-What is the significance of using 31P localized magnetic resonance spectroscopy in the assessment of head and neck tumors?,"31P localized magnetic resonance spectroscopy of head and neck tumors--preliminary findings. Magnetic resonance imaging (MRI) is a powerful tool for accurate assessment of the anatomic extent of head and neck neoplasms. The development of methods for spatial localization by use of multiply tuned radio frequency coils that permit the measurement of multiple nuclear MR spectra (1H and 31P) from precisely defined volumes of interest has provided a basis for integrating spectroscopy into the clinical MRI examination. This offers a means for noninvasive monitoring of relative concentrations of mobile metabolites within a tumor. With the use of imaging to determine proper coil placement, a test-retest variance of about 17% is seen on MR spectroscopy. Data are presented from MRI/MRS studies for four head and neck lesions: (1) a squamous cell carcinoma of the lip; (2) a juvenile angiofibroma extending into the nasal cavity; (3) a massive chondrosarcoma of the nasal septum; and (4) a cervical nodal metastasis of a squamous cell carcinoma of the pharynx. Spectra are evaluated by comparison of relative concentrations of phosphorus compounds. The concentrations of phosphomonoesters and phosphodiesters are significantly higher in the neoplasms studied than in normal skeletal muscle. The developing role of integrated MRI/MRS to monitor the response of malignant neoplasm to radiation therapy is discussed."
-How did Streptococcus pneumoniae infection affect the metabolic responses and performance capacity of rats during swimming exercise?,"Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats. The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection."
-What are the current challenges in treating congestive heart failure and its high mortality rate?,"Congestive heart failure. New frontiers. Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome."
-How was leuprolide acetate used to manage symptoms of severe fibrocystic breast disease in the study?,Management of severe fibrocystic disease of the breast with leuprolide acetate. Symptoms of severe fibrocystic disease of the breast were successfully ameliorated in two patients as a result of treatment with daily subcutaneous LA without adverse effects. A state of drug-induced hypogonadotropic hypogonadism appears to be responsible for the clinical effect and is further suggestive of the hormonal dependence of this common disorder.
-Are surgical procedures performed by residents as safe as those performed by attending staff?,"Safety of surgical procedures performed by residents. The outcome of surgical procedures on the gallbladder performed by surgical residents in a university hospital was compared with the outcome of those performed by the attending staff. More than 60% of the operations (643/1084) were done by residents under the direct supervision of the attending surgeon. We found no differences in the rate of technical complications, postoperative morbidity and mortality, or length of hospitalization between the two groups. Thus, resident surgery under appropriate guidance is safe and does not compromise the quality of patient care or operative outcome."
-What complications did the patients with chickenpox pneumonia experience in this case report?,"Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation."
-How does acetylcholine influence pancreastatin secretion in the QGP-1N cell line?,"Acetylcholine regulates pancreastatin secretion from the human pancreastatin-producing cell line (QGP-1N). Studies were made of pancreastatin (PST) secretion from a human PST-producing cell line (QGP-1N) in response to various secretagogues. Cells with immunoreactivity for PST were observed in monolayer cultures of QGP-1N cells. Carbachol stimulated PST secretion and the intracellular Ca2+ mobilization concentration dependently in the range of 10(-6)-10(-4) M. The PST secretion and Ca2+ mobilization induced by carbachol were inhibited by atropine. The calcium ionophore (A23187) stimulated PST secretion. However, cholecystokinin and gastrin-releasing peptide did not stimulate either PST secretion or Ca2+ mobilization. Secretin also did not stimulate PST secretion. The glucose concentration in the culture medium had no effect on PST secretion. These results suggest that PST secretion is mainly regulated by acetylcholine through a muscarinic receptor, and that an increase in intracellular Ca2+ plays an important role in stimulus-secretion coupling in QGP-1N cells."
-What are the potential causes of delayed visual loss following head trauma according to the study?,"Delayed visual loss due to trauma of the internal carotid artery. The group of six patients in this study experienced delayed visual loss following head trauma. Visual loss occurred from 1 day to 13 years after the initial injury. All patients suffered indirect trauma to the internal carotid artery resulting in formation of either an aneurysm or pseudoaneurysm or a carotid-cavernous fistula. Review of the radiologic and clinical findings was performed in six patients. The diagnosis was established by computed tomography, magnetic resonance imaging, and angiography. All patients had follow-up clinical evaluation and imaging studies. Treatment by neurosurgical or interventional neuroradiologic procedures resulted in significant visual improvement in five patients. Different pathophysiologic mechanisms could be correlated with the delayed visual loss produced by the two types of lesions. The pathologic changes associated with the aneurysms/pseudoaneurysms included direct compression of optic nerves and/or chiasm and intracranial hematoma. A carotid-cavernous fistula caused delayed visual loss by either hematoma at the orbital apex or compression of the chiasm and/or optic nerves by saccular dilatation of the cavernous sinus. The delayed onset of decreased vision following head trauma should alert the physician to the possibility of a traumatic aneurysm/pseudoaneurysm or a carotid-cavernous fistula. Different neuro-ophthalmologic symptoms can usually be correlated with the pathologic changes demonstrated by neuroimaging procedures."
-What were the key findings regarding exercise-related sudden ischemic death in the study of 17 resuscitated victims?,"Clinical and angiographic observations on resuscitated victims of exercise-related sudden ischemic death. The clinical and angiographic findings of 17 resuscitated victims of exercise-related sudden ischemic death are reported in an attempt to elucidate the mechanism(s) of these deaths. Ten survivors developed cardiac arrest during or after sporting activities (group A) and 7 others during or after an exercise stress test (group B). There were 15 men and 2 women. The mean age of group A was 46 years and of group B 55 years. Coronary risk factors, as well as previous angina and myocardial infarction, were more frequent in group B. Only 3 of the 17 survivors had anginal symptoms before sudden death. Sudden death in group A was associated with acute myocardial infarction in 8 and unstable angina in 2 and was associated in group B with acute myocardial infarction in 2, unstable angina in 3 and silent ischemia in 2. Coronary angiography was acutely performed in 15 patients. In most patients the ischemia-related coronary artery was totally or subtotally occluded. Clinical and angiographic findings indicate that exercise-related sudden ischemic death was due to an acute coronary event--in most cases unexpected and unpredictable. It is suggested that exercise-induced intracoronary changes were probably responsible for the development of acute coronary (sub)occlusion and sudden death."
-What is the significance of the Shope papilloma-carcinoma complex in rabbits for understanding human papillomavirus-associated malignancies?,"Establishment from Shope carcinoma induced in an inbred rabbit of culture cell lines with various potentials for differentiation and tumorigenicity. Shope papillomas induced by cottontail rabbit papilloma-virus (CRPV) in domestic rabbits frequently regress spontaneously or, failing to do so, convert into squamous cell carcinomas at a high rate. This papilloma-carcinoma complex in rabbits provides an experimental model for human papillo-mavirus-associated malignancies. The aim of this study was to prepare an experimental system in inbred rabbits by establishing culture cell lines of the tumor. Squamous cell carcinoma developed from a Shope papilloma that had been induced 6 months previously by inoculating CRPV into an inbred B/J rabbit. By in vitro culturing of the tumor cells, cell lines with potentials for terminal differentiation and tumorigenicity were established. Cloning yielded sublines that varied in these potentials and possessed episomal and integrated CRPV genomes as revealed by Southern hybridization in both one- and two-dimensional electrophoresis. Major CRPV-specific transcripts were similarly observed both in well-differentiated and in poorly differentiated sublines. Immunofluorescence with syngeneic rabbit antibody against tumor-specific antigens localized such antigens mainly in the nuclei of the cells of these sublines. This experimental system allows experiments that were not feasible in randomly bred rabbits."
-How do limited access to healthcare and cultural barriers impact neurological care for minority populations in the United States?,"Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies."
-What is xeroderma pigmentosum (XP) and how does it affect patients neurologically?,"Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system."
-What morphometric findings were observed in the brain stems of patients with Joseph disease using computed tomography?,"Brain stem atrophy in Joseph disease: a morphometric study using two-dimensional (area) measurement by computed tomography. Eight Japanese patients with Joseph disease were studied using computed tomography (CT). Morphometric analysis using the two-dimensional (area) measurement by CT was performed in the infratentorial region. The brain-stem index, an index of brain-stem atrophy or pontine atrophy, revealed a significant decrease (P less than 0.01), with a mean of 66.7% when compared with 16 control subjects. The patients showed a significant increase (P less than 0.01), with a mean of three times that of the controls in the fourth ventricular index, an index of fourth ventricular dilatation. There were no differences in the cerebellar index, an index of cerebellar atrophy, between these patients and the controls, although the patients had an increased number of visible cerebellar vermian (2.0, SD 0.7) and hemispheric sulci (2.6 SD 0.6) as compared with the controls (vermian sulci: 0.4, SD 0.7: hemispheric sulci: 0). These data indicate severe pontine atrophy, fourth ventricular dilatation with mild involvement of the cerebellum and correlate well with the common pathological features of Joseph disease. The present morphometric evaluation by CT may be useful in the clinical diagnosis of Joseph disease."
-How does the day of the menstrual cycle affect the incidence of postoperative nausea and vomiting in women undergoing laparoscopy?,"The incidence of postoperative nausea and vomiting in women undergoing laparoscopy is influenced by the day of menstrual cycle. Postoperative nausea and vomiting is a major cause of postoperative morbidity. It can lead to increased recovery time, delaying patient discharge and an increase in hospital costs. Past studies have shown that postoperative nausea and vomiting is more frequent in women than men, appears to elevate around the time of menarche and is reduced around the time of menopause. This retrospective review of a one-year experience of laparoscopic tubal ligation at our institute examined the effect of menstrual cycle on postoperative nausea and vomiting. The anaesthetic and surgical techniques were consistent for all patients. Patient data included age, weight, last day of menstrual cycle, the length of anaesthetic, the dose of inhalational agent, the dose of narcotic, emesis on emergence and whether or not droperidol was used. Of the the 235 patients in the study, the incidence of nausea and vomiting was 28%. One hundred fifty-eight had had no preoperative antiemetic and 77 had received droperidol. These two groups were analyzed separately. The incidence in the group not receiving droperidol was 33.5% and in the droperidol group, 16.9% (P less than 0.01). The incidence of nausea and vomiting was higher on the first eight menstrual days (51.6 vs 21.6, P less than 0.001), was highest on day five of the menstrual cycle and lowest on days 18, 19, and 20 where there was no nausea and vomiting. Droperidol reduced the incidence of postoperative nausea and vomiting but the variation in postoperative nausea and vomiting during the cycle persisted."
-What percentage of patients survived long-term after receiving the Bio-Medicus ventricular assist device during cardiac surgery?,"Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients."
-What are the key applications of PET scanning in clinical oncology?,"The applications of PET in clinical oncology. With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology."
-What were the key findings regarding the response of patients with systemic sclerosis to nifedipine and captopril in this study?,"Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril. PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed ""borderline"" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder."
-How did oral administration of myelin antigens affect the progression of experimental autoimmune encephalomyelitis in Lewis rats and strain 13 guinea pigs?,"Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the Lewis rat and strain 13 guinea pig. Oral administration of proteins is a long-recognized method of inducing antigen-specific peripheral immune tolerance. We previously showed that oral administration of myelin basic protein suppresses monophasic experimental autoimmune encephalomyelitis in the Lewis rat when it is given in association with immunization and prior to disease onset. As a potential therapy for human autoimmune disease, it is crucial to determine whether oral tolerance can ameliorate an ongoing immune response. We therefore asked whether oral administration of myelin antigens, after sensitization and disease expression has occurred, could affect immunological, clinical, or pathological features of experimental autoimmune encephalomyelitis. Chronic relapsing experimental autoimmune encephalomyelitis was induced in the Lewis rat and strain 13 guinea pig by immunization with whole guinea pig cord homogenate, complete Freund's adjuvant, and Mycobacterium tuberculosis. Following recovery from the first attack, animals were orally given bovine myelin, guinea pig myelin, or guinea pig myelin basic protein three times per week for up to 3 months. Animals receiving myelin products orally had decreased severity and frequency of clinical relapses, decreased delayed-type hypersensitivity responses to myelin antigens, diminished inflammation in the central nervous system (CNS), and decreased areas of CNS demyelination. In the rat, guinea pig myelin basic protein was as effective as guinea pig myelin in ameliorating the disease and also resulted in decreased serum anti-myelin basic protein antibody levels. No exacerbation of disease or worsening of pathological findings occurred in the animals given myelin products. These results demonstrate that oral administration of myelin antigens can suppress chronic relapsing experimental autoimmune encephalomyelitis and have direct relevance to therapy of human demyelinating disorders such as multiple sclerosis."
-What diagnostic techniques were used to identify and confirm the intrahepatic arterioportal fistula in this patient?,"Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed."
-What characteristics of focal hepatic lesions can help differentiate between benign and malignant tumors using MR imaging?,"Focal hepatic lesions: differentiation with MR imaging at 0.5 T. Magnetic resonance (MR) examinations of 43 patients with 95 focal hepatic lesions (diameter, greater than 1 cm) were analyzed for lesion shape, homogeneity, and relative signal intensity compared with normal liver parenchyma, spleen, and skeletal muscle. On T1-weighted, balanced, and T2-weighted images, most metastases (74%), cavernous hemangiomas (76%), and cysts (82%) were smooth and round or oval, while the hepatocellular carcinomas all had irregular borders (40%) or were lobulated (60%). All lesions with irregular borders were malignant. Seventy percent of metastatic lesions, 85% of cavernous hemangiomas, and 100% of simple hepatic cysts were of homogeneous signal intensity, while 60% of hepatocellular carcinomas were inhomogeneous. Logistic regression analysis of multiple lesion characteristics showed that inhomogeneous lesions had a high likelihood of malignancy, while markedly hyperintense lesions had a very low probability of being malignant, regardless of other traits. Homogeneous lesions that were isointense or hyperintense compared with spleen on balanced images but were not markedly hyperintense on T2-weighted images also had a high likelihood of malignancy."
-What percentage of stage I testicular cancer patients experienced recurrence in the Testicular Cancer Intergroup Study?,"Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study. The Testicular Cancer Center Intergroup Study entered surgically staged patients with nonseminomatous tumor and metastases limited to the regional lymph nodes into a previously reported cooperative trial of immediate versus delayed therapy for positive retroperitoneal node disease. Patients with negative nodes (stage I) were placed in an observation registry with specified treatment strategy upon relapse. Of 264 stage I cancer patients 27 (10.2%) had recurrence: 5 of these 27 patients died after recurrence of the testicular malignancies, while 4 other nontumor-related deaths have occurred. Pre-lymphadenectomy staging characteristics observed to predict significantly node positivity are the results of radiological examinations, presence of tumor invasion, vascular invasion and tumor histology. In a multiple logistic regression analysis with these variables, misclassification still occurs in more than a fourth of the patients. Future refinements in diagnosis may allow for better prediction of these patients at risk to have positive lymph nodes and ultimately recurrence. Presently, if assessment of nodal involvement is the objective, noninvasive procedures are not an adequate substitute for surgical staging with modified lymphadenectomy."
-What distinctive features of crackling lung sounds were found in patients with different respiratory conditions?,"Crackles in patients with fibrosing alveolitis, bronchiectasis, COPD, and heart failure. We have studied the crackling lung sounds of ten patients with cryptogenic fibrosing alveolitis, ten with bronchiectasis, ten with chronic obstructive pulmonary disease, and ten with heart failure by analyzing frequency, waveform, and timing of crackles. The upper frequency limit of inspiratory sounds was higher in CFA than in COPD or in HF. The period of crackling was shorter in COPD than in CFA or BE. Inspiratory crackling terminated significantly earlier in COPD than in CFA, BE, or HF. The initial deflection width and the two-cycle duration of the expanded waveforms of crackles were smaller in CFA than in BE, COPD, or HF. The largest deflection width was smaller in CFA than in BE, HF, or COPD and smaller in BE than in HF. The results indicate that crackling lung sounds in different diseases have distinctive features and that their analysis can be of diagnostic value."
-What novel treatment strategies have been explored for Parkinson's disease?,"Parkinson's disease: new treatment strategies. Recent interest has focused on two novel approaches to the treatment of Parkinson's disease-medications to slow or arrest disease progression, and cerebral transplantation. Two recent studies have demonstrated that selegiline can slow, although not halt, the progression of recent-onset Parkinson's disease. The data are sufficiently compelling to justify the use of this drug in most new patients. It also seems reasonable to extrapolate from the data and offer this medication to all patients but those with the most advanced Parkinson's disease. The current focus on excessive oxidative stress as a causative factor has led some investigators to recommended treating patients with the antioxidant tocopherol (vitamin E). There is no clinical evidence demonstrating its effectiveness, but a current multicenter study is being conducted, with the results expected within the next 2 years. High-dose vitamin E (such as 800 to 2000 U/d), taken for a number of months, is probably harmless. It is probably reasonable, therefore, to allow patients to take this over-the-counter compound until more definitive evidence is available. Another antioxidant, vitamin C, has also been advocated as a means of slowing the progression of Parkinson's disease. There are no studies that demonstrate any clinical effectiveness, and there are also no ongoing studies investigating this issue in patients with Parkinson's disease. The excitement surrounding the initially favorable results of adrenal-brain transplantation has waned with the failure of numerous institutions to replicate the original dramatic success. While mild or occasionally moderate improvement has been noted in subsequent patients undergoing adrenal-brain transplantation, the improvement has not been sufficient to justify the risk and expense of this surgery."
-What was the impact of switching from body ventilators (BVs) to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP) on patients with obstructive sleep apnea?,"Obstructive sleep apnea complicating negative-pressure ventilatory support in patients with chronic paralytic/restrictive ventilatory dysfunction. The purpose of this study was to determine the incidence and severity of obstructive events and oxyhemoglobin desaturation (dSaO2) in 37 patients with paralytic/restrictive ventilatory insufficiency during use of nocturnal ventilatory assistance provided by means of negative-pressure body ventilators (BVs). Thirteen of the 37 patients had mean oxyhemoglobin saturation (SaO2) less than 95 percent and a mean of ten or more episodes per hour when the dSaO2 was greater than or equal to 4 percent (4%dSaO2/h). In all, 26 of the 37 patients had evidence of significant multiple episodes of dSaO2 while asleep on BVs. Polysomnography performed on three of these patients substantiated the obstructive nature of the dSaO2. Twenty-two of the 37 patients who had a mean SaO2 of 90.6 +/- 7.2 percent and a mean of 17.7 +/- 16.1 4%dSaO2/h on BVs were switched to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP). Their mean SaO2 improved to 96.0 +/- 2.2 percent, and the 4%dSaO2/h decreased to 1.2 +/- 1.8 per hour. All symptoms similar to those of obstructive sleep apnea were relieved. We conclude that BV use is associated with significant dSaO2 in over 50 percent of patients. The dSaO2 is predominantly obstructive in nature but may be due to chronic underventilation in patients using less effective BVs. Patients with a mean SaO2 less than 95 percent or 10 or more 4%dSaO2/h may benefit from conversion to NV-PAP via the nose, the mouth, or an oral-nasal interface."
-What significant changes have occurred in rehabilitation approaches for patients with rheumatic diseases over the past decade?,"Rehabilitation in rheumatic diseases. What's new. In the past decade, considerable change has occurred in concepts of rehabilitation in patients with rheumatic diseases. This includes approaches to functional assessment and outcome, new concepts in exercise, and new orthotics."
-How does a family history of coronary artery disease affect hemodynamic responses to exercise in young black boys?,"Family history of myocardial infarction and hemodynamic responses to exercise in young black boys. The influence of family history of coronary artery disease on children's hemodynamic responses to exercise was examined with 25 black boys aged 7 to 10 years. Blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance were evaluated during preexercise, peak exercise, and recovery stages. Children with a family history of CAD exhibited greater systolic blood pressure and total peripheral resistance during preexercise and peak exercise stages than did those without a family history of coronary artery disease. After controlling for preexercise differences, the group with a family history of coronary artery disease exhibited greater increases in systolic blood pressure and less attenuation of total peripheral resistance to peak exercise than the group without a family history of coronary artery disease. Cardiac output indexed by body surface area and stroke volumes were higher at all times in the group without a family history compared with the group with a family history of coronary artery disease. Findings are compared with those of adult studies in terms of influence of family history of coronary artery disease on cardiovascular reactivity to stress."
-What evidence suggests that the chronic lymphocytic leukemia and lymphoblastic lymphoma in this patient originated from the same malignant cell?,"Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed."
-How does the degree of headache relief impact psychological changes in chronic headache patients?,"Psychological changes accompanying non-pharmacological treatment of chronic headache: the effects of outcome. Several prior studies suggest that non-drug treatment for chronic headache is accompanied by concomitant reductions in patients' anxiety, depression and somatization. It is currently unclear, however, whether such beneficial side effects are a function of degree of headache relief or are due simply to receiving treatment. Most work to date in this area has treated outcome as a dichotomous variable. The present report employed a regression approach which treats outcome (degree of headache relief) as a continuous variable in the study of 149 chronic headache patients and their accompanying psychological changes. Anxiety and depression were significantly reduced for headache patients regardless of degree of headache relief. With somatization, however, degree of headache relief had a significant effect; the greater the reduction in headache, the fewer somatic concerns were expressed, especially for mixed headache."
-What was the main purpose of the study on exocrine pancreatic function in children with coeliac disease?,"Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal."
-What is the significance of left atrial spontaneous echo contrast in patients undergoing transesophageal echocardiography?,"Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement."
-What was the main finding regarding resting energy expenditure (REE) in patients with newly detected gastric and colorectal cancers?,"Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients."
-What was the main finding of the study comparing short-term and long-term cefoxitin prophylaxis after radical hysterectomy?,"Comparative efficacy of short-term versus long-term cefoxitin prophylaxis against postoperative infection after radical hysterectomy: a prospective study. We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy."
-What was the response rate and median time to progression for patients with recurrent malignant glioma treated with intravenous carboplatin?,"Intravenous carboplatin for recurrent malignant glioma: a phase II study. Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate."
-What are the bactericidal properties of fibrin gel against different bacterial species in a contaminated hepatic injury model?,"Autologous fibrin gel: bactericidal properties in contaminated hepatic injury. Fibrin glue is an effective hemostatic agent in a variety of clinical situations; its utility is limited by potential transmission of viral infection. We studied the bactericidal properties of fibrin gel (FG) in a murine contaminated hepatic injury model and in vitro by agar plate culture method. Intra-abdominal abscess formation and adhesion rate were assessed following controlled liver injury in association with abdominal contamination with 10(7) Bacteroides fragilis and hepatorrhaphy (H, n = 15) or FG (n = 12). Animals treated by hepatorrhaphy had a significantly greater intra-abdominal abscess rate (15/15 vs. 4/12, p less than 0.05) and adhesion rate (14/15 vs. 6/12, p less than 0.05) than animals treated with FG. Fibrin gel is bactericidal to Bacteroides fragilis, Enterobacter faecium, Escherichia coli, and Staphylococcus aureus but has no effect against Klebsiella pneumoniae or Pseudomonas aeruginosa; the plasma component appears active. Fibrin gel demonstrates significant improvement in adhesion formation and intra-abdominal abscess rate when compared with suture hepatorrhaphy. Fibrin gel appears protective in contaminated hepatic injury."
-What rare ictal phenomenon was investigated in two patients with epilepsy?,"Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions."
-What medical condition was observed in a 16-month-old infant with congenitally-acquired HIV infection?,Acute hemiplegia associated with HIV infection. An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia.
-What is moricizine hydrochloride and what is its primary medical application?,"Moricizine: a new agent for the treatment of ventricular arrhythmias. Over the last several years, a number of new antiarrhythmic agents have come into use. One of these promising new drugs, moricizine hydrochloride (Ethmozine), is now available for use in this country. Although similar in some aspects to both quinidine and lidocaine, Moricizine hydrochloride is in many ways unique. The purpose of this review is to summarize the pharmacologic and physiologic effects of moricizine and to outline its clinical use."
-What was the mortality rate during the initial admission for neonates with oesophageal atresia and/or tracheo-oesophageal fistula in this surgical study?,"Success and failure with neonatal tracheo-oesophageal anomalies. In seven and a half years, one surgical team treated 67 consecutive neonates with oesophageal atresia and/or tracheo-oesophageal fistula. According to Waterston's classification, 28 were in group A, 12 in group B and 27 in group C. The mortality rate during the initial admission was 10 per cent, all seven deaths being unavoidable in infants in group C with multiple anomalies. Birthweight alone had no bearing upon the chances of survival. Primary oesophageal repair, including one suture-fistula procedure and one delayed primary repair, was attempted in 54 (84 per cent) of the 64 patients with atresia and was successful in 46 (85 per cent). All three H-type tracheo-oesophageal fistulae were successfully divided in infants in group A. Recurrent tracheo-oesophageal fistula developed in four (7 per cent) infants, one of whom (group A) underwent successful repair. One disrupted anastomosis was successfully resutured (group A), so an intact oesophagus was finally achieved in 51 patients, of whom six (12 per cent) developed anastomotic strictures and 21 (41 per cent) underwent surgery for gastro-oesophageal reflux. Of the 60 early survivors, 10 (17 per cent) underwent aortopexy for tracheomalacia. Whenever possible, primary repair is advocated in all infants. Even for those in group C with multiple, severe associated anomalies, the combined early and late mortality was no greater following primary repair (7 died of 12 operated) than after staged repair (4 died of 7 operated), but major anastomotic complications were more common in infants in group C (5 out of 19) than in those in groups A and B (3 out of 38)."
-How did the quality of life differ between patients taking atenolol and nifedipine GITS during the 20-week antihypertensive therapy trial?,"Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system. To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation."
-What was the significance of culturing the calcified lymph nodes in this patient's case?,"Esophagobronchial fistula and mediastinal tuberculosis. A 59-year-old man was seen with what preoperatively was thought to be an acquired esophagobronchial fistula secondary to an old burned-out infection with tuberculosis. At operation the gross and microscopic findings were most compatible with a congenital H-shaped esophagobronchial fistula. However, cultures of calcified lymph nodes grew Mycobacterium tuberculosis. The need for culturing calcified tissue to assure proper treatment is emphasized."
-How does acute appendicitis present differently in patients with AIDS/HIV infection compared to immunocompetent patients?,"Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality."
-What was the success rate of antitachycardia pacing in treating tachycardia episodes in this study?,"Reduction in defibrillator shocks with an implantable device combining antitachycardia pacing and shock therapy. Implantable defibrillators reduce the risk of sudden death in patients with malignant ventricular arrhythmias, but significant restriction in quality of life can occur as a result of frequent device activation. To determine if a device that provides both antitachycardia pacing and shock therapy can safely reduce the frequency of shocks after implantation, 46 consecutive patients undergoing initial implantation of a defibrillator were studied. In all patients, the implanted device provided antitachycardia pacing and shock therapy. Detected tachycardia characteristics and the results of therapy were stored in the device's memory. There were 42 men and 4 women, aged 26 to 71 years (mean 58.7 +/- 13.5). Left ventricular ejection fraction ranged from 13% to 67% (mean 32.2 +/- 13.4%) and 31 patients had experienced one or more episodes of cardiac arrest. Induced arrhythmias included sustained monomorphic ventricular tachycardia in 38 patients, nonsustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. Over a total follow-up period of 255 patient-months (range 1 to 13, mean 6.1), 25 patients experienced spontaneous arrhythmic events. In 22 patients, 909 episodes of tachycardia were treated by antitachycardia pacing, which was successful on 840 occasions (92.4%). Acceleration of ventricular tachycardia by pacing therapy was estimated to have occurred 39 times. Syncope occurred once during pacing-induced acceleration of ventricular tachycardia. Forty-four episodes of tachycardia in seven patients were treated directly by shocks because of short tachycardia cycle length; 88% of all detected tachycardias were treated without the need for shocks. Four patients died from cardiorespiratory failure and one patient died suddenly without any detected tachyarrhythmia."
-What are the primary methods for treating active esophagogastric variceal bleeding and preventing its recurrence?,"Bleeding esophagogastric varices. Ways to treat active episodes and prevent recurrence. Bleeding from esophagogastric varices carries a high mortality rate. Active variceal bleeding can usually be temporarily controlled medically with a combination of intravenous vasopressin and nitroglycerin, with balloon tamponade, or with endoscopic sclerotherapy. Because of the high likelihood of recurrence, long-term treatment, such as repeated sclerotherapy, propranolol therapy, or shunt surgery, is necessary. The proper selection of such measures requires consideration of the site of variceal bleeding, local availability of specialized techniques, and patient factors. Only liver transplantation reverses the liver damage and offers hope of improved long-term survival. As success at identifying high-risk patients by endoscopic features improves, propranolol or other pharmacologic prophylaxis may become an acceptable treatment."
-What method is described for reorienting the left ventricular long-axis from myocardial transaxial tomographic data?,"Reorientation of the left ventricular long-axis on myocardial transaxial tomograms by a linear fitting method. A method is described for reorientating the left ventricular (LV) long-axis from myocardial transaxial tomographic data. On a midventricular transverse slice and on a midventricular sagittal slice, the apical and basal limits are selected successively by the operator. The linear activity profiles between these two limits are plotted line by line. In each profile, the two points with the maximum counts in the septal and lateral walls on the transverse slice, or in the anterior and inferior walls on the sagittal slice, are detected. The intermediate point with the minimum counts is then determined. The set of points with minimum counts are fitted by a straight line using the least squares method. This line is taken as the LV long-axis. In a series of 15 cases with stress-delayed 201Tl SPECT, the reproducibility of the reorientation with this semi-automatic method was compared with manual selection of the LV long-axis. In all patients, a successful reorientation was obtained with the present method. The reproducibility was significantly better with the semi-automatic method than with the manual selection of the LV long-axis."
-What was the primary finding of the study regarding nocturnal airflow obstruction in children with allergic asthma?,"Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma. A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine without (group 2) nocturnal airflow obstruction, and an age matched control group. All drugs were withheld for three days before and during the study. On day 4 each child was admitted to hospital and a series of measurements was made every four hours for 24 hours. These included measurements of the forced expiratory volume in one second (FEV1), heart rate and sinus arrhythmia gap from an electrocardiogram (an indirect measure of parasympathetic activity) and urine sampling for determination of catecholamine and N'-methylhistamine concentrations (measures of sympathetic activity and histamine release respectively). Urinary N'-methylhistamine excretion was significantly higher over the 24 hours in children in group 1 than in children in group 2, and overnight values were also significantly higher in children in group 1 than those in group 2. Mean (SEM) values (mumol/mol creatinine) were 154.6 (11.2) in group 1 and 110 (11.2) in group 2 for 2400-0400 hours samples and 139.2 (13.1) and 101.2 (10.6) 0400-0800 hours samples. There was no evidence of decreased sympathetic or increased parasympathetic activity in association with the nocturnal airflow obstruction; noradrenaline concentrations were increased in group 1. These observations indicate that nocturnal airflow obstruction is associated with increased release of histamine overnight."
-What was the main finding regarding regional cerebral blood flow in patients after cardiac arrest?,"Regional cerebral blood flow after human cardiac arrest. A hexamethylpropyleneamine oxime single photon emission computed tomographic study. We studied 30 patients 24 hours after out-of-hospital cardiac arrest and 13 age-matched normal controls with the use of technetium Tc 99m-hexamethylpropyleneamine oxime single photon emission computed tomography. All patients were followed up for 12 months or until death. Frontal hypoperfusion (anteroposterior perfusion ratio, less than 0.90) was observed in 23 patients (77%). In eight patients who remained comatose and died, the total size of perfusion defects was larger (38% +/- 20%) than in the 21 patients who recovered consciousness (24% +/- 14%), but the anteroposterior ratio was similar in both of these patient groups (0.83 +/- 0.09) and significantly lower than in the controls (0.96 +/- 0.03). During follow-up, both the anteroposterior perfusion ratio and the relative defect size improved, but frontal hypoperfusion was still observed in seven of 13 patients. After cardiac arrest, regional cerebral blood flow is characterized by frontal hypoperfusion that tends to improve over time but that persists in most patients."
-How do nitrendipine and removal of extracellular calcium ions affect tetanic responses in frog toe muscles?,"Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle. The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the ""late negative afterpotential"" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers."
-What percentage of splenic lesions were found to be hypoechoic in the sonographic study?,"Sonography of focal lesions of the spleen. The sonographic appearances of benign and malignant splenic lesions in 154 patients are illustrated. Sixty-six of the 154 patients had malignant splenic lesions; 55 of these had malignant lymphoma and 11 had splenic metastatic lesions. The lesions were hypoechoic in 64 cases (97%), including all cases of malignant lymphoma, and were hyperechoic in two. Eighty-eight patients had benign splenic lesions; findings included cysts, infarcts, abscesses, hemangiomas, and calcifications."
-What was the outcome of the prospective assessment of the rebound tenderness test in patients with abdominal pain?,Rebound tenderness test. The usefulness of the rebound tenderness test in indicating peritonitis was prospectively assessed in 142 unselected patients admitted as emergencies with abdominal pain and tenderness. It was found to be of no predictive value.
-What rare complication can occur after local steroid injection of a ganglion cyst on the hand?,"Localized depigmentation after steroid injection of a ganglion cyst on the hand. Presented is the case of a man who had localized depigmentation after local injection of triamcinolone diacetate. Search of the literature indicates that this is a rare complication of such therapy. Localized depigmentation may have important cultural implications for dark-skinned patients. There is some experimental evidence that less-potent and shorter-acting steroid preparations have a lower likelihood for depigmenting side effects, and such agents may be more appropriate when injecting subcutaneous structures to prevent this complication."
-What are the key diagnostic challenges associated with identifying Enterobius egg granuloma in medical pathology?,"Enterobius egg granuloma of the vulva and peritoneum: review of the literature. Two cases of Enterobius granuloma containing eggs only are reported. The first case involved the vulva, where no such granuloma has been reported previously. The coexistence of peritoneal granuloma and rectal adenocarcinoma in the second case suggests the possibility of direct penetration of the damaged colonic wall by the parasite, as emphasized by several previous reports of neoplastic involvement and perforation of the intestinal wall in cases of ectopic infections. The diagnostic criteria of Enterobius eggs granuloma, which might be a diagnostic dilemma for pathologists who are not familiar with such criteria, are described herein."
-What is the significance of thiamine deficiency in chronic hemodialysis patients according to the case report?,"Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report. We report the case of a patient with terminal renal disease on chronic hemodialysis who developed acute thiamine deficiency as confirmed by erythrocyte transketolase determinations. The patient presented with a confusional state and severe memory disturbances, but other classical features of Wernicke's encephalopathy were absent. Almost all central nervous system symptoms rapidly disappeared after thiamine therapy. Therefore the possibility of thiamine deficiency must be considered in patients on chronic dialysis who present with central nervous system disturbances, even if all of the classical features of Wernicke's encephalopathy are not present."
-What was the primary objective of the study on transjugular intrahepatic portosystemic shunt?,"Percutaneous transjugular portosystemic shunt. OBJECTIVE.--To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension. DESIGN.--Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months. PATIENTS.--All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids. MAIN OUTCOME MEASURES.--Shunt patency and recurrent variceal hemorrhage. RESULTS.--Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up. CONCLUSION.--Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage."
-What was the percentage of true histiocytic neoplasias found among malignant lymphoma and related conditions in this Japanese study?,"Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan. Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%."
-What factors in childhood can predict future high blood pressure?,"Childhood predictors of future blood pressure. Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults."
-What is the relationship between anemia and postoperative apnea in former preterm infants undergoing inguinal hernia repair?,"Anemia and postoperative apnea in former preterm infants. To examine the association between anemia and postoperative apnea in former preterm infants, 24 former preterm infants of less than 60 weeks postconceptual age undergoing inguinal hernia repair were studied. A hematocrit of at least 25% was required for study participation. General endotracheal inhalational anesthesia, supplemented with neuromuscular blockade and controlled ventilation, was used. No barbiturates or opioids were administered. Respiratory pattern and heart rate were recorded for at least 12 h postoperatively using an impedance pneumograph. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the hematologic profile of the infant. Nineteen patients had a hematocrit of 30% or greater (group 1). Their mean (+/- standard deviation [SD]) gestational age was 33.5 +/- 2.7 weeks and postconceptual age 45.5 +/- 4.6 weeks. Five infants had a hematocrit less than 30% (group 2). Their mean gestational age (+/- SD) was 32.4 +/- 3.2 weeks and postconceptual age 43.6 +/- 5.5 weeks. Anemic infants had an 80% incidence of postoperative apnea versus 21% in infants with a normal hematocrit (P less than .03). In the infants who developed postoperative prolonged apnea and/or bradycardia, a prior history of apnea was equally present in both groups (21% in group 1 and 20% in group 2). This study shows that anemia in former preterm infants can be associated with an increased incidence of postoperative apnea."
-What are the general characteristics and treatment approaches for haemangiomas in different parts of the urinary tract?,"Haemangioma of the urinary tract: review of the literature. General features. Haemangiomas are benign vascular tumours. They can regress spontaneously as a result of fibrosclerosis, suggesting a conservative approach wherever possible. Asymptomatic haemangiomas do not require treatment. Renal haemangioma. In all, 198 cases have been reported. The lesion is usually solitary and unilateral and occurs most often in the pyramid, and in the mucosa or subepithelial tissue of the pelvis. In some cases a tentative diagnosis of haemangioma has been made by means of selective renal angiography and pre- or per-operative renoscopy. Partial nephrectomy is recommended in cases of minor haemangioma. Ureteric haemangioma. Six cases have been described. When haemangioma is suspected a conservative operation is recommended. Bladder haemangioma. A total of 106 cases have been reported. Many of the tumours had the characteristics of an iceberg, with considerable extravesical extension making endoscopic management less suitable because of the possibility of massive haemorrhage or recurrence. Consequently, many authors prefer local excision. In the case of endoscopic treatment the patient should be prepared for open surgery. Urethral haemangioma. Twenty cases have been described. The lesions often extend further than is immediately apparent. Endoscopic management is recommended for small lesions and, in the case of more extensive lesions, open exploration is advised followed by appropriate urethral reconstruction."
-What was the most common gastrointestinal complication in patients who underwent cardiopulmonary bypass surgery?,"Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group."
-What is the key finding in the histologic examination of the small intestine in this case of familial enteric neuropathy?,"Familial enteric neuropathy with pseudoobstruction. We report a case of autosomal dominant chronic intestinal pseudoobstruction secondary to a familial enteric neuropathy. Esophagogastrointestinal manometry studies in the index case showed decreased postprandial contractile frequency with normal amplitude of pressure activity in the stomach and small bowel. Pupillary function and autonomic reflexes were all normal, excluding an extrinsic autonomic neuropathy of the viscera. Histologic examination of the small intestine by hematoxylin and eosin stains revealed normal smooth muscles but a reduced number of neurons in the myenteric plexus without inflammatory cells or neuroNal intranuclear inclusions. Histologic examination of the myenteric plexus using the sections taken along the longitudinal axis of the intestine, stained with silver by the Smith technique, disclosed decreased numbers of argyrophilic neurons and degeneration of neurons and axons; however, there was no reactive increase in the number of glial cell nuclei. The patient's mother had suffered from chronic intestinal pseudoobstruction, which did not abate following extensive small bowel resection. This is the third family reported with an autosomal dominant enteric neuropathy unassociated with evidence of extrinsic autonomic or peripheral neuropathy. Subtotal resection of the small bowel was followed by recurrence of the pseudoobstruction syndrome in both affected members of the family."
-Does the anatomical position of the vermiform appendix impact the clinical presentation and outcomes of acute appendicitis?,"Does the retrocecal position of the vermiform appendix alter the clinical course of acute appendicitis? A prospective analysis. Ninety-four adult patients undergoing appendectomy for acute appendicitis were prospectively studied during a 2-year period. Patients were divided into retrocecal (group 1; n = 27 [29%]) and anterior (group 2; n = 67 [71%]) groups according to the position of the appendix. There was no statistical difference between the two groups in duration of symptoms, presenting signs and symptoms, and initial white blood cell count. Furthermore, retrocecal appendicitis was not associated with a higher rate of perforation or increased morbidity. We conclude that the retrocecal position of the appendix does not alter the presentation of appendicitis."
-What was the healing rate of transmetatarsal amputations in different patient groups based on revascularization?,"Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized."
-What was the purpose of the isotopic examination of the stomach in patients with chronic nausea and/or vomiting?,"Idiopathic gastroparesis in patients with unexplained nausea and vomiting. Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation."
-How did the researchers correct the human beta S-globin gene in the mouse-human hybrid cell line BSM?,"Correction of a human beta S-globin gene by gene targeting. As a step toward using gene targeting for gene therapy, we have corrected a human beta S-globin gene to the normal beta A allele by homologous recombination in the mouse-human hybrid cell line BSM. BSM is derived from a mouse erythroleukemia cell line and carries a single human chromosome 11 with the beta S-globin allele. A beta A-globin targeting construct containing a unique oligomer and a neomycin-resistance gene was electroporated into the BSM cells, which were then placed under G418 selection. Then 126 resulting pools containing a total of approximately 29,000 G418-resistant clones were screened by PCR for the presence of a targeted recombinant: 3 positive pools were identified. A targeted clone was isolated by replating one of the positive pools into smaller pools and rescreening by PCR, followed by dilution cloning. Southern blot analysis demonstrated that the isolated clone had been targeted as planned. The correction of the beta S allele to beta A was confirmed both by allele-specific PCR and by allele-specific antibodies. Expression studies comparing the uninduced and induced RNA levels in unmodified BSM cells and in the targeted clone showed no significant alteration in the ability of the targeted clone to undergo induction, despite the potentially disrupting presence of a transcriptionally active neomycin gene 5' to the human beta A-globin gene. Thus gene targeting can correct a beta S allele to beta A, and the use of a selectable helper gene need not significantly interfere with the induction of the corrected gene."
-"What was the relationship between DNA ploidy, N-myc gene amplification, and clinical outcome in stage IVS neuroblastoma?","N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required."
-What were the long-term surgical outcomes for patients who underwent lateral cranial base surgery between 1970 and 1987?,"Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis."
-How does the intracerebral temperature compare to the rectal temperature in neurosurgical patients?,"Intracerebral temperature in neurosurgical patients. Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper-constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment."
-What are the three processes related to leukotrienes that are observed during the immediate reaction in bronchial asthma?,"The potential roles of leukotrienes in bronchial asthma. Leukotrienes (LTs), in particular LTC4, LTD4, and LTE4, have been shown to be capable of participating in the induction of three related processes observed during the immediate reaction in bronchial asthma: edema formation, mucus secretion, and muscle contraction. Despite impressive evidence potentially implicating the LTs, the role of LTs in asthma is still unproved, and a positive answer to their critical actions in causing airflow obstruction will require studies with specific antagonists."
-What is the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft (CABG) surgery?,"Functional recovery of hibernating myocardium after coronary bypass surgery: does it coincide with improvement in perfusion? To determine the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft surgery (CABG), 49 patients were studied. Radionuclide angiography was performed before, 1 month after, and 6 to 12 months after CABG to evaluate regional wall motion. Exercise thallium-201 myocardial perfusion imaging was done before and 1 month after CABG to assess regional perfusion. Preoperative asynergy was observed in 108 segments, and 74 of them showed an improvement in wall motion 1 month after CABG (segment A). Sixty-six of these segments (89%) were associated with an improvement in perfusion. Eight segments that had not improved 1 month after CABG demonstrated a delayed recovery of wall motion 6 to 12 months after CABG (segment B). However, seven of eight segments (88%) already showed an improvement in perfusion 1 month after CABG. A total of 82 segments exhibited functional recovery after CABG and were considered hibernating segments. In the preoperative study segment B more frequently had areas of akinesis or dyskinesis than segment A (75% vs 34%, p less than 0.05). The mean percent thallium-201 uptake in segment B was lower than that in segment A (74% +/- 9% vs 83% +/- 8%, p less than 0.05). Functional recovery of hibernating myocardium usually coincided with an improvement in perfusion. However, delayed functional recovery after reperfusion was observed in some instances. Severe asynergy and severe thallium-201 defects were more frequently observed in these segments with delayed recovery. Hibernating myocardium might remain stunned during those recovery periods."
-What are the key challenges patients with HIV infection face in rehabilitation medicine?,"Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine. Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder."
-How does the extent of small bowel resection in Crohn's disease patients affect the absorption of cholecalciferol and 25-hydroxycholecalciferol?,"Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome."
-What alternative treatment was used for the patient with Wilson's disease when low-dose D-penicillamine caused severe neurological deterioration?,"Zinc sulphate therapy for Wilson's disease after acute deterioration during treatment with low-dose D-penicillamine. A 30-year-old woman with Wilson's disease was treated with low-dose D-penicillamine. After 12 days, treatment was changed to zinc sulphate because of severe neurological deterioration. The patient subsequently improved within a few days. During a follow-up period of 20 months, the effectiveness of therapy was evaluated by measuring copper and zinc levels in plasma and urine, and by 64Cu-loading tests. We conclude that sulphate therapy may be a satisfactory alternative, even when rapid deterioration occurs in the early stages of D-penicillamine treatment."
-What were the key findings of the 15-year follow-up study on cardiovascular risk factors in primary hyperparathyroidism?,"Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases. The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT."
-How do the reflex responses of airway smooth muscle in piglets change between 2 and 10 weeks of age?,"Maturation of respiratory reflex responses in the piglet. Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation."
-What complication occurred after platelet transfusion following a successful PTCA procedure?,Abrupt vessel closure following platelet transfusion post-PTCA. A successful PTCA was complicated by abrupt closure following a platelet transfusion which was given for control of local bleeding. Possible mechanisms of abrupt closure are discussed. Recommendation is made to avoid giving platelet transfusion following PTCA.
-What is a porencephalic cyst and how can it potentially occur during fetal intravascular transfusion?,"Porencephalic cyst: a complication of fetal intravascular transfusion. A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication."
-What was the 5-year patency rate for different types of grafts used in infrapopliteal bypass surgery?,"Infrapopliteal bypass for severe ischemia: comparison of autogenous vein, composite, and prosthetic grafts. Results of 253 consecutive bypass grafts to infrapopliteal arteries were reviewed. Most (92%) were placed for rest pain (103) or tissue loss (130). Autogenous veins were used in 175 (69%) cases, composite vein-prosthetic grafts were used in 45 (18%), and prosthetic grafts alone were used in 33 (13%). Follow-up ranged from 0 to 101 months (mean, 19 months); 37 grafts (15%) were lost to follow-up. The operative mortality rate was 4%, and 5-year patient survival rate was 44%. Limb salvage was 82% at 5 years. The 5-year patency of vein grafts (63%) exceeded that of both composite (28%) and prosthetic (7%) grafts (p = 0.005 and p = 0.00007, respectively); but the patency of composite and prosthetic grafts did not differ significantly (p = 0.29). The patency of reversed vein (59%) and in situ vein grafts (74%) was not significantly different at 5 years (p = 0.34). Patency was also not affected by the site of the proximal or distal anastomoses or diabetes. The major determinant of long-term patency in infrapopliteal reconstructions continues to be graft material. Composite grafts offered no clear advantage over prosthetic grafts, and both should be used only when there is no other alternative to amputation."
-What were the common problems and rehabilitation interventions encountered in patients with AIDS?,"Experience with rehabilitation in the acquired immunodeficiency syndrome. Patients with the acquired immunodeficiency syndrome (AIDS) represent a novel referral population for rehabilitation services. Limited information about the rehabilitation needs of individuals with human immunodeficiency virus infection is available. We reviewed 51 consecutive patients with AIDS referred to a rehabilitation consult service. Common problems encountered included generalized deconditioning (27%) and neurologic dysfunction (45%). Neurologic presentations were diverse and included hemiparesis, diffuse cognitive dysfunction and dementia, myelopathy, myopathy and peripheral neuropathy. Other patients were referred for wound care as well as the management of the local effects of Kaposi's sarcoma, various musculoskeletal syndromes and new onset blindness. Problems identified included impaired mobility (76%), difficulty with self-care (57%), impaired cognition (29%) and uncontrolled pain (37%). Among the rehabilitation interventions utilized were therapeutic exercise (73%), gait aids (45%), bathroom and safety equipment (45%), orthotics (29%), vocational counseling (4%), pain management (29%) and whirlpool treatments (10%). Five patients were too ill or refused treatment. We conclude that AIDS patients referred for rehabilitation have a wide variety of physical deficits, demonstrate a considerable degree of functional impairment and may require multiple rehabilitation interventions."
-What are the typical symptoms and diagnostic challenges of adnexal torsion in postmenopausal women?,"Adnexal torsion. An unusual cause of abdominal pain in postmenopausal women. Adnexal torsion is a rare cause of abdominal pain in older women. Because the presenting symptoms and signs are vague, the diagnosis is not often considered. Lower abdominal pain with nausea and vomiting are usual in patients with torsion. Ultrasonography or computed tomography are useful diagnostic tests. Two case reports of older patients with adnexal torsion are presented to emphasize the diagnostic features of this entity, including lower abdominal pain, nausea and vomiting, and abdominal mass. Although the condition is uncommon, adnexal torsion should be considered in the differential diagnosis of acute abdominal pain."
-Which two genes have been identified as influencing the onset of autoimmune type 1 diabetes in nonobese diabetic mice?,"Genetic analysis of autoimmune type 1 diabetes mellitus in mice Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17."
-Does Helicobacter pylori infection increase the severity of mucosal injury caused by naproxen or aspirin?,"Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin."
-What is the origin of the extra chromosome 21q in Down syndrome cases with de novo Robertsonian translocation t(14q;21q)?,"Down syndrome due to de novo Robertsonian translocation t(14q;21q): DNA polymorphism analysis suggests that the origin of the extra 21q is maternal. Down syndrome is rarely due to a de novo Robertsonian translocation t(14q;21q). DNA polymorphisms in eight families with Down syndrome due to de novo t(14q;21q) demonstrated maternal origin of the extra chromosome 21q in all cases. In seven nonmosaic cases the DNA markers showed crossing-over between two maternal chromosomes 21, and in one mosaic case no crossing-over was observed (this case was probably due to an early postzygotic nondisjunction). In the majority of cases (five of six informative families) the proximal marker D21S120 was reduced to homozygosity in the offspring with trisomy 21. The data can be best explained by chromatid translocation in meiosis I and by normal crossover and segregation in meiosis I and meiosis II."
-What are the key differences in oxygen transport patterns between cardiogenic and septic shock patients in this study?,"Oxygen transport in cardiogenic and septic shock. OBJECTIVE: To review clinical studies of oxygen transport in cardiogenic and septic shock. DESIGN: Descriptive and prospective studies. SETTING: University hospital multi disciplinary ICU. PATIENTS: Critically ill cardiogenic and septic shock patients greater than 18 and less than 80 yrs of age. INTERVENTIONS: The responses to volume loading with colloid or crystalloid and infusion of catecholamines are documented with baseline hemodynamic and oxygen transport measurements before and after administration of catecholamines. MEASUREMENTS AND MAIN RESULTS: Nineteen patients in cardiogenic shock were studied. In three patients, invasive systemic mean arterial pressure was greater than 80 mm Hg and cardiac index was greater than 2.0 L/min.m2. In all patients, there were increases in oxygen extraction ratio that averaged 48 +/- 18 (SD) %. However, in 30 septic shock patients, extraction ratio was 24 +/- 2%. In both groups, the response to therapy was an increase in mixed venous oxygen saturation from 54 +/- 16% to 69 +/- 8% in cardiogenic patients (p less than .001) and from 75 +/- 2% to 80 +/- 1% in septic shock (p less than .01). CONCLUSIONS: There are widely differing oxygen transport patterns in cardiogenic and septic shock that may have implications for therapy."
-"What medical condition did the 35-year-old man have, and how was it treated?","Repair of a cerebrospinal fluid perilymph fistula primarily through the middle ear and secondarily by occluding the cochlear aqueduct. A 35-year-old man had a 5-year history of fluctuating hearing loss in his only hearing ear. History and diagnostic tests indicated a perilymph fistula, a diagnosis subsequently confirmed by exploration. Primary and secondary repairs temporarily ameliorated symptoms. A spinal fluid to middle ear fluid pathway was identified by radioactive tracer. A patent cochlear aqueduct indicated on computed tomography scan was found and repaired through a posterior cranial fossa approach. Hearing was preserved, remaining relatively stable during the 2-year follow-up period."
-What are the new therapies for gallstone management that have been developed in the past decade?,New trends in gallstone management. Many new therapies for the management of gallstone disease have been pioneered in the past decade. The object of this review is to equip the surgeon with the answers to all of the questions a patient will ask about gallstone therapy; the review is therefore didactic as well as comprehensive.
-What was the main finding regarding pulmonary artery wedge pressure (PAWP) and cardiac performance in patients with aneurysmal subarachnoid hemorrhage?,"Cardiac performance indices during hypervolemic therapy for cerebral vasospasm. The effect of hypervolemic preload enhancement on cardiac performance was systematically analyzed in nine patients following aneurysmal subarachnoid hemorrhage. The patients ranged in age from 34 to 63 years, and none had a history of cardiac disease. Each patient underwent placement of a flow-directed balloon-tipped catheter and the following measurements were taken during hypervolemic therapy: pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), cardiac index (CI), stroke volume index (SVI), and left ventricular stroke work index (LVSWI). After baseline measurements were recorded, hetastarch or plasmanate was infused intravenously at 300 cc/hr. Thermal output determination and pressures were measured every 15 minutes. The PAWP did not correlate in a statistically significant fashion with the CVP in the ranges recorded; however, a statistically significant correlation did exist between PAWP increases and increases in CI, SVI, and LVSWI (p less than 0.01). There was no statistical correlation between PAWP increases above 14 mm Hg and improvement in cardiac performance as evidenced by CI, SVI, and LVSWI measurements. It is concluded that CVP is an unreliable index of cardiac performance during hypervolemic therapy and that, in previously healthy individuals, a PAWP of 14 mm Hg is associated with maximum cardiac performance."
-What were the key histologic and ultrastructural findings observed in the Leeds-Keio prosthetic anterior cruciate ligament after 18 months of implantation?,"Histologic and ultrastructural findings of tissue ingrowth. The Leeds-Keio prosthetic anterior cruciate ligament. A light and electron microscopy investigation was performed on a Leeds-Keio ligament removed because of rupture 18 months after implantation to repair an anterior cruciate ligament. The investigation showed fibrous connective tissue on the plane of the main stress force. There was elastin and adequate vascularization interspersed with Type I collagen fibrils in the area most distant from the ligament. The tissue near the Dacron fibers was highly cellular with a matrix of infrequent, thin collagen fibrils and abundant fine granular material. The growth of the host tissue occurred in and around a Leeds-Keio ligament in response to tensile stresses."
-What surgical technique was used to treat syndactyly with osseous fusion of the distal phalanges?,"Surgical method for treatment of syndactyly with osseous fusion of the distal phalanges. For the interdigital space plasty to correct a syndactyly with fusion of the distal phalanges, we adopted a new operative procedure, covering the exposed distal bone with local rectangular flaps designed transversely on both dorsal and volar surfaces. A full-thickness skin graft from the groin region covers the remaining raw surface. The procedure was performed in six patients, and the flaps measured 6 mm (width) x 12 to 16 mm (length) in four patients, 5 x 15 mm in one patient, and 5 x 18 mm in one patient. Partial necrosis was observed in only one patient, in whom a narrow flap of 5 x 18 mm was used. In the other five patients, however, the results were satisfactory on both external appearance and function during the follow-up period of 3 to 6 years."
-How many patients preferred ultrasound over flexible cystoscopy in the detection of recurrent bladder tumours?,"Flexible cystoscopy compared with ultrasound in the detection of recurrent bladder tumours. A combination of transrectal and transabdominal ultrasound was compared with flexible cystoscopy as a means of detecting recurrent bladder tumours. The study group comprised 50 patients who had previously had rigid cystoscopy. They underwent combination ultrasound in the out-patient department 1 week before flexible cystoscopy. Combination ultrasound identified 25 patients with recurrent tumours and flexible cystoscopy identified 26. Thirty-four patients (68%) preferred ultrasound, 10 (20%) preferred flexible cystoscopy, 3 (6%) preferred general anaesthesia and rigid cystoscopy and 3 (6%) had no preference. The main objection to ultrasound was the use of the transrectal probe."
-What is the key advantage of stab evulsion phlebectomy for treating truncal varicose veins compared to traditional surgical methods?,"Ambulatory stab evulsion phlebectomy for truncal varicose veins. The management of primary varicose veins is evolving. Recovery time, cost, recurrence rate, and cosmesis are critical determinants. Classic ""high ligation"" and ankle-to-groin stripping is expensive, results in a long convalescence, and may produce unacceptable scarring and possible permanent nerve injury. This report describes the technique of stab evulsion phlebectomy performed in an outpatient setting. Under loco-regional anesthesia, and after high ligation, existing tributary and trunk varicosities are evulsed with specially designed hooks. The multiple stab incisions, 1.5- to 3-mm long, are closed with adhesive strips. Fifty-six patients, with 69 involved limbs, have been operated on during the past 9 months. Postoperative pain and complications were minimal. Convalescence was eliminated and all patients immediately resumed normal daily activities. Cosmesis was excellent. This technique is based on hemodynamically accurate principles. It effectively removes all varicosities, eliminates the proximal source of reflux, and disconnects potentially outflowing perforators, yet leaves in situ undamaged trunk veins, which may be used as potential vein grafts."
-What imaging features help distinguish between primary central nervous system lymphoma and toxoplasmosis in AIDS patients?,Primary central nervous system lymphoma versus toxoplasmosis in AIDS. The imaging studies of 16 patients with acquired immunodeficiency syndrome (AIDS) and proved primary central nervous system (CNS) lymphoma were reviewed. All studies included computed tomography (CT); six also included magnetic resonance (MR) imaging. A periventricular lesion was seen in 50% of patients. At least one such lesion exhibited subependymal spread or ventricular encasement in 38%. One-third of lesions in three of five patients who underwent nonenhanced CT were hyperattenuating. Five lesions were at least in part hypointense on T2-weighted MR images. The specificity of these findings was evaluated with a similar review of the imaging studies in 28 patients with AIDS and proved toxoplasmosis. Only 3% of lesions were periventricular. None exhibited subependymal spread or encasement. None were hyperattenuating on nonenhanced CT scans. Similar findings in other CNS lesions in AIDS patients could not be found in the literature. A focal enhancing mass with subependymal spread on CT or MR images and hyperattenuation at nonenhanced CT were the most reliable features in distinguishing between primary CNS lymphoma and toxoplasmosis in AIDS patients.
-What was the predictive accuracy of electrophysiologic localization for single and multiple accessory pathways in this study?,"Predictive accuracy of electrophysiologic localization of accessory pathways. Operative ablation of accessory pathways depends critically on preoperative localization when technical limitations preclude complete intraoperative mapping. To assess the accuracy of localization, 345 patients undergoing operative ablation were studied; 316 (91.6%) had a single accessory pathway and 29 (8.4%) had multiple accessory pathways. The electrophysiologic study was diagnostically complete and accurate in 294 patients (93%) with a single accessory pathway and 19 (61%) with multiple accessory pathways. A left lateral accessory pathway was most accurately localized with excellent sensitivity (99%) and positive predictive value (98.5%). Diagnostic errors occurred in 33 patients because of 1) incorrect localization (n = 16), 2) failure to detect a second pathway (n = 9), and 3) diagnosis of a second pathway not verified intraoperatively (n = 8). Multiple pathways were more prevalent in the group with errors (33.3% vs. 5.8%, p = 0.0001), as were unidirectional pathways (48.5% vs. 24.3%, p = 0.003). It is concluded that preoperative localization of accessory pathways is sufficiently accurate to allow intraoperative mapping to be brief and focused."
-What method is proposed for estimating the optimum ventricular catheter length when intraoperative ultrasound is not available?,Index for optimum ventricular catheter length. Technical note. The optimum length of a ventricular catheter to be placed in a particular patient may be difficult to determine when either intraoperative ultrasound is not available or considerable time has elapsed between the diagnostic computerized tomography scan and the operation. An index for estimating ventricular length based on the head circumference of the individual is described. This method was tested clinically and proved to be successful.
-What did the population-based study reveal about the influence of gender on multiple sclerosis susceptibility in sibling pairs?,"The influence of gender on the susceptibility to multiple sclerosis in sibships. A population-based study of pairs of relatives (siblings, second- and third-degree) concordant for multiple sclerosis did not show an excess of like-sexed pairs. In addition, data on human lymphocyte antigen typing for sibling pairs concordant for multiple sclerosis did not find an increase in haplotype sharing for like-sexed pairs. These data do not support the notion that sex-related factors influence multiple-sclerosis susceptibility in families."
-How did intermittent negative pressure ventilation (INPV) affect oxygen and carbon dioxide levels in COPD patients with severe hypercapnic respiratory failure?,"Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. With the aim of testing a method that allows increasing concentrations of oxygen to be administered to patients with severe hypoxemia and hypercapnia while avoiding the risk of increasing respiratory acidosis, we studied 17 male patients with advanced chronic obstructive pulmonary disease (COPD) and severe hypercapnic respiratory failure. During 6 h and on one day only, all patients were given intermittent negative pressure ventilation (INPV) together with oxygenation starting at a concentration of 24 percent and increasing to 30 percent. Using this procedure, it was possible to raise arterial PaO2 to safe levels (from 47.2 +/- 3 mm Hg to 61.5 +/- 6 mm Hg, p less than 0.001) without increasing hypercapnia, and a significant drop in PaCO2 levels (from 74.4 +/- 9 mm Hg to 65.6 +/- 12 mm Hg, p less than 0.005) was even observed. One hour after INPV ended, the mean values of PaO2, PaCO2, oxygen saturation, and pH were also significantly better than prestudy values. We conclude that INPV and oxygen therapy with increasing oxygen flow could constitute an alternative option to intubation and mechanical ventilation in cases of severe hypercapnic respiratory failure due to advanced COPD."
-What are the key findings regarding ventricular tachycardia in patients with sarcoidosis based on this study?,"Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin."
-How did the researchers detect DNA sequence polymorphisms in the retinoblastoma susceptibility locus?,"Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. The discovery of RFLPs and their utilization as genetic markers has revolutionized research in human molecular genetics. However, only a fraction of the DNA sequence polymorphisms in the human genome affect the length of a restriction fragment and hence result in an RFLP. Polymorphisms that are not detected as RFLPs are typically passed over in the screening process though they represent a potentially important source of informative genetic markers. We have used a rapid method for the detection of naturally occurring DNA sequence variations that is based on enzymatic amplification and direct sequencing of genomic DNA. This approach can detect essentially all useful sequence variations within the region screened. We demonstrate the feasibility of the technique by applying it to the human retinoblastoma susceptibility locus. We screened 3,712 bp of genomic DNA from each of nine individuals and found four DNA sequence polymorphisms. At least one of these DNA sequence polymorphisms was informative in each of three families with hereditary retinoblastoma that were not informative with any of the known RFLPs at this locus. We believe that direct sequencing is a reasonable alternative to other methods of screening for DNA sequence polymorphisms and that it represents a step forward for obtaining informative markers at well-characterized loci that have been minimally informative in the past."
-"What were the age-adjusted incidence rates of amyotrophic lateral sclerosis for males and females in Harris County, Texas, during the period 1985-1988?","Incidence and prevalence of amyotrophic lateral sclerosis in Harris County, Texas, 1985-1988. The incidence of amyotrophic lateral sclerosis was determined in Harris County, Texas, for the period 1985 through 1988. Amyotrophic lateral sclerosis cases were ascertained from four sources: area neurologists, hospitals, death certificates, and the Muscular Dystrophy Association. The age-adjusted incidences of 1.27 per 100,000 person-years in males and 1.03 per 100,000 person-years in females were lower than recent rates in the northern US, Canadian, and northern European studies but higher than rates in southern European studies. Comparisons with other recent incidence studies show less uniformity in occurrence of amyotrophic lateral sclerosis, in both the overall rates and in the age- and sex-specific patterns, than was suggested by mortality studies. The incidence of amyotrophic lateral sclerosis among blacks and whites was similar. Hispanic males had incidences similar to white males, although a deficit of female Hispanic cases was found in Harris County. The prevalence of amyotrophic lateral sclerosis peaked in the 65- to 74-year age group at 33 per 100,000 population among males and 19 per 100,000 population for females."
-What unique histological feature was observed in the liver of this peripheral T-cell lymphoma case?,"Extensive hepatic granulomas associated with peripheral T-cell lymphoma. A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver."
-What are the most practical and useful techniques for diagnosing perivalvular extension of infection in patients with infectious endocarditis?,"Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review."
-What is microvascular angina and how does it differ from traditional coronary artery disease?,"Microvascular angina. Cardiovascular investigations regarding pathophysiology and management. A significant minority of patients with chest pain who undergo cardiac catheterization are found to have angiographically normal coronary arteries. Over the past 25 years, several studies have shown that a subset have demonstrable abnormalities in coronary flow and cardiac function; however, only a minority of these patients have convincing evidence for myocardial ischemia during stress, and alternative mechanisms have been explored to explain the frequent and debilitating symptoms of pain experienced by the majority of these patients undergoing study. Abnormal visceral nociception appears to be a fundamental abnormality in this population, whether or not demonstrable abnormalities in coronary flow or cardiac function can be demonstrated."
-What is Bazex syndrome and what are its key characteristics?,"Bazex syndrome (acrokeratosis paraneoplastica). An analytic review. Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions."
-How do phalloidin and antamanide help mitigate the side effects of interleukin-2 (IL-2) in rats?,"Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide. Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak."
-What is telangiectatic osteosarcoma and how has its prognosis changed over time?,"Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy."
-How do the contractile responses to norepinephrine and caffeine differ in mesenteric arteries from normotensive and hypertensive rats?,"Agonist-sensitive calcium stores in arteries from steroid hypertensive rats. The present study characterizes cellular calcium stores that are sensitive to norepinephrine and caffeine in arteries from deoxycorticosterone acetate hypertensive rats. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. In calcium-free solution, phasic contractile responses to norepinephrine (5.9 x 10(-9) to 5.9 x 10(-6) M), but not caffeine (0.3-30 mM), were greater in hypertensive arteries. D-600, a calcium channel blocker, or removal of the endothelium did not alter phasic contractions to norepinephrine or caffeine. In contrast, contractions to both norepinephrine and caffeine were inhibited by ryanodine, a drug that depletes calcium from intracellular stores. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl N,N-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites."
-What were the key differences observed between patients with Hodgkin's disease above the diaphragm (ADHD) and below the diaphragm (BDHD) in this study?,"Stage I and II subdiaphragmatic Hodgkin's disease. From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease."
-How does high-resolution contact B-scan echographic imaging help in diagnosing and assessing anterior hyaloidal fibrovascular proliferation?,"Echographic diagnosis of anterior hyaloidal fibrovascular proliferation. High-resolution contact B-scan echographic imaging of the ciliary body and peripheral retina was performed on five eyes with anterior hyaloidal fibrovascular proliferation and media opacity by means of a wide (58 degrees) scanning arc. This technique determined the circumferential and anteroposterior extent of peripheral traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation, which correlated highly with findings at subsequent vitrectomy. Final visual acuity of 20/400 or better was achieved in the two eyes (50%) with more limited peripheral traction detachment. In the presence of media opacity, anterior echographic imaging may allow early detection of traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation and may be useful in characterizing the severity of this condition."
-How reliable is pulse oximetry in assessing collateral blood flow to the hand compared to Doppler ultrasound?,"Pulse oximetry compared with Doppler ultrasound for assessment of collateral blood flow to the hand. Ischaemic injury to the hand after arterial cannulation is a rare but well documented complication and routine testing of the adequacy of collateral circulation is widely advocated. The widespread availability of the pulse oximeter in the operating theatre. its applicability in circumstances where the patient is unable to cooperate, and its dependence on pulsatile blood flow suggest that this device could potentially be usefully applied to the assessment of collateral blood flow. The reliability of the pulse oximeter to detect the presence or absence of collateral circulation was prospectively compared to Doppler ultrasound in 109 hands from 64 adult patients. Nine hands demonstrated inadequate ulnar collateral flow, one hand demonstrated inadequate radial collateral flow and a persistent median artery was found in one hand. In all patients the results of pulse oximeter testing (probe placed on the thumb correlated precisely with the results obtained with the Doppler device (probe located over the lateral aspect of the superficial palmar arch). These results demonstrate pulse oximetry to be a reliable method of assessing collateral blood flow to the hand before arterial cannulation."
-What was the range of ionized calcium levels observed in patients with chronic lung disease?,"Ionized calcium in blood: studies on patients with pulmonary disease. A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01-1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults."
-"What were the key findings regarding macrophages, microglia, and HLA-DR antigens in the fetal and infant brain tissue samples?","Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain. Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA-DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection."
-What are the advantages of using mandibular reconstruction plates for jaw reconstruction?,"Immediate mandibular replacement using reconstruction plates. Mandibular reconstruction at the time of tumor resection remains a surgical dilemma. Primary reconstruction allows for immediate reconstitution of mandibular form and function. Various methods have been attempted, but none enjoys uniform success. With advances in the field of microvascular surgery have come numerous options in replacing these defects. These procedures, however, require special surgical teams and are associated with an increase in operative time as well as morbidity at the donor site. An alternative method involves the use of mandibular reconstruction plates to bridge the defect between segments. This review focuses on 19 patients whose jaws were reconstructed in this fashion. Although not free of complications, mandibular plate reconstruction offers the advantages of (1) lack of donor site morbidity, (2) expediency, (3) excellent mandibular contour, and (4) the ability to reconstruct the condyle when necessary. The technique, results, and complications associated with this procedure are discussed."
-What is the key advantage of the modified craniofacial approach described in the context for ethmoid and anterior skull base surgery?,"Modified approach for ethmoid and anterior skull base surgery. The use of combined craniofacial resection is well established for tumors of the ethmoid bone and the anterior aspect of the base of the skull. Mobilization of the medial fronto-orbital ridge improves the transbasal approach and can be performed with a monobloc bone flap. We describe an en bloc bifrontal craniotomy including the supraorbital ridges and the nasal bones. This provides a wider angle of approach to the anterior aspect of the base of the skull than any other method and avoids retraction of the frontal lobes. This type of bone flap procedure can be performed after a wide periosteal dissection in the coronal area of the scalp alone, without facial skin incision."
-What were the hemodynamic effects of a 24-hour milrinone infusion in patients with severe heart failure?,"Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition. The systemic and pulmonary arterial hemodynamics of 40 patients with severe congestive heart failure were determined during a 24-hour infusion of milrinone (0.5 micrograms/kg/min) after a loading dose of 50 micrograms/kg. A subgroup (n = 18) with severe cardiac pump dysfunction and three patients in cardiogenic shock were analyzed separately; their hemodynamic response was compared with that of the total group (n = 40). After 15 minutes of intravenous therapy with milrinone, the total group (n = 40) showed an increase of 65% in cardiac index; in the subgroup (n = 18) cardiac index increased by 94% after 15 minutes and by 106% after 30 minutes. Likewise, pulmonary capillary wedge pressure decreased after 30 minutes in both the total group (n = 40) and the subgroup (n = 18). The heart rate showed an overall tendency to decrease. The systolic blood pressure tended upward and remained statistically unchanged in the total group, whereas in the subgroup in which pressure was initially low, there was an increase in the systolic pressure after 1 hour and a further increase after 24 hours. Mean arterial pressure also rose in this subgroup. The early improvement in all measured hemodynamic parameters was sustained throughout the 24-hour infusion period. Development of tolerance was not observed, nor were any clinically symptomatic side effects or symptomatic arrhythmias. Thus intravenous milrinone is a safe medication for the rapid and prolonged improvement in hemodynamics, specifically in patients with severely restricted cardiac pumping function."
-How do different antihypertensive agents impact serum lipid profiles?,"Antihypertensive therapy: taking lipids into consideration. Several antihypertensive agents have been found to influence serum lipid profiles. Thiazide diuretics increase total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and slightly reduce high-density lipoprotein (HDL) cholesterol. Most beta-blockers substantially increase triglycerides and lower HDL cholesterol. Angiotensin-converting enzyme inhibitors, calcium channel antagonists, alpha- and beta-blockers, and beta-blockers with intrinsic sympathomimetic activity are lipid neutral. alpha 1-Antagonists (e.g., terazosin and prazosin) lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improve total cholesterol/HDL ratios. Observational epidemiologic studies indicate that the lipid effects of antihypertensive agents are large enough to account for substantial differences in the predicted incidence of coronary heart disease. Combination therapy with the alpha 1-antagonist terazosin plus either thiazides or beta-blockers also ameliorates the adverse lipid effects of these agents used alone. A reasonable approach to managing the lipid problems often associated with hypertension is to advise a cholesterol-lowering, low-sodium diet and weight reduction and to select drugs that alone or in combination do not adversely affect lipid profiles."
-What is the dissociation index (DI) and how does it help in assessing brainstem maturation in infants with cyanosis during feeding?,"Phasic sleep components in infants with cyanosis during feeding. Although brainstem immaturity has been postulated as one of the pathogenesis underlying cyanosis during feeding (CDF), there has been no widely accepted physiologic parameter that reflects brainstem function. We recently proposed that the dissociation index (DI), one of the phasic sleep parameters, is a reliable and quantitative sleep parameter for assessing brainstem maturation during early infancy. In the present study, we evaluated brainstem impairment in infants with CDF using phasic sleep components. Polysomnographies were obtained for 12 infants with CDF who were equally divided into 2 groups: one had or subsequently experienced apparent life-threatening events or sudden infant death syndrome (ALTE-SIDS group) and the other did not (CDF group). Rapid eye movement density and the number of gross movements (body movements, including the trunk, lasting greater than or equal to 2 sec) in the patients were identical to those in the controls. In the CDF group, the decrease of the average DI value from the controls was significantly less than the decrease in the ALTE-SIDS group. CDF may be a mild expression of brainstem immaturity. DI appears to be useful when evaluating infants with cyanosis during feeding."
-What was the surgical success rate for patients with and without asthma in this study of intranasal ethmoidectomy?,"The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present."
-Does chronic triamterene therapy lead to folate deficiency in humans?,"Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency. The diuretic drug triamterene has previously been shown to be a competitive inhibitor of folate absorption in the rat intestine (J Lab Clin Med 1986;108:272-6). We therefore investigated whether human subjects who are taking the drug on a long-term basis are at increased risk of folate deficiency. In each of two free-living populations, a study was performed to compare the folate status of triamterene users with those not taking the drug. The first population consisted of 272 elderly individuals not living in institutions who were participants in a nutrition status survey and who were taking a variety of antihypertensive medications; 32 of these individuals were daily users of triamterene. The hemoglobin concentration, red blood cell (RBC) count, and mean corpuscular volume (MCV) values were not significantly different between the triamterene users and nonusers. The female triamterene users had a slightly higher serum folate level than the female nonusers (p less than 0.04); a similar pattern was observed among the men, although the difference was not statistically significant. The second population consisted of 27 individuals attending a hypertension clinic; 18 subjects were taking 50 to 150 mg of triamterene per day and nine were taking antihypertensive drugs other than triamterene. The hemoglobin concentration, RBC count, MCV, serum folate values, and RBC folate values were found to not differ significantly between the triamterene users and the hypertensive controls (p greater than 0.05). These data suggest that chronic triamterene administration in individuals not living in institutions, at the doses examined in this study, is not associated with indications of folate deficiency."
-What is the relationship between left atrial myxoma and pulmonary haemosiderosis in the given medical case?,Pulmonary haemosiderosis associated with left atrial myxoma. A patient with features suggesting pulmonary haemosiderosis was found to have a myxoma. The pulmonary lesion cleared after excision of the tumour.
-How effective was hematoporphyrin derivative (HPD) in identifying early colonic cancer in rats?,"Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative. Laser excitation of hematoporphyrin derivatives (HPD) localizing in tumors of the tracheobronchial tree and bladder is useful in the identification and treatment of those tumors. A comparable utility for HPD in the endoscopic localization of colonic tumors may be possible. In this study the ability of HPD to identify 1,2 dimethylhydrazine (DMH) induced colon cancer in rats is evaluated. A total of 111 rats were studied with HPD. Sixty-nine rats received weekly injections of DMH (20 mg/kg) and 42 received injections of the vehicle alone. Twenty-four hours after the intravenous injection of 5 mg/kg of HPD, 18 DMH-induced tumors were identified by visual fluorescence using excitation by either a blue light (390-436 nm) or an argon laser (488 and 514 nm). This represented 100% of the visually or microscopically detected tumors. Seventy-five fluorescent areas were noted that did not contain evidence of cancer. The majority (63) of false positive areas contained lymphoid follicles. All but 2 false positive areas (73/75, 97%, p less than .001) were seen in DMH-treated animals, suggesting that they were an artifact of DMH treatment. HPD fluorescence did not identify microscopic dysplasia. We conclude that HPD fluorescence is an effective method of identifying early colonic cancer and may have a potential clinical role in patients at high risk for colorectal cancer."
-Does preoperative and postoperative anticoagulant medication improve the short-term outcomes of lower-limb arterial thromboembolectomy?,"Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study. The value of short-term anticoagulant treatment in improving the early outcome in patients operated on for acute lower-limb ischemia has been debated and so far unproven. In this prospective randomized multi-center study, 188 such patients were randomized on admission, either to preoperative and postoperative anticoagulant medication (AC group, n = 94) or no anticoagulant treatment during the first month after surgery (O group, n = 94). Background factors were evenly distributed in the two groups, and 89% of the cases were considered as embolic. Analysis on an intention-to-treat basis showed no differences in outcome after 30 days. Good results, survivors who had amputation, and patients who died in the two groups are given respectively: AC group, 61%, 9%, 30%; O group, 65%, 11%, 24%. The results were similar in the two treatment groups also if only patients with a cardiac source of embolism were analyzed. Local bleeding complications were more common in the AC group (17% vs 2%, p less than 0.01). It is concluded that preoperative and early postoperative anticoagulant medication should not be routinely administered since such treatment is unlikely to improve the short-term results of lower-limb arterial thromboembolectomy while bleeding complications increase. The possible value of late (beyond 1 month) long-term anticoagulant treatment remains to be studied."
-How does intraperitoneal contrast material improve the detection of peritoneal metastases compared to standard CT examinations?,"Intraperitoneal contrast material improves the CT detection of peritoneal metastases. The preoperative detection of peritoneal metastases from gynecologic malignancies is difficult; in particular, CT often fails to detect peritoneal implants. This study was designed to determine if the administration of intraperitoneal iodinated contrast media would increase the CT detection of such peritoneal metastases. Prospectively, both standard and intraperitoneal contrast-enhanced CT studies of the abdomen and pelvis were performed in 16 patients with suspected gynecologic tumors. All patients then underwent operative staging, with the location and number of metastases documented. The intraperitoneal enhanced CT studies were more sensitive in the detection of peritoneal metastases than standard CT examinations. Whereas routine CT detected peritoneal metastases in seven (64%) of 11 patients with surgically proved implants, the intraperitoneal enhanced CT studies detected peritoneal metastases in all 11 patients. Depending on the specific intraperitoneal compartments involved, the sensitivity of intraperitoneal enhanced CT in the detection of peritoneal metastases was two- to fourfold greater than that of standard CT examinations. Our results suggest that intraperitoneal enhanced CT is superior to standard CT in the detection of peritoneal metastases."
-What was the restenosis rate for patients with unstable angina pectoris compared to those with stable angina pectoris after percutaneous transluminal coronary angioplasty (PTCA)?,"Higher recurrence rate after coronary angioplasty in unstable angina pectoris. PURPOSE: Recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA) is a significant problem, requiring repeat dilation in about one-third of all treated patients. Various clinical and procedure-related predictors have been proposed. Between 1983 and 1987, 257 patients underwent 322 procedures, where 380 stenoses were attempted. Indications were: stable angina pectoris 73%, unstable angina pectoris 22%, other indication 5%. The primary success rate was defined as a less than 50% remaining postprocedure stenosis. FINDINGS: Repeat angiograms were done for 88% of the initially successful cases, either six months after PTCA or if there was a clinical recurrence. Restenosis was defined as a recurrence of a more than 50% diameter stenosis. The restenosis rate was 33% and was significantly higher (p less than 0.05) for unstable (46%) than for stable angina pectoris (29%). There was a nonsignificant tendency to a higher restenosis rate in the left anterior descending artery than in the other coronary vessels. IMPLICATIONS: The increased restenosis rate seen after PTCA for unstable angina pectoris could be caused by a higher activity in systems affecting the proliferative processes in the smooth muscle cells of the arterial wall, which is thought to form the pathophysiologic basis for restenosis after PTCA."
-How did the nutritional status of patients with left ventricular assist device (LVAD) support change from implantation to cardiac transplantation?,"Nutritional assessment of patients with extended left ventricular assist device support. The nutritional status of nine patients with end-stage heart disease who were supported by a left ventricular assist device (LVAD) for more than 30 days while awaiting cardiac transplantation was evaluated. Nutritional status was indicated by the following scale: 0-2, adequate nourishment; 3-5, moderate malnourishment; greater than 5, severe malnourishment. This scale was based on serial assessments of albumin, transferrin, total lymphocyte count, percentage of ideal body weight, midarm circumference, triceps skinfold, and arm muscle circumference. Each variable was compared with established standards before implantation and before transplantation times and assessed 1 point if less than the normal value and 0 points if within the normal range. At the time of LVAD implantation, 5 patients had a score of 0-2, 3 patients had a score of 3-5, and 1 patient had a score greater than 5. At the time of cardiac transplantation, 7 patients had a score of 0-2, 2 patients had a score of 3-5, and no patients had a score greater than 5. The patients who were able to meet at least 50% of their daily caloric and protein requirements by oral intake alone were noted. At LVAD implantation, only 2 patients (22%) met this requirement; however, 6 patients (67%) met this requirement at the time of cardiac transplantation. All 9 patients underwent cardiac transplantation, and 8 survived. Thus, it appears that extended LVAD support and maintenance of hemodynamic stability allow patients to regain the desire and ability to achieve adequate nutritional status, which may considerably reduce their perioperative transplant risks."
-What rare combination of vascular conditions was observed in the patient described in the context?,"Congenital arteriovenous communications and the development of two types of leaking retinal macroaneurysms. We treated a patient with a rare combination of congenital arteriovenous communications and the development of leaking macroaneurysms of different types. Initially, leaking macroaneurysms developed in the shunt area of the arteriovenous communication; later, a preexistent fusiform macroaneurysm in the afferent arteriole of the congenital communication started leaking. Because exudates and fluid from the leaking macroaneurysms reached the fovea, laser treatment was performed to obliterate the macroaneurysms. We assume that after obliteration of the macroaneurysms with laser in the shunt area, the increase of hydrostatic pressure on the thin wall of the fusiform aneurysm of the afferent artery led to its leaking. We saw no signs of vascular occlusion after laser treatment."
-What is post-traumatic syringomyelia and how can it develop after a spinal fracture?,"Post-traumatic syringomyelia following uncomplicated spinal fracture. Two cases of post-traumatic syringomyelia presenting 10 and 41 years after spinal injuries that had caused lumbar vertebral fractures but no lasting neurological deficits are reported. In both patients the caudal end of the syrinx cavities, as shown by MRI, corresponded to the level of the previous vertebral fractures. Patients presenting with post-traumatic syringomyelia after uncomplicated spinal fracture are very rare, and the significance of the past history of spinal trauma may be overlooked."
-How effective was epidermal growth factor in treating chronic wounds in this study?,"Stimulation of healing of chronic wounds by epidermal growth factor. We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing."
-What were the cognitive outcomes for elderly patients with major depression after receiving tricyclic antidepressants or electroconvulsive therapy (ECT)?,"Cognitive outcome following tricyclic and electroconvulsive treatment of major depression in the elderly. OBJECTIVE: This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. METHOD: Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months. RESULTS: Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified. CONCLUSIONS: The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population."
-What were the main findings of the study comparing different anesthetic regimens in pediatric strabismus surgery?,"Effect of propofol on the incidence of postoperative vomiting after strabismus surgery in pediatric outpatients. Vomiting is a common problem after strabismus surgery in pediatric outpatients. We compared the effects of propofol with and without N2O and droperidol to the effects of a conventional regimen consisting of halothane-N2O-droperidol on the recovery characteristics and the incidence of postoperative emesis after strabismus surgery in 120 ASA physical status 1 or 2 children. After induction of anesthesia with halothane-N2O, patients were randomly assigned to one of four groups. Group A (control) received halothane, 66% N2O, and droperidol 75 micrograms.kg-1; group B, propofol 2 mg.kg-1 bolus followed by infusion of 160 microgram.kg-1.min-1; group C, propofol (as in group B) and 66% N2O; and group D, propofol (as in group B), 66% N2O (as in group C), and droperidol 75 micrograms.kg-1. Patients in group B had more episodes of intraoperative oculocardiac reflex responses than patients in group A, but had shorter times to extubation, oral intake, ambulation, and discharge, as well as a lower incidence of postoperative emesis (P less than 0.05). The addition of N2O to the propofol anesthetic regimen (group C) was associated with an increased incidence of emesis (P less than 0.05), whereas the addition of droperidol to the propofol-N2O regimen (group D) did not affect the incidence of emesis compared to the other three groups. We conclude that maintenance of anesthesia with a total intravenous regimen using propofol results in a more rapid recovery and less postoperative emesis than with a halothane-N2O-droperidol regimen."
-What surgical technique was used to address a persistent filtration bleb leak?,Donor scleral graft patching for persistent filtration bleb leak. We report effective and efficient sealing of a persistent leak in a cystic filtration bleb by applying a full-thickness donor scleral patch.
-What is the significance of finding occult submucosal duodenal-wall microgastrinomas in patients with Zollinger-Ellison syndrome?,"Zollinger-Ellison syndrome. A new look at regression of gastrinomas. Of 44 patients with the Zollinger-Ellison syndrome treated at our institution, nine appeared to have undergone ""regression"" of their gastrinomas. Six of the nine patients had sporadic gastrinomas and became permanently eugastrinemic following excision of nodal metastases and total gastrectomy (n = 4), antrectomy (n = 1), or pancreatoduodenectomy (n = 1) (mean survival, 13 years). The other three patients had Zollinger-Ellison syndrome as part of the multiple endocrine adenopathy type 1 syndrome and became temporarily eugastrinemic after total gastrectomy (mean survival, 11 years). Occult submucosal duodenal-wall microgastrinomas (mean size, 3.0 mm) were found to have been serendipitously excised in four patients. Long-term follow-up of these nine patients, as well as of six other patients described in the literature, demonstrates that excision of occult duodenal-wall gastrinomas provides a plausible explanation for the phenomenon of apparent regression of primary gastrinomas and the eugastrinemia that may follow total gastrectomy."
-How do neonates respond hormonally and metabolically to operative stress?,"Hormonal and metabolic response to operative stress in the neonate. It is evident from this review that newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with a suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin."
-What was the main finding of the study regarding neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities?,"Continuation of normal neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities. Detailed serial observations of behaviour were made in four singleton fetuses who were very small for dates and who had persistently absent umbilical artery end diastolic velocities for 2 to 9 weeks duration. All were born preterm for deteriorating maternal disease, and in two there were additional fetal indications for delivery. Behavioural comparison with 45 low risk singleton fetuses, at comparable gestations, revealed no significant differences in the development of behavioural cycles, the proportion of time spent in quiet cycles, or the amount of fetal breathing. None of the fetuses developed an abnormal heart rate pattern. We conclude that prenatal neurobehavioural development may continue apparently unimpaired in the presence of absent umbilical artery end-diastolic velocity of several weeks duration. Long term data of infant outcome are necessary before the clinical significance of this can be assessed."
-What are the potential complications of untreated abdominal aortic thrombosis?,"Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function."
-What were the most common neuro-ophthalmologic signs observed in AIDS patients in this study?,"Neuro-ophthalmologic signs of AIDS: 50 patients. In 50 hospitalized patients with acquired immunodeficiency syndrome, signs of central eye movement limitation (28 cases) were most common. Peripheral eye movement limitations (18), abnormalities of vision (18), and abnormal spontaneous eye movements (15) occurred with about equal frequency. Meningitis (17), usually due to lymphoma (8) or Cryptococcus (8), was the usual cause of peripheral nervous system involvement, while toxoplasmosis (18) was more common than lymphoma (4) or presumed viral causes (8) in producing CNS dysfunction. The midbrain and pretectal (8) were affected about as often as the pontine tegmentum (9), but rostral brainstem lesions appeared to be the result of toxoplasmosis (4) or lymphoma (3), whereas a viral etiology was the presumed cause of most caudal stem involvement."
-What specific changes in medullary catecholaminergic neurons were observed in Parkinson's disease brains compared to normal human brains?,"Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation."
-What was the main objective of the study comparing ivermectin and diethylcarbamazine (DEC) in patients with bancroftian filariasis?,"Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitologic observations. We compared the efficacy of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) for the control of microfilaremia in 60 patients with bancroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but in some cases, transient clearance of microfilaremia was observed in both treatment groups. At one year, recurrent microfilaremia was present in seven patients treated with ivermectin and in five treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremic. Side effects with both treatments were common, but mild. Febrile reactions were more frequent in the ivermectin group; localized reactions consistent with a flare-up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis."
-Does using a drain after cholecystectomy improve patient outcomes?,"Cholecystectomy is safer without drainage: the results of a prospective, randomized clinical trial. Drainage after cholecystectomy remains routine despite the lack of scientific supportive data. Numerous clinical studies in the past have attempted to address this controversy but have failed to resolve the issue for different reasons. These include retrospective design, inclusion of only selected cases, and randomization before surgery. In this study 479 patients undergoing cholecystectomy were randomly allocated to a drainage group (a high-pressure suction drain in Morison's pouch for 48 hours) or a nondrainage group. Randomization was performed at the time of peritoneal closure. All patients undergoing cholecystectomy, both elective and urgent, were included and the operations were performed by all grades of surgeons. There were two deaths from cardiopulmonary causes, both in the drainage group. No patient required reoperation in either group. The incidence of both wound infections (15 vs 5; p less than 0.05) and chest infections (56 vs 19, p less than 0.02) was significantly higher in the drainage group. Three hundred fifty-six patients underwent abdominal ultrasonography 72 hours after surgery. The number of subhepatic fluid collections thus detected was significantly higher in the patients who received a drain (17 vs 6, p less than 0.05). None of these collections was clinically significant. The postoperative hospital stay was longer in the patients with drains (10.3 vs 9.1 days), but this difference failed to reach statistical significance. We conclude from this study that the use of a drain after cholecystectomy serves no useful purpose and is potentially harmful. This practice should be abandoned."
-How can striae of Retzius in dental enamel help in identifying an individual in forensic anthropology?,"Individualization and enamel histology: a case report in forensic anthropology. The cranium of a native Indian child about six years old was found in 1979 near Taseko River, British Columbia, Canada. While the remains matched the report of a child missing for eight years in terms of race, age at death, locale, and elapsed time since death, the cranium and dentition were basically unidentifiable because of the claimed lack of medical or dental history. There was no dental work, and the parents were unknown or dead. We report the presence, in the dental enamel of the primary and secondary dentition, of stress markers, termed striae of Retzius, whose locations correspond well with anecdotal reports and recently discovered medical records which describe the timing of specific episodes of stress. The enhanced probability of personal identification from dental histological stress markers is evaluated."
-What medication was used to manage hypotension during the perioperative period for a patient with idiopathic orthostatic hypotension undergoing coronary artery bypass grafting?,"Idiopathic orthostatic hypotension, midodrine, and anaesthesia. A patient with idiopathic orthostatic hypotension receiving chronic oral midodrine therapy required anaesthesia for coronary artery bypass grafting. A perioperative infusion of phenylephrine was substituted for midodrine, an alpha-2 agonist, enabling hypotension resulting from low systemic vascular resistance to be controlled easily. Anticipated adrenergic receptor denervation hypersensitivity was noted. The only significant perioperative problem was one episode of syncope from orthostatic hypotension during the reambulation period."
-"What medical condition did the patient initially present with, and how was it resolved?","Hemidystonia due to a contralateral parieto-occipital metastasis: disappearance after removal of the mass lesion. A patient presented with left-sided hemidystonia. CT revealed a contralateral parieto-occipital mass lesion compressing the basal ganglia, which were spared by the mass. After microsurgical resection of the tumor, which was verified histologically as a metastasis of a large-cell anaplastic carcinoma, the movement disorder dissolved completely."
-What was the primary finding of this study regarding bradycardia in children with leukemia after sepsis?,"Postsepsis bradycardia in children with leukemia. OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta-adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated."
-What potential complication can occur to the pancreas during extracorporeal shock wave lithotripsy (ESWL) for renal calculus fragmentation?,"Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed."
-What was the purpose of the study on recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers?,"The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination."
-What association was found between HLA-DR1 and the development of multiple basal cell carcinomas in southern Australia?,"Multiple basal cell carcinomas and HLA frequencies in southern Australia. An association between HLA-DR1 and the development of multiple basal cell carcinomas was detected in southern Australia. A reduction in HLA-DR4 was found in patients with basal cell carcinoma compared with a local control group. The relative risk for HLA-DR1 was 2.1, which was lower than that for persons in farther countries from the equator."
-What is a coronary arteriovenous fistula and how rare is it?,Successful operation on a coronary arteriovenous fistula in a 74 year old woman. Coronary arteriovenous fistulas are rare and are usually diagnosed in children or young adults. Most are believed to be congenital. A right coronary arteriovenous fistula was first diagnosed in a patient of 74. Despite her age the fistula was successfully operated on and her symptoms were relieved.
-"What were the effects of different interferons (alpha, beta, and gamma) on human melanoma cell lines in terms of proliferation, differentiation, and cell surface markers?","Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells."
-What diagnostic technique was used to identify cor triatriatum and pulmonary venous stenosis in this adult case?,Cor triatriatum with isolated pulmonary venous stenosis in an adult: diagnosis with transesophageal two-dimensional echocardiography. The diagnosis of cor triatriatum in an adult was made from routine two-dimensional transthoracic echocardiography. The findings of aliasing and turbulence in the roof of the left atrium suggested pulmonary venous stenosis. A transesophageal echocardiogram defined both the hemodynamic features of nonobstructing cor triatriatum and the presence of isolated pulmonary venous stenosis. The clinical use of transesophageal echocardiography with color flow Doppler in the elucidation of complex anatomic substrate is demonstrated.
-What percentage of mastoid surgeries in children were performed for chronic otomastoiditis in this study?,"Mastoid surgery in childhood. The presenting features and operative findings in 105 patients aged 16 years or less undergoing mastoid surgery are reviewed. In 94% surgery was for chronic otomastoiditis, usually acquired, and associated with cholesteatoma in 64%. Post-operative otorrhoea persisted beyond 6 months in 44% and contralateral disease required some form of surgical procedure in 20%. Post-operative hearing thresholds were improved or unchanged in the majority of patients, most of whom underwent cortical or modified radical mastoidectomy. An improvement in the therapeutic results of mastoid surgery in childhood is clearly necessary, but requires a greater understanding of the aetiology of chronic middle ear disease."
-How does Doppler echocardiography help in monitoring cardiac transplant recipients compared to traditional cardiac biopsy?,"Doppler echocardiography for rejection surveillance in the cardiac allograft recipient. Echocardiography is noninvasive, allows real-time visualization of the heart, and can be performed serially without harmful biologic effects. It is also relatively inexpensive compared with other diagnostic modalities used for cardiac transplant rejection surveillance, such as cardiac biopsy, computed tomography, and magnetic resonance imaging. It is free of the potential complications associated with cardiac biopsy, such as accidental disruption of cardiac valves or chordae tendineae, ventricular septal perforation, introduction of bacteria, and the difficulty of obtaining adequate sampling for effective diagnosis as a result of formation of scar tissue. Unlike biopsy, echocardiography does not cause the patient anxiety and discomfort or use many physician and instrument or laboratory resources. Because the results of echocardiography are available within minutes compared with the hours usually needed for biopsy results, it allows prompt decisions regarding patient clinical care and treatment. In our work to date, echocardiography has not replaced the cardiac biopsy in surveillance of rejection in the cardiac transplant patient, but rather has become a useful adjunct to it. When echocardiographic findings indicate changes characteristic of rejection, biopsies are performed earlier, leading to earlier diagnosis and treatment. Furthermore, when echocardiographic findings are stable and negative for rejection, the number of routine cardiac biopsies performed can be reduced. This article discusses the use of echocardiography in surveillance of the cardiac transplant patient and the ability of echocardiography to augment the biopsy and clinical regimens in assessing cardiac allograft rejection."
-How do different alpha 1-adrenergic receptor blockers affect the incidence of abnormal automaticity in ischemic Purkinje fibers?,"Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype. BACKGROUND. Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101. METHODS AND RESULTS. In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment. CONCLUSIONS. Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment."
-What complications did the 12-year-old girl develop after receiving chemotherapy for osteogenic sarcoma?,"Secondary myelodysplastic syndrome complicating therapy for osteogenic sarcoma. A 12-year-old girl with nonmetastatic osteogenic sarcoma received treatment with doxorubicin, methotrexate, cisplatin, cyclophosphamide, bleomycin, and dactinomycin. She developed unexplained persistent pancytopenia after completion of chemotherapy. Twenty-three months after the initial diagnosis of osteosarcoma an evaluation revealed a bone marrow pattern consistent with the diagnosis of refractory anemia with excess blasts, and karyotype analysis showed characteristic findings of therapy-related myelodysplasia (loss of chromosomes 5 and 7, as well as 12p and 17p deletions). Bone marrow transplantation from an human leukocyte antigen (HLA)-compatible sibling donor was performed 26 months after the diagnosis of the primary malignancy. Although it is unproven that the alkylating agents administered to this patient were responsible for the myelodysplastic syndrome, careful follow-up of osteosarcoma patients who receive alkylating agents is warranted."
-What was the most common gastrointestinal complication in patients who underwent cardiopulmonary bypass surgery?,"Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group."
-How does the pH level affect gastrin secretion from antral G-cells?,"Much ado about gastrin [editorial; comment] The regulation of gastrin secretion from antral G-cells is of major importance in the physiologic control of acid secretion. Gastrin secretion is highly dependent upon gastric intraluminal pH and is inhibited significantly by a pH of less than 3.0. Acute gastric alkalinization greater than pH 6.0 with antisecretory agents such as H2-receptor antagonists or H+/K+ ATPase inhibitors has little impact on fasting serum gastrin levels but promotes an enhanced sustained rise in meal-stimulated gastrin release. Courses of standard therapy with both H2-antagonists and H+/K+ inhibitors cause a significant rise in 24 h integrated plasma gastrin levels that is inversely correlated to the 24-h integrated gastric acidity. The rise in fasting or integrated plasma gastrin levels observed in patients treated with H2-antagonists is small and of unclear clinical significance. Therapy with antisecretory agents leads to earlier ulcer relapse than with other agents. A variety of factors have been proposed to explain the earlier ulcer relapse rate, including secondary hypergastrinemia with rebound acid hypersecretion after discontinuation of the drug. Secondary hypergastrinemia may also lead to tolerance to prolonged courses of H2-antagonists therapy with a decrease in acid inhibition. This may contribute to break-through ulcer recurrence during maintenance H2-antagonist therapy. However, the relative importance of hypergastrinemia and tolerance to H2-antagonists compared with other factors such as baseline gastric acid secretion, smoking status, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori status is difficult to assess."
-What was the purpose of using Indium-111-leukocyte imaging in conjunction with 99mTc-iminodiacetic derivative (IDA) scintigraphy for detecting acute cholecystitis?,"Indium-111-leukocyte imaging in acute cholecystitis. Eleven patients with suspected acute cholecystitis underwent sequential 99mTc-iminodiacetic derivative (IDA) and 111In-white blood cell (WBC) imaging to determine if 111In-WBCs accumulate within an acutely inflamed hemorrhagic gallbladder wall and, thus, could be employed as a reasonable alternative to 99mTc-IDA scintigraphy in detecting acute cholecystitis. Seven patients had surgically confirmed acute cholecystitis. Of these cases, five had a true-positive 99mTc-IDA and 111In-WBC, one an indeterminate 111In-WBC and true-positive 99mTc-IDA, and one a true-positive 111In-WBC and false-negative 99mTc-IDA scan. The remaining four patients did not have acute cholecystitis. All visualized their gallbladder within 1 hr after 99mTc-IDA administration and none had 111In-WBC gallbladder wall uptake. Both 111In-WBC and 99mTc-IDA scintigraphy accurately detected acute cholecystitis: hepatobiliary scintigraphy demonstrated a cystic duct obstruction and 111In-WBC imaging detected the inflammatory infiltrate within the gallbladder wall. The sensitivity and specificity of each was 86% and 100%, respectively."
-What was the overall response rate in the study of recurrent and/or metastatic head and neck squamous cell carcinoma treated with cisplatin-based chemotherapy?,"Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy. One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What was the main objective of the study on visual evoked potentials in migraine patients?,"Visual evoked potentials and background EEG activity in migraine. To investigate whether quantification of the background EEG during a visual evoked potential (VEP) study is of value for the diagnosis of migraine we studied 8 unmedicated migraineurs between attacks, and 10 age-matched controls. Three paradigms were used: the first two concerned pattern-reversal VEPs with different analysis times (500 and 1500 ms), and in the third paradigm the pattern did not reverse. Power spectra were calculated for individual responses, and the delta, theta, alpha and beta areas of the averaged spectra were noted as indicators of background reactivity. Alpha and beta powers were consistently but not significantly higher in the migraine group. The difference was too small to be of value as a diagnostic test. Alpha power was (not significantly) lower in the presence of photic stimulation than in its absence. As this was the case in both groups photic stimulation does not explain the higher alpha powers in the migraine group. We conclude that EEG background activity during the VEP does not distinguish reliably between migraineurs and controls."
-How does interferon-gamma affect the bone marrow response to lipopolysaccharide after hemorrhagic shock?,"Interferon-gamma reverses bone marrow inhibition following hemorrhagic shock. Hemorrhagic shock has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide. Interferon-gamma has been shown to improve the immune response following experimental shock and injury; however, its effect on myelopoiesis is controversial. This study was performed to determine whether treatment with interferon-gamma will improve the bone marrow response to lipopolysaccharide after hemorrhagic shock. Rats subjected to either shock or a sham procedure were allocated into three groups: (1) control rats received no further treatment; (2) lipopolysaccharide-treated rats received saline for 3 days and then were challenged with lipopolysaccharide to stimulate myelopoiesis; and (3) interferon-treated rats received interferon-gamma (7500 U subcutaneously 1 hour after shock and then every day for 3 days) and lipopolysaccharide as in group 2. Serum colony-stimulating factor levels were measured 6 hours and bone marrow white blood cell count and granulocyte-macrophage colony-forming units (CFU-GM) were measured 24 hours following lipopolysaccharide administration. In sham-treated rats, lipopolysaccharide increased CFU-GM 77% compared with controls. In contrast, treatment with lipopolysaccharide decreased CFU-GM 43% following shock. Treatment with interferon-gamma increased CFU-GM in all animals and reversed the decline in CFU-GM seen in shocked lipopolysaccharide-treated animals. Serum colony-stimulating factor levels were unaffected by either shock or interferon-gamma administration. These data demonstrate that interferon-gamma exerts a stimulatory effect on bone marrow following shock and restores the myelopoietic response to lipopolysaccharide."
-What methods were used to study the proliferative activity of neuroendocrine tumours in this research?,"Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations. The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment."
-What were the survival rates for different groups of patients undergoing hepatic resection for hepatocellular carcinoma?,"Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period. During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively."
-How did tamoxifen therapy affect the incidence of contralateral breast cancer in postmenopausal breast cancer patients during the randomized trial?,"Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer."
-What are the key differences between B-cell and T-cell types of clear-cell immunoblastic lymphoma (IBLC) in terms of morphologic and clinical characteristics?,"Immunoblastic lymphoma with abundant clear cytoplasm. A comparative study of B- and T-cell types. The morphologic, phenotypic, molecular genetic, and clinical features of 34 cases of clear-cell immunoblastic lymphoma (IBLC) are described. Sixteen cases were of B-cell type (IBLC-B) and 18 cases were of T-cell type (IBLC-T). There were no significant differences in the morphologic characteristics of the neoplastic cells in the two types, although IBLC-B was less likely to be polymorphic than IBLC-T. Interfollicular proliferation, a higher mitotic rate, infiltration by eosinophils, and an increase in capillary-sized blood vessels were also features of IBLC-T, whereas necrosis and fibrosis were more extensive in IBLC-B. Patients with IBLC-B were predominantly female, whereas those with IBLC-T were predominantly male. The mean age was 62 years for those with IBLC-B and 46 years for those with IBLC-T. Patients with IBLC-B usually had lower-stage disease, but there was no significant difference in survival rate between those with IBLC-B and those with IBLC-T. Although most cases of IBLC have been considered to be of peripheral T-cell origin, the authors conclude that IBLC-B is more common than previously considered and that clear-cell morphologic characteristics are not a reliable indicator of T-cell type."
-What was the estimated reduction in death rate and recurrence rate for patients treated with levamisole in this melanoma study?,"Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guerin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma."
-How do the intrarenal hemodynamic parameters differ between the stenotic and contralateral kidneys in patients with renovascular hypertension?,"Glomerular hypertension in renovascular hypertensive patients. Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Forty patients with essential hypertension and 40 patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for effective renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as afferent arteriolar resistance (RA), efferent arteriolar resistance (RE) and glomerular hydrostatic pressure (PG) in each kidney. Normal values of intrarenal hemodynamic parameters were obtained in 24 normotensive subjects without ureteral catheterization, assuming each kidney had the half function of both kidneys. Systemic mean arterial pressure did not differ between essential and renovascular hypertension (141 +/- 3 vs. 148 +/- 3 mm Hg). Effective renal plasma flow and glomerular filtration rates were decreased in the stenotic kidney of RVH (98 +/- 8, 24 +/- 2 ml/min/m2), while increased in the contralateral kidney (195 +/- 11, 48 +/- 2), compared with the right kidney of essential hypertension (162 +/- 8, 33 +/- 1). Although effective renal plasma flow rate was not different from normal (191 +/- 8), glomerular filtration rate was significantly higher in the contralateral kidney of RVH than in normal (38 +/- 1). RA was elevated due to the stenotic lesion in the stenotic kidney (28,500 +/- 1,900 dyns.sec.cm-5), while the elevation in the contralateral kidney (10,800 +/- 600) was less than in the right kidney of essential hypertension (14,900 +/- 1,200). RE (5,800 +/- 300) in both kidneys of RVH was higher than in the right kidney of essential hypertension (4,500 +/- 200)."
-What is the significance of recognizing graft-vs-host disease-like histology in small intestinal biopsy specimens from patients with common variable immunodeficiency?,Small intestinal lesion resembling graft-vs-host disease. A case report in immunodeficiency and review of the literature. We report graft-vs-host disease-like histology in a small intestinal biopsy specimen that was obtained from a patient with common variable immunodeficiency and related T-cell defect. We include findings from immunohistochemical studies and follow-up information. Review of the literature yielded only a small number of histologically documented cases of this lesion without previous bone marrow transplantation. Awareness of this clinicopathologic entity is important in the interpretation of gastrointestinal biopsy specimens.
-What was the maximum tolerated dose of CPT-11 in this Phase I study of non-small-cell lung cancer treatment?,"Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance."
-How did the number of preoperative chemotherapy courses affect tumor necrosis and surgical outcomes in patients with osteosarcoma?,"Increased survival, limb preservation, and prognostic factors for osteosarcoma. Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery."
-What is a mesenchymoma of the chest wall and how rare is it in children?,"Mesenchymoma of the chest wall in children. Benign chest wall mesenchymoma in children is an extremely rare disease. Only 20 patients have been reported in the world literature. We report a chest wall mesenchymoma in a 2-year-old boy who was admitted to the hospital after a routine chest roentgenogram showed a mass in the right upper chest wall. The patient was asymptomatic. Clinical examination was negative, but chest roentgenograms and computed tomography showed a mass in the right upper chest wall involving the third rib. A 2 x 2 x 1.5-cm tumor was excised totally with partial resection of the third rib. The histology of the lesion corresponded to a mesenchymoma (hamartoma) of the chest wall. Our patient has been followed up for 8 years without recurrence."
-What was the primary treatment approach for chiasmal and hypothalamic gliomas in infants and children during the study period?,"Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease."
-What is the significance of the prolonged postischemic ventricular dilatation observed in the 99mTc MIBI scan?,"Transient prolonged postischemic ventricular dilatation documented by 99mTc MIBI scan. We describe two cases of prolonged postischemic ventricular dilatation during myocardial scintigraphy with 99mTc MIBI, the new perfusion tracer that has only negligible redistribution. Ventricular dilatation, caused by true chamber dilatation and/or subendocardial ischemia, was still present over two hours after the induced ischemic episode, suggesting a prolonged duration of such a commonly believed fleeting scintigraphic finding."
-What was the main purpose of the clinical study involving lidoflazine in cardiac arrest survivors?,"A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial II Study Group BACKGROUND. Abnormalities of cellular calcium homeostasis have been implicated in the pathophysiology of postischemic encephalopathy. Calcium-entry-blocking drugs inhibit the influx of calcium into cells and have been shown to mitigate postischemic encephalopathy in animal models. METHODS. Five hundred twenty patients with cardiac arrest who remained comatose after the restoration of spontaneous circulation were randomly assigned to receive three doses of lidoflazine, an experimental calcium-entry blocker, or a placebo and were followed for six months. Four patients were lost to follow-up. Treated patients received an intravenous loading dose (1 mg per kilogram of body weight) of lidoflazine and two subsequent doses (0.25 mg per kilogram) 8 and 16 hours after resuscitation. The investigators were blinded to treatment assignment. RESULTS. There was no statistically significant difference between the lidoflazine group (n = 259) and the placebo group (n = 257) in the proportion of patients who died during the six-month follow-up (82 vs. 83 percent), who survived with good cerebral recovery (15 vs. 13 percent), or who survived with severe neurologic deficit (1.2 vs. 1.9 percent). Analysis of the best level of recovery achieved at any time during follow-up also did not show a difference between the treatment groups: 24 percent of those given lidoflazine and 23 percent of those given placebo recovered good cerebral function (normal or only moderately disabled cerebral performance) at some time. CONCLUSIONS. The administration of lidoflazine after cardiac arrest was not found to be beneficial. Our data do not support the routine use of this calcium-entry-blocking drug in comatose survivors of cardiac arrest."
-What is an ileal neobladder and what makes it an optimal bladder substitution technique?,"The ileal neobladder. The ileal neobladder in many respects approximates the theoretically ideal continent urinary diversion. The technique, while more technically demanding than the performance of the standard ileal loop diversion, is not difficult, particularly for surgeons used to performing radical retropubic prostatectomies. The ileal neobladder appears to approximate most closely the optimal bladder substitution. Although currently feasible only in males, future considerations could conceivably involve urologists working with their colleagues in gynecology and colorectal surgery to extend the benefits of bladder substitution using the ileal neobladder to selected patients having cystectomy for associated gynecologic or colorectal malignancies."
-What was the surgical success rate for patients with and without asthma in this study of intranasal ethmoidectomy?,"The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present."
-What conservative treatment method was used to manage vesicovaginal fistulas in the described cases?,Conservative treatment of vesicovaginal fistulas by bladder drainage alone. We describe 4 cases of conservative management of vesicovaginal fistulas occurring as a complication of abdominal and vaginal hysterectomy. In all cases treatment involved simple bladder drainage for periods ranging from 19 to 54 days. At follow-up all patients remained dry. Such spontaneous closure of vesicovaginal fistulas following adequate bladder drainage has not been previously reported.
-How did early captopril administration affect infarct expansion and left ventricular segment length in patients with acute myocardial infarction?,"Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04)."
-How can AIDS prevention programs help in controlling the spread of hepatitis B virus in sub-Saharan Africa?,"How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa For developing countries the cost-benefit of vaccination in the control of hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that, compared with south-east Asia, infection occurs later in childhood and spread is horizontal rather than vertical, investigation of the method of spread of HBV may result in a means of control other than by vaccination. In the meantime, because of the overlap in the means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking advantage of existing AIDS prevention programmes to educate people about how to avoid both HBV and HIV infections."
-What are the key characteristics of pulmonary angiitis and granulomatosis syndromes in terms of clinical presentation and radiologic features?,"Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions."
-How does core temperature affect splanchnic sympathetic nerve activity in rats during environmental heating?,"Splanchnic sympathetic nerve activity and circulating catecholamines in the hyperthermic rat. The mechanisms responsible for the initial rise in splanchnic vascular resistance with environmental heating are controversial, and those responsible for the subsequent fall in splanchnic resistance in the severely hyperthermic animal are unknown. Thus we examined the effect of environmental heating on plasma catecholamine concentration, splanchnic sympathetic nerve activity (SNA), and select blood chemistries. In one study, 25 male Sprague-Dawley rats (270-300 g) were assigned to one of five groups on the basis of their core temperature (Tc, 37, 39, 41, 43, or 44 degrees C) at death. Heart rate (HR), mean arterial pressure (MAP), and Tc were monitored during heat stress under alpha-chloralose anesthesia (12.5 mg.ml-1.h-1). At each predetermined Tc, an aortic blood sample was drawn and analyzed for mean plasma concentration of norepinephrine (NE), epinephrine (E), Na+, K+, and lactate. From 41 to 43 degrees C, NE and E rose significantly, and the animals became hyperkalemic and lactacidemic. In a separate study, we quantitated SNA from the greater splanchnic nerve during heat exposure of artificially respired animals anesthetized with pentobarbital sodium (50 mg/kg). MAP, splanchnic SNA, and Tc were recorded. Tc was elevated from 37.0 +/- 0.12 to 41.3 +/- 0.18 degrees C in 70 min by increase of ambient temperature to 38 degrees C in an environmental chamber. Splanchnic SNA was 54 +/- 8 spikes/s at a Tc of 37 degrees C and increased significantly as Tc exceeded 39 degrees C (P less than 0.05)."
-How does clonidine affect blood pressure and hemodynamic responses differently in normal subjects compared to tetraplegic patients?,"Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action. BACKGROUND. Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated. METHODS AND RESULTS. The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors. CONCLUSIONS. Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension."
-What were the treatment methods used for prostatic cancer in the study involving 63 patients?,"Morbidity of modified pelvic lymphadenectomy and radiotherapy for prostatic cancer. The records of 63 patients treated by pelvic lymphadenectomy and radiotherapy at the University of Tennessee, Memphis, Baptist Memorial Hospital of Memphis, and the Memphis Veterans Affairs Hospital were reviewed. Of those patients, 45 received external beam radiation therapy to the prostate while 16 were treated by Iodine-125 implantation. Two patients had only staging lymphadenectomy. The incidence of postoperative and late complications were analyzed."
-How did the application of a smooth Teflon clip to the inferior vena cava affect the incidence of pulmonary embolism in patients undergoing radical cystectomy?,"Application of smooth Teflon clip to inferior vena cava during radical cystectomy to prevent postoperative pulmonary embolism. Between 1976-1986, a smooth Teflon clip was applied to the inferior vena cava of 56 patients who underwent radical cystectomy for bladder cancer. The purpose of the clip is to narrow the lumen of the inferior vena cava so that large emboli will be trapped and thus prevented from reaching the lungs. These 56 patients were compared with a group of 26 historical controls who underwent radical cystectomy without application of such a clip between 1967-1976. One patient (1.8%) whose vena cava was clipped had a pulmonary embolus which was fatal. Four (15.4%) of the 26 control patients had postoperative pulmonary emboli, the embolic event being fatal in 3 (11.5%). Application of the smooth Teflon clip to the inferior vena cava significantly lessens the incidence of pulmonary embolism following radical cystectomy."
-Who was Paul Broca and what significant medical procedure did he perform in 1871?,"Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization."
-What makes coronary restenosis a significant challenge in interventional cardiology?,"Coronary restenosis: what have we learned from angiography? Coronary restenosis remains a major problem for interventional cardiology not only by virtue of its frequency, but also because of the current inability to prevent it. Symptomatic status and non-invasive evaluation have been used to study restenosis, but both lack specificity and sensitivity, particularly in patients with multivessel disease. Angiography remains the reference standard. Several arbitrary definitions have been used, some related to visual estimates of coronary stenosis and others to quantitative angiographic techniques. In another approach, linear modeling is used to assess minimal luminal diameter of lesions on restudy. Although angiographic studies have been essential in the study of restenosis, questions concerning the underlying mechanism and pathophysiology remain. The development of animal models that closely resemble human restenosis should allow evaluation of pathophysiologic mechanisms and development of new strategies to prevent the problem."
-What are the main sources of mortality data for shigellosis in developing countries?,"Mortality due to shigellosis: community and hospital data. Almost all fatal cases of shigellosis occur in developing countries, and data on mortality are generally compiled from three sources: investigations of epidemics caused by Shigella dysenteriae type 1, surveillance of endemic diarrheal disease, and reports from hospitals. Attack rates during epidemics of dysentery due to infection with S. dysenteriae type 1 have ranged from 1% to 33%, and case-fatality rates have ranged from 1% to 7%. In Matlab, a rural district in Bangladesh, most diarrhea-related deaths and approximately 25% of all deaths among children 1 through 4 years of age are attributable to dysentery. In 1984, an epidemic of dysentery was associated with a 42% increase in the death rate in that age group. At the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, the fatality rate for 970 inpatients with shigellosis was 11% in 1988, with most deaths occurring among malnourished children who were infected with Shigella flexneri. Control of mortality from shigellosis will require prevention of epidemic S. dysenteriae type 1 disease and endemic S. flexneri infections in children who live in countries with a high prevalence of malnutrition."
-How does diclofenac affect the healing of gastroduodenal mucosal lesions according to the study?,"Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions."
-What is auriculotemporal syndrome (ATS) and how does it relate to temporomandibular joint (TMJ) surgery?,"Auriculotemporal syndrome following the preauricular approach to temporomandibular joint surgery. Forty-seven joints in 28 patients were examined 4 months to 10 years after temporomandibular joint (TMJ) surgery via a modified preauricular approach. Many patients had undergone multiple procedures. None of the patients had any subjective or objective evidence of auriculotemporal syndrome (ATS), although patients in previous studies with more extensive incisions have demonstrated ATS. It was concluded that ATS is an unlikely complication following TMJ surgery. A small incision without an oblique superior extension may further reduce the risk."
-How does left ventricular hypertrophy (LVH) impact cardiovascular health and what role do calcium channel blockers play in managing this condition?,"Left ventricular hypertrophy: impact of calcium channel blocker therapy. Left ventricular hypertrophy (LVH) of the concentric type is the classic cardiac adaptation to sustained arterial hypertension. Data from the Framingham cohort have shown that patients with LVH have a severalfold higher risk of sudden death, acute myocardial infarction, and other cardiovascular morbidity than those with normal hearts. Common sequelae of LVH are ventricular ectopy, impaired ventricular contractility, myocardial ischemia, and decreased left ventricular filling. The benefits of antihypertensive therapy should not be limited to lowering arterial pressure, but should extend to preventing or reducing target organ damage. A variety of antihypertensive agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, antiadrenergic drugs, and, to a lesser extent, beta blockers, have been shown to reduce LVH and to improve left ventricular filling. We have shown that calcium channel blockers diminish ventricular ectopy in parallel with the reduction of LVH, whereas antihypertensive therapy with diuretics neither reduced LVH nor suppressed ventricular ectopy, although it lowered arterial pressure to a similar extent. Whether or not these cardiac changes with antihypertensive therapies will improve cardiovascular morbidity and mortality in patients with LVH remains to be documented."
-What was the unusual finding in this patient's case that led to a pathological confirmation during nephrectomy?,"Intrarenal pancreatic cyst. A case report of intrarenal true cyst of the pancreas is presented. The patient presented with flank pain. Her diabetes and hypertension were well-controlled. The cause of the pain was presumed to be a cystic renal mass, which proved to be of pancreatic origin only after the pathologic confirmation from the nephrectomy specimen."
-How has the understanding and diagnosis of preeclampsia changed over time according to the given context?,"Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased."
-What unique medical technique was used to manage a through-and-through knife injury of the aortic arch in this case report?,"Artificially induced ventricular fibrillation in the management of through-and-through penetrating wounds of the aortic arch: a case report. Case report of a 28-year-old woman in whom a through-and-through knife injury of the aortic arch is presented. The hemorrhage could not be brought under control by conventional means and was handled by artificially induced temporary electric fibrillation of the heart, direct suture, and immediate defibrillation. The patient made an uneventful recovery."
-How does profound cerebral hypothermia (Ttm less than 10 degrees C) compare with deep hypothermia (15 degrees C) in terms of neurologic outcomes after circulatory arrest in dogs?,"Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery. Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia."
-How does the location of the sample volume affect the transmitral filling measurements in pulsed Doppler echocardiography?,"Dependency of the pulsed Doppler-derived transmitral filling profile on the sampling site. In previous reports that evaluated pulsed Doppler transmitral filling, the sampling site has varied; we examined the effect of the sample volume location on Doppler measurements. Studied were 97 patients: 58 with normal echocardiograms, 20 with mitral regurgitation, and 19 with miscellaneous cardiac diseases. Transmitral filling was recorded at the mitral anulus and at the left atrial and left ventricular (LV) sides of the mitral tips. As the sample volume was moved from the mitral anulus to the LV side, the peak velocity and time-velocity integral of early diastole increased (40.6 +/- 13.8 versus 59.0 +/- 19.0 cm/sec, 5.26 +/- 1.65 versus 8.35 +/- 2.37 cm; p less than 0.001) as did those of late diastole (48.7 +/- 11.5 versus 57.5 +/- 17.0 cm/sec, 3.48 +/- 0.97 versus 4.59 +/- 1.39 cm; p less than 0.001). The late-to-early diastolic peak velocity and time-velocity integral ratios and the late-to-total diastolic time-velocity integral ratio decreased (1.33 +/- 0.51 versus 1.06 +/- 0.41, 0.71 +/- 0.24 versus 0.58 +/- 0.19, 0.40 +/- 0.09 versus 0.36 +/- 0.08; p less than 0.001). The dependency of these indices on the sampling site was in the same degree in all three groups. However, the peak filling rate normalized to mitral stroke volume (4.71 +/- 1.43 versus 4.63 +/- 1.32 l/sec; p = NS) was not influenced by the sample volume location; thus this parameter may be more reliable for assessing LV filling."
-Is anticoagulation completely contraindicated in hemorrhagic cardioembolic stroke?,"Hemorrhagic cardioembolic stroke: is anticoagulation absolutely contraindicated? Hemorrhagic cerebral embolism should not be considered an absolute contraindication to immediate low-dose systemic anticoagulation. Low levels of anticoagulation may give some protection from recurrent embolism while minimizing the risks of intracranial bleeding. Until further studies are available, these decisions must be made on a case-by-case basis, supported by limited scientific information."
-What are the key advantages of laparoscopic cholecystectomy compared to conventional cholecystectomy?,"Laparoscopic cholecystectomy: 111 consecutive cases. Laparoscopic cholecystectomy removes the gallbladder through three or four puncture wounds in the abdominal wall. The technique reduces the recuperative time to full activity, from as long as 4 wk to as little as 3 days, compared with conventional cholecystectomy. We herein present our initial experience with this procedure. In this series of 111 laparoscopic cholecystectomies, there were no mortalities and only one morbidity. Thirty-nine patients (35%) had a history of prior abdominal surgery. Fourteen underwent laparoscopic lysis of adhesions. Intraoperative cholangiograms were performed in 24 patients (21%), demonstrating choledocholithiasis in three. Two of the three patients underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP); in the other, laparoscopic common bile duct exploration was performed. In each case, the common bile duct (CBD) was completely cleared of stones. Incidental laparoscopic appendectomy was also performed in three patients. The average time for completion of laparoscopic cholecystectomy in cases of chronic cholecystitis was 40 min. If the gallbladder was acutely inflamed, the procedure took a mean of 126 min. This series had a higher percentage of patients (19%) with acute cholecystitis then previously reported; therefore, the 2% conversion rate in this series emphasizes the broad applicability of the technique. The average length of stay in the hospital was 1.4 days, and patients returned to work in about 7 days."
-How did infection and malnutrition affect liver glutathione and cytochrome P450 levels in the experimental rat study?,"Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition. OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients."
-"What is the significance of the ""Metsovo lung"" phenomenon in Greece?","Metsovo lung outside Metsovo. Endemic pleural calcifications in the ophiolite belts of Greece. Endemic PCs and high incidence of malignant mesothelioma from household use of asbestos have been reported in Metsovo in northwestern Greece (""Metsovo lung""). In the present study, we present similar findings in six more areas of Greece. Like Metsovo, all these areas are located within ophiolite belts. Like Metsovo, material similar to ""Metsovo whitewash"" has been used for various domestic uses. Asbestos fibers (chrysotile, antigorite and tremolite) were found in three of the six areas. Also, in two, MPM has been diagnosed. These findings suggest that ""Metsovo lung"" occurs in several areas of Greece and has similar etiology and epidemiology."
-How does the radionuclide technique (VEST) help in detecting silent myocardial ischemia during balloon angioplasty?,"Validation of continuous radionuclide left ventricular functioning monitoring in detecting silent myocardial ischemia during balloon angioplasty of the left anterior descending coronary artery. Silent myocardial ischemia has been inferred from transient ST-segment depression during continuous electrocardiographic monitoring. Recently, continuous ambulatory monitoring of left ventricular (LV) function using a radionuclide technique (VEST) has demonstrated episodes of significant silent LV dysfunction in the absence of electrocardiographic changes. To validate the demonstration of silent LV dysfunction with this technique, 12 men were studied during percutaneous transluminal coronary angioplasty. A total of 18 left anterior descending coronary artery balloon inflations were performed. Balloon inflations at 8 +/- 2 atm (4 to 10 atm) lasted 70 +/- 16 seconds. Seventeen of 18 inflations were associated with a decrease in LV ejection fraction greater than 0.10. Mean LV ejection fraction decreased from 0.53 +/- 0.08 to 0.28 +/- 0.11 (p less than 0.0001). In contrast, there was pain in only 10 inflations and ST-segment changes in 7. LV dysfunction was associated with a minimal increase in end-diastolic volume (4 +/- 3%, p less than 0.003), and a major increase in relative end-systolic volume (69 +/- 43%, p less than 0.001). These data suggest that continuous monitoring of LV function with the VEST can sensitively detect silent ischemic decreases in LV function occurring during angioplasty, and provide further validation of the use of this technique for detecting silent myocardial ischemia."
-What is the relationship between primary sclerosing cholangitis and bone mineral density?,"The metabolic bone disease of primary sclerosing cholangitis. The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis."
-How do propofol and methohexital differ in their effects on left ventricular performance and hemodynamic parameters?,"Left ventricular performance during propofol or methohexital anesthesia: isotopic and invasive cardiac monitoring. Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect."
-How does the orientation of a lipid-water interface affect the chemical shift artifact in magnetic resonance imaging?,"Chemical shift artifact: dependence on shape and orientation of the lipid-water interface. On magnetic resonance images, chemical shift artifact (CSA) can be seen at a planar lipid-water interface oriented within the plane of the phase-encoding and section-select directions (ie, perpendicular to the frequency-encoding direction). Phantoms and a clinical case were used to demonstrate that when a lipid-water interface is curvilinear (eg, spherical) or planar but not oriented along the section-select direction, CSA may be absent or diminished. This effect can be seen at interfaces of normal structures (kidneys, bladder) as well as at interfaces with pathologic lesions such as lipid-containing dermoids. Not only is this effect dependent on section thickness, field of view, matrix size, and receiver bandwidth, but it is also strongly dependent on the orientation of the interface with respect to the section-select direction. Knowledge of the factors that can alter CSA is important since it is used to distinguish lipid-containing from nonlipid-containing structures of similar signal intensities."
-How does exercise echocardiography compare to electrocardiography as a screening test for coronary artery disease?,"Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography. We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease."
-How can nutrition therapy potentially help in managing immune dysfunction in critically ill patients?,Potential of parenteral and enteral nutrition in inflammation and immune dysfunction: a new challenge for dietitians [published erratum appears in J Am Diet Assoc 1991 Aug;91(8):913] Advances in the understanding of the interrelationship between immunology and nutrition indicate that immune dysfunction in critically ill patients is linked with nutrient deficiency and abnormal acute-phase response to illness. Immune dysfunction requires special nutrition therapy and metabolic support; immunoregulation by nutrition manipulation may lead to specific immunotherapies for defined groups of patients. The success of dietary strategies must be measured not only by metabolic indexes but also by effects on immune function. The health profession must combat immune dysfunction and inflammation for the sick and frail patients under its care.
-What were the main risk factors for cerebrovascular events in patients with acute myocardial infarction according to the GISSI trial?,"Cerebrovascular events after myocardial infarction: analysis of the GISSI trial. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). OBJECTIVES--To describe the epidemiology of cerebrovascular events in patients given or not given fibrinolytic treatment and to assess the prognostic implications and risk factors. DESIGN--Case series derived from the GISSI randomised trial. SETTING--176 coronary care units in Italy giving various levels of care. PATIENTS--5860 patients with acute myocardial infarction treated with 1.5 million units of intravenous streptokinase and 5852 patients not given fibrinolytic treatment. MAIN OUTCOME MEASURES--Cerebrovascular event, sex, age, blood pressure, history of previous infarct, site of infarction, and Killip class. RESULTS--99 of 11,712 patients (0.84%) had a cerebrovascular event. Older age, worse Killip class, and anterior location of infarction seemed to be risk factors for cerebrovascular events (40/3201 aged 65-75 v 42/7295 aged less than 65, odds ratio 2.18; 9/437 class 3 v 55/8277 class 1, 1.81; and 57/4878 anterior v 24/4013 posterior, 1.96). No significant difference was found in the rate of cerebrovascular events between patients treated with streptokinase and controls (45/5852 (0.92%) streptokinase v 54/5860 (0.77) control). More patients in the streptokinase group than in the control group had cerebrovascular events (especially haemorrhagic strokes) on day 0-1 after randomisation (27 streptokinase v 7, control), although this was balanced by late events in control patients (54 streptokinase v 45 control at one year). The mortality of patients who had a cerebrovascular event was higher than that of those who did not (47% (47/99) v 11.6% (1350/11,613]. CONCLUSIONS--Although the incidence of cerebrovascular events complicating myocardial infarction was low, they increased morbidity and mortality. Treatment with streptokinase did not significantly alter the incidence, but age and poor haemodynamic state were associated with an increased risk."
-"What surgical approach was used for treating orbital floor and rim fractures in this study, and what were its advantages?","Treatment of 813 zygoma-lateral orbital complex fractures. New aspects. A 10-year experience with surgical treatment of 813 zygomalateral orbital complex fractures is reviewed. Regardless of the type or severity of the fracture pattern, concomitant fractures of the orbital floor and rim were approached exclusively through the transconjunctival approach without a lateral canthotomy. The advantages of this approach compared with the subciliary access are the avoidance of a visible scar and markedly reduced incidence of postoperative lower eyelid complications such as ectropion and edema. Implants of lyophilized dura or cartilage and autogenous bone were used to reconstruct orbital floor defects. Malar asymmetry is a frequent complication of zygoma fractures resulting from inadequate three-dimensional reduction. Methods for accurate reduction and stabilization, indications for closed and open reduction, and management of the fractured infraorbital rim are emphasized. The indications for miniplates vs wire ligatures for the infraorbital rim are discussed. Long-term follow up and evaluation of the results with regard to the fracture pattern, complications, maxillary sinus dysfunction, and facial and orbital symmetry are presented."
-What was the key finding regarding lymphocyte response to group A haemolytic streptococcal antigens in patients with chronic plaque psoriasis?,"Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis. The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed."
-What is the prevalence of celiac or superior mesenteric artery stenoses among male veterans evaluated for peripheral vascular disease?,"Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients."
-What medical treatments were used for lichen sclerosus and squamous hyperplasia in this clinical study?,"Lichen sclerosus and squamous hyperplasia of the vulva. A clinical study of medical treatment. One hundred thirty-eight cases of nonneoplastic epithelial disorders of the vulva treated with medical therapy from 1984 to 1988 were evaluated at the University of Florence, Florence, Italy. The 67 cases of lichen sclerosus were treated with testosterone propionate or progesterone ointment for 32 weeks. The 31 cases of squamous hyperplasia were treated with corticosteroid ointment for 16 weeks. The 40 patients with lichen sclerosus associated with squamous hyperplasia were treated with corticosteroid ointment for 12 weeks and then with testosterone propionate ointment for another 20. To evaluate the efficacy of the treatments, the patients were examined before and after therapy. The evaluation took into account the symptoms and gross appearance of the lesions, which were given a score of 1-3. Considering all the cases evaluated, a total regression of symptoms occurred in 82 patients (59.4%), while a partial regression occurred in 37 (26.8%). Furthermore, there was a total regression of gross changes in 68 cases (49.3%) and a partial one in 43 (31.1%). The best results were obtained with squamous hyperplasia, which lichen sclerosus, alone or associated with squamous hyperplasia, yielded less successful results."
-What were the key findings of the study on the Duhamel operation for treating idiopathic megarectum and megacolon?,"Results of the Duhamel operation in the treatment of idiopathic megarectum and megacolon. The results of the Duhamel operation in patients with idiopathic megarectum and megacolon have been reviewed. Twenty patients (14 males, six females) underwent the Duhamel operation over a 17-year period for this condition. The mean age at operation was 25 years; the mean age of onset of constipation was 3 years; and the mean follow-up period was 4.5 years. All the resected colons were of enlarged diameter. There was agreement between the preoperative radiographs and the operative specimens with regard to which parts of the rectum and colon were dilated. Subjective feelings of well-being were generally improved by surgery, as was bowel frequency in ten patients. Soiling, straining, abdominal pain and distension were, however, common after operation. Early complications were also common and five patients required further surgery for constipation. The Duhamel operation for megarectum and megacolon is characterized by an improved sense of well-being and improved bowel frequency, but it is associated with the persistence of many symptoms and further surgery is often required."
-What are the key clinical considerations when managing cocaine-induced thrombocytopenia and hypertension during early pregnancy?,"Acute transient thrombocytopenia associated with cocaine abuse in pregnancy. A case is described of cocaine-induced severe transient thrombocytopenia associated with a hypertensive crisis at 21 weeks' gestation. Liver function tests and coagulation studies were all within normal ranges. Blood pressure was controlled with hydralazine. This clinical presentation, similar to severe preeclampsia, should be considered in the differential diagnosis of acute hypertension and low platelet count, especially in early gestations when preeclampsia is relatively rare. Unlike severe preeclampsia, for which active intervention and delivery are usually selected, cocaine-related hypertension-thrombocytopenia, especially in very premature gestations, may warrant conservative management."
-What treatment was found effective for adult patients with severe abdominal complications of Henoch-Schonlein purpura?,"Successful treatment of adult Henoch-Schonlein purpura with factor XIII concentrate. We report the cases of three adult patients with severe abdominal complications of Henoch-Schonlein purpura who had low activity of factor XIII during the acute phase of the disease. In all three cases, abdominal symptoms and purpura immediately responded to heat-treated, placenta-derived factor XIII concentrate. No adverse effects were experienced. Factor XIII concentrate replacement should be considered as the initial treatment for severe abdominal symptoms in adult Henoch-Schonlein purpura associated with a decreased level of factor XIII activity."
-What percentage of patients in the study experienced a decrease in arterial oxygen saturation levels during colonoscopy?,"An evaluation of multiple clinical variables for hypoxia during colonoscopy. One hundred consecutive patients undergoing routine colonoscopy were evaluated for changes in arterial oxygen saturation levels. All of the patients were monitored with the Nellcor N-200 pulse oximeter (Nellcor Incorporated) by finger probe and received supplemental oxygen when SaO2 levels decreased below 90 per cent. Forty patients demonstrated a decrease in SaO2 to less than 90 per cent after intravenous sedation but prior to colonoscopy, 14 patients demonstrated a decrease in SaO2 to less than 90 per cent during colonoscopy, and 46 patients maintained SaO2 levels greater than 90 per cent at all times. No statistical differences were found when these three groups were compared for age, body surface area, drug dosage, smoking history and a history of pre-existing hypertension, diabetes, arrhythmias, angina or myocardial infarction and pulmonary disease. These data indicate that all patients undergoing colonoscopy should be placed on supplemental oxygen. We further recommend continuous cardiac and pulse oximetry monitoring when available."
-What unusual cause of pneumoperitoneum was revealed in this case report?,"Recurrent pneumoperitoneum following vaginal insufflation. The authors report a case of a 24-year-old nulligravida woman who presented to the hospital with complaints of severe abdominal pain and radiographic evidence of pneumoperitoneum. She had two prior nondiagnostic laparotomies for similar complaints and radiographic findings. After a careful sexual history was taken the patient revealed that she had sexual intercourse preceding every similar episode including this one, during which her partner forcefully blew air into her vagina. Pneumoperitoneum associated with vaginal insufflation has been previously reported in two multigravida patients with and without anatomic abnormalities. When pneumoperitoneum is present in the absence of gastrointestinal symptoms or trauma, a meticulous sexual history should be made to avoid unnecessary laparotomies."
-What were the key findings of the study regarding the performance of the new radiopaque balloon-expandable coil stent in pigs?,"Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs. BACKGROUND. Intracoronary stents may be effective when used as ""bail-out"" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited."
-What unique characteristics were found in the promoter region of the human platelet-derived growth factor A-chain gene?,"Promoter region of the human platelet-derived growth factor A-chain gene. The platelet-derived growth factor (PDGF) A- and B-chain genes are widely expressed in mammalian tissues and their homodimeric gene products appear to regulate the autocrine growth of both normal and transformed cells. In this study, we analyzed the 5' flanking sequences of the human PDGF A-chain gene to seek elements important to regulating its transcription. The promoter region was exceptionally G + C-rich and contained a ""TATA box"" but no ""CAAT box."" The transcription start site was identified 845 base pairs 5' to the translation initiation site by S1 nuclease mapping and by primer extension. Both in vitro transcription and transient expression of the chloramphenicol acetyltransferase gene linked to the PDGF A-chain 5' flanking sequences established that the putative promoter region was active, and RNase H mapping established that the three characteristic mRNAs (1.9, 2.3, and 2.8 kilobases) used the same transcription start site, which was used in normal endothelial cells and in two human tumor cell lines that express high levels of A-chain transcripts. The results established an exceptionally G + C-rich promoter region and a single transcription start site active for each of the three mRNAs of the PDGF A-chain gene. DNA sites of potential importance in mediating the activation of the PDGF A-chain gene in normal cells and in transformed cell lines expressing high levels of PDGF A chain were identified."
-"What was the primary objective of the multicenter, prospective trial involving the Nd:YAG laser in treating endometriosis and pelvic adhesions?","Operative laparoscopy with the Nd:YAG laser in the treatment of endometriosis and pelvic adhesions. A multicenter, prospective trial was initiated to test the effectiveness and safety of the Nd:YAG laser equipped with artificial sapphire contact tips for the laparoscopic treatment of pelvic pain. Ninety-three women were enrolled in the study, 37 with endometriosis alone, 47 with endometriosis complicated by pelvic adhesions, and 9 women with adhesions alone. In over 90% of adhesions and 96% of endometriotic implants the Nd:YAG laser could be delivered to the site and be used to restore normal anatomy. The exception was deep bowel involvement with endometriosis, which was not treated. The majority of women had marked reduction or resolution of their symptoms for up to 12 months postoperatively. We conclude that the use of the Nd:YAG laser is an appropriate method to laparoscopically treat pelvic pain resulting from endometriosis or pelvic adhesions."
-What challenges do physicians face when treating patients who have used designer drugs?,"'Designer drugs'. Treating the damage caused by basement chemists. Use of ""designer drugs"" has created a new dilemma for physicians. Generally, it is possible to recognize symptoms and signs of intoxication that fit a specific class of substances, such as amphetamine-like effects for the phenylethylamines and opioid effects for the fentanyl analogues. Designer compounds have crossed these boundaries, and toxicology laboratories cannot readily identify them. For now, physicians must rely on clinical presentation and treat accordingly."
-What percentage of patients with high-energy midface fractures experienced orbital dislocations in the study?,"High-energy orbital dislocations: the possibility of traumatic hypertelorbitism. In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness."
-How does the combination of hemorrhage and intracranial hypertension affect thromboxane A2 production in the brain?,"Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2. BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock."
-How do oxygen-derived free radicals impact myocardial injury during coronary microvascular embolization?,"Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization BACKGROUND. Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization."
-What percentage of heart failure patients die suddenly before reaching New York Heart Association class IV symptoms?,"Genesis of arrhythmias in the failing heart and therapeutic implications. Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life."
-How did the perceived beliefs of others and attitudes impact regimen compliance among myocardial infarction patients two years after the intervention?,"Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens."
-What was the overall response rate of the high-dose cisplatin with dacarbazine and tamoxifen treatment in patients with metastatic melanoma?,"High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine."
-What are the key diagnostic modalities used for accurately classifying subtypes of lymphoma and leukemia?,"Cytologic diagnosis of leukemia and lymphoma. Values and limitations. The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented."
-How does left ventricular mass relate to symptoms and cardiac function in childhood dilated cardiomyopathy?,"Left ventricular mass in childhood dilated cardiomyopathy: a possible predictor for selection of patients for cardiac transplantation. To determine the relationship of left ventricular hypertrophy (as assessed by mass) to symptoms and cardiac function in chronic childhood dilated cardiomyopathy, 17 long-term survivors (12 asymptomatic, 5 symptomatic) were studied at a median follow-up of 6.25 years (1.25 to 16.8 years). Left ventricular mass, dimension, wall stress, and contractility (relationship between velocity of circumferential fiber shortening and end-systolic wall stress) were assessed by echocardiography. These data were compared to measurements at the onset of disease. At follow-up, mass decreased significantly from the onset in the asymptomatic patients but remained elevated in the symptomatic patients (101 +/- 35 gm/m2 to 54 +/- 12 gm/m2, p = 0.001; 122 +/- 55 gm/m2 to 198 +/- 115 gm/m2, p = 0.23, respectively). Shortening fraction and contractility were both significantly lower in the symptomatic group compared with the asymptomatic group at follow-up (shortening fraction = 21 +/- 7% vs 29 +/- 5%, p = 0.02; contractility = -0.24 +/- 0.14 circ/sec vs -0.05 +/- 0.11 circ/sec, p = 0.01). Follow-up wall stress was slightly higher in symptomatic patients compared with asymptomatic patients. Three symptomatic patients had progressive hypertrophy and either died or required transplantation. Higher left ventricular mass is associated with the presence of symptoms, depressed contractility, and slightly higher wall stress. Persistence or progression of hypertrophy may be a poor prognostic sign in survivors of childhood dilated cardiomyopathy. Measurement of mass may be useful to indicate the necessity for closer follow-up to select patients for cardiac transplantation before hemodynamic decompensation."
-How do immune complexes modulate granuloma formation in patients with chronic schistosomiasis?,"Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins."
-How did the patient's Cushing's disease potentially contribute to the development of cutaneous alternariosis?,"Cushing's disease and cutaneous alternariosis. Alternaria species are common plant pathogens, but a rare cause of human infection. We present a patient with cutaneous alternariosis that revealed a relapse of an old case of Cushing's disease. Immunosuppression following the excessive glucocorticoid production seemed to contribute to the development of dermatosis. We also present a review of the literature on the association of Cushing's disease and cutaneous alternariosis. Our case is unique because the ketoconazole therapy that we used was successful in the treatment of both diseases."
-What surgical technique was used to successfully treat the esophagocutaneous fistula in this case report?,"Esophagocutaneous fistula after anterior cervical spine surgery and successful treatment using a sternocleidomastoid muscle flap. A case report. An esophagocutaneous fistula following anterior cervical fusion is rare. A 61-year-old man had cervical myelopathy because of ossification of the posterior longitudinal ligament of the cervical spine. Anterior decompression of the cervical spine and anterior fusion with strut bone grafting were performed. A second anterior fusion was done because the graft was dislodged after the patient fell out of bed one month after surgery. An esophagocutaneous fistula occurred three months after the second anterior surgery. One of the causes of this esophagocutaneous fistula was considered to be a pressure necrosis of the esophagus because of to projection of the bone graft. Conservative treatment, which consisted of wound drainage and intravenous administration of antibiotics, was tried but was unsuccessful. A good result was achieved by cancellous bone grafting, closure of the esophageal fistula, and transposition of a sternocleidomastoid muscle flap to the interspace between the esophagus and the cervical spine."
-How does diazepam binding inhibitor (DBI) affect mitochondrial steroidogenesis in Y-1 adrenocortical and MA-10 Leydig cell lines?,"Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. A recognition site for benzodiazepines structurally different from that linked to various gamma-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide diazepam binding inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-1 adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17-50)] and octadecaneuropeptide [DBI-(33-50)]. When DBI purified from rat brain was added to mitochondria prepared from Y-1 and MA-10 cell lines, it increased the rates of pregnenolone formation in a dose-related manner. In both cell lines, maximal stimulation (3-fold) of mitochondrial steroidogenesis was obtained with 0.33 microM DBI, with an EC50 of approximately 0.1 microM. However, DBI concentrations higher than 1 microM caused a smaller increase in pregnenolone formation. Flunitrazepam, a benzodiazepine that binds with high nanomolar affinity to MBR, was recently shown to act as an antagonist of ACTH and LH/hCG-induced steroidogenesis and was found in the present studies to inhibit DBI-stimulated mitochondrial steroidogenesis. During the incubation with mitochondria, DBI was partially processed to different peptide fragments, including octadecaneuropeptide and TTN. To determine whether DBI processing products influence mitochondrial steroid biosynthesis, several DBI fragments and other peptides structurally unrelated to DBI were tested. Among these, only TTN stimulated mitochondrial steroid synthesis in a dose-dependent manner similar to DBI."
-What are the advantages of centrally acting sympatholytic agents in managing hypertension?,"Use of centrally acting sympatholytic agents in the management of hypertension. Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction."
-What was the main finding of the Medical Research Council Vitamin Study regarding the prevention of neural tube defects?,"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid."
-What are the key findings of the study regarding the distribution of neurofilament protein epitopes in cortical Lewy bodies?,"Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (Mr) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport."
-How can sexually transmitted diseases impact the reproductive health of women and their offspring?,"Preventing fetal damage from sexually transmitted diseases. The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death. An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially. Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well. Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections. Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections."
-What are the two main groups of drugs used in migraine therapy?,"Pharmacology of antimigraine drugs. The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT1-like receptors, beta-adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT1-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine."
-What are the most practical and useful techniques for diagnosing perivalvular extension of infection in patients with infectious endocarditis?,"Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review."
-What are the primary aims of treatment for patients with heart failure?,"Assessing drugs for the treatment of heart failure. The aims of treatment in patients with heart failure, as with any other condition, are to relieve symptoms and prolong life. A secondary objective is to do so at the lowest possible economic cost. When treatment of the cause of heart failure is possible--which usually means some form of surgery, but could include treatment of a primary disease, such as thyrotoxicosis--then this is obviously the treatment of choice. In patients for whom there is no such definitive treatment, a wide and increasing variety of drugs are available. When new antifailure drugs are to be developed there are therefore two problems: first, to ensure that they are more effective than placebo treatment, and second, to compare them with existing drugs. Both of these tests can present ethical difficulties, for it is unreasonable to withhold established effective treatment in order to conduct a placebo-controlled trial, and when drugs are being compared, it is unlikely that any new medication will be dramatically superior to an old one. The more effective the treatments already available, the harder it becomes to evaluate a new drug."
-How quickly do motor units diminish in muscles affected by amyotrophic lateral sclerosis (ALS) during the first year of disease progression?,"The extent and time course of motoneuron involvement in amyotrophic lateral sclerosis. The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction."
-How does prolonged hypoxia affect prostacyclin production and adenylate cyclase activity in rat pulmonary arteries?,"Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat. Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta-adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia."
-How was the treadmill score calculated in this study of outpatients with suspected coronary artery disease?,"Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease BACKGROUND. The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS. We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS. Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS. The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment."
-How did iodine-131-3F8 radioimmunoscintigraphy compare to other diagnostic methods in detecting neuroblastoma sites?,"Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection."
-How does the number of metastatic lymph nodes affect the 5-year survival rate in patients with gastric cancer?,"Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer. To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer."
-How does the biopsychosocial model fall short in understanding the role of culture in the experience of illness?,"Culture, illness, and the biopsychosocial model. Family medicine has appropriated the biopsychosocial model as a conceptualization of the systemic interrelationships among the biological, the psychological, and the social in health and illness. For all its strengths, it is questionable whether this model adequately depicts the centrality of culture to the human experience of illness. Culture (as meaning system) is not an optional factor that only sometimes influences health and illness; it is prerequisite for all meaningful human experience, including that of being ill. A more adequate model of the relationship between culture and illness would demonstrate the preeminence of culture in the experience of illness among all people, not just members of ""exotic"" cultures; would view healers as well as patients as dwellers in culture; would incorporate the role of culture as meaning system in linking body, mind, and world; and would promote the significance of the cultural context as a resource for research and therapy."
-How did the levels of von Willebrand factor (vWF) and factor VIII (FVIII) change in renal transplant recipients during the first 4 months after transplantation?,"von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients. In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment."
-What are the key clinical manifestations of liver involvement in Alpers disease?,"Liver involvement in Alpers disease. Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction."
-How does ischemia affect the density and regeneration of nerve fibers?,"Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration."
-How do endogenous free radical scavengers impact gastric ulcer formation in the experimental rat model?,"The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model. The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation."
-What was the overall hospital mortality rate in the urokinase and heparin groups after 16 days in this study of acute myocardial infarction patients?,"Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar."
-What language-related difficulties were observed in patients with progressive supranuclear palsy?,"Language functions in progressive supranuclear palsy. Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy."
-How does the growth cycle of malaria parasites in erythrocytes contribute to the periodic nature of malaria fever?,"Periodic and chaotic host-parasite interactions in human malaria. It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite."
-How did hypotensive epidural anaesthesia impact the quality of cement-bone interface in total hip arthroplasty?,"Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. We selected 20 matched pairs of patients who had had total hip arthroplasty by the same surgeon using the same cemented technique. Matching was by age, sex, height, weight and diagnosis. One of each pair had received hypotensive epidural anaesthesia, with less than 300 ml blood loss: the other had normotensive general anaesthesia with more than 500 ml of blood loss. Early postoperative radiographs were evaluated independently by three blinded observers, using a scoring criteria which assessed the quality of the cement-bone interface. The results showed that patients who had received epidural anaesthesia had significantly better radiographic scores (p less than 0.02). Our findings suggest that hypotensive anaesthesia facilitates penetration of cement into bone."
-What echocardiographic measurements were found to be risk factors for perioperative death in infants with isolated aortic valve stenosis?,"Echocardiographic estimation of critical left ventricular size in infants with isolated aortic valve stenosis. With the current trend to performing surgical valvotomy for infantile aortic stenosis without cardiac catheterization, there is a need to develop echocardiographic criteria for adequacy of left ventricular size. The echocardiograms and catheterization data of all 25 infants less than 3 months of age undergoing aortic valvotomy for isolated aortic valve stenosis from September 1980 through July 1990 were reviewed. Significant differences (p less than 0.05) between the survivors and nonsurvivors were noted for age at operation (30 +/- 28 vs. 3 +/- 1.5 days), mitral valve diameter (10.1 +/- 1.7 vs. 7.7 +/- 1.5 mm), left ventricular end-diastolic dimension (18.4 +/- 6.4 vs. 11.4 +/- 3 mm), left atrial dimensions (15.3 +/- 3.8 vs. 10 +/- 2.4 mm), left ventricular cross-sectional area on the parasternal long-axis echocardiogram (4 +/- 1.9 vs. 2 +/- 1.9 cm2) and angiographically determined left ventricular end-diastolic volume (43 +/- 23 vs. 11 +/- 5 ml/m2). There was no difference with respect to patient weight, body surface area, aortic root dimension or left ventricular ejection fraction. Left ventricular cross-sectional area less than 2 cm2 as measured on the parasternal long-axis echocardiogram was found in 5 of 7 nonsurvivors and 0 of 12 survivors, making this a risk factor for perioperative death (p less than 0.05). Left ventricular end-diastolic dimension less than 13 mm was found in 5 of 6 nonsurvivors and 2 of 17 survivors, making this another risk factor for early mortality (p less than 0.05)."
-What medical condition did the 27-year-old man with osteogenesis imperfecta develop after sustaining a femoral fracture?,Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.
-What were the acute hemodynamic effects of intravenous nicardipine in patients with a healed myocardial infarction?,"Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure. Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation."
-What is bioelectric impedance analysis and how was it used in this study of cirrhotic patients?,"Bioelectric impedance analysis: experience with male patients with cirrhosis. Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of ""compartmentalized"" fluid in the abdomen."
-How did the MR receptor imaging with asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide differ in normal liver tissue versus hepatocellular carcinoma (HCC) tissue?,"Experimental hepatocellular carcinoma: MR receptor imaging. Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules."
-What were the key findings of the study regarding the effects of dexamethasone in treating bacterial meningitis in infants and children?,"The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. BACKGROUND. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San Jose, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis."
-How does collateral circulation impact left ventricular function in patients with total occlusion of the left anterior descending coronary artery?,"Evolution of myocardial ischemia and left ventricular function in patients with angina pectoris without myocardial infarction and total occlusion of the left anterior descending coronary artery and collaterals from other coronary arteries. Repeated episodes of myocardial ischemia might lead to progressive impairment of left ventricular (LV) function. This radionuclide study assessed myocardial ischemia and LV function several years after documented coronary occlusion without myocardial infarction. Over 5 years, 24 consecutive patients, who underwent cardiac catheterization for angina pectoris without myocardial infarction, had isolated total occlusion of the left anterior descending coronary artery with well-developed collateral vessels. Five patients were successfully treated by coronary bypass grafting and 3 by coronary angioplasty. Among the 16 medically treated patients, 1 was lost to follow-up and 1 died (extracardiac death). The mean (+/- standard deviation) follow-up (14 patients) was 48 +/- 15 months. At follow-up, 8 patients still had clinical chest pain, 11 received antianginal therapy, 4 patients had no stress ischemia and the other 10 had greater than or equal to 1 sign of stress ischemia. All patients had a normal LV ejection fraction at rest (mean 60 +/- 3%; range 55 to 65%). Collateral circulation preserves LV function at the time of occlusion and, in some cases, prevents the development of myocardial ischemia; in patients with persisting myocardial ischemia after well-collateralized coronary occlusion, LV function is not impaired at long-term follow-up."
-What was the median survival time for melanoma patients with metastases to two or more lymph node areas?,"The prognosis of melanoma patients with metastases to two or more lymph node areas. The prognosis of melanoma patients who present with metastatic involvement of two or more noncontiguous lymph node regions before the detection of extranodal metastases has not been previously reported. We identified 21 patients with metastatic melanoma in at least two nodal basins in a review of 175 patients with melanoma undergoing lymphadenectomy at the National Cancer Institute. The median survival time of these patients was 46 months, with 55%, 27%, and 17% of the patients alive 2, 5, and 10 years, respectively, after the second lymphadenectomy. Because the prognosis of melanoma patients with metastases to two or more regional nodal areas appears equivalent to that of patients with metastatic involvement of only one regional node site, lymphadenectomy of the involved groups should be performed with therapeutically curative intent."
-What is the Currarino triad and what are its key characteristics in the described family?,"Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality."
-What was the effect of leuprolide acetate depot treatment on uterine volume in women with leiomyomata uteri?,"Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms."
-How does the presence of bile affect bacterial growth and clearance in Escherichia coli peritonitis?,"Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis. The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis."
-What are the main side effects observed in the low-dose recombinant interferon-gamma study?,"Recombinant interferon-gamma (rIFN-gamma) in dermatology. This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients."
-What is the Currarino triad and what are its key characteristics in the described family?,"Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality."
-What multimodality treatment approach was used for patients with malignant pleural mesothelioma in this study?,"Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma. Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach."
-What are the three distinct cell types observed in the adamantinoid basal cell carcinoma during the ultrastructural study?,"Adamantinoid basal cell carcinoma. An ultrastructural study. We describe an adamantinoid basal cell carcinoma that has developed in the mucocutaneous border of the upper lip. An ultrastructural study disclosed three types of cells that were morphologically distinct in the tumor nest. Cells of the first type were basically the same as those of ordinary basal cell carcinoma. Cells of the second type showed varying degrees of cytoplasmic content loss in a worm-eaten pattern and seemed to consist of degenerating cells. Cells of the third type possessed a well-developed rough endoplasmic reticulum filled with medium electron-dense fine substance, which was also seen in the extracellular space. In relationship with the histochemical findings, and based on the histogenesis of adamantinoid basal cell carcinoma, we propose that subpopulations of tumor cells undergo spontaneous degeneration and that the spaces of such disappearing cells are refilled with products containing glycosaminoglycans secreted by another subpopulation of the tumor cells."
-What imaging techniques were used to diagnose choledochal cyst and biliary atresia in the neonates?,"Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management."
-How does the HBx gene of hepatitis B virus contribute to liver cancer development in transgenic mice?,"HBx gene of hepatitis B virus induces liver cancer in transgenic mice. The exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility of placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer."
-What is the significance of bacterial translocation in trauma patients according to the study?,"Bacterial translocation in trauma patients. Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients."
-What were the main objectives of the study on optical properties of myocardium?,"Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength. Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation."
-How does the presence or absence of an androgen receptor affect blood pressure in hybrid male rats?,"Androgen receptor and the testes influence hypertension in a hybrid rat model. The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males."
-What was the primary aim of the study investigating total parenteral nutrition in patients with head and neck cancers?,"Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers. Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration."
-What is the importance of obtaining a comprehensive patient history during preoperative evaluation of a cardiac patient undergoing non-cardiac surgery?,"Preoperative evaluation of the cardiac patient for noncardiac surgery. In summary, obtaining a comprehensive patient history is a critical part of the diagnostic and risk stratification process of the patient with cardiac disease undergoing non-cardiac surgery. Many of the factors associated with perioperative cardiac morbidity are treatable and early and aggressive management appears to have beneficial effects on morbidity and mortality rates."
-What is the rare medical condition described in this case report involving a plasmacytoma and superior vena cava syndrome?,"Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described."
-What is the rare cause of left-sided portal hypertension described in this medical case report?,"Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature."
-How does the accumulation of PrPSc in different brain regions correlate with scrapie infectivity in Syrian hamsters?,"Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases."
-What is the rarity and pattern of association between squamous cell carcinoma of the upper aerodigestive tract and well-differentiated thyroid carcinomas?,"Squamous cell carcinoma of the upper aerodigestive tract associated with well-differentiated carcinoma of the thyroid gland. The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer."
-What are the key endogenous mediators involved in gastroprotection according to the review?,"Mechanisms of gastric mucosal injury and protection. This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy-dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed."
-What percentage of patients in the study had at least one preoperative risk factor?,"Comorbidities and perioperative complications among patients with surgically treated benign prostatic hyperplasia. We address the question of whether or not age and comorbidity are related to intra- and postoperative complications after a transurethral resection. The data are derived from a retrospective, population-based study conducted in Hagen, Germany, which included all patients with an initial prostatectomy for benign prostatic hyperplasia (N = 621) during the five-year period 1984-1988. Seventy-seven percent of the patients had at least one of the following preoperative risk factors: heart disease, hypertension, smoking, chronic obstructive lung disease, and diabetes. There was no intraoperative death. The risk of intraoperative circulatory complications was found to be related to age only for patients without a history of heart diseases or hypertension. The incidence of major complications was 3.1 percent and was significantly higher in the oldest age group. Three patients (0.54%) died postoperatively in the hospital. Infections were the most frequent postoperative complications. The relationship of age and overall postoperative complications was not statistically significant either for patients with (p = 0.121) or without any comorbidity (p = 0.651). Based on this study it seems reasonable to conclude that age is not a clinically relevant risk factor for perioperative complications in patients who have a transurethral resection for benign prostatic hyperplasia."
-"What is the purpose of using a free gastric mucosal flap with microvascular transfer in the reconstruction of malignant lesions in the oral cavity, base of tongue, and oropharynx?","Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered."
-What are the key clinical characteristics of the dominantly inherited mitochondrial myopathy described in this study?,"Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies. We studied a large family with a dominantly inherited mitochondrial myopathy characterized by progressive external ophthalmoplegia, dysphagia, cataract, lactic acidosis, exercise intolerance, and early death. Morphologic studies of muscle biopsies suggested mitochondrial heteroplasmy and revealed ragged-red fibers and decreased histochemical reactions for cytochrome c oxidase and succinate dehydrogenase. Biochemistry showed a partial defect of cytochrome c oxidase and a mild generalized reduction of other mitochondrial enzymes requiring mitochondrial DNA-encoded subunits. Southern blot analysis and PCR amplification showed mitochondrial DNA deletions in muscle of all affected members, but not in lymphocytes or fibroblasts, suggesting a tissue-specific distribution. Deletions were multiple and seemed to increase with time and to correlate with the severity of the disease."
-What correlation was found between periventricular lesions on MRI and the severity of white matter changes in elderly patients?,"Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Magnetic resonance imaging (MRI) was performed postmortem on the brains of 40 patients aged over 60 yrs who had died from causes other than brain disease. Periventricular lesions of increased signal intensity on T2-weighted images, graded as moderate or severe, were found in 10% of the patients in the age group between 60 and 69 yrs, and in 50% between 80 and 89 yrs. Macroscopic and microscopic whole-brain sections were studied in 19 brain specimens (8 with normal white matter, 4 with moderate lesions and 7 with severe lesions of the white matter on MRI). The presence or absence of periventricular lesions on MRI correlated well with the severity of demyelination and astrocytic gliosis. Demyelination was always associated with an increased ratio between wall thickness and external diameter of arterioles (up to 150 microns). A variable degree of axonal loss in Bodian-stained sections was present in the white matter of all brains with demyelination. Dilated perivascular spaces were found and studied morphometrically in 9 brain specimens; their presence correlated strongly with corrected brain weight, but incompletely with demyelination and arteriolosclerosis. Our findings suggest that arteriolosclerosis is the primary factor in the pathogenesis of diffuse white matter lesions in the elderly. This is soon followed by demyelination and loss of axons, and only later by dilatation of perivascular spaces."
-What are the key considerations in sphincter-sparing surgery for patients with ulcerative colitis or rectal tumors?,"Sphincter-sparing surgery. Since World War II, a variety of technical innovations have been introduced to preserve the anal sphincter in patients with chronic ulcerative colitis or tumors of the rectum. Studies of anorectal physiology have yielded guidelines for preserving continence and minimizing morbidity. For example, preservation of the anal rectal angle is essential; the rectal mucosa can be removed without impairing neural mechanisms; construction of a reservoir increases rectal compliance. Following these guidelines, surgeons have introduced new techniques and applications benefiting a larger and more varied patient population. Some technical problems remain, however, and patient selection criteria for restorative rectal surgery need to be refined."
-What was the mean time from symptom onset to diagnosis for patients with an identifiable syndrome in this study of adrenal tumors?,"Efficient management of adrenal tumors. A retrospective analysis was carried out on 121 patients with primary adrenal tumors operated on at 2 Vancouver hospitals between the years 1970 and 1990. The purpose of the study was to identify discriminating factors between the various diagnoses in order to minimize both the time and the cost of the investigative process. There were 57 cortical adenomas, 35 pheochromocytomas, 15 carcinomas, 8 cases of cortical hyperplasia, and 6 miscellaneous tumors. The mean time from the onset of symptoms to diagnosis of those patients presenting with an identifiable syndrome was 48.3 months. Those with a hypertensive syndrome presented significantly later than those with Cushing's syndrome (57.7 months versus 22.8 months, p less than 0.01). There was a significant delay in diagnosis in those patients with hypertension on the basis of an aldosteronoma as compared with those with hypertension secondary to a pheochromocytoma (75.4 months versus 36.1 months, p = 0.02). Cortical carcinomas were significantly larger than benign cortical tumors (12.7 cm versus 5.5 cm). No malignant neoplasm measured less than 5 cm in diameter. Diagnostic sensitivity for intravenous pyelogram (IVP) was 59%, for ultrasound 71%, for venography 50%, for meta-iodobenzylguanidine (MIGB) (pheochromocytoma only) 80%, and for angiography 70%. However, for those patients with adrenal carcinomas, angiography was positive in 100% of cases. Computed tomography (CT) was the most sensitive localizing investigation with a sensitivity of 98%. While other localizing techniques were less sensitive than CT, they may still play a useful role in selected situations. Factors causing delay in diagnosis and the role of the various imaging modalities are discussed."
-What were the key findings of the Jamaican study regarding nutritional supplementation and growth in stunted children?,"Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study. The benefits of nutritional supplementation, with or without psychosocial stimulation, on the growth of stunted children were evaluated. Children aged 9-24 mo with lengths less than -2 SD of the National Center for Health Statistics references (n = 129) were randomly assigned to four groups: control, nutritional supplementation, stimulation, and both interventions. A fifth group with lengths greater than -1 SD was also enrolled. Length, weight, head and arm circumferences, and triceps and subscapular skinfold thicknesses were measured on enrollment and 6 and 12 mo later. Multiple-regression analysis was used to determine the effects of the interventions in which age, sex, initial status, initial dietary intake, and several socioeconomic variables were controlled for. Stimulation had no effect on growth and there was no interaction between the interventions. After 12 mo supplemented children had significantly increased length, weight, and head circumference (all P less than 0.01). The effects of supplementation were not cumulative but occurred in the first 6 mo."
-How is gastric cancer different during pregnancy compared to other periods of a woman's life?,"Gastric carcinoma presenting as an exacerbation of ulcers during pregnancy. A case report. Gastric cancer is unusual during pregnancy. Also, because of the physiologic changes that occur with pregnancy, it is rare to see a worsening of peptic ulcers during pregnancy. A patient with an exacerbation of peptic ulcers presented with gastric carcinoma during pregnancy."
-What are the key diagnostic and treatment strategies for stress fractures in athletes?,"Stress fractures in athletes. How to spot this underdiagnosed injury. Stress fractures are an increasingly common injury in competitive athletes, especially runners. Amenorrheic athletes are at particularly high risk. A radionuclide bone scan should be considered when the index of suspicion for stress fracture is high. Plain radiographs are of little use in establishing the diagnosis in the early stages of the injury. Early diagnosis and prompt institution of conservative therapy allow for a favorable outcome in most cases. Avoidance of or reduced participation in the inciting activity is important for pain control. Certain stress fractures, such as those involving the femoral neck, should be monitored closely and treated aggressively with internal fixation when conservative measures fail. Runners who have exercise-induced amenorrhea should be advised to decrease their training intensity to a level where menses resume. Cyclic therapy with conjugated estrogens and progesterone should also be considered, as should daily calcium supplementation."
-What were the main causes of death among patients treated with human pituitary growth hormone in this study?,"Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom OBJECTIVE--To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN--A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS--All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES--Death or development of neoplasia. RESULTS--110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS--Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review."
-What differences were observed in neutralizing antibody development among patients treated with different interferon-alpha preparations?,"Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1."
-What is the significance of Glial fibrillary acidic protein (GFAP) expression in pleomorphic adenomas and chordomas?,"Glial fibrillary acidic protein expression in pleomorphic adenoma, chordoma, and astrocytoma. A comparison of three antibodies. Glial fibrillary acidic protein (GFAP) is a major constituent of glial cytoplasmic intermediate filaments. Glial fibrillary acidic protein expression has been accepted as a marker of astroglial differentiation or origin. However, GFAP expression has been demonstrated in a variety of normal and neoplastic tissues outside the central nervous system, including pleomorphic adenomas, chordomas, bone, and cartilage. It has been postulated that coexpression of GFAP and vimentin in neoplastic myoepithelial cells in pleomorphic adenomas reflects early chondroid differentiation. Glial fibrillary acidic protein expression in chondromyxoid and chordoid tumors was studied in formaldehyde solution-fixed, paraffin-embedded sections of 20 pleomorphic adenomas and 10 chordomas by the immunoperoxidase method with the use of commercially available monoclonal (n = 2) and polyclonal (n = 1) antibodies. All pleomorphic adenomas and chordomas demonstrated expression of GFAP with the use of the polyclonal antibody (Biomeda Corp [Foster City, Calif]). Variable expression of GFAP was present in 90% (18/20) and 70% (14/20) of pleomorphic adenomas, and in 20% (2/10) and 0% of chordomas, with the use of the two monoclonal preparations (Dakopatts [Glostrup, Denmark] and BioGenex Laboratories [San Ramon, Calif]), respectively. Normal brain tissue and eight astrocytomas were used as ""controls"" to compare staining intensity and quality between the polyclonal and monoclonal anti-GFAP antibodies. Glial fibrillary acidic protein positivity with the polyclonal antibody was more intense than that with either monoclonal antibody despite similar (congruent) distributions of tumor cell types that were stained in control brain and astrocytoma tissues. The GFAP polyclonal antibody was more frequently immunoreactive than the monoclonal antibodies, particularly in cells that exhibited chondroid differentiation. These findings may have practical application in surgical pathology."
-What was the primary purpose of the study on endovascular stents in congenital heart disease?,"Use of endovascular stents in congenital heart disease. BACKGROUND. Balloon expandable intravascular stents have been used to support vessel walls in coronary and peripheral arteries in adults. The purpose of this study was to examine the efficacy and safety of these stents in the treatment of congenital heart disease. METHODS AND RESULTS. Forty-five stents were placed in 30 patients, who were 0.2-30.2 years old (weight, 3.5-76 kg). Patients with areas of stenosis that were difficult to approach surgically were chosen. Stents were mounted over balloons and placed by standard catheterization techniques. Twenty-three patients had branch pulmonary artery stenosis. Thirty-six stents were placed successfully and had reduced pressure gradients from 50.6 +/- 24 to 15.9 +/- 13.4 mm Hg. Five patients had stents placed after atrial surgery: three in obstructed Fontan repairs, one at the superior vena cava-right atrial junction after sinus venous defect repair, and one at the site of a Glenn shunt. Atrial stents reduced pressure gradients from 9.8 +/- 8.2 to 2.0 +/- 2.6 mm Hg. One patient had a stent placed in the descending aorta after coarctation dilation, and the pressure gradient was reduced from 50 to 25 mm Hg. One patient had pulmonary vein dilation with stent placement. Two stents migrated at the time of placement; one required surgical removal, and one was anchored in place by balloon dilation. One patient died within 24 hours of catheterization because of thrombus obstruction of the Fontan repair. Nine patients have undergone recatheterization. All stented vessels have remained at the same caliber as at original stent placement. CONCLUSIONS. We conclude that balloon expandable stents are useful in selected postoperative stenoses in congenital heart disease."
-What potential complication can tissue plasminogen activator (t-PA) cause during treatment of acute myocardial infarction?,"Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable."
-What percentage of patients with clinical stage A1 and A2 prostate cancer were found to have no cancer during radical prostatectomy?,"Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome. Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice."
-What is the overall mortality rate for patients with group B streptococcal endocarditis of the tricuspid valve?,"Group B streptococcal endocarditis of tricuspid valve. We report three cases of group B streptococcal endocarditis of the tricuspid valve. Two patients were intravenous drug abusers. In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve. Half of the patients were intravenous drug abusers. Four of the other patients had underlying conditions. All patients were treated with a penicillin with or without an aminoglycoside. Three patients underwent tricuspid valve surgery. The overall mortality was 20 percent. Both patients who died received medical therapy only."
-What diagnostic technique ultimately revealed the presence of a myocardial abscess in this case of aortic valve endocarditis?,"Coronary artery narrowing due to extrinsic compression by myocardial abscess. A case of aortic valve endocarditis complicated by perivalvular abscess extending into myocardium is presented. Echocardiography and aortography failed to detect the abscess, but coronary angiography revealed its presence by extrinsic compression of left anterior descending and diagonal arteries. Morphological features of this rare cause for coronary narrowing are described."
-What preoperative evaluations are recommended for diagnosing urethral diverticulum and stress incontinence in female patients?,"Surgical treatment of concomitant urethral diverticulum and stress incontinence. Urinary incontinence is frequently associated with a urethral diverticulum in female patients. Preoperative evaluation including a thorough history and physical examination, voiding cystourethrogram, urethroscopy, and urodynamic studies can diagnose both the urethral diverticulum and any concomitant bladder-urethral dysfunction. Preoperative recognition of stress urinary incontinence or patients at risk for this problem postoperatively permits effective treatment with concomitant transvaginal bladder neck suspension and urethral diverticulectomy."
-What surgical technique was used to treat chronic infected hip arthroplasty wounds in this study?,"Treatment of chronic infected hip arthroplasty wounds by radical debridement and obliteration with pedicled and free muscle flaps. Nine patients with extensive wounds of the hip joint due to chronic infection following total hip arthroplasty or internal fixation of fractures of the femoral head and neck have been treated by serial radical debridements to remove infected bone, contaminated remnants of bone cement, and the surrounding fibrotic soft tissues. The resultant deep cavity extending down to the acetabulum has then been obliterated with either pedicled muscle flaps or free muscle flaps. Subcutaneous or transpelvic transposition of rectus abdominis muscle flaps is preferred for smaller defects, but only the free latissimus dorsi muscle flap provides sufficient volume of tissue to obliterate the more extensive hip defects. Systemic antibiotics have been continued only for a short-term course of 14 days postoperatively. There has been no recurrence of infection, with follow-up ranging between 6 months and 3 1/4 years. One patient has undergone reimplantation of a second custom hip prosthesis into the vascularized bed of a free latissimus dorsi muscle flap."
-What technique was used to treat large bony defects after cystectomy in this study?,A modified technique for obliteration of large bony defects after cystectomy. Thirteen cysts treated by enucleation followed by collapsing an osteoperiosteal flap to eliminate dead space are presented. Four of the cysts were dentigerous and nine were radicular. The bony defects ranged in size from 3 to 7 cm in greatest dimension. Healing by primary intention occurred in all cases. This method has been found to be successful in the obliteration of large bony defects after cystectomy.
-"What were the antibody response levels for pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens in infants aged 3 to 8 months and children aged 24 to 30 months after the fourth vaccine dose?","A comparative trial of the reactogenicity and immunogenicity of Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids. Outcome in 3- to 8-month-old infants, 9- to 23-month-old infants and children, and 24- to 30-month-old children. The reactogenicity and immunogenicity of the Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids were compared in 139 infants aged 3 to 8 months, 60 infants and children aged 9 to 23 months, and 99 children aged 24 to 30 months. Good antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens occurred in all age groups after both the third and fourth doses. After the fourth (booster) dose, the mean antibody values in initially seronegative infants vaccinated at 3 to 8 months of age were as follows: anti-PT, 67.8 enzyme-linked immunosorbent assay units (EU) per milliliter; anti-FHA, 149.5 EU/mL; the agglutinin titer was 125.6. The values in initially seronegative children vaccinated at 24 to 30 months of age were as follows: anti-PT, 92.9 EU/mL; anti-FHA, 251.7 EU/mL; the agglutinin titer was 275.8. Reactions following immunization were minimal. Except for drowsiness after the first dose in infants, there were no clinically significant differences in reactions between infants and older children. The findings in this study coupled with the recent demonstration of efficacy of this vaccine in 2-year-old children supports the recent Japanese recommendation to lower the age of immunization with acellular pertussis vaccine combined with tetanus and diphtheria toxoids to 3 months."
-What is a ganglioglioma and how can it cause hemifacial spasm in an infant?,"Hemifacial spasm in an infant due to fourth ventricular ganglioglioma. Case report. The case of an infant is reported in which hemifacial spasm due to a ganglioglioma of the fourth ventricle was relieved by surgery. Previously described causes of hemifacial spasm are summarized, and the relevance of this case to theories on the pathogenesis of the condition is discussed."
-What was the key finding regarding the relationship between spinal cord ischemia duration and neurologic outcomes in the rabbit study?,"The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia."
-What were the long-term surgical outcomes for patients who underwent lateral cranial base surgery between 1970 and 1987?,"Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis."
-How does gastric intramucosal pH relate to mortality rates in critically ill patients?,"Gastric mucosal pH as a prognostic index of mortality in critically ill patients. OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU."
-What percentage of patients showed allelic loss at the retinoblastoma (RB) locus in their ovarian tumor tissues?,"Allele loss at the retinoblastoma locus in human ovarian cancer. To gain a broad spectrum on allelic loss of specific loci in ovarian tumors, we initially examined DNA from 23 pairs of ovarian tumors and matched peripheral blood lymphocyte samples from the same patients, using 27 polymorphic DNA markers distributed on 13 chromosomes. Significant high frequency of allelic deletion (22%-44%) at chromosome 13 loci (D13S31, D13S32, D13S33, and D13S34) at bands q12-q34 was observed in tumor tissues. These results led us to investigate the loss of heterozygosity at the retinoblastoma (RB) locus in ovarian tumors, because the RB gene is a tumor-suppressor gene located at 13q14. Analysis of the variable number of tandem repeat sequence polymorphism in intron 20 in the RB gene revealed that 6 (30%) of 20 patients with informative samples showed allelic loss at the RB locus in their tumor tissues. This loss, of relatively high frequency, suggests that the RB gene, or a closely linked gene, seems to be involved in the development of ovarian cancer."
-What were the most frequently reported prodromal symptoms in soldiers who experienced exertional sudden death?,"Exertional sudden death in soldiers. To address the problem of a significant rise in the incidence of exertional sudden death worldwide, the medical records and necropsy reports of all deaths that occurred in the Israel Defence Forces (IDF) during 1974-1986 were scrutinized. Twenty male soldiers, aged 18-29 yr, died suddenly and unexpectedly within 24 h of strenuous exercise. Necropsy results, available for 90% of the subjects, included underlying cardiac disease in 50% and noncardiac causes of death in 33.3%; the cause of death was unidentifiable in 16.7% of the subjects. Prodromal symptoms in 70% of the subjects are presented as a main focus of this investigation. The most frequently reported symptom was exertional or nonexertional syncope in 40% of the subjects. Chest pain, acute gastrointestinal symptoms, or febrile disease were reported in 30% of the cases. The findings of this research suggest that syncope is a major antecedent symptom of exertional sudden death. An attack of syncope in young conditioned individuals should be followed by thorough medical surveillance, and strenuous exercise should be avoided until this procedure is completed. Sports and military officials have the obligation to promote awareness that strenuous exercise should not be performed in the presence of acute gastrointestinal symptoms or febrile illness."
-How does early chronic administration of clonidine affect portal pressure and mesenteric-systemic shunts in portal vein-stenosed rats?,"Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats. The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day-1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats."
-What was the primary hypothesis tested in this study regarding atrial natriuretic factor in cerebrospinal fluid?,"Cerebrospinal fluid atrial natriuretic factor in intracranial disease. We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury."
-"How did exercise-induced myocardial ischemia affect the peak E and A velocities and E/A velocity ratio in the>>
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-Human question:","Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference)."
-What are the long-term pathologic consequences of CNS treatment for childhood cancer?,"Long-term consequences of CNS treatment for childhood cancer, Part I: Pathologic consequences and potential for oncogenesis. The pathologic changes associated with the treatment of cancer of the nervous system are reviewed. Computed tomographic, magnetic resonance imaging, and positron emission tomographic findings of these abnormalities are described, followed by discussion of the known histopathologic features. For the most part, pathologic effects are primary vascular and/or demyelinating. We review each of these effects at all levels of the neural axis. This review concludes with a discussion of the risk of developing second malignancies. Although this complication is infrequent, the likelihood that survivors of childhood cancer will develop a second malignancy is 10 times that of age-matched controls. This phenomenon in part relates to genetic predisposition, environmental factors, and host susceptibility. These qualifications not withstanding, most studies implicate central nervous system radiation with and without chemotherapy as the primary etiology for second malignancies."
-"What clinical and laboratory features characterize the ""lymphoma syndrome"" in childhood acute lymphoblastic leukemia?","Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the ""lymphoma syndrome"" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL."
-How effective was the 2-mm choledochoscope in exploring small bile ducts and the pancreatic duct during intraoperative procedures?,"Intraoperative use of a 2-mm choledochoscope for the exploration of small bile ducts and the pancreatic duct. Intraoperative visualization of the biliary and pancreatic ducts can be difficult in a nondilated system. Very small extra- and intrahepatic bile ducts occasionally require visualization but do not admit the traditional 6.5-mm intraoperative flexible choledochoscope. We have prospectively examined the use of a 2-mm choledochoscope for the intraoperative evaluation of the biliary and pancreatic ducts in 36 patients. In 27 patients, the choledochoscope was advanced through the cystic duct stump for examination of the common bile duct following cholangiography. The scope was successfully passed into the cystic duct stump and into the common bile duct in 76 per cent of patients. Inability to pass the scope through the cystic duct was usually due to acute angulation of the cystic duct/common duct junction. In an additional five patients, intraoperative cholangiography revealed a filling defect in a very small duct. A choledochotomy was made and the 2-mm choledochoscope was used to exclude the presence of stones in a small bile duct. In four patients the choledochoscope was used during a Puestow procedure to visualize and help extract stones in the tail and head of the gland. No complications occurred in these patients due to the use of the choledochoscope. We conclude that the 2-mm choledochoscope aids in internal visualization of small intra- and extrahepatic bile ducts and the pancreatic duct. It may be useful as an adjunct to cholangiography in determining the nature of filling defects."
-What is hemifacial spasm and how was it diagnosed in this case report?,AAEM case report #21: hemifacial spasm: preoperative diagnosis and intraoperative management. A 75-year-old man developed progressive involuntary hemifacial spasm. Electrophysiologic evidence of abnormal cross-transmission between neurons of the facial nerve was demonstrated. Electrodiagnostic studies were used to confirm the diagnosis preoperatively and determine the adequacy of vascular decompression of the facial nerve intraoperatively.
-What gene rearrangement and deletion mechanisms are involved in the generation of human IgE-secreting cells?,"Generation and cloning of stable human IgE-secreting cells that have rearranged the C epsilon gene. Although the secretion of Ig isotypes other than IgM is generally accompanied by a DNA rearrangement that deletes C mu (and the other IgCH genes located between VDJ and the expressed CH gene), a system has recently been described that generates a high frequency of IgE-secreting cells that have failed to delete IgCH genes or to rearrange their C epsilon genes. These cells, derived from EBV-transformed human PBMC, secrete IgM and IgD as well as IgE. To determine whether the absence of C epsilon rearrangement and CH gene deletion is a general phenomenon for human IgE-secreting cells, we have characterized IgE-secreting cells that are generated by culturing purified human B cells with EBV plus IL-4 in the presence of irradiated human PBMC. In contrast to the earlier observation, we have not been able to detect any cells that demonstrate cytoplasmic staining for IgE and concurrently stain for a second Ig isotype. Stable IgE-secreting cell lines and clones produced by this method have rearranged one of their C epsilon genes and have deleted both C mu genes. These observations demonstrate that the generation of human IgE-secreting cells can involve the same gene rearrangement and deletional mechanisms that lead to the generation of cells that secrete other isotypes."
-What diagnostic method was used to evaluate lower-extremity vascular grafts in this study?,"Lower-extremity vascular grafts placed for peripheral vascular disease: prospective evaluation with duplex Doppler sonography. Eighty-five men with 92 vascular grafts placed for peripheral vascular disease of the lower extremity underwent a total of 264 examinations with duplex Doppler over a 2.5-year period. In 64 patients who underwent more than one examination, the total follow-up encompassed 740 months. In 220 native femoral arteries (96.0%) the peak systolic velocity (PSV) was higher than that in the graft. Arteriovenous shunting was associated with a normal PSV and a markedly elevated diastolic component at spectral analysis. Focal fluid collections were common initially near the graft and usually disappeared uneventfully. An average PSV of 32 cm/sec or less was always associated with impending occlusion. The sensitivity of an average PSV of 40 cm/sec or less to indicate impending graft occlusion by the next visit was only 33%; the specificity, 94%. At initial examination, stenoses were associated with high PSV focally in the graft or low PSV with absent diastolic flow."
-How do migraine sufferers describe their family environment differently compared to headache-free controls?,"The role of family structure, functioning, and pain modeling in headache. In an initial attempt to examine relationships between family functioning and chronic headache disorders, the present study examined: a) family structure characteristics, b) family functioning, and c) family pain modeling. Subjects completed an assessment battery consisting of several measures of family functioning. Analyses showed that migraine sufferers (N = 42) as compared to headache-free controls (N = 59) were more likely to describe their families as emphasizing clear organization, structure, rules, and overall control, but less likely to encourage emotional expression. No differences were found between tension headache subjects (N = 43) and headache-free controls. While only an initial exploration of the importance of family characteristics in chronic headache, these results suggest that there are important differences in headache subjects' (particularly migraine) reports of family environment and functioning."
-What are the five key managerial challenges identified for ensuring effective delivery of cancer services through strategic alliances?,"Community cancer programs as strategic alliances: challenges and guidelines for action. This paper assesses the utility of strategic alliances as a way of expanding and improving the quality of cancer care provided in communities with limited access to major treatment centres. Alliances provide an organizational model for future community-based cancer programs by accommodating a growing need for interdependence among organizations and providers while permitting substantial independence and autonomy. Five managerial challenges to ensuring effective and efficient delivery of cancer services are identified: to secure mutually reinforcing exchanges between and within all levels of cancer care, to develop protocols and programs relevant to the unique characteristics of patients and providers, to provide treatment and cancer control services, to involve interdisciplinary teams of providers at all levels of care and to achieve quality assurance, improvement and evaluation. In addition, the paper includes a set of guidelines to facilitate the implementation of community cancer programs as strategic alliances: reaffirm the role of community oncologists, primary care physicians and nurses as partners in the program; define the structure and culture necessary for commitment rather than simply compliance; redefine the role of management; establish data-monitoring systems; modify reward systems; and set realistic time frames and expectations."
-What were the most common CT findings in patients after liver transplantation?,"Abdominal CT findings after liver transplantation in 66 patients. CT scanning is used frequently to assess the condition of patients after liver transplantation. The CT records of 174 adult patients who underwent liver transplantation were studied retrospectively to determine the number and timing of CT studies as well as the frequency and significance of the findings. One-hundred seventy CT scans were obtained in 66 (38%) of the 174 patients, with a mean of 2.6 scans/patient. The interval between transplantation and scanning was 1 day to 24 months; in 59 (89%) of 66 patients, the first CT scan was obtained within 30 days. The acute indications for CT scanning were fever or leukocytosis in 54 (92%) of 59 patients and abnormal liver function tests in five (8%) of 59 patients. CT scans obtained more than 30 days after transplantation were repeat scans in all but seven patients. Indications in this latter group were the same as for the acute group, plus evaluation of hepatic neoplasia in three patients. CT findings included periportal low attenuation in 41 (62%) of 66 patients; ascites in 25 (38%); splenomegaly in 19 (29%); loculated intraperitoneal noninfected fluid collections in 13 (20%); intrahepatic, splenic, pancreatic, or perihepatic abscesses in seven (11%); hepatic infarction in six (9%); splenic infarction in three (4%); and hepatic calcification in two (3%). Other major abnormalities included inferior vena caval thrombosis (one patient), pseudoaneurysm of the hepatic artery with rupture (one patient), and recurrent hepatocellular carcinoma (one patient). CT scanning after liver transplantation is used predominantly in the acute setting to evaluate for liver infarction or intraabdominal abscess. In this setting, CT showed these abnormalities, in addition to tumor recurrence or vascular abnormalities, in 15 (23%) of 66 patients."
-What were the key differences in outcomes between patients who received prosthetic valves and those who received human allografts during emergency aortic valve replacement for infective endocarditis?,"Comparison of allografts and prosthetic valves when used for emergency aortic valve replacement for active infective endocarditis. Aortic valve replacement (AVR) using allografts is an established method of treating aortic valve disease. It is uncertain, however, whether the increased technical demands of allograft AVR can be justified in emergency operations. This study reports 15 patients treated between 1987 and 1990 for acute bacterial or fungal endocarditis involving the aortic valve. Patients underwent emergency AVR because of severe congestive failure, overwhelming sepsis or cerebral emboli. Eight patients received prosthetic valves (group I: 4 mechanical, 4 porcine) and 7 received human allografts (group II: 5 aortic and 2 pulmonary). The groups were comparable in age (group I, 55 years; group II, 51 years), intravenous drug abuse (group I, 1; group II, 3), and previous AVR (group I, 3; group II, 2). One group I and 4 group II patients had septal abscesses. Additional procedures in group I included mitral valve replacement (2), tricuspid valve replacement (1) and aortic root replacement (1). Additional procedures in group II were mitral valve repair (1), root replacement (1), atrial septal defect closure (1) and aortocoronary bypass (1). Mean bypass times (group I, 189 minutes; group II, 204 minutes) and cross-clamp times (group I; 108 minutes; group II, 121 minutes) were similar. Operative deaths occurred in 4 of 8 group I and 1 of 7 group II patients. All surviving patients have been successfully followed (group I, 28 months; group II, 18 months). No group I patient has required reoperation. One group II patients required reoperation for recurrent infection affecting the allograft, and another group II patient died 10 months postoperatively from noncardiac causes."
-What did the review of 200 consecutive patient case notes reveal about the necessity of specialist opinion in hearing aid prescription?,Hearing aid prescribing: is the specialist opinion necessary? A restructuring of the service for provision of hearing aids has been proposed by the Royal National Institute for the Deaf. This is based on the assumption that very few patients referred for hearing aids have significant ear disease and it is not necessary for them to see an ENT specialist. The case notes of 200 consecutive patients referred to the Hearing Aid clinic were reviewed. In only half of these would a hearing aid have been prescribed without a specialist opinion. The remainder either did not need a hearing aid or required further investigation and surgical or medical treatment. In addition there was significant evidence of lack of expertise amongst General Practitioners in recognizing ear disorders. It is imperative that any patient requiring a hearing aid be seen by someone experienced in otology rather than be dealt with by the General Practitioner alone.
-How does the expression of P-glycoprotein change in bladder cancer patients before and after chemotherapy treatment?,"Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications. We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy."
-How does sucralfate potentially enhance healing in the experimental pig ulcer model?,"Administration of sucralfate prolongs survival of animals with experimental peptic ulceration. Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation."
-How did the variability among surgeons impact postoperative outcomes and survival rates for patients undergoing colorectal cancer surgery?,"Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival. OBJECTIVE--To assess the differences among surgeons in postoperative complications, postoperative mortality, and survival in patients undergoing surgery for colorectal cancer. DESIGN--Prospective study of patients with colorectal cancer managed by one of 13 consultant surgeons, none of whom had a special interest in colorectal surgery. SETTING--Royal Infirmary, Glasgow. PATIENTS--645 sequential patients with colorectal cancer presenting over the six years from 1974 to 1979. MAIN OUTCOME MEASURES--Postoperative complications, postoperative mortality (within 30 days), and survival (up to 10 years); predictive factors for postoperative mortality and survival; and relative hazard rate ratios for individual surgeons. RESULTS--The proportion of patients undergoing apparently curative resection varied among surgeons from 40% to 76%; overall postoperative mortality varied from 8% to 30%. After curative resection postoperative mortality varied from 0% to 20%, local recurrence from 0% to 21%, and the rate of anastomotic leak from 0% to 25%. Survival at 10 years in patients who underwent curative resection varied from 20% to 63%, two year survival in those who underwent palliative resection varied from 7% to 32%, and median survival in those who underwent palliative diversion varied from one to eight months. The hazard rate ratios among individual surgeons, taking into account the identified risk factors, varied from 0.56 to 2.03, from 0.17 to 1.92, and from 0.57 to 1.50 for curative resection, palliative resection, and palliative diversion, respectively. CONCLUSION--There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery were undertaken by surgeons with a special interest in colorectal surgery or surgical oncology."
-"What rare complication of diagnostic cardiac angiography is discussed in this context, and how was it successfully managed?",Coronary occlusion following diagnostic angiography: salvage by intracoronary stenting. Catheter-induced coronary artery dissection and occlusion is a rare but serious complication of diagnostic cardiac angiography. This report describes the successful management of this complication with an intracoronary stent after prolonged balloon inflations and intracoronary thrombolytic therapy were unsuccessful.
-How do serum aluminum levels change during and after plasmapheresis treatment?,"Trace elements and plasmapheresis. The relationship between serum aluminum (Al), zinc (Zn), copper (Cu), and iron (Fe) and plasmapheresis (PP) treatment was examined. Three patients with rheumatoid arthritis, six with myasthenia gravis, and 6 with multiple sclerosis were studied. Serum Al, Zn, Cu, and Fe were measured before and after PP. Plasma was separated by first filtration; a second filtration separated the plasma components. Three liters of plasma were treated in each PP session. With each PP treatment, total protein (TP) removed was 20 +/- 5% and serum albumin removed was +/- 6%. Serum Al rose significantly (p less than 0.01 from 1.1 +/- 0.2 micrograms/dl pre-PP to 2.8 +/- 0.4 micrograms/dl post-PP. Serum Zn, Cu, and Fe decreased significantly (p less than 0.01) from 86.2 +/- 7.4 micrograms/dl, 126 +/- 18 micrograms/dl, and 108 +/- 14 micrograms/dl pre-PP to 58.4 +/- 10.2 micrograms/dl, 104 +/- 6 micrograms/dl, and 82 +/- 16 micrograms/dl post-PP, respectively. Two days after the end of the six-month PP treatment, serum Al levels rose significantly (p less than 0.01), from 1.1 +/- 0.2 micrograms/dl to 3.6 +/- 0.8 micrograms/dl. However, serum TP, serum albumin, and serum Zn, Cu, and Fe did not change significantly. It thus appears essential in PP treated patients, to remove Al from the blood to protect against aluminum intoxication."
-"What were the key findings comparing surgical and percutaneous placement of Greenfield filters in terms of safety, efficacy, and cost?","Analysis of the transition to percutaneous placement of Greenfield filters. To establish whether a transition from surgical to percutaneous placement of Greenfield filters was justified, a review of the safety, efficacy, and cost-effectiveness of the two approaches was conducted. Between 1984 and 1989, 168 filters were placed in 169 patients, 48 surgically and 120 percutaneously. Placement was successful in 45 (94%) of the 48 surgical patients and 120 (99%) of the 121 percutaneous patients. Filter misplacement occurred in three (6%) surgical patients and no percutaneous patients. Clinically evident femoral vein thrombosis occurred in only four (5%) of the percutaneous patients, while inferior vena cava thrombosis occurred in three (3%) of the percutaneous patients. One pulmonary embolus occurred after percutaneous filter placement and resulted in death. The cost of percutaneous placement was 58% that of surgical placement. A retrospective review of the experience in our patient population indicates that safety, cost, and ease of insertion make the percutaneous approach the procedure of choice for Greenfield filter placement."
-What medical condition did the 32-year-old woman develop 20 years after receiving 198Au synoviorthesis for juvenile rheumatoid arthritis?,"Chronic myeloid leukemia in a woman with Still's disease treated with 198Au synoviorthesis. A 32-year-old woman presented with chronic myeloid leukemia 20 years after 2 198Au synoviortheses to her knees for severe juvenile rheumatoid arthritis. She progressed to blast phase of her disease and died from complications of therapy. The literature on rheumatoid arthritis, its therapy, radioisotopes and leukemia is reviewed."
-What is K-edge energy digital subtraction arthrography (KEDSA) and how does it improve the detection of hip prosthesis loosening?,"K-edge digital subtraction arthrography of the painful hip prosthesis: a feasibility study. K-edge energy subtraction radiography is a method for detecting the presence of iodinated contrast material by subtracting two digital radiographs produced by X-ray beams with energies above and below the iodine K edge. We performed a feasibility study on the application of K-edge energy digital subtraction arthrography (KEDSA) to painful hip prostheses. During arthrography, loosening of the prosthesis is implied if contrast material is seen dissecting around the prosthesis, an often difficult detection task because of adjacent prosthesis metal or cement. In conventional arthrography a preliminary mask image is thus used from which films obtained after injection of iodinated contrast material are subtracted. Movement by the patient during this process may preclude subsequent subtraction. With KEDSA, since multiple image pairs may be obtained after the injection of contrast material, the problem of patient motion is virtually eliminated. A conventional X-ray tube operating between 55 and 65 kVp was alternately filtered by iodine and cerium filters to produce the KEDSA images. The apparatus was capable of producing a subtracted image within 3 sec. The technique was applied to phantoms and to six patients immediately after hip arthrography that had been positive for prosthesis loosening. Although of lower spatial resolution, the KEDSA images were, in all cases, positive for loosening in a pattern consistent with the conventional arthrographic images. KEDSA was shown to be successful in detecting extraarticular contrast material. During a single study, subtraction in various imaging planes as well as postexercise subtraction imaging can be accomplished-techniques not heretofore possible in routine subtraction arthrography."
-What were the key findings regarding the sensitivity of 12-lead electrocardiogram versus limb-lead monitoring in detecting ischemia during percutaneous transluminal coronary angioplasty?,"Twelve-lead electrocardiographic evaluation of ischemia during percutaneous transluminal coronary angioplasty and its correlation with acute reocclusion. The sensitivity of the surface 12-lead electrocardiogram and that of standard (limb-lead) monitoring for the detection of ischemia during percutaneous transluminal coronary angioplasty were compared in 115 patients. The purpose was to identify the electrocardiographic leads that provide the most sensitive indicators of coronary ischemia during percutaneous transaluminal coronary angioplasty and to evaluate the ""ischemic fingerprint"" that is obtained with 12-lead electrocardiogram during balloon inflation as a predictor of abrupt reocclusion after successful percutaneous transaluminal coronary angioplasty procedures. During balloon inflations of 30 seconds, ischemia was detected in 61 of 145 vessels (42%) by limb-lead monitoring alone versus 130 of 145 vessels (90%) by 12-lead electrocardiography (p less than or equal to 0.001). In the nine patients (7.8%) who experienced abrupt reocclusion within 24 hours, the electrocardiogram during chest pain after percutaneous transaluminal coronary angioplasty was identical to that obtained during percutaneous transaluminal coronary angioplasty (""ischemic fingerprint""). None of the six patients who had chest pain after percutaneous transaluminal coronary angioplasty without evidence of abrupt reocclusion reproduced their ischemic fingerprint. The suggested optimal leads for monitoring ischemia are as follows: left anterior descending coronary artery, V2, and V3; circumflex artery, V2, and V3; and right coronary artery, III and aVF."
-What type of adenoma was found in the left lung of the 28-year-old woman during autopsy?,"Adenoma of type 2 pneumocytes with oncocytic features. An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly."
-What factors can increase the risk of vasovagal syncope during spinal anesthesia?,Vasovagal asystole during spinal anaesthesia. A patient in whom vasovagal asystole was induced by the performance of a spinal anaesthetic in the upright position is described. This illustrates the importance of routine monitoring of the electrocardiograph during regional anaesthesia. The risk of vasovagal syncope may be increased by the use of the sitting position and by the omission of anxiolytic premedication.
-How do motor initiation and execution differ between normal subjects and Parkinson's disease patients?,"Motor initiation versus execution in normal and Parkinson's disease subjects. We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way."
-What is sonoelasticity imaging and how does it potentially help in detecting neoplasms?,"Sonoelasticity imaging: results in in vitro tissue specimens. The authors present a method for imaging tissue stiffness (sonoelasticity) that has been developed and tested in a laboratory setting by using in vitro canine and human prostate glands. A low-frequency acoustic source was used to induce vibration in tissue under examination, and a color Doppler ultrasound (US) instrument was modified to detect vibration amplitude. The resulting image is a color ""map"" of tissue vibration superimposed on conventional gray-scale US images. Stiffer tissues vibrated less in response to audible sound, regardless of echogenicity. Normal human and canine prostate glands demonstrated a uniform vibration pattern. Four of four human prostatic adenocarcinomas and two stiff inclusions injected into canine prostate glands demonstrated a lack of vibration in comparison with normal surrounding tissue. The authors conclude that while further study is necessary, sonoelasticity imaging may enhance the detection of neoplasms by enabling their identification solely on the basis of stiffness."
-What were the key prognostic factors significantly associated with disease recurrence in clinical stage I endometrial adenocarcinoma according to the multivariate analysis?,"Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Two hundred sixty-four consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and August 1988 were followed prospectively and evaluated for disease recurrence for 8-112 months (mean 51.5). Thirty-three patients (12.5%) developed recurrence or died of disease. In univariate statistical analysis, prognostic factors significantly associated with disease recurrence were as follows: age (mean 68.6 years with versus 60.3 years without recurrence; P = .0001); histology (adenocarcinoma 8.8%, adenosquamous 35.7%, papillary 25%, clear-cell 57.1%; P less than .0001); tumor grade (grade 1, 7.7%, grade 2, 10.5%, grade 3, 36.1%; P less than .0001); depth of myometrial invasion (none 9.8%, less than one-half 7.4%, one-half or greater 29.6%; P = .0001); lymph node status (negative 8.3%, positive 47.6%; P less than .0001); non-nodal extrauterine disease spread (absent 11.0%, present 50%; P = .0003); peritoneal cytology (negative 9.4%, positive 26.3%; P = .004), and tumor size (2 cm or less 7%, greater than 2 cm 17.3%; P = .05). Cervical extension and uterine size had no significant effect on recurrence. Using multivariate analysis, grade 3 tumor (P = .002), advancing age (P = .004), lymph node metastasis (P = .006), and presence of extrauterine disease spread other than lymph node metastasis (P = .038) were the only variables significantly associated with disease recurrence or death. This study supports the new International Federation of Gynecology and Obstetrics surgical staging system for endometrial cancer."
-What percentage of patients developed aneurysms at the surgical repair site during childhood years after coarctation of the aorta repair?,"Preoperative and postoperative ""aneurysm"" associated with coarctation of the aorta. The reported incidence of aortic aneurysm after surgical repair or balloon angioplasty for aortic coarctation varies widely. To determine the incidence of aneurysm formation after surgery, preoperative and postoperative cineangiograms from 65 patients who underwent operation at age 1.5 +/- 3.4 years were examined. Repair included a prosthetic patch in 14 patients, end to end anastomosis in 28 and subclavian flap in 23. Aneurysm was documented by change in contour or irregularities in contour at the repair site or by abnormal dimensions at the repair site, defined by the ratio of the widest measurement at the repair site to the measurement of the aorta at the diaphragm. An aneurysmal bulge above the ductus diverticulum was identified in 14 (23%) of 60 patients preoperatively; the area showed no change 4.72 +/- 4.07 years after surgery. Significant changes at the repair site were seen in only three patients, all of whom had Dacron patch repair. One patient had a change in contour at the repair site, one had an abnormally high repair site to diaphragmatic aorta ratio and one had a progressive increase in this ratio. Thus, during childhood years, 3 (5%) of 65 patients were diagnosed as having aneurysm at the surgical repair site. In conclusion, 1) comparison with preoperative cineangiograms, especially for aneurysmal bulges above the ductus arteriosus, is essential before an aneurysm can be attributed to coarctation repair by any technique, and 2) aneurysm developed only in patients subjected to Dacron patch repair."
-What is unique about the lymphoma case described in this context?,"Ki-1-positive lymphoma developing 10 years after the diagnosis of hairy cell leukemia. The case is described of a 62-year-old man with a 10-year history of hairy cell leukemia (HCL) who subsequently had a large-cell anaplastic or so-called Ki-1-positive lymphoma. Immunocytochemical staining of the lymphomatous node revealed positivity for Ki-1 (CD30) and epithelial membrane antigen in the tumor cells, and flow cytometric analysis showed simultaneous expression of Leu M5 (CD11c) and Leu 14 (CD22). Although HCL has been reported to coexist with both Hodgkin's disease and non-Hodgkin's lymphoma, the authors believe this is the first case in which a Ki-1-positive lymphoma developed in a patient with HCL. The clinicopathologic and immunologic features of both entities are discussed, as is the association of HCL with other neoplasms."
-What is the weaning index (WI) and how is it calculated in this study?,"Evaluation of a new weaning index based on ventilatory endurance and the efficiency of gas exchange. We hypothesized that the ventilatory capacity needed to wean from mechanical ventilation (mv) depends on two variables: ventilatory endurance and the efficiency of gas exchange. We also hypothesized that these variables could be assessed from data readily available at the bedside, including tidal volume (VT) on mv and during spontaneous breathing (sb), ventilator peak inspiratory pressure (Ppk), and patient negative inspiratory pressure (NIP). Ventilatory endurance was evaluated using a modified pressure-time index: PTI = TI/Ttot x Pbreath/NIP, where Pbreath = Ppk x VTsb/VTmv. Defining VE40 as the minute ventilation needed to bring PaCO2 to 40 mm Hg, the efficiency of gas exchange was evaluated by calculating VE40/VTsb = (VE x PaCO2)mv/VTsb x 40. Because high levels of inspiratory effort might cause patients to reduce VTsb and thereby compromise CO2 elimination, we devised a weaning index (WI) that combines ventilatory endurance and the efficiency of gas exchange: WI = PTI x (VE40/VTsb). The study population comprised 38 patients with chronic obstructive pulmonary disease, adult respiratory distress syndrome, pneumonia, neuromuscular disease, and miscellaneous other conditions. They had been mechanically ventilated more than 3 days and were considered by clinical criteria to be ready for weaning. Of 46 weaning trials, 19 were successful, 2 were partially successful, and 25 failed. PTI and VE40/VTsb were higher in patients who failed (p less than 0.05), but neither variable alone had sufficient sensitivity or specificity to predict the outcome of weaning trials accurately."
-What percentage of postmenopausal women experienced persistent side effects from tamoxifen treatment in this study?,"Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance."
-What was the primary objective of the experimental in vivo model described in the study?,"Nephrotoxic potential of Bence Jones proteins BACKGROUND. The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. METHODS. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. RESULTS. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 mumol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 mumol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. CONCLUSIONS. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain-associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains."
-Does the level of axillary lymph node involvement independently predict survival in clinical stage I and II breast cancer patients?,"Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival. We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance."
-What is the purpose of the in situ venous valve construction technique described in the context?,"In situ venous valve construction. A technique of in situ deep venous valve construction based on vein wall intussusception is described. The technique has been used to construct a size-matched, autogenous valve in the femoral vein of the dog. Forty-one valves have been constructed. Immediately after construction, all 41 were patent at ascending phlebography and Harvey's test showed them to be competent. Descending phlebography demonstrated competence in 38 valves. Hydrostatic testing was performed on 27 valves in the vertical position at pressure gradients in the range 0.2-250 cmH2O. Of these, 24 valves were fully competent. Six valves were studied at intervals between 1 and 112 days after construction. All six were competent by Harvey's test and five were competent at descending phlebography. There was no evidence of thrombosis in any valve. This technique may be suitable for replacement of deep venous valves in patients with the calf pump failure syndrome caused by deep venous reflux."
-What was the relationship between the degree of coronary stenosis and mortality in patients who survived an anterior wall Q-wave acute myocardial infarction?,"Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05)."
-How many deaths and new cases of illness are estimated to occur annually in the United States due to occupational diseases?,"The recognition and control of occupational disease. Occupational diseases account each year in the United States for an estimated 50,000 to 70,000 deaths and 350,000 new cases of illness. Often, however, occupational diseases are not correctly diagnosed, because they mimic diseases due to other causes and because most physicians are not well trained in their recognition. Opportunities for prevention and treatment are therefore lost. The occupational history is the most effective means for proper diagnosis of occupational illness. It should routinely be obtained for every patient. A brief but systematic guide for obtaining an occupational history is presented in this report. Also, approaches are summarized for the recognition and diagnosis of such important occupational diseases as occupational cancer, asbestosis and other respiratory disorders, and occupational neuropsychologic disorders. The management and prevention of occupational diseases depend on reduction of hazardous exposures in the workplace and better education of workers, industrial managers, and physicians. This report outlines a program for the control of occupational disease based on (1) preventing exposures in the workplace, (2) premarket toxicity testing of new chemicals and technologies, and (3) astute clinical diagnosis."
-What was the main objective of the North American Symptomatic Carotid Endarterectomy Trial?,"Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators BACKGROUND. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS. Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery."
-How does insulin resistance potentially contribute to increased blood pressure through altered cation transport mechanisms?,"Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What percentage of superficial femoral artery stenoses did not progress after a mean follow-up interval of 37 months?,"The natural history of superficial femoral artery stenoses. Since the natural history of specific superficial femoral artery stenoses is not known, we examined progression rates of superficial femoral artery stenoses in 45 lower extremities found when arteriograms were obtained of 38 patients for symptomatic atherosclerotic disease in the opposite leg or abdomen. These initial superficial femoral artery arteriograms were compared with later arteriograms in 25 limbs, duplex scans in 27 limbs, and both modalities in 7 limbs. After a mean interval of 37 months, most superficial femoral artery stenoses (72%) did not progress. However, 12 superficial femoral artery stenoses progressed (28%; mean follow-up, 37 months, including 7 that occluded (17%). Superficial femoral artery stenoses progressed among patients who complained of symptom progression at a rate faster than that among asymptomatic patients (15.6%/year vs 3%/year; p = 0.006). Superficial femoral artery lesions also progressed more rapidly among patients whose contralateral superficial femoral artery was occluded (10%/year vs 1.6%/year; p = 0.04). By multivariate regression analysis, symptom progression and smoking history were predictive of superficial femoral artery stenosis progression. In the seven patients whose superficial femoral artery stenoses progressed to occlusion, the average rate of stenosis progression was 12%/year (maximum predicted rate, 30% per year by 95% confidence limit). These results indicate that superficial femoral artery stenoses usually progress with synchronous symptomatic deterioration. Other than symptom progression, only cumulative smoking history and contralateral superficial femoral artery occlusion could be associated with superficial femoral artery stenosis progression in this small series."
-What misconceptions about cancer were found among the socioeconomically disadvantaged patients in the study?,"Knowledge and beliefs about cancer in a socioeconomically disadvantaged population. Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors."
-What were the key differences in safety and tolerance between amphotericin B lipid complex (ABLC) and amphotericin B desoxycholate (AB) in the study?,"Comparative safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. Amphotericin B lipid complex (ABLC), a lipid complex formulation of amphotericin B, and amphotericin B desoxycholate (AB) were compared for safety, tolerance, and pharmacokinetics in two groups of eight healthy male volunteers. After a 1-mg test dose, study drug was infused at 0.1, 0.25, and 0.5 mg/kg; the 0.5-mg/kg dose was not given to subjects receiving AB. ABLC caused few acute adverse effects except for mild somnolence (drowsiness) in six volunteers. In addition, three of eight ABLC recipient had asymptomatic, transient serum transaminase elevations that resolved spontaneously. The AB recipients experienced more acute side effects, but only one had a mild shaking chill: three of eight also experienced sleepiness. No significant changes in vital signs, electrocardiogram, oximetry, pulmonary function, or clinical status were observed in either group. Due to its increased estimate volume of distribution and estimated clearance. ABLC yielded decreased amphotericin B levels and area under the serum concentration versus time curve relative to AB."
-How does continuous positive airway pressure (CPAP) affect ventilatory output and pulmonary resistance during different stages of non-rapid-eye-movement (NREM) sleep?,"Effects of sleep-induced increases in upper airway resistance on ventilation. To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone."
-What was the average functional rating of the hips before and after total hip arthroplasty in patients who had childhood sepsis?,"Total arthroplasty of the hip after childhood sepsis. Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood. The average age of the patients was 36.4 years (range 19 to 50). The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80). Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection. The mean functional rating of the hips was 58 points before operation and 90 at the final review. Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration. Acetabular allografts were required in 27 hips (60%). All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all."
-What are the key findings suggesting that the postsurgical hemorrhage resulted from venous thrombosis after AVM excision?,"Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report. A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM."
-How did the use of hyaluronidase affect cell recovery during intestinal perfusion?,"Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease. The recovery of cells arising from small intestinal mucosa alone was studied during continuous perfusion of a closed segment of jejunum. The perfusion technique minimised the contamination of the perfused segment with, for example, proteolytic enzymes from pancreas, allowing recovery of viable cells. The use of hyaluronidase in the perfusion fluid increased the recovery of cells fivefold, the median recovery being 8 x 10(6) cells. The cells were analysed with monoclonal antibodies and flow cytometry. Nearly all cells (98-99%) recovered during perfusion of healthy control subjects and patients with Crohn's disease were epithelial cells. The jejunal cells expressed HLA-DR in similar proportions--around 30%--in patients and control subjects. The ratio between CD4+ and CD8+ lymphocytes was similar (0.2) in control subjects and patients with inactive Crohn's disease but decreased (0.03) in patients with active Crohn's disease in the ileum."
-What is the potential outcome of untreated or late-treated candidal mediastinitis?,"Candidal mediastinitis after surgical repair of esophageal perforation. Candidal mediastinitis, like Boerhaave's syndrome, is uncommon, and both, if treated late or incompletely, frequently result in death. Early recognition and aggressive medical and surgical intervention are the best means to convalescence and cure in both conditions."
-How does the experimental model (open-chest vs. conscious dog) affect the assessment of postischemic myocardial stunning?,"Postischemic myocardial ""stunning"". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog. Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial ""stunning""). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically ""protective"" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What immune system abnormality was observed in the patient with primary sclerosing cholangitis?,"Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study. Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters."
-What is the key characteristic of the chondroblastomalike extraskeletal tumor found in the patient's right thumb?,Chondroblastomalike extraskeletal chondroma. An unusual extraskeletal tumor occurring in the right thumb of a 44-year-old man exhibited histologically a chondroblastomalike appearance. The tumor was characterized by dense proliferation of chondroblastic cells admixed with a few multinucleated giant cells of osteoclast type. The patient had no evidence of local recurrence or metastasis three-and-a-half years after a simple excision.
-How was bile peritonitis managed in this patient without resorting to exploratory laparotomy?,"Novel approach to iatrogenic bile peritonitis. Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice."
-What quantitative liver function tests were found to be significant predictors of survival in patients with cirrhosis?,"Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification."
-What factors were found to be associated with increased elastic recoil after percutaneous transluminal coronary angioplasty?,"Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study. The immediate result of percutaneous transluminal coronary angioplasty is influenced by both plastic and elastic changes of the vessel wall. To evaluate the amount of elastic recoil after coronary balloon angioplasty, the minimal luminal cross-sectional area of the largest balloon used at highest inflation pressure was compared with the minimal luminal vessel cross-sectional area directly after final balloon deflation in 607 lesions (526 patients). Elastic recoil was defined as the difference between balloon cross-sectional area and minimal luminal cross-sectional area of the dilated coronary segment immediately after balloon withdrawal. A videodensitometric analysis technique was used to avoid geometric assumptions on stenosis morphology directly after angioplasty. Mean balloon cross-sectional area was 5.3 +/- 1.6 mm2 and minimal luminal cross-sectional area after angioplasty was 2.8 +/- 1.4 mm2. Reference areas before and after angioplasty did not differ (6.0 +/- 2.6 and 6.2 +/- 2.6 mm2, respectively). Univariate analysis revealed that asymmetric lesions, lesions located in less angulated parts of the artery and lesions with a low plaque content showed more elastic recoil. Lesions located in distal parts of the coronary tree were also associated with more elastic recoil probably related to relative balloon oversizing in these distal lesions."
-What was the key finding regarding CD34 mRNA expression in the B-precursor acute lymphoblastic leukemia cell subpopulations?,"Differentiation in B-precursor acute lymphoblastic leukemia cell populations with CD34-positive subpopulations. B-precursor acute lymphoblastic leukemia bone marrow specimens that contained subpopulations of cells with immunophenotypes corresponding to early (CD34) and late (CD20) and (CD22) stages of normal B-cell differentiation were studied. Subpopulations of cells were isolated according to immunophenotype and then analyzed by both a clonogenic assay and molecular genetic methods. Clonal equivalence of the early and late immunophenotypic subpopulations was confirmed for each case by the demonstration of identical lg gene rearrangements. The in vitro colony-forming assay consistently showed a growth advantage for the CD34+ subpopulations over the CD34- subpopulations. CD34 mRNA was detected readily in these isolated precursor cells. When two specimens in which virtually all of the leukemia cells were CD34+ and CD34+CD20+ and CD34+CD22+ subpopulations were also present the CD34 mRNA was limited to the cells without the late-stage differentiation antigens on their surface. Furthermore, the c-myb mRNA was found only in the subpopulations that also contained CD34 mRNA. Our results show that a limited program of differentiation reminiscent of normal B-cell development may be present in this leukemia."
-What is the gender distribution observed in the study of global T wave inversion?,"Global T wave inversion. Because global T wave inversion has not been specifically characterized, 100 electrocardiograms (ECGs) with this pattern (frontal plane T vector -100 degrees to -170 degrees with precordial T inversion) were prospectively collected from approximately 30,000 consecutively interpreted ECGs and analyzed blindly. There was a striking female predominance (82 women vs. 18 men; p less than 0.0005) despite an essentially equal number of female and male hospital admissions. There was a single statistically significant ECG correlate: a more vertical QRS axis in women (+14.1 degrees +/- 45.3 degrees vs. -5.6 degrees +/- 31.3 degrees; p = 0.034). The T waves were basically symmetric (68%), the influence of this factor usually altering the characteristically asymmetric T wave inversions of right bundle branch block (4 of 5) and left ventricular hypertrophy (21 of 36). Asymmetry was mainly associated with digoxin therapy (21 of 32 patients taking digoxin; p less than or equal to 0.0005) and a corrected QT (QTc) interval (0.433 +/- 0.095) shorter than with symmetric T wave inversions (0.507 +/- 0.074; p less than or equal to 0.0005) though not reaching the degree of shortening expected for digitalization. Twenty-eight patients admitted for acute myocardial infarction and 23 for a central nervous system disorder accounted for the majority of patients with symmetric T wave inversion. Fifteen of 18 patients who had coronary angiography had some degree of coronary artery disease: 3 had angiographically normal coronary arteries."
-What was the suspected pathophysiologic mechanism causing the referred pain in this patient with a spinal cord tumor?,"Somato-somatic referred pain caused by suprasegmental spinal cord tumor. Tactile stimulation of a coin-sized area in a T-2 dermatome consistently triggered a lancinating pain in the ipsilateral C-8 dermatome in a 38-year-old woman. The SEP and an MRI led to a diagnosis of a tumor at the left cervico-medullary junction, much higher than the clinically suspected level. Surgical exploration revealed an exophytic glioma, and the pain was abolished postoperatively. Ephaptic transmission at the tumor site was suspected as a pathophysiologic mechanism."
-What medical condition developed in a 52-year-old man after an inferior wall myocardial infarction complicated by Dressler's syndrome?,Early constrictive pericarditis and anemia after Dressler's syndrome and inferior wall myocardial infarction. Early constrictive pericarditis and anaemia developed in a 52 year old man after he had an inferior wall myocardial infarction complicated by Dressler's syndrome. Total pericardiectomy at the time of coronary artery bypass surgery resulted in complete resolution of signs and symptoms.
-"How does sinorphan, an enkephalinase inhibitor, affect plasma atrial natriuretic factor (ANF) and sodium urinary excretion in cirrhotic patients with ascites?","Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites. We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites."
-What medical procedure was performed to treat the patient's aneurysm in this case report?,"Aneurysm of the distal anterior inferior cerebellar artery unrelated to the cerebellopontine angle: case report. This is a case report of an unusual aneurysm of the distal anterior inferior cerebellar artery. A 44-year-old woman had a severe frontal headache and vomiting of sudden onset. On the day after admission, the patient began to demonstrate nuchal rigidity and difficulty with upward gaze bilaterally. There were no complaints at this time suggestive of a syndrome of the cerebellopontine angle. A computed tomographic scan revealed an intraventricular hemorrhage of the 3rd and 4th ventricles; however, multiple attempts at four-vessel angiography were required before an aneurysm could be demonstrated. On the 28th hospital day, a suboccipital craniectomy using the retromastoid approach in the lateral position was performed. A saccular aneurysm with a surrounding hematoma in the distal anterior inferior cerebellar artery was found and clipped. The operative findings revealed that the aneurysm was unrelated to the cerebellopontine angle. After surgery, the patient had an uneventful recovery and complete resolution of symptoms."
-What was the standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared to the general population?,"Cancer incidence in Norwegian Seventh-Day Adventists 1961 to 1986. Is the cancer-life-style association overestimated? Standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared with the general population was not significantly different from unity (men 91, women 97). Persons converting late in life had a higher incidence than those converting at an earlier age. Respiratory cancers (standardized incidence ratio [SIR] 59, 95% CI = 36 to 91) and cancers with an unspecified site (SIR 53, 95% CI = 25 to 97) were rarer and cancer of the uterine corpus (SIR 164, 95% CI = 109 to 237) was more common in Seventh-Day Adventists before the age of 75 years. Inclusion of all registered Seventh-Day Adventists regardless of religious activity and the relatively low cancer incidence rates in the Norwegian population could contribute to the nonsignificant result with regard to total cancer. Main etiologic factors in cancer development in Norway should be sought in areas where Seventh-Day Adventists do not differ from the general population."
-At what postnatal ages did the rats show the highest incidence of epileptiform EEG activity during hypoxia?,"Epileptogenic effect of hypoxia in the immature rodent brain. The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia."
-What differences were observed in childhood cancer incidence and outcomes between Polynesian and non-Polynesian children in the study?,"Childhood cancer among the Polynesian population. From June 1981 through June 1989, 95 Polynesian children were seen for initial care of malignancy at the Princess Mary Hospital for Children (PMHC). The incidence of malignancy in the Polynesian populations served, the histology of the malignancies, and the outcome of therapy were reviewed and compared with 185 non-Polynesian (non-P) patients seen during the same period. Incidence figures for Polynesians and non-P were similar, but histologic patterns differed, showing an increased occurrence of leukemia, particularly nonlymphoblastic leukemia, an increased occurrence of bone tumors, and a decreased incidence of central nervous system tumors for Polynesians. Survival for Polynesian children with acute lymphoblastic leukemia was worse than for non-P. Survival in all other disease categories was similar."
-What factors were associated with major or minor hemorrhagic events during thrombolytic therapy for acute myocardial infarction?,"Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. OBJECTIVES: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. DESIGN: A multicenter, randomized, controlled trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). INTERVENTIONS: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. MEASUREMENTS: Patients were monitored for hemorrhagic events during hospitalization. MAIN RESULTS: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. CONCLUSIONS: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy."
-How does mifepristone potentially help in treating unresectable meningiomas?,"Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors. The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (greater than or equal to 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective improvement (improved extraocular muscle function or relief from headache). The side effects of long-term mifepristone therapy have been mild. Fatigue was noted in 11 of the 14 patients. Other side effects included hot flashes in five patients, gynecomastia in three, partial alopecia in two, and cessation of menses in two. Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma."
-What is a transscleral leiomyoma and how did it manifest in the 31-year-old woman described in the context?,"Transscleral leiomyoma. A bluish-pink epibulbar lesion, which slowly enlarged over a period of 5 years, developed in a 31-year-old woman. The lesion initially resembled a staphyloma, based on the very thinned overlying sclera, but subsequent evaluation suggested that it was a solid mass. At the time of surgical removal, the mass appeared to have originated in the supraciliary region and to have eroded outward through the sclera. Histopathologically, the mass proved to be a leiomyoma. The authors propose theoretic possibilities to explain the location of this rare type of ocular smooth muscle tumor."
-How effective is electromyographic monitoring in detecting facial nerve injuries caused by carbon dioxide lasers during surgical procedures?,"Detection of intraoperative laser injury to the facial nerve by electromyographic monitoring of facial muscles. Injury to the facial nerve is a significant risk during resection of cerebellopontine angle tumors. To minimize the risk of facial nerve injury, intraoperative electromyographic monitoring of facial musculature is frequently used. However, the reliability of such monitoring systems for detection of thermal nerve injury resulting from the use of carbon dioxide lasers has not been systematically evaluated. We determined the sensitivity of a computerized electromyographic monitor for detection of laser facial nerve injury in an anesthetized rat model. The mandibular and buccal branches of the facial nerve were isolated in 12 rats. A carbon dioxide laser was used to create controlled sites of thermal injury to both nerves over a 3-hour period. When a laser injury was created distal to previous injury sites, electromyographic discharge was noted in 72% to 82% of injuries. Laser injury proximal to previous injury sites was detected with 33% efficiency. These detection rates did not change significantly over a 3-hour period. This preliminary data suggests that electromyographic monitoring of facial musculature allows detection of facial nerve injury caused by carbon dioxide lasers."
-"What were the key differences in acute coronary lesions among patients with unstable angina, sudden coronary death, and acute myocardial infarction?","Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. The frequency and type of acute lesions in the four major (right, left main, left anterior descending, left circumflex) epicardial coronary arteries were examined at necropsy in 14 patients with unstable angina pectoris, 21 patients with sudden coronary death and 32 patients with a fatal first acute myocardial infarction. None of the 67 patients had a grossly visible left ventricular scar (healed myocardial infarct) and only the group with acute myocardial infarction had left ventricular myocardial necrosis. Although the frequency of intraluminal thrombus was similar in patients with unstable angina (29%) and sudden death (29%) and significantly lower than in those with acute infarction (69%) (p = 0.02), the thrombus in the patients with unstable angina and sudden death consisted almost entirely of platelets and was nonocclusive, whereas the thrombus in the group with acute infarction consisted almost entirely of fibrin and was occlusive. The frequency of plaque rupture was insignificantly different in the groups with unstable angina (36%) and sudden death (19%), and was significantly lower than in the group with acute infarction (75%) (p = 0.02). The frequency of plaque hemorrhage was insignificantly different in the groups with unstable angina (64%) and sudden death (38%) and was significantly lower than in the group with acute infarction (90%) (p = 0.04)."
-What imaging features are characteristic of adrenal hemangioma on magnetic resonance imaging?,"Adrenal hemangioma: an unusual adrenal mass delineated with magnetic resonance imaging. Adrenal hemangioma should be included in the differential diagnosis of any large calcified adrenal mass. We report to our knowledge the eighth surgically removed lesion and describe its appearance on magnetic resonance imaging. This imaging includes features seen in hemangiomas elsewhere, in particular a heterogeneous mass with enhancing peripheral high intensity foci on T1 images."
-What modifications were made to the standard aortography technique to improve visualization of lower limb arteries?,"A modified technique of pre-operative aortography to demonstrate the complete arterial tree of the lower limb. One hundred consecutive aortograms were studied to establish the efficacy of conventional arteriography in demonstrating distal vessels and the pedal arch. The standard technique was modified by using a long injection time, a large volume of contrast material (iopamidol 370), prolonged filming and multiple exposures of the feet. On the basis of these examinations each limb was classified as having aorto-iliac disease (18 limbs), superficial femoral disease (103 limbs), combined segment disease (28 limbs) or generalised disease (51 limbs). Calf and ankle arteries were seen in 196 of the 200 limbs (98%). Patency of the pedal arch was established in 184 (92%). Fourteen percent of the group of patients with combined segment disease did not have their pedal arch visualised and this group contained most of the examination failures. This modified method of aortography can demonstrate the entire arterial tree from the aorta to the foot in 92% of limbs with symptomatic chronic atherosclerotic disease. This allows the majority of peripheral vascular reconstructions to be planned and performed without the need for intra-operative arteriography."
-What is the recommended treatment for cerebral air embolism and how effective is it when administered late?,"Hyperbaric treatment of cerebral air embolism sustained during an open-heart surgical procedure A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment."
-What were the key findings of the study regarding the growth of human basal cell carcinomas transplanted to beige-nude mice?,"Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJ/bgJ nu/nu (beige-nude) mice. The purpose of this study was to measure growth parameters of transplanted basal cell carcinoma (BCC) to beige-nude mice during a 4-month observation time. Forty male beige-nude mice were transplanted with human BCC with our reported subcutaneous implantation technique. Initial volume and wet weight were determined for each tumor. The tumors were measured every 2 weeks by calipers with a final volume determined at 120 days, at which time the tumors were harvested, weighed, and processed for routine histology. Thirty-two tumor sites were positive for persistent tumor at harvest. Tumor volumes declined by an average of 51% and average tumor weight by 33%. There were increased numbers of mast cells surrounding the BCC tumor lobules. These results indicate that BCC can survive for 120 days in the beige-nude mouse."
-Does carbon dioxide laser treatment disperse human papillomavirus deoxyribonucleic acid during genital infection procedures?,"Carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields. The possibility of dispersing viral deoxyribonucleic acid during carbon dioxide laser treatment of human papillomavirus-containing genital infections has been investigated with a commercially available dot blot hybridization technique. The viral ribonucleic acid probes were specific for groups of human papillomavirus types 6/11, 16/18, and 31/33/35. Laser energy was delivered by continuous-wave mode and the plume of smoke was evacuated by a vacuum suction system. Samples were taken with Dacron swabs from lesional tissues of 43 patients as well as from the treated areas and from the 5 cm surrounding normal skin before and after laser vaporization. Human papillomavirus deoxyribonucleic acid was identified in swabs from 34 of 43 (79%) lesional tissues and 7 of 43 (16%) treatment fields. Although a trend for higher human papillomavirus deoxyribonucleic acid positivity in laser margins after therapy (7/43, 16%) than before (4/43, 9%) was observed, the rates were not statistically significant. It is concluded that carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields and the adjacent normal epithelium. Viral contamination of treated areas may be reduced by positioning the fume evacuator within 1 cm of the field of laser vaporization and cleaning the treated areas and surrounding tissue after therapy."
-What is Bouveret's syndrome and how does it typically manifest?,"Bouveret's syndrome: an unusual twist on the classic cause. Bouveret's syndrome is a duodenal obstruction caused by a gallstone, manifested mostly as a gastric outlet obstruction. We have reported an instance of Bouveret's syndrome caused by two separate stones, either of which could independently have caused the obstruction. It is imperative to be sure that the obstruction is relieved before terminating the operative procedure."
-What is the primary medical intervention discussed for managing retroperitoneal hemorrhage from renal angiomyolipoma in a patient with polycystic kidney disease?,"Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited."
-What is the primary purpose of the study on CGS 16949A (fadrozole hydrochloride) in postmenopausal women with metastatic breast cancer?,"Specificity of low dose fadrozole hydrochloride (CGS 16949A) as an aromatase inhibitor. CGS 16949A (fadrozole hydrochloride), a potent cytochrome P450-mediated steroidogenesis inhibitor, blocks aromatase at low doses, but other biosynthetic steps at higher concentrations. Recent studies demonstrated inhibition of C11-hydroxylase, corticosterone methyloxidase-II, and deoxycorticosterone to corticosterone conversion with this agent at some-what higher concentrations than those required for blockade of aromatase. Based upon phase I studies, we postulated that relatively selective inhibition of aromatase might be possible if sufficiently low doses of CGS 16949A were used. A phase II study in 54 postmenopausal women with metastatic breast cancer examined the effects of low dose CGS 16949A on estrogen, mineralocorticoid, and glucocorticoid secretion. Two dose schedules and two dose levels were chosen based upon our prior dose escalation protocol study. Plasma estrone, estradiol, and estrone sulfate as well as urinary estrone and estradiol fell equally with 1.8-4 mg CGS 16949A given either on a twice daily or three times daily dose schedule. Isotopic kinetic studies demonstrated an 84% decrease in the rate of conversion of androstenedione to estrone to 0.40 +/- 0.07% (patients receiving 1.8-4 mg CGS 16949A daily). With these three regimens, basal levels of aldosterone and cortisol did not change significantly over a 12-week period of observation. Clinical examination, plasma electrolytes, and urinary sodium/potassium ratios suggested no biological evidence of mineralo-corticoid deficiency. ACTH-stimulated cortisol concentrations, however, were blunted at each dose level compared to pretreatment values. Nonetheless, peak responses exceeded 550 nmol/L, or a basal to peak difference of 190 nmol/L or greater, in 97% of instances. This probably reflected inhibition of C11-hydroxylase, since basal and ACTH-stimulated levels of 11-deoxycortisol were increased in response to CGS 16949A. Androstenedione and 17 alpha-hydroxyprogesterone also exhibited an upward trend in response to drug treatment. ACTH-stimulated aldosterone levels were blunted to a greater extent than those of cortisol, probably as a reflection of corticosterone methyloxidase type II blockade. Overall, the results suggest that CGS 16949A, at doses of 1.8-2 mg daily, blocks aromatase effectively and does not produce clinically important inhibition of cortisol or aldosterone biosynthesis. Thus, this agent can probably be used safely without glucocorticoid or mineralocorticoid supplementation."
-What are the different histologic patterns of isolated neurofibromas of the conjunctiva observed in the study?,"Isolated neurofibromas of the conjunctiva. We studied four histologically verified cases of isolated neurofibromas of the conjunctiva. The histologic pattern was diffuse in two patients, plexiform in one patient, and solitary in one patient. Simple excision was curative in all cases. We emphasize the importance of distinguishing neuromas (which may be associated with multiple endocrine neoplasia) from neurofibromas."
-What is a double anal canal and how can it develop as a complication of chronic constipation?,"Double anal canal: complication of rectal fecalith. Fecaliths and stercoraceous ulcerations are well-known complications of chronic constipation. The authors present the case of a double anal canal in an elderly man. This anorectal fistula (complex anal fistula) developed as a complication of an impacted rectal fecalith with resultant stercoraceous ulceration. Eventually, a persistent epithelialized canal developed and was demonstrated at double-contrast barium enema examination. The patient remained continent at all times."
-What percentage of patients with closed-head injury were discharged in a vegetative state according to the Traumatic Coma Data Bank Report?,"Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report. To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state."
-What were the key findings regarding the prognosis of B-cell and T-cell diffuse large-cell lymphomas in this Stanford study?,"Similar outcome of treatment of B-cell and T-cell diffuse large-cell lymphomas: the Stanford experience. Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone."
-"What type of cancer was successfully treated in this case report, and how long did the patient survive after the surgical intervention?","Long survival after excision of a primary malignant melanoma of the oesophagus. A woman who had a large primary malignant melanoma of the oesophagus, with evidence of submucosal invasion and several local metastases, underwent resection two years after the onset of retrosternal pain and has survived for 12 years with no recurrence."
-What were the main findings of the study regarding the use of beta-adrenergic-antagonist drugs in preventing gastrointestinal bleeding in patients with cirrhosis and esophageal varices?,"Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. BACKGROUND. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS. After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity."
-What were the key findings from the renal biopsy in the patient with Donohue syndrome?,"Glomerulopathy in patient with Donohue syndrome (leprechaunism). OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen."
-How does endolymphatic pressure differ between normal and hydropic ears in guinea pigs?,"The measurement and manipulation of intralabyrinthine pressure in experimental endolymphatic hydrops. Three to four months after unilateral surgical ablation of the endolymphatic duct and sac, endolymphatic and perilymphatic pressures were measured in both the normal and hydropic ears of 11 guinea pigs. In normal ears, endolymphatic pressure always approximated perilymphatic pressure. Endolymphatic pressure exceeded perilymphatic pressure in all ears with hydrops, except one in which these pressures were equal. The effect of postural inversion on inner ear pressures were studied in both normal and hydropic inner ears. Normal ears showed endolymphatic and perilymphatic pressure to rise equally during this maneuver. In hydropic ears, the difference between endolymphatic and perilymphatic pressure was notably reduced from measurements obtained in the prone position. This study indicates that an alteration in pressure regulation within the inner ear may be important in the pathogenesis and manifestation of experimental endolymphatic hydrops in the guinea pig. Physiologic mechanisms and clinical implications of these results are described."
-What was the cumulative success rate of custom-made distal femoral prostheses at five and seven years?,"Prosthetic replacement of the distal femur for primary bone tumours. Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery."
-What are the key neurological features observed in patients with endemic cretinism across different types of the syndrome?,"The neurology of endemic cretinism. A study of two endemias. Endemic cretinism is the most severe manifestation of dietary iodine deficiency. Two forms of the syndrome are traditionally described: neurological and myxoedematous. Although this classification highlights the important neurological sequelae of the disorder it implies that myxoedematous cretins have an alternative mechanism. Further, the nature of the neurological deficit associated with both types of endemic cretinism has received scant attention in recent times considering that it remains a common disorder in many parts of the world. The nature and extent of the neurological deficit found in endemic cretinism was investigated in 104 cretins from a predominantly myxoedematous endemia in western China and in 35 cretins from central Java, Indonesia, a predominantly neurological endemia. We found a similar pattern of neurological involvement in nearly all cretins from both endemias, regardless of type (myxoedematous or neurological), and of current thyroid function. Hallmarks of the neurological features included mental retardation, pyramidal signs in a proximal distribution and extrapyramidal signs. Many patients exhibited a characteristic gait. This probably reflected pyramidal and extrapyramidal dysfunction, although joint laxity and deformity were important contributing factors. Other frequently encountered clinical features were squint, deafness, and primitive reflexes. Cerebral computerized tomography (CT) revealed basal ganglia calcification in 15 of 50 subjects. The presence of basal ganglia calcification was confined to cretins with severe hypothyroidism. Otherwise, cerebral CT scanning demonstrated only minor abnormalities which did not contribute to the localization of the clinical deficits. We conclude that the same neurological disorder is present in both types of endemic cretinism reflecting a diffuse insult to the developing fetal nervous system. These clinical findings support the concept of maternal and fetal hypothyroxinaemia, arising from severe iodine deficiency, as the primary pathophysiological event in endemic cretinism. Differences between the two types of cretinism may be explained by continuing postnatal thyroid hormone deficiency in the myxoedematous type, which results in impaired growth, skeletal retardation and sexual immaturity."
-What rare complication did the patient experience following a middle and lower lobectomy?,"Pulmonary vein thrombosis following bilobectomy. Acute thrombosis of the pulmonary vein following lobectomy or bilobectomy is a rare complication with no standard guideline for diagnosis or management. In this report, we present a case of right upper lobe vein thrombosis following a middle and lower lobectomy. Diagnosis was confirmed by ventilation-perfusion lung scan, pulmonary angiogram, and bronchoscopy. The patient was treated conservatively with no further complications and had a partial recovery of the circulation to the right upper lobe. A review of the literature is also presented along with the experimental data demonstrating the mechanisms of recovery."
-What percentage of women with atypical squamous cells on Papanicolaou smears were found to be positive for HPV DNA in the study?,"Atypical squamous cells. A case-series study of the association between papanicolaou smear results and human papillomavirus DNA genotype. Thirty women with ""atypical"" squamous cells but not cervical intraepithelial neoplasia (CIN) on their Papanicolaou smears were tested for the presence of human papillomavirus (HPV) with the Southern blot hybridization technique. The Papanicolaou smears were reviewed for the presence of atypical squamous cells according to Patten's criteria. Comparison groups consisted of 30 patients with normal, 29 patients with CIN I and 24 patients with CIN II Papanicolaou smears. Ten of the 30 women (33%) with atypical cells on Papanicolaou smears were positive for HPV DNA as compared to 17% with normal and 59% with CIN I or II Papanicolaou smears. HPV 16 was present in 70-80% of the HPV DNA-positive patients in each Papanicolaou smear group. Concurrent CIN was also identified on colposcopically directed biopsies in 27% of the patients with squamous atypia. Patients with atypical squamous cells on Papanicolaou smears had coexisting HPV infection and CIN in about one-third of the cases. Colposcopy and further follow-up are recommended for such patients."
-How does the injury current affect the excitability of normal tissue during acute regional myocardial ischemia?,"Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. During acute regional myocardial ischemia, a ""current of injury"" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the ""ischemic"" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia."
-How does intraoperative facial nerve monitoring with electrical stimulation (IFNMES) help predict facial nerve function during acoustic tumor removal?,"Intraoperative facial nerve monitoring: prognostic aspects during acoustic tumor removal. Intraoperative facial nerve monitoring with electrical stimulation (IFNMES) has become an integral part of acoustic tumor surgery. We reviewed the records of fifty-six patients who underwent translabyrinthine acoustic tumor removal with IFNMES. There was excellent correlation between intraoperative facial nerve activity and immediate postoperative facial nerve function (24 hours after surgery and at hospital discharge). Our data would suggest that patients who exhibit less than 500 microvolts of ongoing EMG activity during surgery, and who yield at least a 500-microvolt contraction when stimulated with 0.05 milliamps at the brainstem after tumor removal, can expect an excellent immediate facial nerve result (grade I or II)."
-What is the typical treatment approach for diskitis in children according to the study?,"Diskitis in children. Thirty-six patients diagnosed with diskitis from 1978 to 1988 and followed for an average of 29.2 months were reviewed. The study included 23 boys and 13 girls with an average age of 5.3 years. The initial symptoms varied, but distinct clinical patterns emerged and were identifiable in different age groups. Both the leukocyte count and sedimentation rate were elevated. Routine roentgenograms were positive for intervertebral disk space narrowing in 82% of cases, technetium bone scans positive in 72%, and magnetic resonance imaging positive in all recent cases. Treatment consisted of bed rest for all patients, plaster casts for 50%, antibiotics for 40%, and traction for 23%. Regardless of the treatment combination, the course of the disease in most children is benign. At the completion of the study, all patients were asymptomatic including three children who had recurrences. In spite of being asymptomatic, 74% had persistent roentgenographic changes. The administration of antibiotics appears to be appropriate when indicated, i.e., failure to respond to immobilization. Disk space aspiration or biopsy should be reserved for those cases that are refractory to immobilization and antibiotics."
-How does external leg counterpressure affect cardiovascular parameters in simulated mild hypovolemia?,"The autotransfusion effect of external leg counterpressure in simulated mild hypovolemia. We examined the cardiovascular response of external leg counterpressure in healthy volunteers at 100 mm Hg compression pressure. To stimulate mild hypovolemia, measurements were made with the subjects in a 60 degrees head-up tilt position. Left ventricular end-diastolic volume (LVEDV) and cardiac output (CO) were calculated from two-dimensional echocardiography. Flow through the inferior vena cava (IVC) below the origin of the hepatic veins was determined by the Doppler ultrasound technique. The application of counterpressure significantly increased LVEDV, CO, and arterial blood pressure over that seen with tilting without the device. These responses were accompanied by a small but significant increase in IVC flow. We therefore concluded that external leg counterpressure transferred blood to the central circulation by compression of the venous capacitance vessels (an autotransfusion effect) in mild hypovolemia, but such an effect may not benefit patients in a hypovolemic shock state because of the small amount of translocated blood."
-How do cardiovascular reflexes differ between Parkinson's disease patients and healthy subjects in this study?,"Cardiovascular reflexes and autonomic dysfunction in Parkinson's disease. Cardiovascular reflexes were analysed in a group of 20 patients suffering from Parkinson's disease and in 12 age-matched healthy subjects, in order to ascertain the incidence and degree of autonomic dysfunction. The following were measured: heart rate variation during normal breathing, postural change (30/15 ratio) and during the Valsalva manoeuvre: blood pressure variation after standing. These measurements were taken at least 12 h after therapy had been withdrawn and were repeated after therapy had been resumed. Significant changes in the different heart rate variation indices were found in the parkinsonian patients which correlated with the duration and severity of the extrapyramidal symptomatology. After standing the patients showed a significant drop in blood pressure, when compared respectively with their base values and with the response in controls. Anticholinergic drugs had no significant effect on the heart rate variation indices, whereas antiparkinsonian therapy seems to have contributed to the drop in blood pressure after standing."
-What are the potential clinical manifestations of dysfibrinogenemia during pregnancy?,"Dysfibrinogenemia associated with thrombosis and third-trimester fetal loss. A case report. Dysfibrinogenemias are rare genetic disorders that are clinically silent, cause a mild bleeding tendency or have thromboembolic manifestations. During pregnancy they often cause hemorrhage and first-trimester abortions. A patient with a severe thrombotic tendency during pregnancy had a third-trimester fetal loss."
-What were the comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction?,"Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study. BACKGROUND. Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS. One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS. The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications."
-What method was used to assess DNA profiles in the oral exfoliative cytologic study?,"Detection of field change in oral cancer using oral exfoliative cytologic study. Four smears were taken from the normal buccal mucosa of 55 oral cancer patients and 76 cancer-free patients. In each case, two were stained by the Papanicolaou method and two underwent Feulgen hydrolysis. Quantitative assessment of nuclear area (NA) and cytoplasmic area (CA) of the Papanicolaou smears was undertaken using a semiautomatic image analysis system. DNA profiles were assessed from the Feulgen smears using a Vickers M85 microdensitometer (Vickers Instruments, York, England) and were found to be diploid for all patients. Results were then analyzed with respect to those patients who took alcohol, tobacco, combination of alcohol and tobacco, and those who took neither. A significant reduction in CA for the oral cancer group (P equals 0.001) but no change in NA (P equals 0.74) was observed. A detailed analysis of alcohol and tobacco habits could identify no significant role for these two factors, in the reduction in cytoplasmic area. Such field change may prove to be of value in predicting the development of second malignant tumors."
-What percentage of respondents in the Norwegian population study believed penicillin to be effective against viral infections?,"Fever: knowledge, perception and attitudes. Results from a Norwegian population study. To investigate the layman's knowledge, perception and attitudes regarding normal body temperature, fever, infections and the effect of penicillin on virus infections a representative sample of the Norwegian population (619 women and 592 men over the age of 15) was interviewed in 1988 as part of a monthly national opinion poll. One-third thought body temperatures up to 40.5 degrees C to be life-threatening, but the results do not justify the application of the term 'fever phobia' as described in other studies based on non-representative samples. More respondents were afraid of viral infections (48%) than bacterial infections (9%), which may be due to the media focus upon the HIV/AIDS epidemic. Thirty-five per cent believed penicillin to be effective against virus infections. Educational programmes on fever should also include information about virus infections and their treatment."
-How does fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) help in assessing the response to cancer therapy?,"Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects."
-What rare medical condition is described in this case report involving the cauda equina?,Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis.
-How does compression-ischaemia nerve block differently affect warm sensation and heat-induced pain in human volunteers?,"Differential effect of compression-ischaemia block on warm sensation and heat-induced pain. The effect of compression-ischaemia nerve block on psychophysical thresholds for warm sensation and heat-induced pain was studied on 19 normal human volunteers. Although those two sensory submodalities should be predicted to block simultaneously, based on the fact that both are served by unmyelinated primary afferents, it was actually found that warm sensation was much more vulnerable to compression-ischaemia than heat-induced pain. This is interpreted as resulting from different summation requirements for each of the two sensory modalities; sensation of warmth depends on spatial summation to a larger extent than heat-induced pain. Such differential vulnerability is in line with recent clinical studies reporting deterioration of warm sensation associated with preservation of heat pain in peripheral nerve disorders caused by diabetes, ageing and other neuropathic processes."
-What challenges are associated with detecting and treating acoustic schwannomas in children?,"Acoustic schwannomas in children. The clinical presentation and treatment of three cases of acoustic schwannoma occurring in children are described. All the tumors were detected late, when they had attained a large size and were extremely vascular. The use of preoperative tumor embolization as an adjunct to surgical excision is discussed."
-What characteristic of Doppler ultrasound helps differentiate between bland thrombus and tumor thrombus in the main portal vein?,Hepatofugal arterial signal in the main portal vein: an indicator of intravascular tumor spread. Five patients with thrombosis of the main portal vein underwent Doppler ultrasound (US). Three of these patients had confirmed hepatocellular carcinoma. Doppler US allowed differentiation between bland thrombus and tumor thrombus in two of the three patients. Tumor thrombus of the main portal vein was characterized at US by an intraportal arterial waveform in a hepatofugal direction.
-How can forensic experts differentiate between hydrocephalic calf and human calvariae?,"Differentiation of hydrocephalic calf and human calvariae. Occasionally, partial calvariae of hydrocephalic calves are found in forensic contexts and mistakenly identified as human. Such specimens can be properly identified through immunological assessment of associated soft tissue, microscopic analysis of associated hair, and morphological comparison with documented museum specimens. Morphological comparison should focus on the form of the occiput, supraorbital grooves, and bulbous vault and presence of coronal processes."
-What are the key risk factors for infusion-related phlebitis in peripheral intravenous catheters?,"Risk factors for infusion-related phlebitis with small peripheral venous catheters. A randomized controlled trial. OBJECTIVE: To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters. DESIGN: A randomized trial of two catheter materials, with consideration of 21 potential risk factors. SETTING: A university hospital. PATIENTS: Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter. INTERVENTIONS: House officers or ward nurses inserted the catheters, and each insertion was randomized to a catheter made of tetrafluoroethylene-hexafluoropropylene (FEP-Teflon) or a novel polyetherurethane without leachable additives (PEU-Vialon). MEASUREMENTS: Research nurses scored insertion sites each day for inflammation and cultured catheters at removal. RESULTS: The Kaplan-Meier risk for phlebitis exceeded 50% by day 4 after catheterization. intravenous antibiotics (relative risk, 2.00), female sex (relative risk, 1.88), prolonged (greater than 48 hours) catheterization (relative risk, 1.79), and catheter material (PEU-Vialon: FEP-Teflon) (relative risk, 0.73) strongly predicted phlebitis in a Cox proportional hazards model (each, P less than 0.003). The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection (relative risk, 6.19), phlebitis with a previous catheter (relative risk, 1.54), and anatomic site (hand: forearm, relative risk, 0.71; wrist:forearm, relative risk, 0.60). The low incidence of local catheter-related infection was comparable with the two catheter materials (5.4% [95% CI, 3.8% to 7.6%] and 6.9% [CI, 4.9% to 9.6%]); none of the 1054 catheters prospectively studied caused bacteremia. CONCLUSIONS: Multiple factors, including the infusate and the duration of cannulation, contribute to the development of infusion-related phlebitis. The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon, and PEU-Vialon can permit longer cannulation with less risk for phlebitis. The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy."
-What medical condition was the surgical depilation primarily used to treat in this study?,"Surgical depilation for the treatment of pseudofolliculitis or local hirsutism of the face: experience in the first 40 patients. Forty patients underwent surgical depilation for pseudofolliculitis barbae or local hirsutism of the face during a 15-year period. The operative method and its results and pitfalls are discussed. Although it is not the treatment of choice, this operation is very useful when other therapy has not been successful. This seems especially true in male-to-female transsexuals."
-How do the muscle characteristics of Himalayan Sherpas differ from sedentary lowlanders and Caucasian climbers?,"Muscle structure and performance capacity of Himalayan Sherpas. The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg(-1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross-sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density."
-What was the purpose of the study on isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis?,"Test-retest reliability of isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis. The purpose of this study was to evaluate and compare the test-retest reliability of isokinetic torque measurements in the involved and uninvolved knee musculature of 20 subjects with spastic hemiparesis. An isokinetic dynamometer was used to measure maximal voluntary knee extension and flexion at 60 degrees and 120 degrees/s. Peak torque (PT) and average peak torque (APT) data were collected from five repetitions on two separate occasions. Average peak torque was defined as the mean of the PT values obtained during each of the five repetitions. Spasticity was measured in the involved knee musculature prior to isokinetic testing using the Ashworth Scale. Pearson Product-Moment Correlation Coefficients and intraclass correlation coefficients (ICCs) were high (greater than or equal to .90) for both knees for PT and APT at both angular velocities. No clinically meaningful differences were found between the Pearson correlation coefficients and the ICCs of the involved versus the uninvolved knee for any testing conditions. We concluded that isokinetic evaluation of torque, as measured by PT and APT in subjects with spastic hemiparesis, can yield reliable results in both extremities."
-What is the purpose of the thrombogenic microballoon developed in this research?,"Thrombogenic microballoon for cerebral aneurysms, arteriovenous malformations, and carotid cavernous fistula occlusion. Preliminary technical note. A thrombogenic microballoon was developed to overcome the problems of cerebral aneurysm rupture during microballoon inflation and incomplete aneurysm obliteration by microballoons with subsequent fatal rupture. These complications occur in about 35% of reported series with current microballoon embolization techniques. The wall of the new thrombogenic microballoon allows 80% aneurysm occlusion by inflation, thus avoiding mechanical rupture, and at the same time it produces a blood clot in the space remaining between the microballoon and the aneurysm wall. This clot undergoes fibrosis with firm adherence of the microballoon to the aneurysm wall. Experimental evidence is presented to support these conclusions. This thrombogenic microballoon system is also applicable to carotid-cavernous fistulas and arteriovenous malformations."
-What surgical technique was developed to safely perform resternotomy in patients with valved conduits adherent to the sternum?,"Resternotomy in patients with valved conduits adherent to the sternum. Twenty-two patients with valved conduits adherent to the sternum underwent resternotomy. Mean age was 10 +/- 6 years, and mean conduit age was 4 +/- 4 years. Diagnoses were D-transposition (7), truncus arteriosus (7), univentricular heart (6), Taussig-Bing anomaly (1), and corrected transposition (1). The majority of patients (68%) had reoperation for outgrown or degenerated conduits. In 17 patients, the sternum was opened with a chisel. Two of these patients sustained conduit neointimal collapse from manipulation, and 3 had conduit tear requiring immediate cardiopulmonary bypass through the femoral vessels. In the last 5 patients, the sternum was opened above and below the conduit, and the inner table was chiseled and left attached to the conduit avoiding injury and undue conduit manipulation. Cardiopulmonary bypass and operation were carried out uneventfully. We believe that the recent technique described provides a safe alternative approach to valved conduits adherent to the sternum."
-How did the QRS vector changes correlate with infarct size and left ventricular ejection fraction in patients treated with recombinant tissue-type plasminogen activator (rt-PA)?,"Dynamic QRS-complex and ST-segment monitoring in acute myocardial infarction during recombinant tissue-type plasminogen activator therapy. The TEAHAT Study Group. Changes of the QRS complex are the electrocardiographic expression of irreversible injury of the myocardium. In humans, the process of infarction occurs over several hours. A more rapid development of QRS changes has been reported in patients treated with thrombolytic agents. Patients with strongly suspected acute myocardial infarction (AMI) included in a placebo-controlled trial of 100 mg of recombinant tissue-type plasminogen activator (rt-PA) were monitored for 24 hours with continuous, on-line vectorcardiography. The magnitude of the QRS vector changes correlated with infarct size estimated by the maximal value of lactate dehydrogenase-1 (r = 0.69, p less than 0.001) as well as with left ventricular ejection fraction 30 days after randomization (r = 0.49, p less than 0.001). Treatment with intravenous rt-PA limited total QRS vector change but the QRS vector changes observed occurred more rapidly and reached a plateau 131 minutes earlier in patients treated with rt-PA than in those receiving placebo (p less than 0.01). A certain pattern of highly variable ST vector magnitude was identified and was associated with higher maximal lactate dehydrogenase-1 values (23 +/- 13 vs 14 +/- 10 mu kat/liter, p less than 0.001) and a tendency to higher 1-year mortality (24 vs 9%, p = 0.08) than in patients without this pattern. In patients with this pattern, rt-PA did not affect maximal lactate dehydrogenase-1, time to maximal creatine kinase and final magnitude of QRS vector change."
-How do pulse pressure patterns in hypertensive pregnant women relate to birth weight and gestational age?,"Peripheral pulse pressure patterns in pregnancy hypertension. Maternal heart rate and pulse pressure patterns were examined in 30 hypertensive pregnant women using noninvasive methodology described previously. ""Narrow"" and ""wide"" pulse patterns were identified. Narrow cutaneous pulse pressure patterns, which are thought to be caused by vasoconstriction, were associated with lower birth weight infants (1870 +/- 983 versus 3225 +/- 838 g; P less than .001) and earlier deliveries (34.2 +/- 5.2 versus 37.9 +/- 2.8 weeks; P less than .05). The data suggest that these adjunctive maternal cardiovascular-system evaluation techniques may be useful in identifying patients at risk of adverse perinatal outcome by detecting vasospasm of the peripheral microcirculation."
-What techniques were used to detect right-to-left vascular shunting in patients with stroke or neurologic defects?,"Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound. Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization."
-What was the purpose of the study on intrathecal fibrinolytic therapy in patients with aneurysmal subarachnoid hemorrhage?,"Effect of intrathecal fibrinolytic therapy on clot lysis and vasospasm in patients with aneurysmal subarachnoid hemorrhage. A prospective series of 30 patients with a single, angiographically verified aneurysmal subarachnoid hemorrhage (SAH) was studied for the effect of intrathecal thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) on outcome, angiographic vasospasm, and computerized tomography (CT) findings after surgery. The patients included fulfilled the following criteria: operation was performed by Day 3 after the hemorrhage, CT showed only blood in the basal cisterns, and the patient had a single aneurysm or multiple aneurysms that could be treated surgically at the same operation. The patients were divided into groups of 10, with patients receiving 3, 10, or 13 mg of rt-PA in a single intracisternal injection at the end of the operation. There were no differences between the treatment groups in overall outcome. One patient from the 3-mg rt-PA group developed a postoperative intracerebral hemorrhage, and one patient from the 10-mg rt-PA group had a postoperative epidural hematoma. There was one death in the 13-mg rt-PA group that was caused by inclusion of a segment of pericallosal artery in the clip. In all treatment groups a reduction was observed in the amount of blood seen on the postoperative CT scans compared to the preoperative CT scans. The reduction in SAH grade between the 10-mg and 13-mg rt-PA groups was significant (p less than 0.05). The difference in the severity of angiographic vasospasm between the 3-mg and 13-mg rt-PA groups was also significant (p less than 0.05)."
-What were the 4-year actuarial local control and disease-free survival rates for patients undergoing resection in this study of retroperitoneal soft tissue sarcoma?,"Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma. From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance."
-How did the patient develop a meningioma 30 years after receiving a Torkildsen shunt and irradiation treatment?,"Meningioma: the role of a foreign body and irradiation in tumor formation. A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented."
-How did the researchers use PET and radiolabeled microspheres to measure critically ischemic myocardial tissue during acute coronary occlusion?,"Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET. Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography."
-What happened to the patient's auditory evoked potentials after the acoustic neurinoma excision surgery?,"Progressive deterioration of auditory evoked potentials after excision of an acoustic neurinoma: case report. The authors report the case of a 17-year-old girl who underwent excision of bilateral neurinomas of the cerebellopontine angle. Although her auditory evoked potentials were well maintained during the operation, they deteriorated gradually and progressively for the following 2 months. This seemed to reflect degeneration of the cochlear nerve fibers initiated by operative manipulation in the cerebellopontine angle in a patient who had no hearing when she awoke from surgery."
-What is diffuse pulmonary hemorrhage and what are its key clinical manifestations?,"Diffuse pulmonary hemorrhage. Diffuse pulmonary hemorrhage is a syndrome consisting of hemoptysis, anemia, and air-space consolidation. The radiologic appearance is non-specific. Pulmonary hemorrhage may be due to a number of different causes. The differential diagnosis and the diagnostic approach are different in the immunologically intact host as compared with the immunocompromised host. This article reviews the main diagnostic considerations in diffuse pulmonary hemorrhage."
-What are the key characteristics of gonococcal endocarditis during pregnancy based on the case report?,"Gonococcal endocarditis complicating pregnancy: a case report and literature review. The incidence of gonorrhea has decreased substantially in the past decade. Disseminated gonorrhea is more common in women than in men, although gonococcal endocarditis is more common in men. Disseminated gonorrhea is most commonly described in women during menses or pregnancy. Only two cases of gonococcal endocarditis during pregnancy have been reported in the literature since 1942. We report a patient who experienced sudden hemodynamic decompensation at 30 weeks' gestation, resulting in fetal death. Aortic valve replacement was performed, but extensive involvement of the aortic root made complete eradication of infection impossible and eventually resulted in maternal death."
-How do the biomechanical properties of the ankle joint differ between hemiparetic stroke patients and normal subjects?,"Biomechanical changes at the ankle joint after stroke. The resistance of the relaxed ankle to slow displacement over the joint movement range was measured on both sides of a group of hemiparetic stroke patients, in whom spasticity had been established for at least one year and who showed no clinical signs of contractures. The ankle joints of the age-matched normal subjects were flexible over most of the movement range, showing dramatically increasing stiffness only when the foot was dorsiflexed beyond 70 degrees, with a neutral range between 90-100 degrees, and a less dramatic increase in stiffness during plantarflexion. Hemiparetic patients showed identical curves to the normal subjects on the ""healthy"" side, ipsilateral to the causative cerebral lesion, but were significantly stiffer in dorsiflexion on the contralateral side, without change in the minimum stiffness range or during plantarflexion. Therefore significant changes in passive biomechanical properties occur at the affected ankle of hemiparetic subjects, predominantly as the result of a loss of compliance in the Achilles tendon, although an increase in the passive stiffness of the triceps surae may also occur. The contribution of these changes to the locomotor disability of hemiparetic patients is discussed."
-How did the medical team use auditory brainstem responses to help map electrodes in a child with cochlear ossification?,"Multichannel cochlear implant and electrically evoked auditory brainstem responses in a child with labyrinthitis ossificans. Ossification of the cochlea following meningitis presents a surgical challenge. Electrode mapping, especially in the young child, is difficult given the uncertainty of electrode contact with viable neural elements. This paper reviews surgical technique and the use of auditory brainstem responses to map the electrodes. A 4-year-old child deafened by meningitis at age 20 months had bilateral cochlear ossification by computed tomography. At surgery, a canal wall-down mastoidectomy and closure of the ear canal were performed. A trough around the modiolus was drilled, and the electrode array was placed in it. Post-operatively, the patient gave aversive or no responses to electrode stimulation. To assess electrode function, auditory brainstem responses to individual electrode activation were obtained under general anesthesia. Functioning electrodes could thus be selected for mapping. The patient now responds well to sound."
-What is the significance of left ventricular diastolic collapse in the context of regional cardiac tamponade?,"Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade. BACKGROUND. Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. METHODS AND RESULTS. We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. CONCLUSIONS. We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients."
-What was the effect of balloon dilation on the diameter of stenotic Blalock-Taussig shunts in patients with cyanotic heart disease?,"Percutaneous transluminal balloon angioplasty of stenotic standard Blalock-Taussig shunts: effect on choice of initial palliation in cyanotic congenital heart disease. To date, attempted balloon dilation of stenotic standard Blalock-Taussig shunts has been largely disappointing. It has been suggested that this may be due to the use of balloons of insufficient diameter. Balloon dilation of stenotic Blalock-Taussig shunts was attempted with use of relatively large balloons in five patients (11 to 67 months old) with cyanotic heart disease who were becoming progressively cyanotic and polycythemic (hemoglobin 17.9 +/- 1.1 g/dl) because of discrete shunt stenosis at the site of pulmonary anastomosis. Balloon diameters selected were equal to or within 1 mm of the unobstructed proximal shunt diameter. Before balloon dilation the diameter at the site of the stenosis was 2.8 +/- 0.8 mm (range 1.7 to 4); after balloon dilation it was 5.7 +/- 1.1 mm (range 4.5 to 7.5). The diameter increased in all patients (range 2.0 to 3.5 mm); the mean increase was 2.8 +/- 0.2 mm (p less than 0.005). Expressed as a percent, the increase in diameter at the stenosis ranged from 80% to 182.4% (mean 108.2 +/- 16.8%). Before balloon dilation the systemic oxygen saturation was 72.8 +/- 9.2% (range 55% to 80%) and after balloon dilation it was 83.6 +/- 2.9% (range 80% to 87%). A satisfactory increase (range 6% to 25%) in blood oxygen saturation was seen in all patients; the mean increase was 10.8 +/- 3.2% (p less than 0.01). At follow-up, the oxygen saturation by pulse oximetry was 85.8 +/- 2.9% (mean 5.8 +/- 1.7 months after balloon dilation) and the hemoglobin was 15.6 +/- 1.9 g/dl (mean 6.6 +/- 1.5 months after balloon dilation)."
-How do limited access to healthcare and cultural barriers impact neurological care for minority populations in the United States?,"Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies."
-What was the most frequent recognized abnormality in the study of cerebral infarction among young patients?,"Cerebral infarction in young people. A study of 148 patients with early cerebral angiography. The aetiology of strokes was studied in a hospital based series of patients aged up to 40 years with precise clinical and radiological criteria. One hundred and forty five patients (75 males and 73 females) aged five to 40 years with cerebral ischaemia were evaluated. Aetiology was heterogeneous and could be classified into seven groups. Cerebral arteriograms were performed in all cases and indicated the aetiological diagnosis in most patients. Embolism was the most frequent recognised abnormality (38.4%). There were no complications of arteriography. Arterial dissections discovered by arteriography were the cause of the stroke in 10.1% of the patients. Atherosclerosis was diagnosed in 32 cases and was the commonest cause (21.6%). In one fifth of cases no cause was found. Contraceptive drugs were considered as potential cause of ischaemic stroke in 11.5%, cardiac diseases in 12.8% and haematological disorders in 8.1%. Other potential causes included migraine, inflammatory diseases, pregnancy and lacunas. Follow up in 126 cases showed that many patients had good functional recovery."
-What were the predominant indications for knee arthrodesis using an intramedullary nail in this study?,"Arthrodesis of the knee with an intramedullary nail. The cases of twenty patients who had an arthrodesis in which an intramedullary nail was used for stabilization were reviewed at an average follow-up of six years. The predominant indications were infection after total knee arthroplasty and post-traumatic pain and instability. Other indications included aseptic loosening of the components of a total knee arthroplasty, reconstruction after resection of a giant-cell tumor, non-union of a fracture of the distal part of the femur or the proximal part of the tibia, and failed external-compression arthrodesis. Success was achieved in seventeen patients (85 per cent), and functional stability immediately postoperatively was gained in all twenty. Of the three patients in whom the arthrodesis failed, all had sustained an intraoperative fracture, and infection eventually developed. Of the twelve nails that were secured to the greater trochanter with a loop of stainless-steel wire, none showed evidence of proximal migration. Of the eight nails that were not thus secured, two migrated proximally, necessitating removal of the nail. Two drawbacks to this operation are the long duration and the large amount of blood that is lost. The major advantage is that a high percentage of patients have progression to a stable fusion despite serious problems. Furthermore, all but seven patients (including the six who had a tumor or who had sustained an intraoperative fracture) were able to bear full weight by the second postoperative week. Only a few patients needed an external support for walking."
-How do thromboxane A2 and serotonin contribute to platelet-mediated obstruction in coronary artery stenosis?,"Role of thromboxane and serotonin as mediators in the development of spontaneous alterations in coronary blood flow and neointimal proliferation in canine models with chronic coronary artery stenoses and endothelial injury. Platelet-mediated obstruction of stenotic and endothelium-injured coronary arteries may be important in the abrupt progression from chronic stable to unstable coronary heart disease syndromes in patients. Transcardiac accumulation of thromboxane A2 and serotonin has been demonstrated in patients as chronic stable angina is converted to unstable angina. In this study in anesthetized open chest dogs with coronary artery stenosis and endothelial injury, thromboxane A2 and serotonin were shown to be important mediators of intermittent coronary obstruction caused by platelet aggregation and dynamic vasoconstriction. Furthermore, thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists, singly and together, provided substantial protection against repetitive platelet aggregation and dislodgment in canine models with coronary artery stenosis and endothelial injury even when systemic catecholamine concentrations were markedly elevated. These same observations apply in chronically instrumented, awake, unsedated dogs with coronary artery stenosis and endothelial injury in which recurrent platelet attachment and dislodgment cause cyclic flow alterations that may be prevented by thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists. Chronically instrumented dogs with coronary stenosis and endothelial injury in which recurrent platelet attachment and dislodgment occurred also developed neointimal proliferation of varying severity within 10 days to 3 weeks; the morphologic appearance of the neointimal proliferation was identical to that found in patients who develop restenosis after coronary angioplasty."
-How does a leucine to isoleucine substitution in the retroviral envelope surface glycoprotein affect the lytic properties of the Friend murine leukemia virus?,"Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain."
-What is mesonephric rest hyperplasia and how can it be misdiagnosed?,"Mesonephric rest hyperplasia. A potential diagnostic pitfall. A case of mesonephric rest hyperplasia, an incidental finding in the hysterectomy specimen of a 48-year-old woman, was initially misdiagnosed as a well-differentiated cervical adenocarcinoma. We highlight the histologic, histochemical, and immunohistochemical features of this potential diagnostic pitfall and review the relevant literature."
-What are the potential disadvantages of the subclavian flap aortoplasty procedure in treating coarctation?,"Coarctation: do we need to resect ductal tissue? A review of the literature as well as a retrospective review of 100 neonates undergoing operation for coarctation at Children's Hospital in Boston between 1972 and 1984 has not established clear superiority for either resection and end-to-end anastomosis or subclavian flap aortoplasty with respect to risk of recurrent coarctation. However, there is histological evidence that the juxtaductal coarctation shelf is composed of smooth muscle of ductal origin, which subsequently fibroses. This abnormal tissue may be at risk for late aneurysm development, particularly if balloon dilatation angioplasty is required. The fact that this abnormal tissue is not removed by the subclavian flap procedure is one of the inherent disadvantages of that procedure. Other disadvantages include the need to sacrifice the left subclavian artery and the fact that, unlike resection and end-to-end anastomosis, the subclavian flap procedure does not lend itself to augmentation of the hypoplastic distal aortic arch. Furthermore, occasionally a secondary coarctation membrane is present within the distal aortic arch, and though it is readily detected during the resection procedure, it can be missed with the subclavian flap procedure. Based on these considerations rather than on a demonstrated superiority of either procedure, my colleagues and I currently prefer resection and end-to-end anastomosis over subclavian flap aortoplasty."
-What variations were observed in the classical activation pattern during atrial flutter entrainment in the canine sterile pericarditis model?,"Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo. BACKGROUND. Recently, we used a custom designed ""jacket"" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels. METHODS AND RESULTS. In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a ""classical"" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry. CONCLUSIONS. The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the ""figure-eight"" reentrant circuit."
-What was the primary aim of the study on nasal calcitonin in treating post-traumatic algodystrophy?,"The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration. For this reason, we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post-traumatic algodystrophy in a prospective randomized double-blind study. We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment. There was, however, a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover. Possible reasons for this lack of clinical and skeletal effect are discussed."
-What is the primary diagnostic procedure for identifying blunt traumatic bladder rupture according to this study?,"Blunt traumatic bladder rupture: the role of retrograde cystogram. STUDY OBJECTIVE: We evaluated the importance of microscopic and gross hematuria and the role of retrograde cystography and computed tomography (CT) in the diagnosis of blunt traumatic bladder rupture. DESIGN: All cases at a Level I trauma center between January 1, 1986, and March 31, 1989, were reviewed retrospectively. SETTING: Level I trauma center, university hospital. TYPE OF PARTICIPANTS: All patients with acute blunt abdominal trauma admitted to this Level I trauma center. INTERVENTIONS: The patients' charts were reviewed with emphasis on mode of diagnosis, treatment, and outcome. MEASUREMENTS AND MAIN RESULTS: Twenty-one patients had bladder rupture. All 21 had hematuria with more than 50 RBCs/high-power field, 17 gross and four microscopic. Twenty patients underwent retrograde cystography, which accurately identified bladder rupture, and one was found at laparotomy for other injuries. Seven patients had CT of the abdomen and pelvis, which failed to demonstrate bladder rupture. There were no associated urethral injuries in any of the patients with bladder rupture. CONCLUSION: Significant (more than 50 RBCs/high-power field) hematuria is the principal indication for evaluation for blunt bladder injury, and retrograde cystography is the diagnostic procedure of choice. CT is neither sensitive nor specific enough as primary diagnostic modality."
-What novel mutation was discovered in the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis patients?,"A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients. Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G----T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration."
-What are the main advantages of bopindolol in treating hypertension?,"Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension. Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism)."
-What were the key findings of the NHLBI PTCA Registry comparing outcomes of percutaneous transluminal coronary angioplasty in patients with stable versus unstable angina pectoris?,"Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: a report of the 1985-1986 NHLBI PTCA Registry. In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985-May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p less than 0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p less than 0.001). Incidence of major patient complications (p less than 0.01) and of emergency coronary bypass surgery (p less than 0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979-1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single- and multi-vessel coronary disease."
-What was the purpose of comparing laser-assisted thrombolysis (LAT) with enzymatic thrombolysis (ET) in the experimental treatment of thrombotic vascular occlusion?,"Experimental treatment of thrombotic vascular occlusion. The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01)."
-What is the Pena-Shokeir phenotype and what are its key pathological characteristics in an infant born to a cocaine-using mother?,"Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage."
-What percentage of patients in the study experienced otolaryngic complications during cancer chemotherapy?,"The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed."
-What percentage of patients with stage D2 prostate cancer showed elevated plasma chromogranin-A levels in the study?,"Elevated plasma chromogranin-A concentrations in prostatic carcinoma. Chromogranin-A is considered a sensitive immunohistochemical tissue marker in neuroendocrine prostatic carcinoma. We report that the plasma chromogranin-A level was elevated in 48% of 25 patients with stage D2 prostate cancer, and suggest that this marker can be used to monitor the clinical course of these patients."
-What is the recommended surgical procedure for treating thoracic myelopathy caused by ossification of the ligamentum flavum (OLF)?,"Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment. The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force."
-What is the significance of a negative exercise thallium test in patients with critical residual stenosis after thrombolysis for acute myocardial infarction?,"Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction. BACKGROUND. After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia. METHODS AND RESULTS. The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1-16.3). CONCLUSIONS. The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance."
-How does the genetically engineered toxin DAB486IL-2 specifically target and kill leukemic cells?,"Therapeutic effects of genetically engineered toxin (DAB486IL-2) in patient with chronic lymphocytic leukaemia. In DAB486IL-2 the receptor-binding domain of native diphtheria toxin is replaced by human IL-2 sequences. This recombinant fusion protein is selectively cytotoxic for cells bearing high-affinity IL-2 receptors--eg, leukaemic cells. A patient with chronic lymphocytic leukaemia who did not respond to gamma interferon and conventional antileukaemic drugs has responded to DAB486IL-2."
-What was the prevalence of autoantibodies in different pregnancy conditions according to the study?,"The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment."
-What is the proposed relationship between autonomic dysreflexia and atrial fibrillation in patients with high-level spinal cord injury?,"Atrial fibrillation associated with autonomic dysreflexia in patients with tetraplegia. Atrial fibrillation is an arrhythmia characterized by disorganized atrial depolarizations and an irregular ventricular response. Most patients with atrial fibrillation have underlying cardiac pathology. This paper presents the cases of three patients with high-level spinal cord injury and symptoms of autonomic dysreflexia who developed atrial fibrillation without any cardiac or metabolic disease that would predispose them to this. The paper proposes that autonomic dysreflexia might predispose a patient to atrial fibrillation by altering the pattern of repolarization of the atria, making the heart susceptible to a reentrant type of arrhythmia. High-level spinal cord injured patients may be at increased risk for the development of atrial fibrillation, an arrhythmia which, if left untreated, can increase the incidence of an embolic cerebrovascular accident that could further impair the patient's functional status."
-What techniques were used to extend the exposure of the distal internal carotid artery in the anatomic dissection study?,"Selection of the approach to the distal internal carotid artery from the second cervical vertebra to the base of the skull. Although several approaches for exposure of distal internal carotid artery lesions have been reported, the precise anatomic levels for which each of these maneuvers are most appropriate have not been well described. Since these techniques may require preoperative preparation, it is useful to determine in advance how much exposure will be needed and to select the most suitable and effective technique. We used anatomic dissection in 12 human cadaver specimens (24 carotid bifurcations) to define the limits of distal internal carotid artery exposure by several commonly advocated methods. The standard anterior approach along the sternocleidomastoid muscle allowed exposure of the internal carotid artery to the level of the upper one third of the second cervical vertebra. The upper limit of this exposure was extended to the middle of the first cervical vertebra by division of the posterior belly of the digastric muscle. Anterior subluxation of the mandible increased the distal exposure of the internal carotid artery to the superior border of the first cervical vertebra. Styloidectomy in combination with the preceding maneuvers extended the exposure an additional 0.5 cm cephalad. Lateral mandibulotomy did not significantly extend exposure beyond that obtained with mandibular subluxation and styloidectomy. Exposure of the internal carotid artery in the 1 cm immediately below the base of the skull required a posterior approach with mastoidectomy."
-How does cardioversion with multiple shocks potentially impact the diagnosis of myocardial infarction?,"Time course of creatine kinase release after termination of sustained ventricular dysrhythmias. Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern."
-What is the significance of the mitral valvuloplasty performed 5 years after the repair of a sinus venosus atrial septal defect?,"Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty."
-What was the attitude of Danish anaesthetic departments towards using lumbar regional anaesthesia in patients receiving prophylactic anticoagulant therapy?,"Lumbar regional anaesthesia and prophylactic anticoagulant therapy. Is the combination safe? A survey has been carried out in all Danish anaesthetic departments (n = 80) regarding the attitude towards the use of epidural/spinal lumbar analgesia in patients who were receiving prophylactic anticoagulant therapy for the prevention of thromboembolism. About 60% of the departments used the techniques in patients receiving low-dose heparin and no side effects had been experienced. Spinal and epidural anaesthesia were in general regarded as being contraindicated in patients fully anticoagulated with vitamin K antagonists. In the world literature, the attitude towards the combination is conflicting. No randomised trial has been performed and complications are almost entirely confined to patients fully anticoagulated with vitamin K antagonists. Only one case of an epidural haematoma has been recorded when subcutaneous low-dose heparin was used as thromboprophylaxis."
-What adverse reactions did patients experience when receiving subcutaneous methadone for cancer-related pain?,"Local toxicity with subcutaneous methadone. Experience of two centers. We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone."
-How does calcification affect the mechanical response of rabbit arteries during balloon dilation?,"Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation. BACKGROUND. Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term ""hardening of the arteries."" METHODS AND RESULTS. To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients. CONCLUSIONS. It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial ""hardening"" associated with atherosclerosis."
-Does the timing of aneurysm surgery after subarachnoid hemorrhage affect the development of delayed cerebral ischemia?,"Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia. A consecutive series of 145 patients with acute aneurysmal subarachnoid hemorrhage (SAH) were operated on within 7 days of SAH and were prospectively evaluated over a 4-year period to determine if the timing of aneurysm surgery influenced the development of delayed cerebral ischemia. All patients were managed with a standardized policy of urgent surgical clipping and treatment with aggressive prophylactic postoperative volume expansion. Patients with delayed ischemic symptoms were additionally treated with induced hypertension. Forty-nine patients underwent surgery on Day 0 or 1 (Group 1) post-SAH, 60 patients on Day 2 or 3 (Group 2), and 36 patients on Days 4 through 7 (Group 3). Postoperative delayed cerebral ischemia developed in 16% of (Group 1) patients, in 22% of Group 2 patients, and in 28% of Group 3 patients. Cerebral infarction resulting from delayed cerebral ischemia developed in only 4% of Group 1 patients, 10% of Group 2 patients, and 11% of Group 3 patients. A bad clinical outcome as a result of delayed cerebral ischemia occurred in one Group 1 patient (2%), two Group 2 patients (3%), and one Group 3 patient (3%). Preoperative grade was not significantly correlated with the incidence or severity of delayed cerebral ischemia at any time interval except that patients in modified Hunt and Hess Grade I or II who underwent surgery on Day 0 or 1 after SAH had no strokes or bad outcomes from delayed cerebral ischemia. This study demonstrates that there is no rationale for delaying aneurysm surgery based on the time interval between SAH and patient evaluation."
-What is the potential benefit of L-carnitine treatment for patients with ornithine transcarbamylase deficiency?,"Carnitine deficiency associated with ornithine transcarbamylase deficiency. An infant with X-linked recessive ornithine transcarbamylase deficiency is described who also had severe deficiency of plasma and liver carnitine during normoammonemic periods. Treatment with L-carnitine (100 mg/kg/day) for 12 months decreased the frequency of hospitalizations for hyperammonemia, although it did not alter his neurologic status. This report demonstrates that persistent carnitine deficiency may be present in patients with ornithine transcarbamylase deficiency even when plasma ammonia is normal. Carnitine evaluation and supplementation may be important in the treatment of patients with this metabolic disorder."
-How do primary dysfunctions in neural control of arterial pressure potentially contribute to the development of hypertension?,"Do primary dysfunctions in neural control of arterial pressure contribute to hypertension? This article is a summary of the physiological and clinical evidence that links the cause of essential hypertension to the brain. We stress the potential importance of a biochemical disturbance in the central role of angiotensin II in the regulation of arterial pressure. While the evidence is compelling, we acknowledge the need for further complete studies on this timely subject."
-"What is the relationship between oral contraceptive use, liver cell adenoma, and the potential progression to hepatocellular carcinoma?","Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation. From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine-needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as ""hepatocellular carcinoma"" and 9 as ""consistent with liver cell adenoma."" The cytologic diagnoses were confirmed in the follow-up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma."
-What were the ovarian ablation failure rates for breast cancer patients above 40 years old in the two different radiation dose schedules?,Ovarian ablation failures by radiation: a comparison of two dose schedules. Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.
-"What similarities were found in olfactory dysfunction among Alzheimer's disease, Parkinson's disease, and the parkinsonism-dementia complex of Guam?","Olfactory dysfunction in three neurodegenerative diseases. Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate."
-What is the predominant method for evaluating nonpalpable breast lesions detected by mammography?,"Mammographic guidewire localization of nonpalpable breast lesions. Guidewire-directed biopsy is the predominant method of evaluating nonpalpable breast lesions detected by mammography. It is an accurate and safe procedure for obtaining a histologic evaluation of abnormal tissue, leading to early diagnosis and improved survival rates. This report reviews 526 needle localizations and biopsies of nonpalpable breast lesions performed in two community hospitals over a 39-month period and compares early results with those achieved in the last 13 months of the study. This review indicates that as experience in using this modality increased, the cancer detection rate increased and the percentage of invasive cancers decreased. The percentage of cancers detected in the final 13 months of the study (19%, Group II) was higher than in the first 26 months of the study (13%, Group I). Although microcalcifications were found in 24 per cent of the mammograms leading to a diagnosis of cancer, they did not prove to be a reliable indicator of malignancy in this study."
-"What was the mean incidence rate of Parkinson's disease per year in the Local Health Service of Ferrara, Italy, between 1967 and 1987?","Parkinson's disease in Ferrara, Italy, 1967 through 1987. Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type."
-What was the outcome of transhepatic electrohydraulic lithotripsy in the 50 patients studied?,"Common bile duct and intrahepatic stones: results of transhepatic electrohydraulic lithotripsy in 50 patients. Percutaneous, transhepatic, intracorporeal, electrohydraulic shock wave lithotripsy was performed in 50 patients after failure of endoscopic treatment (n = 43) or directly in patients with a strictured hepaticojejunostomy (n = 7). Twenty-seven patients had common bile duct stones; 23, intrahepatic stones. Three steps were used: A transhepatic bilicutaneous fistula was created, a wide communication between the bile duct and the gut was established, and contact shock wave lithotripsy was performed under endoscopic guidance. Afterward, 46 patients were free of stones. In four patients with diffuse intrahepatic lithiasis, only 75% of stones could be cleared. Severe complications, seen in 11 patients (hemobilia necessitating transfusion [n = 6], bile duct perforation resulting in cholangitis [n = 3], acute pulmonary edema [n = 1], and hemothorax [n = 1]), were fatal in four patients; all occurred early in the study. The authors modified their technique by dilating the biliary tract in two sessions 3 days apart, waiting 6 days for the tract to mature, and then introducing the cholangioscope directly through the skin, significantly reducing complications and mortality (P less than .005)."
-How does mucociliary clearance change in asthmatic patients during and after an acute exacerbation?,"Changes in mucociliary clearance during acute exacerbations of asthma. Previous studies have suggested that mucociliary clearance (MC) is impaired in asthmatic subjects. If so, impaired clearance may be an important factor in acute exacerbation. We proposed that if MC plays a significant role in acute illness, MC should be impaired during the exacerbation but improve after recovery. To test this hypothesis, five asthmatic patients with attacks requiring hospitalization underwent measurement of MC using radiolabeled aerosol and a gamma camera. They were studied on the second or third day after admission with repeat measurements after discharge. Spirometry was performed before all studies. After an equilibrium xenon scan (133Xe), which defined lung borders and measured regional volume, radiolabeled saline particles containing technetium-labeled (99mTC) sulfur colloid were deposited and used to label airway mucus. Deposition patterns were matched by regulating particle distribution and breathing pattern. MC was then measured as percentage retention of radioactivity at 10-min intervals for 2 h. When hospitalized, 96.0 +/- 2.06% (SEM) of the initial radioactivity was retained in the lung after 2 h, indicating little clearance of mucus from the lung. In fact, no significant changes were detected when activity at 120 min was compared with measurements at 10 min (99.2 +/- 0.22%, NS). After discharge clearance was markedly enhanced. That is, retention of lung activity was significantly lower at all time intervals from 10 min onward, with only 70.9 +/- 3.86% retained at 120 min (p = 0.008). During an asthmatic attack warranting hospital admission, MC is significantly impaired, with marked improvement following recovery."
-How do changes in circulating pancreatic enzymes and protease inhibitors relate to the development of ERCP-induced pancreatitis?,"The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors. The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis."
-How does hypoxia affect glucose transport in skeletal muscle?,"Stimulation of glucose transport in skeletal muscle by hypoxia. Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia."
-What is tegmental dehiscence and what are its potential clinical manifestations?,"Tegmental dehiscence and brain herniation into the middle ear cleft. The tegmen tympani may occasionally be breached by herniation of the temporal lobe with or without dural cover. The clinical presentation may be obvious with CSF otorrhoea but less so with apparent middle ear effusion, CSF rhinnorrhoea, conductive hearing loss, recurrent meningitis or intracranial sepsis. Diagnosis requires suspicion of the condition, which may be aided by radiological imaging. Surgical repair is to be recommended: various techniques are available but bone enveloped by fascia placed by subtemporal approach is preferred. The features of this problem are highlighted by four cases."
-What are the key clinical and biochemical characteristics of the 32-year-old patient with chronic GM1 gangliosidosis?,"A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies. Clinical and biochemical studies are reported on a 32-year-old man with GM1 gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM1 ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM1 ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM1 ganglioside beta-galactosidase activity was only 10% of normal. These findings suggest that impaired GM1 ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM1 gangliosidosis."
-What treatment was used to manage the patient's intractable axial dystonia after spinal instrumentation for scoliosis?,"Intrathecal baclofen for intractable axial dystonia. Following spinal instrumentation for scoliosis, a patient developed intractable axial dystonia refractory to conservative medical management. We describe the successful treatment of this dystonia with a continuous infusion of intrathecal baclofen and the subsequent long-term management."
-What is the primary goal of treatment for metastatic breast cancer?,"The treatment of metastatic breast cancer. While metastatic breast cancer is not curable, it is treatable. Its treatment is associated with a relatively high rate of success, and patients are able to maintain a good quality of life for periods ranging from a few months to several years. This knowledge should encourage both the patient and the oncologist to maintain treatment as long as potentially effective therapeutic methods are available. Progress is ongoing both in the development of new forms of treatment and in new ways of using and combining already existing therapeutic modalities. There is still no established ""best"" or ""only"" first treatment of metastatic breast cancer. When secondary and later treatment is to be undertaken, the task of selecting the most appropriate treatment becomes even more complex. It is only through controlled clinical trials that useful therapeutic guidelines will develop. Treatment is a joint endeavor involving both the physician and the patient. Communication must remain open. In the final stages of the illness, treatment should be directed toward the relief of distressing symptoms and anxiety."
-What unusual presentation of cryptococcal infection was observed in the HIV-positive patient described in this case report?,Cryptococcal pleural effusion preceding cryptococcal meningitis in AIDS. The authors report a case in which a small cryptococcal pleural effusion preceded the development of severe cryptococcal meningitis in an HIV-positive patient. The appearance of an isolated transient pleural effusion is a very unusual presentation for AIDS-related complications. The authors suggest that cryptococcal infection be considered in this setting.
-What is the estimated number of premature deaths in the United States in 1985 attributed to smoking-related diseases?,"Smoking-attributable mortality and years of potential life lost--United States, 1988. Smoking is a leading cause of diseases associated with premature mortality in the United States; in 1985, these diseases accounted for an estimated 390,000 premature deaths. In this report, mortality data and estimates of smoking prevalence for 1988 are used to calculate smoking-attributable mortality (SAM), years of potential life lost (YPLL), and age-adjusted SAM and YPLL rates for the United States. Calculations were performed using Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC II) software, which includes relative risk estimates for 22 adult (i.e., greater than or equal to 35 years of age) smoking-related diseases and relative risk estimates for four perinatal (i.e., less than 1 year of age) conditions. Age-, sex-, and race-specific mortality data for 1988 were obtained from CDC's National Center for Health Statistics. Data on burn deaths caused by cigarettes were obtained from the Federal Emergency Management Agency. The estimated number of deaths among nonsmokers from lung cancer attributable to passive smoking was obtained from a report of the National Academy of Sciences. Age-, sex-, and race-specific current and former smoking prevalence rates in 1988 for adults aged greater than or equal to 35 years and for women aged 18-44 years were estimated by linear extrapolation using National Health Interview Survey data for 1974-1987."
-What are the questionable cancer treatment practices found in Tijuana and other Mexican border clinics?,"Questionable cancer practices in Tijuana and other Mexican border clinics. Tijuana, Mexico, has become a refuge for cancer patients who have been convinced that they may be cured of their terminal illness by unconventional, unproved, and disproved methods offered in the border clinics. About a dozen United States promoters have joined with Mexican colleagues to offer a variety of treatments. Some patients are diagnosed using standard methods prior to arrival at the clinics, but many healthy individuals are misdiagnosed as having cancer or ""precancer"" and are then treated there. Others are told they have been cured or are improving even though they still have active disease. The modalities and regimens used are often referred to as ""metabolic therapy"" and, for the most part, are either not based on sound scientific principles or have been shown in controlled clinical trials to be useless or even dangerous. A basic metabolic regimen consists of three phases: detoxification with fasting and bowel cleansing, strengthening the immune system with numerous ""supplements,"" and attacking cancer with ""natural and non-toxic"" chemicals. Popular treatments include injections of hydrogen peroxide, large quantities of pressed liver and carrot juice, coffee enemas, infusions of Laetrile mixed with massive doses of vitamins and dimethylsulfoxide (DMSO), special diets, and a host of other pseudoscientific regimens. Unfortunately, no evidence exists that any of these modalities is more effective than no treatment at all. Patients traveling to the Mexican border clinics for metabolic therapy are subjecting themselves to costly and hazardous regimens, especially if they forgo responsible medical care in the process. The American Cancer Society, therefore, strongly urges individuals with cancer not to seek treatment with metabolic therapies in the Mexican border clinics."
-What did the study reveal about Ki-67 reactivity and proliferative activity in different histological subtypes of breast carcinoma?,"Ki-67 staining in histological subtypes of breast carcinoma and fine needle aspiration smears. Thirty four cases of invasive breast carcinoma were analysed for heterogeneity of Ki-67 reactivity in a tumour, and proliferative activity in various histological subtypes was compared. The growth factions determined in areas of central and peripheral tumour were the same. Mucinous and lobular carcinoma showed lower Ki-67 activity than ductal carcinomas. When ductal carcinomas were subdivided according to their dominant growth pattern, the carcinomas with a solid or comedo growth pattern showed the highest proliferative activity. These results largely confirm data from previous cell kinetic studies on the incorporation of radioactively labelled thymidine. A correlation between the growth fraction determined by Ki-67 in fine needle aspiration smears and cryostat sections of corresponding tumours was shown, implying that the immunostaining of cytological smears gives a reliable impression of the growth fraction of a tumour and may therefore be used in prospective studies."
-What was the healing rate of transmetatarsal amputations in different patient groups based on revascularization?,"Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized."
-What medical specialties are involved in investigating the relationship between esophageal motility disorders and unexplained chest pain?,"The relationship between esophageal motility disorders and microvascular angina. Patients with unexplained chest pain have caused investigators in cardiology, gastroenterology, and psychiatry to find abnormalities with overlap among the three specialties. This article reviews the data concerning the potential interrelation of chest pain of cardiac or esophageal origin."
-What are the key challenges and uncertainties associated with using deep brain stimulation for pain control in humans?,"Deep brain stimulation: a review of basic research and clinical studies. Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control."
-How did A-LAK cells demonstrate their ability to establish contact with metastatic melanoma cells in this murine model?,"Establishment of cell-to-cell contact by adoptively transferred adherent lymphokine-activated killer cells with metastatic murine melanoma cells. A murine model of pulmonary B16 melanoma was used to study the infiltration into metastases of lymphokine-activated killer (LAK) cells and adherent lymphokine-activated killer (A-LAK) cells and, specifically, to study whether A-LAK cells are able to leave the tumor microcirculation and establish cell-to-cell contact with malignant cells. Fluorescence microscopy demonstrated that A-LAK cells accumulated in metastases twice as efficiently as LAK cells during interleukin-2 stimulation. Electron microscopy of pulmonary metastases 16 hours after administration of 2.5 x 10(7) A-LAK cells revealed A-LAK cells, identified by the presence of typical two-compartment granules, in direct contact with melanoma cells. This finding was confirmed by using A-LAK cells prelabeled with polycationized ferritin. In conclusion, our observations demonstrate unambiguously the ability of adoptively transferred A-LAK cells to establish contact with extravascular metastatic melanoma cells."
-How did the cardiovascular responses of hypertensive and nonhypertensive patients differ during social interactions in the coronary care unit?,"A comparison of hypertensive and nonhypertensive coronary care patients' cardiovascular responses to visitors. Patients with and without hypertension in a coronary care unit (n = 24) were compared with respect to cardiovascular responses to both a family visit and an interview by an investigator. Variables for each of the four cardiovascular indicators (systolic blood pressure, diastolic blood pressure, heart rate, and premature ventricular contractions) included the value before, the highest value during, the lowest value during, and the value after each social interaction condition. The highest group means for systolic blood pressure and heart rate were significantly higher for patients with hypertension than for patients without hypertension under both the interview and visit conditions. Differences in cardiovascular responses were not significantly greater for family visits than for interviews for patients with hypertension compared with those without hypertension. Thus, although hypertensive patients had greater cardiovascular reactivity to both social interaction conditions than nonhypertensive patients in the coronary care unit, family visits were no more physiologically stressful than a comparative interaction condition."
-What was the primary objective of the study involving surgical manipulation of primate cerebral arteries in established vasospasm?,"Surgical manipulation of primate cerebral arteries in established vasospasm. It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported. Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (greater than 40% reduction in vessel caliber compared to baseline, p less than 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation."
-"What was the frequency of pulmonary embolism at autopsy during the 1980s in the surgical department of Malmo, Sweden?","Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. A retrospective analysis was undertaken of all surgical patients in Malmo, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy. The analysis included a comparison with the earlier analysed and reported time period from 1951 to 1980. A continued high frequency of pulmonary embolism at autopsy was seen during the 1980s (20.3 per cent of deaths, 31.7 per cent of autopsies). Of the 391 autopsy-verified pulmonary emboli found between 1981 and 1988, 113 (28.9 per cent) were considered fatal, 104 (26.6 per cent) contributed to death and 174 (44.5 per cent) were incidental. Few patients had symptomatic deep vein thrombosis or pulmonary embolism before death. The overall frequency of major pulmonary embolism in surgical patients remained unchanged (0.3 per cent). The frequency of major postoperative pulmonary embolism showed an increase during the 1950s and 1960s (maximum 0.4 per cent) but a decrease in the last 5-year period of the 1970s (0.3 per cent), which has earlier been reported upon. This decrease continued during the 1980s (0.2 per cent) (P less than 0.05). An increase was found in the number of patients operated on who had autopsy-proven pulmonary embolism and who received thromboprophylaxis. Pulmonary embolism continues to be a major cause of death in surgical patients; however, postoperative major pulmonary embolism has shown a reduction in the last 15-year period."
-How does acetylcysteine improve hemodynamics and oxygen transport in patients with fulminant hepatic failure?,"Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. BACKGROUND. When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. METHODS. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. RESULTS. In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn.sec.cm-5 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. CONCLUSIONS. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen."
-"What are the two major pathological alterations observed in the mutant rats zitter, tremor, and spontaneously epileptic rat (SER)?","CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER. The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER."
-What were the most prevalent pathogens identified in the pneumonia cases among Filipino children in this study?,"Etiology of infection and morphologic changes in the lungs of Filipino children who die of pneumonia. Histopathologic studies and isolation of virus and bacteria in culture were carried out for 71 children less than 5 years of age with fatal pneumonia. A potential microbial etiology was identified for 61 children (86%): bacteria for 19 (27%), virus for 16 (23%), and virus plus bacteria for 26 (37%). Staphylococcus was the most prevalent pathogen, alone or in combination with other organisms, followed by Pseudomonas aeruginosa. Viral infection may predispose to bacterial infection in some children. A correlation of clinical course, results of cultures, and morphologic changes revealed cofactors that may have contributed to a fatal outcome. Lung abscess, pericarditis, myocarditis, endocarditis, and meningitis were associated with bacterial infection. Many patients in this study had severe bronchopneumonia, with a high prevalence of complications such as abscess (62%), atelectasis (40%), pericarditis (28%), and empyema (7%). Such complications added to multiple infections, measles, and malnutrition contributed to the fatal outcome in these children."
-How sensitive is magnetic resonance imaging in detecting dysplastic lesions in temporal lobe epilepsy?,"Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations. Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical-white matter architectonic pattern in 2 patients with moderate cortical dysplasia. In the remaining 3 patients, magnetic resonance imaging findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the detection of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy."
-What were the five-year patency rates for femoro-femoral and ilio-femoral grafts in this study?,"Femoro-femoral or ilio-femoral bypass for unilateral inflow reconstruction? Femoro-femoral and ilio-femoral bypass are two popular options for unilateral inflow reconstruction. In order to evaluate these alternative approaches, the records of 70 consecutive patients who underwent either femoro-femoral (n = 50) or ilio-femoral (n = 22) grafts were retrospectively reviewed. There were 46 men and 24 women, ranging in age from 27 to 84 years (mean: 66 years). Operative mortality was 10% for all femoro-femoral procedures, including 50% for emergent, 14% for synchronous, and 0% for solitary procedures; mortality was 9% for all ilio-femoral grafts including 20% for synchronous and 6% for solitary procedures. Among the elective solitary procedures, there was no significant difference with respect to operative time, blood loss, fluid requirement, time until resuming an oral diet, or duration of postoperative course for the two procedures. Five-year patency was 93% for all ilio-femoral and 57% for all femoro-femoral grafts. Although femoro-femoral bypass has been the more popular option for unilateral inflow reconstruction in this and other institutions, these findings justify the more widespread use of ilio-femoral bypass."
-What is the function of the vasoactive intestinal peptide (VIP) receptor identified in this study?,"Cloning and expression of the human vasoactive intestinal peptide receptor. Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands."
-What is the rare cause of left-sided portal hypertension described in this medical case report?,"Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature."
-What were the age-adjusted incidence rates for squamous cell carcinoma and basal cell carcinoma in men and women in New Hampshire and Vermont?,"Incidence of nonmelanoma skin cancer in New Hampshire and Vermont. A survey of skin cancer occurrence between June 1979 and May 1980 among residents of New Hampshire and Vermont identified 277 cases of squamous cell carcinoma and 1761 cases of basal cell carcinoma. The age-adjusted incidence rates for squamous cell carcinoma (32 per 100,000 in men, 8 per 100,000 in women) and for basal cell carcinoma (159 per 100,000 in men, 87 per 100,000 in women) were similar to those reported in other populations in the northern United States. Skin cancer incidence was particularly high among men more than 70 years of age and a large proportion (greater than 30%) of patients 55 years or older had a history of at least one previous skin cancer."
-What are the key clinical features associated with T-cell ALL cases having the t(11;14) translocation?,"Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations."
-"How does the affinity of thyroxine-binding globulin differ between hepatocellular carcinoma patients, cirrhotic patients, and normal subjects?","Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease. To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma."
-What is the key difference between parenchymal and reticuloendothelial iron overload in the liver as revealed by MR imaging?,"Parenchymal versus reticuloendothelial iron overload in the liver: distinction with MR imaging Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial (RE) cells after blood transfusions or rhabdomyolysis. Magnetic resonance images of patients with decreased liver signal intensity on T2-weighted images at 1.5 T were blindly compared in an effort to distinguish these conditions. In each of five patients with hemochromatosis, the pancreas had low signal intensity, but splenic signal intensity was decreased in only one. In contrast, only three of the 16 patients with RE iron overload had low pancreatic signal intensity, while all of these patients either had low splenic signal intensity (n = 14) or previously underwent splenectomy (n = 2). Distinction among these causes of iron deposition is clinically important because parenchymal iron overload from hemochromatosis may produce significant tissue damage, while the RE iron of transfusions and rhabdomyolysis is of little clinical consequence."
-What was the 5-year survival rate for elderly patients with locoregional breast cancer treated with tamoxifen alone?,"Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy."
-What did the study reveal about blood pressure responses in black and white children during a stressful video game?,"Stability of ethnic differences in children's pressor responses during three annual examinations. In this study, 395 healthy children had blood pressure and heart rate measured both at rest and during a stressful video game. Identical measurement procedures were used for three annual examinations. Consistently, black children demonstrated significantly greater pressor responses than white children. In view of the greater prevalence of hypertension among black adults than white adults, these data suggest that blacks exhibit hemodynamic irregularities well before the onset or diagnosis of hypertension."
-How does baseline skin microcirculation differ between patients with primary Raynaud's phenomenon and control subjects?,"Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon. 1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group."
-What were the different management approaches used for various types of choledochal cysts in this study?,"Variation in management based on type of choledochal cyst. The management of 23 patients treated for choledochal cysts at the Oregon Health Sciences University between 1969 and 1990 is reviewed. The median age was 27 years, with a range from 1 month to 90 years. Seventy-eight percent of patients presented with abdominal pain, and 35% were jaundiced. Three patients presented with cholangitis, two with cyst rupture, and one with recurrent pancreatitis. Nine patients had had previous biliary surgery. The diagnosis was made in all patients with ultrasound and/or cholangiography. Fifteen patients (65%) had type I cysts, 2 had a type II cyst, 5 (22%) had type III cysts, and 1 had a type IV cyst. Stones were present in four (17%) cysts, and all excised cysts were benign. Seventeen patients with type I and II choledochal cysts had complete cyst excision and choledochoenterostomy. Four of five patients with type III cysts had endoscopic cyst incision and drainage, while the fifth patient had transduodenal cyst excision and sphincteroplasty. The patient with a type IV cyst had extrahepatic cyst excision and choledochojejunostomy. There were no operative deaths. Two postoperative complications occurred: cholangitis and a prolonged ileus. All patients had resolution of their pain and jaundice. Two patients had late cholangitis. Cyst excision and choledochojejunostomy are the treatment of choice for types I and II choledochal cysts. Extrahepatic cyst excision and choledochojejunostomy may be adequate treatment for type IV cysts. Endoscopic incision and drainage is appropriate for selected patients with type III cysts."
-How does the combination of tetracycline and corticosteroid affect the development of crystalline stromal opacities in rabbit corneas infected with Streptococcus mitis?,"Characterization of infectious crystalline keratitis caused by a human isolate of Streptococcus mitis. Streptococcus mitis isolated from a human with infectious crystalline keratitis was injected intrastromally into corneas of adult New Zealand white rabbits that were treated with tetracycline hydrochloride, methylprednisolone acetate, or a combination of tetracycline and methylprednisolone. Animals were followed up for up to 44 days; untreated corneas and those treated with tetracycline developed no disease or ""fluffy"" stromal infiltrates with overlying epithelial defects representing an abscess. Corneas treated with the combination of tetracycline and corticosteroid usually developed crystalline stromal opacities that on histopathologic examination were shown to be intrastromal aggregates of cocci. Transmission electron microscopy of crystalline lesions within 10 days of infection revealed typical cocci intermixed with a fibrillar material having periodicity characteristic of fibrinogen or fibrin, and immunoperoxidase staining for fibrinogen was positive. By 1 month, electron microscopy revealed aggregates of degenerated bacteria that were surrounded by cellular processes of activated keratocytes. Our studies demonstrate a model for crystalline keratitis in which organisms are seen to reside within the stroma for up to 44 days without an inflammatory response. Periocular corticosteroids appear to be necessary to create this model. It is possible that the organisms are isolated from the host response by fibrin or by keratocytes."
-What advantages does intraoperative transesophageal echocardiography (TEE) offer in assessing surgical repair of congenital heart defects in children?,"Application of intraoperative transesophageal echocardiography in infants and small children. Intraoperative echocardiography is gaining increasing acceptance in the assessment of the surgical repair of congenital heart defects. Because of its ideal imaging location, intraoperative transesophageal echocardiography (TEE) has been especially helpful in evaluating pulmonary venous return and the integrity of the left atrioventricular valve following mitral valvuloplasty, complete atrioventricular valve repair and correction of complex congenital heart disease. It has not been routinely used in infants and small children because of a prohibitively large probe size. We report the successful use of a recently developed ""pediatric"" TEE probe capable of Doppler and color flow imaging in two patients less than 7 years of age. No complications were encountered. Recommendations regarding optimal probe imaging positions in infants are provided."
-What are the key steps in treating patients who survive out-of-hospital cardiac arrest?,"Current treatment of patients surviving out-of-hospital cardiac arrest. Most out-of-hospital cardiac arrests result from the sudden onset of a sustained ventricular arrhythmia in the absence of a new myocardial infarction. Individuals who survive cardiac arrest are at high risk for recurrent arrhythmias and sudden unexpected death. To prevent recurrent cardiac arrest, effective treatment must be provided during hospitalization after the initial episode. Caring for the survivor of cardiac arrest requires a detailed clinical investigation to define the underlying cardiac anatomy and left ventricular function and to elucidate the mechanism and characteristics of the patient's arrhythmia. Appropriate antiarrhythmic therapy, such as drugs or a nonpharmacological intervention (eg, implantable cardioverter-defibrillator), is then selected based on these considerations. In addition, ischemia is treated aggressively with beta-adrenergic blocking agents and, when appropriate, with surgical coronary artery revascularization."
-What is the significance of Tissue Polypeptide Antigen (TPpA) in detecting central nervous system metastases in breast cancer patients?,"Tissue polypeptide antigen activity in cerebrospinal fluid: a marker of central nervous system metastases of breast cancer. Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition."
-How did the researchers investigate the roles of thrombin inhibition and platelet membrane glycoprotein IIb/IIIa in platelet deposition after balloon angioplasty?,"Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model. BACKGROUND. Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. METHODS AND RESULTS. In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. CONCLUSIONS. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters."
-What was the cause of subarachnoid hemorrhage in the seventy-one-year-old Japanese man?,"Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery."
-How does interleukin-4 (IL-4) affect the growth of Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) cells?,"Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL."
-How did aztreonam and cefotaxime compare in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients?,"Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients. Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population."
-"How do passive upright tilting, Valsalva maneuver, and respiration affect the atrial flutter cycle length?","Effects of posture, Valsalva maneuver and respiration on atrial flutter rate: an effect mediated through cardiac volume. The effects of passive upright tilting from 0 degrees to +60 degrees (n = 27), Valsalva maneuver (n = 16) and respiration (n = 10) on the rate of atrial flutter were studied in 27 patients. After tilting to +60 degrees, the atrial flutter cycle length shortened in all patients from 247.5 +/- 7 to 236.7 +/- 6.9 ms (range of shortening 1 to 21 ms, p less than 0.001). The Valsalva maneuver (strain of 40 mm Hg) shortened the flutter cycle length during the strain (phase 2) from 242.2 +/- 4.6 to 230.5 +/- 5 ms (range of shortening 2 to 19 ms, p less than 0.001). In 10 patients whose respiration was monitored, the flutter cycle length consistently prolonged during inspiration and shortened during expiration. Combined beta-adrenergic and muscarinic receptor blockade in six patients did not significantly alter the flutter cycle length at rest or the effects of the various maneuvers on the changes in flutter cycle length. This study revealed that the atrial flutter cycle length can be shortened by passive upright tilting, the strain phase of the Valsalva maneuver and expiration. Changes in flutter cycle length were independent of autonomic tone, implying that by decreasing cardiac volume, these maneuvers affect characteristics of the atrial flutter circuit, thereby producing dynamic changes in the rate of atrial flutter."
-What is neoplastic angioendotheliomatosis (NAE) and how did it manifest in the two described cases?,"Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months."
-How do DNA ploidy and cell proliferation index relate to survival rates in Stage B2 and C colorectal adenocarcinoma?,"DNA ploidy and cell kinetic measurements as predictors of recurrence and survival in stages B2 and C colorectal adenocarcinoma. DNA content and cell proliferation were measured by flow cytometry on paraffin-embedded Stage B2 or C colorectal adenocarcinomas from 694 patients enrolled in adjuvant trials conducted by the North Central Cancer Treatment Group. Patients with diploid tumors had a higher survival rate than those with nondiploid tumors (P less than 0.001). The proliferation index (the sum of the percent of cells in S-phase plus those in G2M phase) was also a strong prognostic factor (P less than 0.001). The ploidy and proliferation data were combined, and the patients in the favorable group (diploid and low proliferative index) had a 5-year survival of 74% compared with 54% for the unfavorable group (high proliferative index or nondiploid, P less than 0.001). This grouping was prognostic for survival in B2 (P less than 0.001), C (P = 0.013), colon (P less than 0.001), and rectal (P = 0.026) patient subsets. This study indicates that cell kinetic parameters are important and independent prognostic factors for Stages B2 and C colorectal cancer."
-What is poststenotic dilatation and how does it develop in arteries?,"Poststenotic dilatation. Partial narrowing of arteries produces poststenotic dilatation. This appears as a dilation of the vessel wall 1 to 3 centimeters distal to the area of a partial stenosis. When a stenotic band is placed in dogs, poststenotic dilatation develops rapidly, often within eight to ten days. Moderate stenoses that produce a bruit and thrill are effective in eliciting poststenotic dilatation, whereas very tight and very mild stenoses usually are ineffective. Thus, development of poststenotic dilatation requires the presence of flow disturbances sufficient to produce an audible bruit and a palpable thrill. Although the exact flow disturbance is uncertain, statis, increased lateral pressure, cavitation, abnormal shear stresses and turbulence all have been postulated to be the cause of poststenotic dilatation. Of these, experimental studies support abnormal shear stresses and turbulence as the most likely causes. Whatever the flow disturbance, it must make the wall vibrate to produce poststenotic dilatation. Vibrations are thought to produce alterations in wall elastin and possibly in vascular smooth muscle tone. This leads to dilatation of the vessel. If the dilatation is slight, removal of the stenosis may cause reversal of poststenotic dilatation with recovery beginning within hours of correction of the stenosis. If the dilated area is enlarged to twice normal diameter, it may exhibit permanent aneurysmal changes and, therefore, requires resections with reanastomosis. Arteries that are dilated to as little as one-third more than normal size may contain areas of ulceration with overlying thrombus. These vessels also may require resection with reanastomosis."
-How do running shoes and spikes affect pronation and torsion angles compared to running barefoot?,"The effects of shoes on the torsion and rearfoot motion in running. Excessive pronation is accepted as a good indicator for various running injuries. The least amount of pronation takes place when running barefoot. The latest investigations show that this is connected to a large torsional movement between forefoot and rearfoot which can be influenced by the shoe sole construction. The shoes which are in use among runners in track and field are basically of two types, running shoes (in general torsionally stiff) and spikes (torsionally flexible). The possibly varying effect of these shoes on the shoe/foot motion in running is not known. The purpose of this investigation was therefore to show whether the pronation angle and the torsion angle differ when running barefoot, with spikes, and with running shoes (forefoot touchdown, N = 9 left and right). A film analysis provided the angular movements of the lower leg, rearfoot, and forefoot as well as pronation and torsion in the frontal plane. The results show that at touchdown the torsional movements with both shoe types are quite different from those of running barefoot. With shoes, the torsion angle is reduced back to zero--with running shoes more than with spikes--and the pronation angle is increased beyond the barefoot values (P less than 0.01). In order to reduce the risk of injury, both shoe types should be improved--the running shoes with respect to torsion and the spikes with respect to pronation."
-What was the significance of blood group antigen immunoreactivity in the study of superficial esophageal carcinomas?,"Immunohistochemical studies of blood group-related antigens in human superficial esophageal carcinomas. A total of 63 surgically resected esophageal carcinomas (including 49 superficial esophageal carcinomas) and histologically normal tissue adjacent to the superficial carcinoma (nontumorous epithelium) were examined immunohistochemically for the blood group antigens (BGA) A, B, H, Lewisa, Lewisb, Lewisx, and Lewisy. Deletion of an expected A, B or H antigen occurred in 12 (24.5%) of the 49 superficial carcinomas and three (21.4%) of the 14 advanced carcinomas. Incompatible expression of an unexpected A or B antigens occurred in only one case (1.6%) in the carcinoma. In the clinicopathologic study, there was a significant correlation between immunoreactivity of Lewisa and depth of cancer invasion (chi-square test, P less than 0.05). In the superficial carcinoma, there were significant correlations between immunoreactivity of Lewisx and lymph node status (chi-square test, P less than 0.05), immunoreactivity of Lewisy and prognosis (Z test, P less than 0.05), and incompatible expression of Lewisb for tumor against nontumorous epithelium and histologic variation (chi-square test, P less than 0.01). The functional significance of alternations in BGA expression that may be associated with oncogenesis is not clear. However, immunohistochemical determination of BGA may be a more advantageous marker to predict the patient's clinical course in superficial esophageal carcinoma."
-What percentage of patients with extraadrenal retroperitoneal paragangliomas had hypertension in this study?,"Extraadrenal retroperitoneal paraganglioma: clinical, pathologic, and CT findings. Paragangliomas of the retroperitoneum arise from specialized neural crest cells distributed along the aorta in association with the sympathetic chain. In order to ascertain characteristic CT features of extraadrenal retroperitoneal paragangliomas to differentiate them from other retroperitoneal tumors, 31 discrete tumors and two cases of paragangliomatosis in 28 patients were reviewed retrospectively, and the CT features were correlated with clinical and pathologic findings. There were 16 men and 12 women. Average age was 37 years (range, 11-70 years). Twenty-four patients (86%) had hypertension. Of these, catecholamine levels were elevated in all 18 patients who had biochemical studies. Four patients (14%) had malignant paragangliomas. The discrete tumors were classified by location as suprarenal (26%), renal hilar (32%), or infrarenal (42%). Suprarenal paragangliomas could not be distinguished from the ipsilateral adrenal gland on CT. The average size of functional tumors was smaller (7.0 cm) than that of nonfunctional tumors (12.0 cm), but the sizes of the two groups overlapped. Smaller tumors were more likely to be homogeneous and have well-defined margins than were larger tumors. Our findings indicate that extraadrenal retroperitoneal paragangliomas are functionally active more often than previously reported and that they are readily detected by CT as soft-tissue masses closely associated with the entire length of the abdominal aorta. However, no CT feature was found that was unique for paraganglioma."
-What unique pattern of nystagmus was observed in a patient with posterior medullary haemorrhage?,"Upbeat and downbeat nystagmus occurring successively in a patient with posterior medullary haemorrhage. In a patient with posterior medullary haemorrhage, first upbeat and later downbeat nystagmus occurred in the primary position. The lesion was limited to the posterior and medial part of the medulla. Clinical and electro-oculographic examination first showed upbeat nystagmus in the primary position and upgaze, with downbeat nystagmus in downgaze. Two and a half months later, there was downbeat nystagmus in the primary position and downgaze and upbeat nystagmus in upgaze."
-How does gadolinium contrast enhance the detection and delineation of choroidal melanoma in magnetic resonance imaging?,"Magnetic resonance imaging of choroidal melanoma with and without gadolinium contrast enhancement. Choroidal melanoma is the most common intraocular tumor and is uniquely suited for evaluation by magnetic resonance imaging (MRI) because of the paramagnetic effect of the melanin molecule. The authors performed T1-, T2-, and proton-density-weighted MRI on 34 patients with choroidal melanoma. Nineteen patients received gadolinium contrast, T1-weighted images were superior in both detecting and delineating tumors, showing increased contrast-to-noise ratios over other images. Gadolinium contrast further increased this ratio. These images are presented as evidence that gadolinium-enhanced MRI is valuable in the evaluation of choroidal melanoma."
-"What were the main findings comparing standard external CPR, open-chest CPR, and cardiopulmonary bypass in this canine myocardial infarct model?","Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model. STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB."
-What was the purpose of the study on creatine kinase MB (CK-MB) time-activity curve in patients with acute myocardial infarction?,"Indices of reperfusion in patients with acute myocardial infarction using characteristics of the CK-MB time-activity curve. The purpose of this study was to identify indices of coronary artery reperfusion in patients treated with thrombolytic therapy for acute myocardial infarction (AMI) by means of characteristics from the serum creatine kinase (CK) isoenzyme MB time-activity curve. Frequent blood sampling as performed in three groups with a first AMI: 29 patients treated with intravenous thrombolytic therapy who had a patent infarct-related artery with normal flow (TIMI-3) at acute catheterization (reperfusion group); four patients with a persistently closed infarct-related artery (no reperfusion group); and 44 patients who did not receive any therapy aimed at coronary reperfusion (no thrombolytic therapy group). In the latter group we prospectively estimated that 25% would have spontaneous reperfusion. A physiologically based computer-calculated multi-compartment method was used to determine the characteristics of the serum CK-MB time-activity curve. In addition to demonstrating an earlier increase, a shorter time to peak of serum CK-MB and a lower estimated infarct size in the reperfusion group (p = 0.025 to 0.00001), the appearance rate constant (k1) and time from estimated initial increase to peak of CK-MB in the blood stream (tRP) were significantly different from those values in the no thrombolytic therapy group (p less than 00001). A cutoff level indicating reperfusion if k1 was greater than 0.185 or tRP was less than 16.5 hours demonstrated overlapping values between these two groups in only four patients (k1), two patients (tRP), and six patients with a combination."
-What makes interstitial ectopic pregnancies more dangerous compared to other tubal pregnancies?,Ruptured interstitial pregnancy presenting as an intrauterine pregnancy by ultrasound. Interstitial pregnancy is an uncommon subset of ectopic pregnancy in which the conceptum implants in the intrauterine portion of the fallopian tube. These pregnancies tend to progress further before rupture than do other tubal pregnancies and subsequently have greater propensity for massive intra-abdominal bleeding and maternal demise. Abdominal ultrasound can be deceptive in evaluating interstitial ectopic pregnancies. Transvaginal ultrasonography is more sensitive in the diagnosis of early ectopic pregnancy. Knowledge of the application and limitations of both transabdominal and transvaginal ultrasound will assist the emergency physician in the timely evaluation of this potentially lethal condition.
-How accurate is transrectal sonography in detecting neurovascular bundle invasion in prostate cancer patients?,"Carcinoma of the prostate: value of transrectal sonography in detecting extension into the neurovascular bundle. Detection of involvement of the neurovascular bundles (NVB) by tumor is important in deciding whether sexual function can be preserved in patients undergoing radical prostatectomy for prostatic cancer. The nerve branches innervating the corpora cavernosa have a rather constant association with the capsular arteries and veins of the prostate, forming the periprostatic neurovascular bundle, which can be identified intraoperatively and spared during radical surgery, thus preserving potency. We examined 160 patients with biopsy-proved clinical stage A or B adenocarcinoma with transrectal sonography before radical prostatectomy to determine how useful the procedure is for predicting tumor extension into the NVB. Correlation with pathologic serial sections was obtained in each patient. The sonograms depicted the NVB on both sides in 77 patients (50%), on the right side only in 13 (8%), and on the left side only in 36 patients (23%). In 29 patients (19%) neither neurovascular bundle could be identified on the sonograms. Ninety-one tumors in this series showed evidence of extraglandular spread pathologically, which was posterolateral or into the NVB in 70 tumors involving 82 hemispheres. Using transrectal sonography, we correctly identified invasion of the NVB in 54 cases and missed it in 28 cases. NVB invasion was predicted incorrectly with transrectal sonography in 51 cases; absence of involvement of the NVB was correctly predicted in 177 hemispheres. The sensitivity of sonography for predicting invasion of the NVB was 66%, with a specificity of 78% and an accuracy of 75%. Positive predictive values and negative predictive values were 51% and 86%, respectively. We conclude that transrectal sonography currently suffers from lack of sufficient spatial resolution to detect accurately invasion of the NVB."
-How does C4b-binding protein (C4bBP) affect the host response to Escherichia coli infection?,"C4b-binding protein exacerbates the host response to Escherichia coli. Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What factors were found to be associated with better functional recovery after traumatic transtentorial herniation?,"Functional recovery after traumatic transtentorial herniation. To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation."
-What is the association between L-tryptophan ingestion and eosinophilic fasciitis (EF) according to the study?,"Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Recently, a causative association has been made between the ingestion of levotryptophan (L-tryptophan) and the eosinophilia-myalgia syndrome (EMS), a new entity manifested by peripheral blood eosinophilia, myalgias, constitutional symptoms, and cutaneous edema with fibrosis. Contaminated levotryptophan preparations produced at a single manufacturing company between October 1988 and June 1989 have been implicated in all EMS cases. In this study, we analyzed retrospectively 49 patients with cutaneous fibrosis for a history of levotryptophan use. Levotryptophan ingestion prior to the onset of their disease was reported by 11 (65%) of 17 patients with eosinophilic fascilitis (EF), two (20%) of 10 patients with localized scleroderma, and none of 22 patients with systemic sclerosis. The onset of levotryptophan-associated cutaneous disease preceded the availability of contaminated levotryptophan preparations in seven (54%) of 13 patients. One patient with levotryptophan-associated generalized morphea also had lichen sclerosus et atrophicus and acanthosis nigricans, findings not previously reported in patients with EMS. In addition, we compared the clinical and laboratory features of levotryptophan-associated EF and idiopathic EF. Myalgias, muscle weakness, paresthesias, morpheaform plaques, cutaneous ulcers, and livedo reticularis were more common in patients with levotryptophan-associated EF. We conclude that levotryptophan-associated EF and localized scleroderma were present before the presumed date of contaminated levotryptophan availability. The clinical spectrum of cutaneous fibrosis associated with the ingestion of levotryptophan includes generalized morphea and EF, which are similar though not identical to their idiopathic counterparts."
-What percentage of subjects in the study had adenomas detected during screening colonoscopy?,"Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men. Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated."
-What was the average number of bypasses per patient in this direct coronary surgery without extracorporeal circulation?,"Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients Between May 1978 and March 1990, 700 patients were operated on with direct coronary surgery without extracorporeal circulation (ECC): 529 (76 percent) were male and 171 (24 percent) were female. The average age was 64 years (range, 35 to 86 years), 454 (65 percent) had unstable angina, 163 (23 percent) had stable angina, 51 (7 percent) had postmyocardial infarction angina, and 32 (5 percent) had acute myocardial infarction at the moment of the operation. In this series of patients, all branches of the coronary arteries were bypassed; the mammary artery was used in 40 percent of the cases, the average bypass per patient was 2.2 (range, 1 to 5), and 26 percent had associated disease of high risk to undergo ECC. The morbidity was 4 percent and the mortality for this series of patients was 1 percent; the probability of survival at seven years was 90 percent. This experience shows us that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated disease, in some cases of acute transmural infarction, and also for patients who need coronary angioplasty. Also, it can improve the relation cost/benefit in coronary surgery."
-What was the main finding of the study regarding the use of diazepam in emergency treatment of seizures in children?,"Diazepam and intubation in emergency treatment of seizures in children. STUDY OBJECTIVES: This study was undertaken to determine the incidence of endotracheal intubation after the use of diazepam compared with phenobarbital or phenytoin in emergency treatment of seizures in children. DESIGN: The records of all children (98) were reviewed in a case-control fashion. A logistic regression model was used to determine whether there was an association between diazepam administration and intubation, adjusting for all other covariates (age, weight, convulsion time before first anticonvulsant was given, response latency, diagnosis, and therapy). SETTING: All children were treated in an emergency department and then transported to a tertiary pediatric center by a pediatric transport team. TYPE OF PARTICIPANTS: All patients were children, with a median age of 2.7 years (range 0.17 to 15.3 years). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only the use of diazepam was found to be significantly associated with intubation after adjusting for all other covariates (adjusted odds ratio, 49.4; P less than .001). In the comparison of diazepam versus phenobarbital or phenytoin used as the first anticonvulsant, median response latency did not differ (27.0 vs 32.5 minutes, P greater than .83). CONCLUSION: A significant association was found between diazepam use and intubation. Response latency was not shorter when diazepam was used as the initial anticonvulsant compared with phenobarbital or phenytoin."
-What is the significance of a 'sentinel bleed' after pancreatoduodenectomy?,"Arterial hemorrhage after pancreatoduodenectomy. The 'sentinel bleed'. Experienced centers report reduced operative mortality after pancreatoduodenectomy for cancer, but significant complications continue to occur in as many as 25% of patients. Anastomotic disruption leads to sepsis in the pancreatic bed where major vascular structures have been exposed by regional lymphadenectomy, creating a setting for arterial erosion or ligature slough and massive hemorrhage. Dehiscence of the pancreatojejunostomy is a particular risk. We treated five patients with arterial hemorrhage after pancreatoduodenectomy, all of whom had had ""sentinel"" bleeding from the abdominal drains or gastrointestinal tract. Results of endoscopy were misleading in two patients. Three of five patients were saved by prompt recognition, early operation, and, in one instance, angiographic embolization. Sentinel bleeding after pancreatoduodenectomy indicates local sepsis and probable anastomotic dehiscence. Recognition of its significance and prompt response may prevent exsanguination."
-What was the purpose of the study on neurophysical signs assessment among patients with head injuries?,"Observer variation in assessing neurophysical signs among patients with head injuries. As an early phase in the development of a valid and reliable measure of the neurophysical sequelae after head injury, we carried out assessments of interrater agreement on representative items. The purpose of this study was to determine the degree of agreement among expert raters who independently measured neurophysical signs on patients undergoing physical rehabilitation after brain injury. Agreement was described using the index of crude agreement, expected agreement and Kappa. Therapists showed a high degree of agreement on those items forming part of a routine neurological assessment: prehension, coordination, voluntary movements and tendon reflexes. Crude agreement ranged from 77.8-100%. There was considerable discordance in assessing muscle tonus, equilibrium and protective reactions, spinal reflexes, tremor and dysmetria (crude agreement ranged from 49.7-97.9%). Although, the number of subjects was small, the information generated from this study will be useful in refining our instrument for the assessment of neurophysical signs."
-What are the potential complications of untreated abdominal aortic thrombosis?,"Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function."
-What method was used to screen four large families for potential genetic linkages related to hypertension?,"Use of the robust sib-pair method to screen for single-locus, multiple-locus, and pleiotropic effects: application to traits related to hypertension. Robust sib-pair linkage analysis can be used as a screening tool in the search for the potential involvement of single-loci, multiple-loci, and pleiotropic effects of single loci underlying phenotypic variation. Four large families were each ascertained through one adult white male with essential hypertension. The robust sib-pair method was used to screen these families for evidence of linkage between 39 quantitative traits related to hypertension and 25 genetic marker loci. All traits were analyzed on the untransformed, square-root and log-transformed scales. Among other findings, there is a suggestion of linkage between the 6-phosphogluconate dehydrogenase locus on chromosome 1p36 and mean fifth-phase diastolic blood pressure. There may also be linkage between the following markers and traits: the adenylate kinase-1 marker and/or the Lewis blood group marker and the traits height, weight, and biacromial breadth; the glyoxylase I marker and the traits upper-arm circumference and suprailiac skinfold thickness; the ABO blood group and adenylate kinase-1 markers on chromosome 9q34 and the third component of complement marker on chromosome 19p13 and dopamine-beta-hydroxylase; and the P1 blood group and the traits weight and 1-h postload serum glucose level."
-What was the method used to manage neuropathic cancer pain in patients who did not respond to conventional analgesics?,"Subcutaneous lidocaine for treatment of neuropathic cancer pain. Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient."
-What are the key differences in breast cancer characteristics based on age and mammographic presentation?,"Not all nonpalpable breast cancers are alike. Clinical and mammographic data of 1009 consecutive patients were correlated with histopathologic data of 1144 biopsy specimens of nonpalpable breast lesions to better define the presentation and biologic behavior of early breast cancer. Patients with malignant neoplasms (269 [24%] of 1144 specimens) were older (mean age, 62.1 years) than patients with benign lesions (mean age, 54.9 years). Furthermore, patients with invasive disease were older (mean age, 63.3 years) than patients with noninvasive disease (mean age, 58.5 years) with an overall increased risk of invasive cancer per year of 1.035. A 58% incidence of invasive cancer was detected for lesions characterized by calcifications, while the incidence of invasive cancer was 84% for isolated mass lesions (relative risk, 4.31 for masses). Isolated mammographic calcifications associated with cancer appeared in a younger population and were significantly associated with noninvasive ductal cancer. Breast cancer presenting as a mammographic mass appeared in an older group and was highly associated with the presence of invasive disease."
-What were the effects of different lipid emulsions on hepatic lipid content and liver histology in rats receiving total parenteral nutrition?,"Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats. The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups."
-What are the two N-methyl-D-aspartate (NMDA) antagonists tested in this study for their anticonvulsant properties?,"Anticonvulsant activity of two orally active competitive N-methyl-D-aspartate antagonists, CGP 37849 and CGP 39551, against sound-induced seizures in DBA/2 mice and photically induced myoclonus in Papio papio. Two novel N-methyl-D-aspartate (NMDA) antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid CPG 37849 and the corresponding 1-ethyl ester CGP 39551, were tested as anticonvulsants in DBA/2 mice and photosensitive Senegalese baboons, Papio papio. In DBA/2 mice, CGP 37849 is more potent than CGP 39551 when administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) (ED50 for suppression of clonic seizures at 60 min: i.c.v. 0.038 and 0.21 nmol; i.p. 3.40 and 19.1 mumol/kg, respectively). When administered orally in mice, the two compounds are approximately equipotent (ED50 CGP 37849, 35.2 mumol/kg; ED50 CGP 39551, 28.1 mumol/kg). The time course of action of CGP 39551 is exceptionally prolonged: 42 mumol/kg i.p. protects against clonic seizures for 48 h. Protection provided by other NMDA antagonists in mice is of much shorter duration: 2-amino-5-phosphono-pentanoic acid (AP5) 1 h, 2-amino-7-phosphono-heptanoic acid (AP7) 4 h, 2-amino-7-phosphono-heptanoic acid 1-ethyl ester 3 h, 4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) 2 h, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) 4 h, and CGP 37849 4 h. After oral administration of the drugs, the therapeutic index (TI = ratio of the ED50 values for rotorod performance and anticonvulsant protection) remains relatively constant at 5.9-7.2 for 3 h (CGP 37849) and 4.0-6.1 for 24 h (CGP 39551). After i.p. administration, the TI values are CGP 37849 at 1 h 2.4, and at 3 h 20.0, CGP 39551 at 1 h 2.3, at 3 h 7.1, and at 24 h 3.6. In baboons, acute administration of CGP 37849 at doses of 48-191 mumol/kg intravenously (i.v.) suppresses photically induced myoclonus for at least 285 min, with severe side effects at the highest dose tested. CGP 39551 at doses of 169-675 mumol/kg i.v. shows weak anticonvulsant activity only at the highest dose tested (accompanied by severe side effects). CGP 37849 at 48-96 mumol/kg orally (p.o.) fails to protect against photically induced myoclonus up to 4 h after administration, but 191 mumol/kg (40 mg/kg) p.o. produces complete suppression of seizures after 24 h. On the other hand, CGP 39551 at 169 mumol/kg (40 mg/kg) p.o. produces total suppression of seizure activity at 4 h with a longer duration of anticonvulsant action (2-3 days).(ABSTRACT TRUNCATED AT 400 WORDS)."
-What was the primary aim of the geriatric-anesthesiologic intervention program for elderly patients with femoral neck fractures?,"A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay."
-What are the limitations of routine testicular scanning in diagnosing acute scrotal conditions?,"Testicular scanning: evaluating the acute scrotum in the clinical setting. In a retrospective study of patients with acute scrotal pain presenting to the hospitals of Southern Illinois University School of Medicine from January 1982 until September 1987, determination was made of the appropriate use of testicular scan for definitive diagnosis. Though the testicular scan is a highly sensitive and specific examination in the identification of testicular torsion, we believe its routine use in clinical practice is limited. Appropriate utilization of the examination requires its use in high-risk groups with equivocal physical findings or in patients with unusual presentations of age, anatomy, or neurologic deficit. The scan if used for routine screening of the acute scrotum would result in needless delays and unjustifiable expense when it is mandatory that the treatment be immediate surgical exploration."
-"What distinguishes the ossifying jaw fibromas in this syndrome from the ""brown tumors"" of hyperparathyroidism?","Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the ""brown tumors"" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in ""brown tumors."" The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct."
-"What medical condition did the 83-year-old woman have, and what was the suspected origin of her tumor?",Carcinoma erysipeloides. We report an 83-year-old woman with carcinoma erysipeloides due to an occult carcinoma. Immunohistochemical study of skin biopsies showed reactivity to S-100 protein and human milk fat globule antigen indicating that the tumour originated in the breast.
-What was the purpose of performing intraoperative transesophageal echocardiography in patients with atrioventricular septal defect?,"Intraoperative transesophageal echocardiography of atrioventricular septal defect. To determine the accuracy and utility of single-plane transesophageal echocardiography in analyzing atrioventricular (AV) septal defect, intraoperative transesophageal echocardiography was performed before and after institution of cardiopulmonary bypass in 16 patients (age 24 days to 14 years, weight 3 to 47 kg). Prebypass transesophageal echocardiography (including two-dimensional echocardiography, Doppler color flow mapping and pulsed wave Doppler ultrasound) correctly diagnosed divided AV valve, common AV valve and unbalanced AV valve, as well as atrial or ventricular septal defect, or both, in all cases. It correctly analyzed AV valve regurgitation in all 10 patients with right and all 14 with left AV valve regurgitation and correctly analyzed 30 of 33 additional cardiac anomalies. Transesophageal echocardiography was able to detect the absence of normal pulmonary venous connections but failed to demonstrate all of the complex anomalous pulmonary venous connections in three patients with atrial isomerism. Postbypass transesophageal echocardiography documented the absence of a significant residual shunt in 11 of 11 patients undergoing corrective surgery and verified residual AV valve regurgitation in 7 of 9 patients with tricuspid regurgitation and 11 of 13 with mitral regurgitation. Transesophageal echocardiographic information that altered or refined the surgical treatment was obtained in 5 (31%) of 16 patients. Epicardial and transesophageal echocardiography results were concordant in all 13 patients in whom both were performed. Transesophageal echocardiography provides useful and accurate imaging of the important two-dimensional, pulsed wave Doppler ultrasound and Doppler color flow mapping features in AV septal defect."
-What is the significance of the patient's survival in this case of primary angiosarcoma of the brain?,Primary angiosarcoma of the brain. We have described a 32-year-old black woman who had a primary angiosarcoma of the right occipital lobe. All three previously reported cases have been fatal within 1 year. Our patient is doing well more than 3 1/2 years after surgery.
-How might abnormal liver enzyme metabolism potentially contribute to the development of Parkinson's disease?,"Abnormal liver enzyme-mediated metabolism in Parkinson's disease: a second look. If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies."
-What is the potential serious late complication of aortic bifurcation surgery discussed in this medical report?,"Bilateral ureteral obstruction following aortobifemoral bypass graft. In this report we present a case of bilateral ureteral obstruction, a potentially serious late complication of aortic bifurcation surgery. The incidence, aetiology, clinical presentation and treatment are discussed."
-What was the main finding of the study regarding bacterial colonization in necrotizing enterocolitis?,"Does patient age or intestinal pathology influence the bacteria found in cases of necrotizing enterocolitis? To evaluate the relationship between bacterial colonization in neonatal peritonitis and patient age or intestinal pathology, we retrospectively reviewed peritoneal culture results from 96 infants having surgery for necrotizing enterocolitis. Microorganisms recovered mirrored those usually found as fecal flora within the neonatal intensive care unit. These reflect, in turn, the abnormal colonization intrinsic to care in the intensive care nursery. Analysis revealed no significant correlation between the disease and either age of the infant or intestinal site of disease."
-What were the clinical findings in patients with obstruction of the infrarenal portion of the abdominal aorta?,"Obstruction of the infrarenal portion of the abdominal aorta: results of treatment with balloon angioplasty. Our experience in the treatment of stenoses of the infrarenal portion of the abdominal aorta with balloon angioplasty in 27 patients is reported. Clinical findings were lower limb claudication (all patients), impotence (eight patients), and blue-toe syndrome (two patients). The underlying disease was atherosclerosis in 24 patients and nonspecific aortoarteritis in three patients. Dilatation was successful in all patients. Embolic occlusions of the left common iliac artery (one patient) and left superficial femoral artery (one patient) were the only major complications. Claudication in the affected limb continued in the first patient; the second died when diagnostic angiography, performed 3 months after angioplasty, caused a severe atheroembolus. Of the other 25 patients, nine of the 10 followed up for 13-48 months and all seven followed up for 3-8 months were free of symptoms. Six of eight patients with sexual dysfunction had normal function after angioplasty. Seven patients still awaited follow-up and one was lost to follow-up. Our experience suggests that balloon angioplasty is an effective treatment of stenoses of the infrarenal portion of the abdominal aorta."
-What imaging technique was used to diagnose the pulmonary artery aneurysm in this case report?,Magnetic resonance imaging of pulmonary artery aneurysm. Pulmonary artery aneurysm is a rare condition. We have presented what we believe to be the first case in the English literature to be diagnosed by magnetic resonance imaging.
-Which two monoclonal anti-idiotope antibodies (Ab2) were able to induce specific anti-TAA-specific (Ab1') responses in rabbits?,"Analysis of anti-tumor antibodies in mice and rabbits induced by monoclonal anti-idiotope antibodies. Eight different mouse monoclonal anti-idiotope antibodies (mAb2) generated against a mouse monoclonal anti-human melanoma proteoglycan Ag (MPG) antibody (mAb1), MEM136, were tested for their ability to induce anti-MPG responses in mice and rabbits. All Ab2 were idiotypically cross-reactive and combining site-specific as demonstrated by competitive cross-inhibition studies and their ability to inhibit the binding of MEM136 to the melanoma cells, Colo38. However, only two Ab2, IM32 and IM06, were able to induce specific anti-TAA-specific (Ab1') responses in rabbits. When IM32 and IM06 were tested in allogeneic stains of mice for the induction of anti-MPG responses, only IM32 produced an Ab1' response. In mice, the Ab3 response induced by IM32 is idiotypically cross-reactive with its Ab1. Furthermore, the IM32-induced murine Ab3 and MEM136 recognized a similar MPG epitope on the melanoma cells because the Ab3 inhibited the binding of MEM136 to melanoma cells. The Ab3 induced by IM32 and IM06 in rabbits also recognized a similar epitope as the Ab1. In rabbits, the Ab3 response induced by IM32 and IM06 were idiotypically cross-reactive with each other. However, additional studies indicated that the majority of Ab3 induced by IM32 were IM32 Id-specific and lacked IM06 idiotopes. Further experimentation indicated that IM32-induced rabbit Ab3 were biologically active as demonstrated by the ability of the Ab3 to inhibit melanoma cell invasion in a Matrigel assay."
-What correlation was observed between large amplitude sensory action potentials and myelopathy in the study?,"Large amplitude sensory action potentials in myelopathy: an observation. Subjects with at least one sensory action potential (SAP) amplitude greater than 2 SD above the age-matched mean during standard nerve conduction tests were evaluated for evidence of spinal cord disease. From a total of 153 subjects, 16 had at least one large amplitude SAP and 12 of 16 (75%) had a documented myelopathy. While a mechanism has yet to be determined, this observation suggests that SAP amplitudes greater than 2 SD above normal may be correlated with clinical evidence of injury to the central nervous system."
-What was the primary symptom experienced by the patient with recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue?,"Recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue. Torsion of the adnexa is rare, and diagnosis is difficult because of the sparse clinical findings. I describe a patient with recurrent torsion of the right adnexa, involving a cystadenoma of aberrant ovarian tissue. Her only symptom was recurrent right-sided pelvic pain."
-What is the effectiveness of optic nerve sheath decompression in treating patients with acute and chronic papilledema?,"Treatment of pseudotumor cerebri by primary and secondary optic nerve sheath decompression. We performed optic nerve sheath decompression in 53 patients (101 eyes) with pseudotumor cerebri and visual loss. Sixty-nine eyes (85 patients) with acute papilledema uniformly had improved visual function after optic nerve sheath decompression. Of 32 eyes with chronic papilledema (18 patients), only ten had improved visual function after optic nerve sheath decompression. This difference was significant (P = .0001). Thirteen eyes required secondary or tertiary optic nerve sheath decompression after an initial successful result. Eleven of 13 eyes had improved visual function after repeat optic nerve sheath decompression. We believe that patients with acute papilledema and visual loss should be offered optic nerve sheath decompression, and if symptoms recur, repeat optic nerve sheath decompression is a safe and effective treatment option."
-What was the main finding of the randomized trial comparing ticarcillin and clavulanate with gentamicin and clindamycin in patients with complicated appendicitis?,"A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis. Secondary bacterial peritonitis is usually a polymicrobial infection of facultative gram-negative aerobic and anaerobic organisms. Treatment consists of operation and broad-spectrum antibiotic administration. The antibiotic treatment of choice in these infections has been the combination of gentamicin and clindamycin. However, this combination can have toxic side effects and necessitates frequent monitoring of serum levels. Beta-lactam antibiotics provide broad-spectrum coverage and low toxicity, but can be inactivated by species of bacteria producing beta-lactamase enzymes. Clavulanic acid is a potent inhibitor of beta-lactamases and has been shown to extend the efficacy of ticarcillin to bacteria producing these enzymes. This combination was compared with gentamicin and clindamycin in 99 consecutive patients with complicated appendicitis. Eradication of identified pathogens was greater in the ticarcillin and clavulanate group (98 per cent) than in the gentamicin and clindamycin group (92 per cent), even for the subgroup of organisms producing beta-lactamases (97 versus 90 per cent eradication). Complications and clinical response were not significantly different between the two treatment groups. Ticarcillin and clavulanic acid is a safe and effective alternative to gentamicin and clindamycin in the treatment of secondary bacterial peritonitis and offers advantages in dosing simplicity and freedom from ototoxic and nephrotoxic effects."
-What was the accuracy of fine needle aspiration cytologic procedures in diagnosing malignant mammary masses in this study?,"The accuracy of malignant diagnoses established by fine needle aspiration cytologic procedures of mammary masses. Fine needle aspiration cytologic studies are being used with increasing frequency to diagnose carcinoma of the breast. To determine whether or not a diagnosis of carcinoma established by cytologic examination is sufficiently accurate to proceed to treatment without tissue confirmation, we have examined our results in a series of 109 patients who had 111 aspiration cytologic procedures followed by open biopsy between January 1985 and June 1987. From this group, 39 specimens were read as malignant and 19 were read as suspicious. Thirty-eight of 39 specimens with positive readings were from lesions that proved to be malignant on subsequent open biopsy. Seventeen of 19 suspicious specimens were also from malignant lesions. Three of 17 specimens that were inadequate and nine of 36 negative specimens were from lesions that were later shown to be malignant. Our single false-positive result occurred on cells that had been air dried during preparation in the early months of experience with this technique at our institution. Re-evaluated later in our series, the same specimen was called suspicious rather than malignant. We conclude that a positive reading on fine needle aspiration is highly accurate. The positive predictive value should be 100 per cent, once experience is gained in preparing and interpreting the material. Open biopsy is necessary for inadequate, negative or suspicious specimens to exclude a malignant lesion if the clinical or mammographic findings are consistent with carcinoma."
-What is neurocutaneous melanosis and what are its key characteristics?,"Neurocutaneous melanosis: definition and review of the literature. Neurocutaneous melanosis is a rare congenital syndrome characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The syndrome is thought to represent an error in the morphogenesis of the embryonal neuroectoderm. We review 39 reported cases of neurocutaneous melanosis and propose revised criteria for diagnosis. Most patients with neurocutaneous melanosis presented in the first 2 years of life with neurologic manifestations of increased intracranial pressure, mass lesions, or spinal cord compression. Leptomeningeal melanoma was present in 62% of the cases, but even in the absence of melanoma, symptomatic neurocutaneous melanosis had an extremely poor prognosis. Useful diagnostic procedures include cerebrospinal fluid cytology and magnetic resonance imaging with gadolinium contrast. Patients may be aided by palliative measures such as shunt placement to reduce intracranial pressure. Dermatologists in their follow-up of patients with large or multiple congenital melanocytic nevi should be aware of this condition, to aid in prompt diagnosis and because the treatment of cutaneous lesions may be altered in the presence of symptomatic neurocutaneous melanosis."
-What is the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in treating pancreatic duct stones in patients with chronic calcifying pancreatitis?,"Extracorporeal shock wave lithotripsy of pancreatic duct stones. Chronic calcifying pancreatitis presents a major clinical problem, often requiring extensive surgery. Extracorporeal shock wave lithotripsy (ESWL) offers a new therapeutic option. We applied ESWL after endoscopic sphincterotomy of the pancreatic orifice in eight patients with impacted pancreatic duct stones. An electromagnetic lithotriptor (Siemens Lithostar, Erlangen, FRG) was used. Patients were treated in prone position under fluoroscopic control. A mean of 6,813 shock waves (range 1,500-10,000) was delivered in one or two sessions. Disintegration of stones was achieved in 6/8 patients, initial relief of pain in 7/8 patients, and total clearance of the pancreatic duct in 3/8 patients. One patient had an exacerbation of her pancreatitis one day after ESWL, which resolved rapidly with medical treatment. No other complications were observed. Four of five patients with fragmented stones had no abdominal complaints at follow-up (mean 17 months, range 3-27). Three patients in whom ESWL was not completely successful (two without and one with partial fragmentation) underwent an operation according to Puestow. Two of them still have abdominal complaints after surgery. From these data, we conclude that ESWL of pancreatic duct stones is a promising new alternative for surgery, when endoscopic stone extraction fails."
-What are the key characteristics of Superparamagnetic iron oxide (SPIO) particles in MR imaging of the liver and spleen?,"Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years. Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins."
-How does the polymerase chain reaction (PCR) method compare to viral isolation in detecting herpes simplex virus (HSV) in genital lesions?,"Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative."
-"What combination of immunosuppressive drugs did the authors use to treat serpiginous choroiditis, and how effective was the treatment?","Triple agent immunosuppression in serpiginous choroiditis. Serpiginous choroidopathy is a progressive choroidal inflammatory disorder that typically has a variable saltatory course. Response to steroids is uncertain. By using azathioprine, cyclosporine, and prednisone in combination, the authors have observed rapid remission of active disease in five patients. Remissions have been maintained for periods up to 18 months. Because of the synergistic effects of this combination, doses could rapidly be reduced to maintenance levels without reactivation. Disease in two patients recurred immediately after discontinuation of low-dose therapy but was arrested when therapy resumed. Triple agent immunosuppressive therapy is well tolerated and appears to be effective."
-How does hypertension affect the expression of platelet-derived growth factor (PDGF) receptors in rat aorta and heart?,"Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF alpha- and beta-receptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF beta-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF alpha-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF beta-receptor mRNA levels. Aortic PDGF beta-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF alpha-receptor steady-state mRNA levels were unchanged in DOCA-salt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF beta- and alpha-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF beta-receptor. They also indicate that tissue-specific expression of the genes of the PDGF ligand/receptor system are differentially regulated in hypertension."
-What is the purpose of subglottic laryngeal closure in patients with severe neurological disease?,"Subglottic laryngeal closure for aspiration. Aspiration may be life threatening, particularly in those patients with severe central neurological disease. From such a group of patients, several were identified who had severe laryngeal dysfunction and aspiration. The majority of patients in this subgroup existed in a neurologically vegetative state. In an attempt to reduce the degree of aspiration they experienced, the procedure of subglottic laryngeal closure was performed. Essentially, the operation is designed to isolate the tracheal airway from the incompetent larynx. The aim is to protect the lower airway from pharyngeal contamination. In all 5 patients there was a marked improvement in general and pulmonary health."
-What is the most effective and safest form of anesthesia for newborn circumcision according to the context?,"Pain in neonatal circumcision. Because newborn circumcision is a quick and safe surgical procedure, any method to relieve pain must be almost risk-free in order to be acceptable. General anesthesia and narcotic analgesia are not appropriate. Dorsal penile nerve block (DPNB) with lidocaine hydrochloride is probably the most effective and safest form of anesthesia for newborn circumcision currently available, but it can cause significant local and systemic reactions. Only a limited number of cases of DPNB have been reported and we feel that this procedure should be used cautiously until there is more published evidence of its safety. Alternative methods of pain relief including oral acetaminophen and topical anesthesia should also be studied. Of special interest is recent evidence that a sucrose-flavored pacifier is an effective analgesic during newborn circumcision."
-What are the key differences between pre-T and thymic acute lymphoblastic leukaemia (ALL) in terms of immunological features and clinical characteristics?,"Heterogeneity of T cell lymphoblastic leukaemias. Twenty eight out of 170 consecutive cases of acute lymphoblastic leukaemia (ALL) were examined. They were of T cell origin, with the following distribution: seven (28%) cases had pre-T or prothymic features; nine (36%) cases showed early thymocytic features, six (24%) had cortical features; and three (12%) had a ""mature"" phenotype. The remaining three cases could not be sub-classified. A striking finding was that pre-T ALL differed from intrathymic ALL not only in the absence of both E rosettes and intrathymic differentiation antigens, but also in the expression of two non-lineage specific antigens HLA-DR and CD10. Both antigens appear in the bone marrow from the very first stages of lymphoid differentiation, implying that the origin for pre-T ALL is bone marrow. A comparison of the clinical features of pre-T and thymic ALL showed that pre-T ALL disease showed a pattern more similar to non-T ALL disease: a lower incidence of mediastinal mass, absence of extrahaematopoietic disease, lower white cell counts and haemoglobin concentrations, and a higher incidence of bone pain. No obvious difference in response to treatment was apparent. The results show that T-ALL is not only a heterogeneous immunological group but also suggest that it may have different origins: bone marrow for pre-T ALL and the thymus for thymic ALL."
-What is the new provocative test described for chronic mesenteric ischemia?,"A new provocative test for chronic mesenteric ischemia. A new provocative test for chronic mesenteric ischemia is described, based upon the demonstration of a fall in the intramural pH of the small bowel after introduction of a test meal into the stomach. Intramural pH (pHI) is determined indirectly by tonometry, utilizing a tonometer passed per os. Postoperative assessment of revascularization procedures is also possible by the same technique. Application of the test in an 84-yr-old woman showed good correlation between a preoperative fall in jejunal intramural pH and abdominal pain, and the absence of a fall postoperatively after successful revascularization."
-How does the expression of the human HLA-B27 transgene affect susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination in different mouse haplotypes?,"Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination. Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse."
-What is the significance of ventricular arrhythmias in children with a structurally normal heart?,"Ventricular arrhythmias in children with an apparently normal heart. Ventricular ectopy occurs frequently in normal children. In the presence of a normal heart, these arrhythmias, including asymptomatic, nonsustained ventricular tachycardia, carry a benign prognosis and are not associated with sudden, unexpected death. However, complex ventricular arrhythmias frequently indicate the presence of underlying cardiac disease; patients with such arrhythmias must undergo an appropriately thorough evaluation before decisions regarding prognosis and the need for therapy can be made."
-What is the significance of detecting fetal seizure activity during ultrasound?,Does fetal seizure activity mean a poor outcome? A case report. Fetal seizure activity is very rare: only three cases have been reported. A case of fetal seizure activity was detected with ultrasound. Such activity can be associated with a poor outcome.
-How does the carbon-14-urea breath test help in quantifying Helicobacter pylori infection and assessing gastritis severity?,"Quantification of Helicobacter pylori infection in gastritis and ulcer disease using a simple and rapid carbon-14-urea breath test. Gastric urease was studied isotopically in 230 patients with biopsy-proven normal mucosa or chronic gastritis, including 59 patients with ulcer disease. Carbon-14-urea was given in 25 ml of water without substrate carrier or nutrient-dense meal, and breath samples were collected over a 60-min period. The amount of 14CO2 excreted at 10 min was independent of the rate of gastric emptying and was not quantitatively influenced by the buccal urease activity. The 10-min 14CO2 values discriminated well between Helicobacter pylori positive and negative patients (94% sensitivity, 89% specificity) and correlated with the number of organisms assessed by histology. The test was a good predictor of chronic gastritis (95% sensitivity and 96% specificity), and a quantitative relationship was observed between 14CO2 values and the severity and activity of the gastritis. In H. pylori positive patients, breath 14CO2 was found to be similar in patients with and without ulcer disease, suggesting that the number of bacteria is not a determining factor for the onset of ulceration."
-"How does the presence of HCV RNA in serum relate to the progression of non-A, non-B hepatitis?","A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. BACKGROUND. Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis. METHODS. We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 10 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a ""nested"" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome. RESULTS. HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease. CONCLUSIONS. During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease."
-What are the key symptoms and characteristics of acute narrow-angle glaucoma as described in this case report?,"Narrow-angle glaucoma presenting as acute, painless visual impairment. A 42-year-old woman presented with the acute onset of bilateral blurred vision that occurred immediately after bending over. She denied pain or any other associated symptoms. Markedly increased intraocular pressure readings were found. Treatment for acute narrow-angle glaucoma was initiated, and normal vision returned. This case represents an atypical presentation of acute narrow-angle glaucoma, a true ophthalmological emergency. The pathophysiology and treatment options of this disease process are summarized."
-What is the sensitivity of thallium-201 single-photon emission computed tomography during adenosine-induced coronary hyperemia for diagnosing coronary artery disease?,"Assessment of coronary artery disease using single-photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia. Thallium-201 myocardial imaging during dipyridamole-induced coronary hyperemia has been an accepted method for diagnosing coronary artery disease (CAD) and risk stratification. Adenosine is a powerful short-acting coronary vasodilator. Initial results of thallium imaging during adenosine infusion have been encouraging. In 132 patients with CAD and in 16 patients with normal coronary angiograms, adenosine was given intravenously at a dose of 0.14 mg/kg/min for 6 minutes and thallium-201 was injected at 3 minutes. The thallium images using single-photon emission computed tomography were abnormal in 47 of the 54 patients (87%) with 1-vessel, in 34 of 37 patients (92%) with 2-vessel and in 40 of 41 patients (98%) with 3-vessel CAD. The sensitivity was 92% in the 132 patients with CAD (95% confidence intervals, 86 to 96%). In patients with normal coronary angiograms, 14 of 16 patients had normal thallium images (specificity, 88%; 95% confidence intervals, 59 to 100%). The results were very similar when subgroups of patients were analyzed: those without prior myocardial infarction, elderly patients and women. The nature of the perfusion defects (fixed or reversible) was assessed in relation to whether the 4-hour delayed images were obtained with or without the reinjection technique. In patients who underwent conventional delayed imaging, there were more fixed perfusion defects than in patients with reinjection delayed imaging (16 vs 0%, p less than 0.0001). The adverse effects were mild, transient and well tolerated. Thus, adenosine thallium tomographic imaging provides a high degree of accuracy in the diagnosis of CAD. The use of the reinjection technique enhances the ability to detect reversible defects."
-What is the significance of the malignant schwannoma found in this xeroderma pigmentosum patient?,"Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D. A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum."
-How does adenosine affect pulmonary vascular resistance in patients with primary pulmonary hypertension?,"Adenosine as a vasodilator in primary pulmonary hypertension BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension."
-How did the study assess the reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses between two different echocardiography centers?,"Reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses: comparison between two echocardiography centers. Doppler echocardiography has been widely used as a noninvasive method to quantify valvular heart diseases. This study assessed the variability between 2 echocardiography centers concerning 2-dimensional and Doppler echocardiographic results in the quantification of mitral and aortic valve stenoses. Forty-two patients were studied by 2 different echocardiography centers in a blinded, independent fashion. In patients with aortic and mitral valve stenosis, mean and maximal flow velocities were measured. The aortic valve orifice area was calculated according to the continuity equation. Mitral valve orifice area was determined by direct planimetry and by pressure half-time. In patients with an aortic valve stenosis, a close relation between the 2 centers was found for the maximal and mean flow velocities (coefficient of correlation, r = 0.72 to 0.92; coefficient of variation, 3.7 to 7.7%). A close correlation and a small observer variability was found for the flow velocity ratio determined by flow velocities measured in the left ventricular outflow tract and over the stenotic valve (r = 0.88; coefficient of variation, 0.01 +/- 0.009). In contrast, there was a poor correlation between the diameter of the left ventricular outflow tract and the aortic orifice area (r = 0.36 and 0.59, respectively). In patients with a mitral valve stenosis, mean and maximal velocities were closely correlated (r = 0.85 and 0.77, respectively). Velocities were not found to be significantly different between the 2 centers. Variability between the 2 centers for the mitral valve orifice area was 9.8% (2-dimensional echocardiography) and 5.7% (pressure half-time)."
-How do the hypercarbic ventilatory responses (HCVR) of heart-lung transplant recipients compare to those of normal control subjects?,"Hypercarbic ventilatory responses of human heart-lung transplant recipients. To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition."
-What was the initial presentation of the 10-year-old boy that led to the discovery of his obstructive sleep apnea syndrome?,"Antral choanal polyp presenting as obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome (OSAS) in children is commonly caused by adenotonsillar hypertrophy. The diagnostic criteria of OSAS in children are not so well delineated as in adults. We report the first case of antral choanal polyp presenting as OSAS in a 10-year-old boy that initially presented to the child psychiatry service for behavior disturbance, enuresis, and daytime somnolence. Overnight electroencephalogram sleep study revealed events consistent with OSAS. Multiple inhalant allergies, chronic maxillary sinusitis, and obstructive adenoid hypertrophy were diagnosed by the allergy and otolaryngology services. The child was scheduled for adenoidectomy when his sleep apnea symptoms persisted following antimicrobial therapy. Examination under anesthesia revealed a normal adenoid bed and a large left antral choanal polyp. Polypectomy was performed as dictated by parental consent. Postoperatively treatment with an intranasal steroid was begun. However, polypoid nasal mucosa recurred in 2 months and a Caldwell-Luc procedure was performed. Subjective reports following surgery indicated improvement in daytime irritability, attention, and mood. A follow-up overnight electroencephalogram sleep study confirmed resolution of OSAS."
-What percentage of leukemic children in the study were persistently positive for anti-HCV antibodies?,"Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia."
-What is the significance of fatty infiltration in the liver for diagnosing medium chain acyl CoA dehydrogenase deficiency?,Fatty infiltration in the liver in medium chain acyl CoA dehydrogenase deficiency. Fatty infiltration of the liver at postmortem examination has been recommended as a criterion for selection of infants who have died suddenly and unexpectedly for further biochemical investigation for disorders of fatty acid oxidation. We describe a boy with medium chain acyl CoA dehydrogenase deficiency who died four months after diagnosis and in whom only minimal hepatic fatty infiltration was found.
-How does the DNA ploidy pattern relate to tumor cell aggregation and metastasis in poorly differentiated stomach adenocarcinoma?,"Nuclear DNA content, tumor cell aggregation, and metastatic events in patients with poorly differentiated adenocarcinoma of the stomach. Data on 100 patients who had undergone resection for poorly differentiated adenocarcinoma of the stomach with serosal invasion were examined to assess the prognostic significance of the DNA distribution pattern in relation to the histologic tumor cell aggregation pattern. DNA distribution patterns were classified into low and high ploidies and tumor cell aggregation patterns were classified into free-cell, small nest, and large nest types. The rates of high ploidy in the free-cell, small nest, and large nest types were 23.1%, 48.0%, and 66.7%, respectively, with a significant increase according to the degree of aggregation. The high ploidy group and large nest type had a higher incidence of lymphogenous and hematogenous metastasis than the low ploidy group and free-cell type, respectively. DNA ploidy had no prognostic value for the free-cell type of tumor, but differences in prognosis and the incidence of metastasis between the DNA ploidies were evident in the nest-forming type. Aneuploid tumors consisting of a poorly differentiated adenocarcinoma were those with nest formation, from the standpoint of histologic structure and metastatic behavior. The DNA analysis of poorly differentiated adenocarcinomas was of prognostic value, especially in the nest-forming type."
-What was the peak level of interferon-gamma detected in urine samples after intravesical BCG therapy?,"Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity."
-What is asymptomatic bacterascites and how does it differ from spontaneous bacterial peritonitis?,"Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required."
-What was the main objective of the study conducted by the National Heart Foundation of Australia Coronary Thrombolysis Group?,"A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group. BACKGROUND. This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS. A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS. We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function."
-What is the potential primary treatment for patients with detrusor sphincter dyssynergia and failed sphincterotomy according to the study?,"Permanent urethral stents for detrusor sphincter dyssynergia. A series of 22 patients, most of whom had spinal injuries with detrusor sphincter dyssynergia, have had Medinvent Wallstents placed across the distal mechanism. All but 8 patients had undergone outflow surgery and 11 had had repeated unsuccessful sphincterotomies. The proximal end of the stent was placed over the verumontanum unless fertility was contemplated, when it was placed immediately below the verumontanum. Fifteen patients achieved complete voiding after placement of the first stent; 3 developed bladder neck obstruction after stenting, but in 1 of these cases resolution occurred after bladder neck incision. The 3 patients with artificial urinary sphincters failed to improve after stenting. Use of the urethral stent for patients with detrusor sphincter dyssynergia and failed sphincterotomy is a major advance. It should probably be the primary treatment in selected cases. Its effect on fertility is currently under assessment."
-How does the Tax protein of HTLV-I contribute to cellular transformation through transcription factor pathways?,"Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation."
-What unusual complication occurred during the sinography of a pancreatic pseudocyst in the described case?,"Drainage of a pancreatic pseudocyst: an unusual complication. A 34-year-old white woman had external drainage of a pancreatic pseudocyst. During sinography, contrast medium filled perigastric varices, causing septic shock. From this experience, we believe that although sinograms are helpful, they should be preceded by prophylactic administration of antibiotics and that contrast material should be sterile. The drainage catheter should be removed as soon as possible."
-What was the most commonly affected test of lung function in patients with advanced liver disease?,"Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance."
-What were the key findings comparing hand-sewn and stapled anastomosis techniques in oesophageal surgeries?,"Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomoses. A total of 611 patients with carcinoma of the oesophagus or gastric cardia were operated on between July 1982 and December 1989. Resection was performed in 491 patients (one-stage, 483; two-stage, eight), bypass operation in 97, and 23 had exploration alone. The anastomoses of 580 patients with one-stage resection and bypass operations were evaluated. Hand-sewn anastomosis using a single layer of continuous absorbable monofilament suture was performed in 304 patients (221 resections and 83 bypasses). A stapled anastomosis was performed on 276 patients (262 resections and 14 bypasses). Following resection, there were 11 (5 per cent) anastomotic leaks in the hand-sewn group and ten (3.8 per cent) in the stapled anastomosis group (P = 0.69). Excluding anastomotic leaks, hospital mortality and anastomotic recurrence, stricture occurred in 18 of 172 hand-sewn anastomoses (10.5 per cent) and in 57 of 195 stapled anastomoses (29.2 per cent) (P less than 0.001). In patients who had bypass operations there were 12 anastomotic leaks, ten in the hand-sewn group (12.0 per cent) and two in the stapled anastomosis group (14.3 per cent). Only two of the discharged patients with bypass developed anastomotic strictures, a low incidence probably because of short survival. In addition, there were 245 subsidiary anastomoses made in the abdomen by the hand-sewn method as part of the reconstructive procedure, and there was one leak. The results of this non-randomized study suggest that hand-sewn anastomosis using a single layer continuous technique for the oesophagus is as safe as the use of circular staplers; hand-sewn anastomosis is less likely to become stenotic."
-What makes it important to distinguish between general fatigue and depression-related fatigue in cancer patients?,"Depression and chronic fatigue in cancer patients. Fatigue is a very common symptom among cancer patients. It is crucial to diagnose those patients for whom the fatigue is a symptom of depression, and to treat them appropriately. The key to providing complete and satisfying care is to identify and address the psychologic, social, and medical vulnerabilities of each cancer patient. No one is in a better position to accomplish that than the primary physician."
-What are the potential hepatic vascular lesions associated with azathioprine-induced liver disease?,"Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis. Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present."
-What was the purpose of the study on intradermal hepatitis B vaccine administration?,"The immunogenicity and safety of intradermal hepatitis B vaccine. BACKGROUND. One of the chief barriers to a greater use of hepatitis B vaccine is the high cost of the vaccine itself. A number of small research trials have shown that an adequate immune response can be induced at a much lower cost by administering one tenth of the vaccine using an intradermal technique. The purpose of this study was to ascertain whether these results could be replicated in a larger clinical trial. METHODS. Vaccine recipients included health care providers, police officers, and firefighters. Recipients were given 0.1 mL of plasma-derived hepatitis B vaccine intradermally on days 1, 30, and 180. Antibody response was measured on day 210, with seroconversion defined as a sample-to-negative (S/N) ratio of greater than or equal to 10. Any local and systemic side effects were documented. RESULTS. Six hundred sixteen individuals completed the vaccination series, and seroconversion occurred in 534 (86.7%). The rate of seroconversion in those younger than 40 years was 91.2% and in those 40 years and older was 75.1%. The mean S/N ratio was 154.9 (range 0 to 620) and decreased with increasing age (r = -.25, P = .0001). Side effects were largely limited to local reactions. CONCLUSIONS. The results support the use of the intradermal technique as a cost-effective alternative to the intramuscular route in individuals younger than 40 years. The intradermal technique may be used in older individuals if titers are obtained to assure seroconversion. Because of the restricted availability of the plasma-derived vaccine used in this study, similar trials with recombinant vaccine should be undertaken."
-What trends were observed in the occurrence of hemorrhoids in the United States and England based on the study's analysis?,"Temporal changes in the occurrence of hemorrhoids in the United States and England. Although numerous etiologic risk factors have been proposed, the pathogenesis of hemorrhoids remains unknown. The present investigation assesses the temporal distribution of hemorrhoids as depicted by physician visits, hospital discharges, and surgical procedures to provide further insight into potential etiologic risk factors. The analysis was based on five data sources: from the United States, the National Disease and Therapeutic Index (NDTI), the National Hospital Discharge Survey (NHDS), and the Commission on Professional Hospital Activities (CPHA); from England and Wales, the Morbidity Statistics from General Practice (MSGP) and the Hospital In-patient Enquiry (HIPE). Results demonstrated a consistent decline in all data sources from the United States. The decrease occurred in males and females similarly and was most striking in those aged 45-64 years. Physician visits and hospital discharges for hemorrhoids in England and Wales likewise declined although the decrease was not as dramatic. The consistency of the temporal distributions among the two countries, as well as among the different sources, suggests that the observed decline may, in fact, reflect an overall decrease in the occurrence of hemorrhoidal disease."
-What was the main finding of this study regarding kidney protection during aortoiliac surgery in renal transplant patients?,"Aortoiliac surgery in renal transplant patients. Fifteen patients who had undergone renal transplantation 3 months to 25 years earlier were operated on for treatment of complicated aortoiliac atherosclerosis; eight had aneurysms and seven had stenotic or obstructive lesions. Except for the first patient, operated on in 1973, in whom the kidney was protected by general hypothermia, no special measure was used to protect the kidneys. A transient increase in creatinemia occurred in 11 patients during the postoperative period, whereas creatinine values remained unchanged in the other four. All patients had regained renal function identical to the + preoperative state in less than 10 days; three of them had significant improvement as a result of correction of a lesion that was impairing renal blood flow. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided an adequate surgical technique is used. This technique avoids the complex methods employed in the majority of previously reported cases and appears to be a safe procedure."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-What was the purpose of screening the expression cDNA library from the human melanoma cell line A375 with sera from melanoma patients?,"Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution."
-What were the key differences between the standard approach and the integrated approach in treating chronic pelvic pain in this clinical trial?,"A randomized clinical trial to compare two different approaches in women with chronic pelvic pain. One hundred six patients with chronic pelvic pain were randomly allocated to one of two treatment groups. In the standard-approach group, organic causes of pelvic pain were excluded first and diagnostic laparoscopy was routinely performed. If no somatic cause could be found, attention was given to other causes such as psychological disturbances. In the second group an integrated approach was chosen. From the beginning equal attention was devoted to somatic, psychological, dietary, environmental, and physiotherapeutic factors. In this group, laparoscopy was not routinely performed. Both groups were similar with respect to clinical characteristics of the patients and the severity of their pain as assessed by various pain parameters. Postcoital pain was reported by 27% of the patients. Twenty percent of the patients had had negative sexual experiences such as childhood sexual abuse or rape. Evaluation of the pain 1 year after the institution of treatment revealed that the integrated approach improved pelvic pain significantly more often than the standard approach for three out of four pain parameters (P less than .01). Laparoscopy played no important role in the treatment of pelvic pain. It is concluded that equal attention to both organic and other causative factors from the beginning of therapy is more likely to result in a reduction of pelvic pain than is a standard approach."
-What is the definition of multivessel disease in the context of this study?,"Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infarction. Therefore to better define the short-term prognostic value of early coronary angiography, and specifically the prognostic significance of multivessel coronary artery disease, the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome. All patients received intravenous thrombolytic therapy (tissue plasminogen activator, urokinase, or both agents) and underwent cardiac catheterization within 90 minutes of the initiation of therapy. Multivessel disease, defined as the presence of greater than or equal to 75% luminal diameter stenosis in two or more major epicardial arteries, was documented in 236 patients. When compared with the group of patients without multivessel disease, this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain. Although the severity of the infarct zone dysfunction was similar in the two groups (-2.77 +/- 1.00 vs -2.50 +/- 1.09 SD/chord, p = NS), global left ventricular ejection fraction was lower in the group with multivessel disease (48.6 +/- 12.4% vs 51.8 +/- 10.6%, p less than 0.01). This was associated with a significant difference in the function of the noninfarct zone. Whereas this region was hyperkinetic in the group with minimal or single-vessel disease, it was hypocontractile or dyskinetic in those with multivessel disease (+0.66 +/- 1.53 vs -0.52 +/- 1.73 SD/chord, p = 0.0001)."
-How does magnetic resonance imaging (MRI) help in managing diabetic foot infections?,"Impact of magnetic resonance imaging on the management of diabetic foot infections. This combined retrospective/prospective study evaluated the value of magnetic resonance imaging (MRI) in 18 diabetic patients with apparent foot infections. The goal was to define the impact of MRI on directing the expedient and accurate surgical intervention so important in achieving optimal preservation of limb tissue and function. We found that MRI provides a rapid and reliable means of ""viewing"" the diabetic foot. Unsuspected or poorly localized abscess cavities can be pinpointed for thorough drainage with minimal exploration. An abscess can be differentiated from cellulitis or osteomyelitis. Moreover, persistent fever following drainage of a foot abscess can be reliably evaluated via MRI, obviating the need for empiric surgical reexploration. This exciting noninvasive imaging technique leads to the most accurate surgical drainage of foot abscesses and, at the same time, can prevent unnecessary surgical exploration of the tenuous diabetic foot."
-How do posttranscriptional mechanisms contribute to protein increase during renal compensatory growth?,"Regulation of gene expression in renal compensatory growth. Compensatory renal hypertrophy is characterized by an increase in cell protein content. There are a number of different cellular mechanisms by which such an increase could be mediated. The relative contributions of transcriptional and posttranscriptional regulation of gene expression to the increase in constitutively expressed cellular proteins were examined in mouse kidneys undergoing compensatory growth following unilateral nephrectomy (UNI-NX). Over the 14-day study period, total protein per kidney increased by up to 37%. Northern blot analysis of the expression of the mRNAs for a number of genes associated with cell growth indicated that there was no significant increase in steady-state levels of these selected genes in nephrectomized compared with sham-operated animals. In vitro assays to measure transcriptional regulation of the same set of genes in compensatory growth showed no increase in the rate of transcription. However, transcription of the 18S ribosomal RNA gene was increased 24 hours after nephrectomy. Immunoblots of two representative proteins showed that the concentration of these proteins in total kidney protein remained constant in the different experimental groups. Since total protein increased, the concentration of these proteins in the hypertrophied kidney must have increased. Taken together, these data suggest that posttranscriptional mechanisms may account for the increase in at least some constitutively expressed proteins in cells undergoing compensatory growth."
-How does hydralazine prevent nitroglycerin-induced hemodynamic tolerance in experimental heart failure?,"Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. BACKGROUND. Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS. Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS. The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin."
-How does clonidine affect vesical and somatic reflexes in patients with suprasacral spinal cord lesions?,"Clonidine inhibits vesico-sphincter reflexes in patients with chronic spinal lesions. When administered systemically to spinalized animals, clonidine, the prototypic alpha 2 adrenergic receptor agonist, purportedly acts at spinal sites to suppress motor responses related to painful peripheral and vesical stimulation and spasticity, and to improve vesicourethral coordination. Hence, the action of clonidine (400 micrograms in three divided doses in a 16-hour span) on spinal vesical and somatic reflexes was examined in five patients with suprasacral spinal cord lesions by assessing volume-induced micturition reflexes and limb motor discharges that occurred spontaneously or were elicited by noxious and nonnoxious cutaneous stimulation. Clonidine caused a significant reduction in (1) blood pressure, (2) amplitude of detrusor contraction, and (3) vesical external urethral sphincter dyssynergia. Limb motor electromyography discharges were not markedly attenuated, although spatiotemporal changes (eg, irradiation, after-discharges) were observed in some of the patients. The results are ascribed to binding to spinal cord alpha 2 adrenergic receptors located on segmental and intersegmental (propriospinal) interneurons, released from descending inhibition, with greater motor system specificity on striated sphincter innervation. Clonidine may be clinically effective in the treatment of hyperactive micturition reflexes in patients with chronic spinal lesions."
-How does caffeine affect postprandial blood pressure in elderly subjects?,"The effect of caffeine on postprandial hypotension in the elderly In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension."
-What challenges do urinary tract infections (UTIs) pose for young women and the healthcare community?,"Advances in the understanding and treatment of urinary tract infections in young women. Despite relative ease of management, the high rate of urinary tract infections (UTI) among young women presents substantial problems for the health care community. Although the majority of UTIs in young women are simple and uncomplicated, the rate of recurrence is substantial. Each treatment of UTI recurrence brings greater antibiotic resistance, requiring the use of broader spectrum and more expensive antibiotic therapy. Moreover, infection in patients with underlying urinary tract or systemic diseases can lead to serious medical and financial consequences. A better understanding of antibiotic resistance, particularly in regard to beta-lactamase-producing pathogens, has allowed us to develop more appropriate criteria for selecting antibiotics as well as the duration of therapy. The overall cost for treating UTIs in young women is a substantial health care expenditure, and requires an ongoing examination of new information concerning pathogenesis and available antibiotic therapies."
-What was the survival rate for infants undergoing staged repair of interrupted aortic arch and ventricular septal defect between 1979 and 1990?,"Staged repair of interrupted aortic arch and ventricular septal defect in infancy. Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants."
-How do CEA levels in peripheral and draining venous blood correlate with the risk of hematogenous metastasis in colorectal cancer patients?,"Colorectal cancer patients with high risk of hematogenous metastasis: correlation with CEA levels in peripheral and draining venous blood during the period of operation. Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood during the period of operation, and pre- and post-operatively detected hematogenous metastases were examined in 78 patients with colorectal cancer. The metastases were found in 28 patients (HM group), but not found in the other 50 patients (non-HM group). The mean values (43 and 198 ng/ml) and positive rates (61 and 96%) greater than 5 ng/ml of p- and d-CEA levels in the HM group were significantly higher than those (6 and 14 ng/ml, and 22 and 48%, respectively) in the non-HM group. The differences (mean 184 ng/ml and positive rate 49%) of d-CEA levels between both groups were more significant than those (39 ng/ml and 30%) of p-CEA levels. The mean value (155 ng/ml) and positive rate (82%) greater than 5 ng/ml of the gradient between d- and p-CEA levels (d-p CEA gradient) in the HM group were significantly higher than those (8 ng/ml and 34%) in the non-HM group. These results suggest that patients with a high risk of hematogenous metastases are more effectively checked by the determination of d-CEA levels and d-p CEA gradient than of p-CEA levels, and that they are patients with positive d-CEA and d-p CEA gradient levels."
-What are the key characteristics and management strategies for neurofibromatosis-2?,"Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described."
-How did endoscopic variceal sclerotherapy affect portal venous pressure gradient in cirrhotic patients?,"The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy."
-What improvements are suggested for emergency medical services in the United States to enhance patient care and response times?,"Role of emergency medical services. For thrombolytic therapy to be effective in the treatment of acute myocardial infarction, the patient must enter the health care center delivery system in an efficient manner. Some entry delays are due to patient decisions and interactions with others. In the United States, prehospital care is delivered by a variety of different systems, varying from public service types such as fire-department based to private types of service. These personnel vary in level of training from paramedics with a high level of training to Emergency Medical Technicians-Ambulance with basic training (first aid), even less in some areas. The training should be upgraded so that training as an emergency medical technician with the ability to defibrillate would be the minimum level for emergency ambulance personnel; wherever economically and logistically feasible, ambulance personnel should be paramedics. Although the 911 emergency telephone system exists in some areas, there is no centralized, universal system for access, causing confusion and delays in obtaining care in critical situations such as cardiac arrest. There is a need for a national emergency number--911--with the ability to identify the calling number and address. Since dispatchers have little medical dispatch training, needed instructions are not given to the caller, which can reduce the patient's chance of survival. Trained dispatchers are needed to dispatch resources efficiently and to offer assistance until trained rescuers arrive. Ambulances are inefficiently located in some areas of the United States, slowing response to the patient."
-What is effort thrombosis of the axillosubclavian vein and how is it typically treated?,"Effort thrombosis of the axillosubclavian vein: a disabling vascular disorder. In the natural history of this disorder, resumption of normal activity after a period of recuperation (following an episode of thrombosis) frequently leads to symptoms of upper extremity venous hypertension exacerbated by using the arms in the overhead position. This position can be demonstrated venographically to further occlude collateral vessels in thoracic outlet. A number of patients develop more extensive symptoms of neurogenic thoracic outlet syndrome. Anticoagulation may protect the collateral vessels and interrupt the period of active clot propagation resulting in a better functional result than would be expected from the natural history of the thrombotic event. In our experience, local Urokinase was the most effective means for reestablishing venous patency. With clot dissolution the underlying compression of the vein at the thoracic outlet can be demonstrated. Balloon angioplasty should not be undertaken in the acute setting nor prior to relieving the tendinous compression. The acute phlebitic process should resolve under the protection of Coumadin for three months. At that time it can be determined more effectively which patients require additional therapy. Removal of the first rib will decompress the axillosubclavian vein and the thoracic outlet collaterals permitting the vein to regain its normal configuration particularly in younger patients with more acute onset of compression. In those patients with more chronic compression the vein becomes stenotic. Improvement of the luminal configuration has been accomplished with transvenous balloon angioplasty without the necessity for venous reconstructive procedures in this series. Patients with Paget-Schroetter syndrome have a symptom complex which often reflects more extensive neurovascular compression at the thoracic outlet than that which might result from venous hypertension alone. Although thrombolytic therapy can restore patency of the axillosubclavian vein, first rib resection is necessary to relieve the external compression. This procedure was very effective in patients who had restoration of subclavian vein patency, and to a lesser degree in those with residual occlusion."
-Who was Paul Broca and what significant medical procedure did he perform in 1871?,"Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization."
-How was HLA class I antigen expression evaluated in patients with chronic hepatitis B?,"HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy."
-What method did researchers use to detect regional disparities in ventricular recovery in patients with long QT syndrome?,"Dispersion of ventricular repolarization in the long QT syndrome. To identify markers of dispersion of the ventricular repolarization in the idiopathic long QT syndrome, body surface potential maps were analyzed in 40 such patients (mean age +/- standard deviation 21 +/- 11 years) and in 30 healthy control subjects (mean age 24 +/- 7 years). In each subject, 117 chest leads were recorded and maps of the integral values of the QRST interval were calculated. A multipolar distribution of the values, a marker of gross electrical inequalities of repolarization, was found only in 4 patients. To detect minor regional disparities of ventricular recovery, all the ST-T waveforms were analyzed in each subject. The ST-T waves were represented by a discrete series of potential values. The ""similarity index"" was computed by applying a principal component analysis, which represents (in percent) to what extent 1 fundamental pattern of ST-T reproduces all the recorded waveforms. The mean value of the similarity index was significantly lower in patients with long QT syndrome than in control subjects (49 +/- 10 vs 77 +/- 8%, p less than 0.0001). A value less than 61% (corresponding to 2 standard deviations below the mean value for controls) was found in 35 of 40 patients and in only 1 control subject (sensitivity 87%, specificity 96%). Thus, the similarity index is a more sensitive marker than the multipolar distribution of QRST integral maps in revealing electrical disparities of the ventricular recovery times."
-What is spatial misregistration in MR imaging of the CNS and how does it occur?,"Spatial misregistration of vascular flow during MR imaging of the CNS: cause and clinical significance. Spatial misregistration of signal recovered from flowing spins within vascular structures is a common phenomenon seen in MR imaging of the CNS. The condition is displayed as a bright line or dot offset from the true anatomic location of the lumen of the imaged vessel. Its origin is the time delay between application of the phase- and frequency-encoding gradients used to locate spins within the plane of section. The principal condition necessary for the production of spatial misregistration is flow oblique to the axis of the phase-encoding gradient. Flow-related enhancement (entry slice phenomenon), even-echo rephasing, and gradient-moment nulling contribute to the production of the bright signal of spatial misregistration. Familiarity with the typical appearance of flow-dependent spatial misregistration permits confirmation of a vessel's patency; identification of the direction of flow; estimation of the velocity of flow; and differentiation of this flow artifact from atheromas, dissection, intraluminal clot, and artifacts such as chemical shift."
-How did the surgical management of invasive squamous cell carcinoma of the vulva change at Indiana University between 1974 and 1988?,"Trends in the operative management of invasive squamous carcinoma of the vulva at Indiana University, 1974 to 1988. From January 1974 to March 1988, 150 patients with primary invasive squamous cell carcinoma of the vulva underwent surgery at Indiana University. There has been a trend toward more conservative surgical management of this disease. To determine the impact of this trend on clinical outcome, cases were divided into three groups according to date of operation: group I, 1974 to 1978; group II, 1979 to 1983; and group III, 1984 to 1988. Overall, 80 patients had en bloc radical vulvectomy and groin dissection, 20 had modified radical vulvectomy and bilateral groin dissection through three separate incisions, and 36 had modified radical vulvectomy and unilateral superficial groin dissection. Fourteen patients had other operations. Forty-two patients (27.3%) had radiotherapy in addition to surgery. Among the three groups, there were no differences when mean age, International Federation of Gynecology and Obstetrics stage distribution (1988 system), mean lesion size, mean depth of invasion, or grade distribution were compared. A significant trend toward more conservative surgical therapy was observed. En bloc radical vulvectomy was performed in 77.4% of group I patients, 71.1% of group II patients, and 35.8% of group III patients (p less than 0.001). Mean days of hospitalization were also reduced significantly. Group I had a mean stay of 30 days, group II had a mean stay of 23 days, and group III had a mean stay of 11 days (p less than 0.001). Mean operative blood loss (group I, 754.8 ml; group II, 620.0 ml; group III, 393.6 ml; p = 0.03), mean units of blood transfused (group I, 1.4 units; group II, 1.3 units; group III, 0.4 units; p less than 0.01), and mean hours of operating time (group I, 3.7 hours; group II, 3.7 hours; group III, 3.2 hours; p = 0.02) were also reduced."
-What are the potential advantages and challenges of using a detubularised bowel segment in cystoplasty?,"Detubularisation in cystoplasty: clinical review. Cystoplasty using a detubularised bowel segment is preferable to using a tubularised length of intestine. This has been shown experimentally to result in a reduction in the contractility of the neobladder, although contractions are not completely abolished. Incontinence, especially nocturnal, may still be a problem. Assessment of renal function has shown a marked incidence of upper tract dysfunction despite detubularisation. All patients remain at risk of upper tract obstruction following cystoplasty. Because bowel contraction waves are brought on by distension, it may be possible either to postpone or to prevent the onset of contractions by avoiding an excessive build-up of bladder volume. Clean intermittent self-catheterisation is an efficient means of emptying the bladder, although sphincter rebalancing may also be required."
-How did extracorporeal shock-wave cholecystolithotripsy (ESWL) affect gallbladder contractility in the studied patients?,"Altered gallbladder contractility after extracorporeal shock-wave cholecystolithotripsy. Change in gallbladder contractility after biliary extracorporeal shock-wave lithotripsy (ESWL) may significantly influence the clearance of fragments after successful gallstone fragmentation. We assessed changes in gallbladder contractility in response to an oral fatty meal in 50 patients 1 month after biliary ESWL (all fragments were smaller than 3 mm) and also in a separate group of 10 patients 3 months after complete clearance of fragments. The prevalence of persistent lumen-obliterating contraction of the gallbladder after biliary ESWL also was analyzed in 325 patients. Gallbladder contractility remained unchanged in 30, increased in nine, and decreased in 11 of the 50 patients. The average reduction in the fasting gallbladder volume after lithotripsy was 28% (p less than .001). Gallbladder contractility remained unchanged 3 months after complete clearance of fragments in six of 10 patients studied separately. A decrease (n = 2) or increase (n = 2) in contractility was seen in the remaining patients. No significant difference occurred in the average ejection fraction of the gallbladder before lithotripsy and after complete clearance of the fragments. Thirty-four of the 325 patients who have so far undergone biliary ESWL had a completely contracted gallbladder with no lumen visible on sonography. The gallbladder returned to a relaxed state in half of these patients within 1-9 months. Thus, biliary ESWL did not significantly alter gallbladder contractility in 60% of patients. A significant reduction in the volume of the fasting gallbladder occurred after lithotripsy. Successful clearance of fragments did not improve the contractility of stonebearing gallbladders in the majority of patients."
-What modifications were made to the transcochlear approach to improve surgical exposure in the cerebellopontine angle region?,"The modified transcochlear approach to the cerebellopontine angle. We have modified the transcochlear approach to improve exposure of the anterior petrous apex, clivus, anterior cerebellopontine angle, and the prepontine region. These changes include resection of the external auditory canal, middle ear, glenoid fossa, and posterior zygomatic arch. This approach provides improved exposure of the petrous carotid artery, jugular bulb, and clivus. It offers the largest and most lateral access to the anterior cerebellopontine and prepontine region. The results of this approach in 11 patients are discussed."
-What were the key differences observed between radiofrequency and direct current catheter ablation in the experimental study on dogs?,"Comparison of catheter ablation using radiofrequency versus direct current energy: biophysical, electrophysiologic and pathologic observations. The effects of catheter ablation with radiofrequency versus direct current energy were compared in 18 dogs assigned to two groups (of 9 dogs each). Each dog underwent a single ablation at two sites in the left ventricle at energy levels of 100, 200 or 300 J delivered in unipolar configuration to six dogs each. A transient decrease in left ventricular systolic pressure (from 121.3 +/- 24.5 to 94.2 +/- 18.7 mm Hg, p less than 0.01) and wall motion abnormality were noted in dogs with direct current shock. The left ventricular ejection fraction decreased (from 50 +/- 2% to 34 +/- 3%, p less than 0.001) shortly after direct current ablation but improved 4 weeks later to 43 +/- 3%. There were no significant changes in left ventricular pressure, wall motion or ejection fraction in dogs in the radiofrequency ablation group. Sustained ventricular tachycardia (greater than or equal to 30 s) was seen immediately after direct current shock in all dogs, and one dog died of intractable ventricular fibrillation. A 24-h ambulatory electrocardiographic (ECG) monitor obtained immediately after the procedure showed multiple runs of ventricular tachycardia in all dogs exposed to direct current ablation but in only three dogs that underwent radiofrequency ablation. No differences were found in peak creatine kinase, complete blood count with smear and B-beta 15-42 fibrinopeptide levels. Pathologically, direct current-induced lesions were larger (mean length x width x depth 10.9 x 7.5 x 5.2 vs. 4.8 x 4.6 x 4.3 mm) and were poorly circumscribed with inhomogeneous margins of necrosis."
-What was the most significant factor affecting recurrence rate in patients with colorectal liver metastases according to the study?,"The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. An increased interest in surgical treatment of liver metastases from colorectal origin has evolved recently. However not all patients benefit from this approach, with early recurrence and death still being encountered. To evaluate clinical as well as perioperative factors that might significantly affect the outcome of patients with completely resected colorectal liver metastases, we examined 116 patients who underwent resection between September 1987 and August 1989. Median follow-up time was 13.2 months (0.6 to 31.4 months). The overall survival rate was 91% at 1 year and 75% at 2 years. Median survival was not reached. Median disease-free survival time was 11.5 months, with 49.4% and 21.2% of the patients being free of disease at 1 and 2 years, respectively. By univariate analysis, site of primary colorectal cancer, preoperative carcinoembryonic antigen (CEA) level, size of metastases, number of metastases, length of operation time, percentage mean arterial pressure, number of hypotensive episodes, duration of hypotensive episodes, and whole blood transfusion significantly affected recurrence rate following resection. However only site of primary tumor, CEA, number of metastases, and number of hypotensive episodes remained significant in the multivariate analysis. The most significant single factor that affected recurrence rate was the number of hypotensive episodes during the operative procedure. It is concluded that hypotensive episodes, even when well controlled, should be avoided during operation to maximize the chances of cure and prolong disease-free survival of patients with colorectal liver metastases."
-Why is acetaminophen hepatotoxicity often missed in chronic alcoholic patients?,"Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics. We encountered six alcoholic patients with severe acetaminophen hepatotoxicity during a 2-year period. All patients had marked elevations of aminotransferases and sometimes remarkably high prothrombin times at, or shortly after, presentation. In five of six cases the diagnosis was missed by the physicians initially caring for the patient. The apparent reasons for the missed diagnosis were insufficient history regarding the use of acetaminophen, an inappropriate reliance on blood acetaminophen levels, and lack of knowledge regarding typical aminotransferase elevations in alcoholic hepatitis vs acetaminophen toxicity. The initial clinical presentation of acetaminophen hepatotoxicity in chronic alcoholics is easily recognized clinically and is distinct from acetaminophen hepatotoxicity in suicide ingestions and from alcoholic hepatitis. Internists and other physicians should be aware of this entity and rely on the clinical picture and the history of acetaminophen use to confirm the diagnosis."
-What alternative explanation is proposed for the genesis of closed-lock symptoms in temporomandibular internal derangement?,"An alternative explanation for the genesis of closed-lock symptoms in the internal derangement process. Clinical and surgical data on 194 operated joints (135 patients) were used to substantiate a new concept challenging the presumed natural history of temporomandibular internal derangement (ID). A number of findings were incompatible with the traditional depiction of a progressive process based on gradual changes in disc position and shape. These findings were a lack or correlation between increasing age and the stages of the process; the percentage of patients in the third stage (closed lock) with limited opening (less than 25 mm) too severe to be caused solely by a nonreducible, displaced disc; the unexpectedly high incidence (greater than 50%) of normally shaped discs in the third stage of the process. A specific condition of severe and stubborn limited maximal mouth opening caused by total cessation of gliding, liable to occur at any age and unrelated to disc shape or position, which responds successfully to simple treatment by lavage and lysis, pressured injection, or arthrocentesis, was discerned. Lack of gliding was attributed to adherence of the disc to the fossa by a reversible effect such as a vacuum and/or decreased volume of synovial fluid of high viscosity. This condition was deemed worthy of an independent identity, dissociated from disc displacement, as a causative factor in the second and third stages of ID, and particularly as an aid to accurate diagnosis and treatment."
-What percentage of acoustic neurinomas in this study were confined to the intracanalicular area?,"Intracanalicular acoustic neurinomas. The cases of 16 patients with acoustic neurinomas confined to the intracanalicular area are presented. These represent 2.7% of the 600 patients with acoustic neurinomas consecutively operated upon at the Neurosurgical Clinic at Nordstadt Hospital during the last 8 years. The comparatively earlier onset of vestibular symptoms and signs was characteristic of this group and precipitated diagnosis. The diagnostic reliability of magnetic resonance imaging was at least equivalent to that of air computed tomographic cisternography. Complete tumor removal was accomplished via the suboccipital approach in all patients, with 100% preservation of facial nerve and facial function; the cochlear nerve was preserved anatomically in 100% of the patients and functionally in 57%. No recurrence has occurred during follow-up periods of up to 8 years in all 16 patients. A broad spectrum of the current literature is considered, and purely intracanalicular acoustic neurinomas are discussed with regard to clinical characteristics, diagnostic steps-including neuroradiological and neurophysiological approaches-and surgical treatment and results."
-What makes gall bladder perforation a challenging medical condition to diagnose early?,Acute gall bladder perforation--a dilemma in early diagnosis. Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls.
-What percentage of men were found to have a genital human papillomavirus infection among the sexual partners of women treated for genital condylomata acuminata?,"Genital human papillomavirus infection in men. Diagnosis and treatment with a laser and 5-fluorouracil. One hundred twenty-eight consecutive men, sexual partners (for more than six months) of women treated for genital condylomata acuminata, were evaluated with colposcopy to assess the percentage of infected men among the couples. Ninety-three (73%) of the men were found to have a genital human papillomavirus infection on colposcopically directed biopsies. All but one patient were treated with outpatient colposcopically guided laser vaporization under local anesthesia (one patient with extensive condylomata required general anesthesia). Two weeks after laser surgery, 5% 5-fluorouracil cream, used in the genital area, was initiated on a weekly basis for two months and every other week for two more months. Patients were followed in the clinic with colposcopy performed every eight weeks for six months to evaluate the regimen's results. Thirty-seven (40%) of the 93 men had ""clinically"" apparent genital HPV infection, and 56 (60%) of the 93 had ""subclinical"" disease (as determined with colposcopy). The majority of the patients (87 of 93, or 94%) responded to one laser treatment followed by 5-fluorouracil cream and had no visible lesions at six months. Colposcopic evaluation of the male partners of infected women and laser surgery followed by topical 5-fluorouracil therapy appear to be safe and effective in controlling genital HPV infection."
-How does 3DFT MR angiography compare to digital subtraction angiography in assessing carotid artery stenosis?,"3DFT MR angiography of the carotid bifurcation: potential and limitations as a screening examination. The authors compared the three-dimensional Fourier transform (3DFT) time-of-flight magnetic resonance (MR) angiograms in 38 patients initially studied with selective intraarterial digital subtraction angiography (DSA) for suspected arteriosclerotic disease of the carotid bifurcation. MR angiograms were successfully obtained in 65 of the 75 carotid arteries (87%) visualized with DSA. DSA and MR angiographic studies were assessed for percentage area stenosis by two independent observers on two occasions. Statistical tests indicated consistency in interpretation for each observer as well as between observers. No significant difference was found between the two modalities in ability to depict changes in percentage area stenosis. For the 32 right carotid arteries in the comparison, the median for the difference between MR angiography and intraarterial DSA was 1.83% (range, -22.38% to 55.60%); for the 33 visualized left carotid arteries, it was 0.00% (range, -20.55% to 49.95%). Receiver operating characteristic analysis indicated that technically adequate MR angiography may be a sensitive screening examination for stenoses."
-How did transoesophageal echocardiography help in diagnosing and managing patients with pericardial haemorrhage after cardiac surgery?,"Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography. After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention."
-What therapeutic intervention led to dramatic and rapid clinical improvement in the case of a 40-year-old woman with eosinophilia-myalgia syndrome and ascending polyneuropathy?,Plasmapheresis in a case of eosinophilia-myalgia syndrome with ascending polyneuropathy. Eosinophilia-myalgia syndrome complicated by ascending polyneuropathy in a 40-year-old woman is described. High-dose intravenous steroids had no beneficial effect on the clinical course. Dramatic and rapid clinical improvement occurred with the use of plasmapheresis. The use of this therapeutic modality should be considered in patients with a similar clinical presentation.
-What were the key findings regarding prosodic features in patients with Parkinson's disease in this study?,"The interpretation of dysprosody in patients with Parkinson's disease. Prosodic features in the speech production of 21 patients with idiopathic Parkinson's disease were tested. The appreciation of vocal and facial expression was also examined in the same patients. Significant intergroup differences were found in the prosody production tasks but, in contrast to previous results, not in the receptive tasks on the recognition and appreciation of prosody and of facial expression. The discrepancy between the production and recognition of prosodic features does not support the suggestion that dysprosody in Parkinson's disease is necessarily a disorder of processing emotional information that could be misinterpreted as a dysarthria."
-What was the purpose of the phase I/II trial involving recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following allogeneic bone marrow transplantation?,"Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical ""good risk"" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients."
-What were the presumed etiologies of rhabdomyolysis/myoglobinuria in the pediatric patients studied?,"Rhabdomyolysis in children: a 3-year retrospective study. The case reports of 4 pediatric patients illustrate the complex clinical scenarios in which childhood rhabdomyolysis/myoglobinuria occurs. Children ranged in age from 8-18 years. Presumed etiologies of rhabdomyolysis/myoglobinuria included Neisseria sepsis, exertion-related episodes, dialysis disequilibrium, and diabetic ketoacidosis. No child developed respiratory or renal failure. all children were discharged with normal muscle power, indicating the benign nature of this disease and the importance of aggressive management."
-What was the outcome of the Strecker stent treatment for renal artery stenosis in the study?,"Renal artery stenosis: preliminary results of treatment with the Strecker stent. Use of the Strecker flexible balloon-expandable tantalum stent for treatment of renal artery stenosis after failed angioplasty or transaortic thromboendarterectomy was evaluated in 10 patients (nine hypertensive, one normotensive). Left (n = 3) and right (n = 5) renal arteries were involved; renal artery stenosis in two patients had developed after kidney transplantation. Indications for stent placement were inadequate immediate postangioplasty response (n = 7), development of considerable restenosis after angioplasty (n = 1), and obstructing intimal flaps following transaortic endarterectomy (n = 2). Stent placement was technically successful (less than 20% residual stenosis) and patency was preserved in eight patients. Of the seven hypertensive patients with successful implantation, two were cured, three had improvement, and two had no change at latest follow-up evaluation (mean, 10.6 months; range, 6-12 months). The Strecker stent may be helpful in treating restenosis after failed revascularization procedures, although the precise indication, true safety, and long-term efficacy of stent placement in renal arteries will not be known until trials with more subjects and longer follow-up periods are completed."
-How can rest-injected thallium-201 imaging help assess the viability of severely asynergic myocardial regions?,"Rest-injected thallium-201 imaging for assessing viability of severe asynergic regions. To evaluate the utility of rest-injected 201Tl initial and delayed images for assessing the viability of severe asynergic regions, we studied 17 patients with apparently prior infarcted myocardium in combination with 99mTc ventriculography before and after revascularization. In 51 regions with severe asynergy, the percent 201Tl uptake was calculated as the ratio of counts on the segment with asynergy to the maximum counts on the normal segment. Eleven of 14 regions with resting 201Tl redistribution (Group 1) had improved wall motion after revascularization. However, 14 of 37 regions without redistribution also improved (Group 2). Twenty-three regions without redistribution or improved wall motion after revascularization (Group 3) had lower regional 201Tl uptake on their delayed images than those in Groups 1 and 2. Moreover, the initial regional uptake of Group 2 was higher than that of Group 3. These results suggest that redistribution on rest-injected 201Tl scans indicates reversibility of severely asynergic myocardium and that high 201Tl uptake in regions without redistribution may predict improvement in wall motion after revascularization. We conclude that 201Tl uptake may be useful as a marker of viability of severe asynergic regions before revascularization."
-What was the outcome of administering ursodeoxycholic acid to a patient with benign recurrent intrahepatic cholestasis?,"Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism. Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid."
-"How do perceptions of physical and emotional distress during infertility treatment differ among patients, nurses, and physicians?","Physical and emotional stress associated with components of the infertility investigation: perspectives of professionals and patients. OBJECTIVE: The present study examined patients', nurses', and physicians' perceptions of the physical and emotional difficulty of infertility treatment. DESIGN: A mail survey method was used. PATIENTS, PARTICIPANTS: Participants included 26 patients, 76 nurses, and 71 physicians from infertility clinics in the United States and Canada. MAIN OUTCOME MEASURES: A rating scale measured the physical and emotional difficulty level of 36 components from the infertility investigation. RESULTS: Nurses rated the emotional and physical distress of patients higher than did patients and physicians, whereas patients rated their distress higher than did physicians. Older nurses and physicians inferred lower levels of physical and emotional distress than did their younger counterparts. A greater breadth of experience with infertility treatments was associated with higher ratings of emotional distress by nurses and lower ratings by physicians. CONCLUSIONS: Patients, nurses, and physicians perceive infertility treatment from unique vantage points creating differences in perceptions that have implications for patient care. Factors including era of professional training, stage of life, and changes resulting from advancing technology are viewed as influencing health care professionals' perceptions of infertility distress."
-How do renal hemodynamics and renin-angiotensin-aldosterone system characteristics differ in normotensive subjects with different parental hypertension backgrounds?,"Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents. BACKGROUND AND METHODS. The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS. The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS. Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension."
-What is the prevalence of acute pulmonary embolism among pediatric patients awaiting heart transplantation in this study?,"Acute pulmonary embolism in pediatric patients awaiting heart transplantation. Acute pulmonary embolism with infarction can delay urgently needed heart transplantation and increase the postoperative pulmonary complications. Few data are available concerning pulmonary embolization in the pediatric patient with end-stage congestive heart failure. Sixty-two consecutive pediatric patients awaiting heart transplantation were monitored for evidence of acute pulmonary embolism. Acute pulmonary infarction was documented by ventilation-perfusion scan, pulmonary angiography or pathologic examination in six patients. The prevalence differed by diagnosis; 5 of 36 patients with dilated cardiomyopathy and 1 of 20 patients with congenital heart disease developed acute pulmonary embolism with infarction. No significant difference in age at the time of transplantation evaluation, duration of congestive heart failure, presence of cardiac arrhythmias or degree of cardiac dysfunction was seen between patients with and without pulmonary embolism. Two-dimensional echocardiography failed to detect the presence of an intracardiac thrombus in four of the six patients. Two patients who developed acute pulmonary infarction are alive after successful heart transplantation. The remaining four patients died within 6 weeks of initiation of anticoagulant therapy before transplantation could safely be performed. In summary, pediatric patients with end-stage congestive heart failure are at risk for acute pulmonary embolism. No specific clinical factor identified those patients who developed acute pulmonary infarction. Anticoagulant therapy is strongly recommended in the pediatric patient with poor ventricular function awaiting heart transplantation."
-What is the relationship between chronic viral hepatitis and hepatocellular carcinoma in the United States according to the study?,"The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Although hepatocellular carcinoma is a relatively uncommon tumor in the United States, it is quite common in sub-Saharan Africa and the Far East, where most cases are associated with infection with the hepatitis B virus. We have studied 99 American patients with hepatocellular carcinoma for evidence of hepatitis B or hepatitis C viral infection and compared these findings to those in a group of matched controls with other cancers. The two groups differed in proportion, with hepatitis B surface antigen in serum being significantly higher in patients with hepatocellular carcinoma (7% vs. 0%, p = 0.009). Antibody to hepatitis C virus was also found more frequently in patients with hepatocellular carcinoma (13% vs. 2%, p = 0.002). The relative risk for hepatocellular carcinoma in hepatitis B surface antigen-positive patients was calculated to be 17.3 and for antibody to hepatitis C virus to be 7.3. The attributable fraction of cases related to the hepatitis B surface antigen carrier state was 6.7% and for patients infected with the hepatitis C virus was 11.4%. Approximately three quarters of cases of hepatocellular carcinoma did not have evidence of either hepatitis C or hepatitis B virus infection. These findings provide strong evidence that hepatitis C virus infection is associated with the development of hepatocellular carcinoma, and in the United States may even play a more important role than the hepatitis B virus."
-What is compartment syndrome and how can it be caused by prolonged use of the lithotomy position during surgery?,"Compartment syndrome complicating prolonged use of the lithotomy position. Two patients with three postoperative calf compartment syndromes, which followed prolonged lithotomy positioning, will be presented. Potential physiologic mechanisms are described, and a review of current cases in literature are summated."
-What percentage of patients received a correct initial diagnosis from the general practitioners in the study?,"Chest pain: an evaluation of the initial diagnosis made by 25 Flemish general practitioners. Twenty-five general practitioners collected information on 318 contacts of patients with a new episode of chest pain, discomfort or tightness. A list of complaints, signs and symptoms were checked, together with the initial diagnosis, made by the GP immediately after the physical examination. The initial diagnosis was compared to a follow-up diagnosis. The gain in certainty was also compared. The GP made a correct initial diagnosis in 82% of patients. In 8% there was a clinically important difference, and seven of 17 episodes of oesophageal disease were missed. For their initial diagnosis, the GP scored 74% certain, 20% uncertain and no diagnosis in 6%. For the final diagnosis, these figures were 88%, 8% and 4%."
-What were the key differences in complications between nonionic (iopamidol) and ionic (diatrizoate) contrast media during percutaneous transluminal coronary angioplasty (PTCA) procedures?,"Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty. To evaluate the effect of contrast agents on percutaneous transluminal coronary angioplasty (PTCA) complications, 913 patients undergoing 1,058 separate PTCA procedures were prospectively randomized to receive either nonionic iopamidol (Isovue-370) [n = 507 PTCA procedures] or ionic contrast media, meglumine sodium diatrizoate (Renografin-76) [n = 551 PTCA procedures]. Angioplasty operators, technicians, nurses and patients were blinded to the agent used. All patients were pretreated with 0.6 mg of atropine sulfate intravenously before any contrast injections. Hypotension (mean arterial pressure less than 65 mm Hg associated with contrast injections) occurred during 8.5% of PTCA procedures in which the patients were receiving iopamidol and during 9.5% of the procedures in which the patients were given diatrizoate (difference not significant). Bradycardia (heart rate of less than 40 beats/min associated with contrast injections) developed during 5.7% of procedures when patients were given iopamidol and during 5.1% of procedures when patients were given diatrizoate (difference not significant). The need for additional atropine or temporary pacing during the procedure was similar for patients given iopamidol and diatrizoate. The overall incidence of ventricular tachycardia or fibrillation, or both, during the procedure occurred less frequently when iopamidol was used compared with diatrizoate (1 vs 2.5%, p = 0.045). These serious ventricular arrhythmias were attributable to contrast injections in 0.6% of the PTCA procedures when iopamidol was given and in 2.0% of the cases in which diatrizoate was the contrast agent (p = 0.09). Only 1 patient had an allergic reaction to the contrast agent, and this was in a patient who received iopamidol."
-How does monocrotaline treatment affect the vascular structure in rat lungs?,"Monocrotaline-induced angiogenesis. Differences in the bronchial and pulmonary vasculature. Vascular corrosion casting was used to search for angiogenesis in the blood vessels of the lungs of rats given monocrotaline. Animals treated with monocrotaline had new well-differentiated arteries and veins on their pleural surfaces. Animals not treated had no large vessel on their pleural surfaces. Animals receiving monocrotaline had capillaries around major arteries that were more dense, widened, and less tubular than normal. These capillaries occasionally occurred in sheets and had blind endings. The control animals had delicate, uniform, tubular capillaries. Alveolar capillaries in both groups showed no evidence of increase in size or number or change in shape. Light microscopy confirmed the finding of new vessels found with the casts. The finding of angiogenesis on the pleural surface and in the bronchovascular bundle, but not in the alveolar capillaries, suggests a basic difference in how these capillary beds respond to angiogenic stimuli. If alveolar capillaries are unable to undergo angiogenesis, concepts of lung development and tumor growth may be significantly altered. The lung may be a unique organ to study angiogenesis because of the different angiogenic potential of its two circulations. Study of these differences may lead to better understanding of inhibition of angiogenesis."
-What medical condition did the patient have that required pulmonary resection and distal pancreatectomy-splenectomy?,Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature. A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy.
-What potential side effect did the study observe in patients treated with valproate?,"Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate."
-What is the kissing balloon technique in coronary angioplasty?,The kissing balloon technique with two over-the-wire balloon catheters through a single 8-French guiding catheter. Some of the newer over-the-wire coronary angioplasty catheters have shaft sizes of 3.0 French (F) or less. The inner diameter of modern 8-F guiding catheters is large enough to accommodate two of such balloon catheters. We report a kissing balloon procedure with two over-the-wire catheters through a single 8-F guiding catheter.
-What is the purpose of autotransplantation of dispersed pancreatic islet tissue in patients with chronic pancreatitis?,"Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis. Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain."
-What was the main finding of the study comparing recombinant tissue-type plasminogen activator (rt-PA) plus heparin with heparin alone in patients with refractory unstable angina?,"Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris. Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina."
-What was the resectability rate and pathologic complete response rate in this Phase I trial of preoperative pelvic radiation therapy and combined leucovorin/5-fluorouracil for unresectable rectal cancer?,"Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer. Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable."
-What is the Siriraj stroke score and how does it help differentiate between supratentorial intracerebral haemorrhage and infarction?,"Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction. OBJECTIVES--To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN--13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING--Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS--Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS--The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION--The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke."
-How do WSP and WSR mice differ in their response to glucocorticoids during ethanol withdrawal?,"Differential modulation by the stress axis of ethanol withdrawal seizure expression in WSP and WSR mice. Withdrawal from both acute and chronic ethanol (EtOH) exposure is associated with increased neural excitability and increased activity of the hypothalamic-pituitary-adrenal axis. There is some evidence that glucocorticoids are necessary for EtOH withdrawal seizure expression. Lines of mice that were selected for severe (WSP) and minimal (WSR) EtOH withdrawal (as estimated from handling-induced convulsion scores) have been shown to differ in their stress response following an acute dose of EtOH. In this study we provide evidence that these lines of mice also differ in their sensitivity to the excitatory effects of glucocorticoids. EtOH withdrawal seizures of WSP mice were significantly increased by chronic and acute corticosterone treatment, whereas those of the WSR mice were unaffected. Neural excitability was decreased in the WSP mice when aminoglutethimide, a glucocorticoid synthesis blocker, was administered. Thus, it appears that genetic differences in EtOH withdrawal seizure severity may be due, in part, to differences in sensitivity to the excitatory effects of glucocorticoids."
-"What was the success rate of percutaneous cholecystostomy in treating patients with persistent, unexplained sepsis?","Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy. Because of the difficulty in diagnosing acute cholecystitis in critically ill patients with severe intercurrent illness by clinical and imaging methods or percutaneous aspiration of the gallbladder, a trial of percutaneous cholecystostomy was performed in 24 patients in the intensive-care unit with persistent, unexplained sepsis after a complete clinical, laboratory, and radiologic search showed no alternative source of infection. Persistent high fevers, despite antibiotic therapy, were present in all patients, with elevated WBC count in 18 patients, vague abdominal tenderness in 11, and septic shock requiring vasopressors in 15. Sonographically, all patients had distended, spherical gallbladders, six had gallstones, eight had wall thickening, three had pericholecystic fluid, and four had Murphy's sign. All patients were seen by a senior abdominal surgeon, who agreed to a trial of percutaneous cholecystostomy. Fourteen patients (58%) responded to percutaneous cholecystostomy, as evidenced by a decrease in WBC count, defervescence, and the ability to be weaned off vasopressors. Bile cultures were positive in four patients. Ten patients (42%) did not respond to percutaneous cholecystostomy; five eventually died of unrelated causes. A respiratory source of infection was eventually found in three of these 10 patients, with no proved source of infection in the remainder. No complications related to catheter insertion occurred in this group of patients. Bile leaks occurred in two patients when the percutaneous cholecystostomy catheter was removed, but without serious consequence. Our experience suggests that a lower threshold for performing percutaneous cholecystostomy in this difficult clinical subset of patients is worthwhile."
-What is the potential cause of hypoglycemia in patients with mesenchymal tumor-associated nonislet cell tumors?,"Impaired formation of the ternary insulin-like growth factor-binding protein complex in patients with hypoglycemia due to nonislet cell tumors. In some subjects with hypoglycemia associated with tumors of mesenchymal origin, high insulin-like growth factor-II (IGF-II) levels have been described in serum and in the tumors. Tumor IGF-II of 10-15 kDa circulates in a 60-kDa complex, in contrast to the ternary 150-kDa complex in which serum IGFs normally circulate together with the IGF-binding subunit (IGFBP-3) and the acid-labile subunit (alpha-subunit). This study examines the molecular distribution and complex-forming activity of the components of the ternary complex in the serum of subjects with mesenchymal tumor hypoglycemia. Total serum IGFBP-3 levels were 60% of normal in tumor patients and appeared at 60 kDa on gel chromatography, shifting after tumor removal to 150 kDa. Total alpha-subunit levels were 40% of normal in patients with tumors, increasing after tumor removal to 70% of normal and changing in elution profile from a peak typical of uncomplexed alpha-subunit to the normal broad peak representing both complexed and uncomplexed alpha-subunit. Although low by RIA, alpha-subunit activity in a ternary complex formation assay was normal, indicating that the ability of free alpha-subunit in the patients' circulation to combine with exogenous IGFBP-3 plus IGF-I was not impaired. In contrast, in an assay that tested the ability of IGF-IGFBP complexes in the patients' circulation to combine with pure alpha-subunit, complex formation activity was 75-85% below normal in preoperative sera, despite low normal IGFBP-3 levels. Therefore, the cause of hypoglycemia in these patients may be the inability of complexes between the abnormal tumor IGF-II and IGFBP-3 to be sequestered in the biologically inactive ternary complex."
-What is the incidence of portal vein thrombosis after distal splenorenal shunt in this study?,"The significance of portal vein thrombosis after distal splenorenal shunt. The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long-term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival."
-What is an iatrogenic epidermoid cyst and how can it occur in the parotid region following ear surgery?,Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed.
-What are the potential major complications associated with endoscopic sinus surgery?,"Fatal and other major complications of endoscopic sinus surgery. Endoscopic sinus surgery has become an acceptable technique for the treatment of chronic sinus disease. This report analyzes five complications which came to my attention. Two cases were orbital:1 bilateral blindness due to damage of the optic nerves, and 1 damage of medial rectus muscle. The other 3 cases were intracranial:two cribriform plate damage with frontal lobe injury and hematoma, and 1 damage of the anterior cerebral artery, resulting in death. This rather novel technique, especially when used by less-experienced surgeons, has major complications similar to what has been reported with the traditional intranasal sphenoethmoidectomy. Knowledge of anatomy, good training, and meticulous surgical technique are very important. Endoscopic sinus surgery in patients with extensive pathology should be used with caution, especially if general anesthesia is selected or if excessive bleeding occurs. It would be beneficial to otolaryngologists to have previous experience in the traditional technique before adopting endoscopic sinus surgery to their armamentarium. Even then, major complications may occur in the hands of very experienced surgeons. Early recognition and proper management of these complications are of utmost importance in order to minimize disability or prevent death."
-What percentage of brachial plexus blocks were incomplete in this study?,"Brachial plexus anesthesia for outpatient surgical procedures on an upper extremity We retrospectively reviewed 543 brachial plexus blocks performed on 526 outpatients. Most (98%) of the blocks were performed by means of the axillary approach. Various techniques were used, including paresthesia, transarterial fixation, nerve stimulation, or a combination of techniques; a high success rate was achieved with each of them. Only 7% of the blocks were incomplete and thus necessitated either general anesthesia or block supplementation with thiopental sodium and nitrous oxide. No persistent neurologic deficit was ascribed to the anesthetic technique. This review indicates that brachial plexus block, especially with use of the axillary approach, is a safe and effective option for outpatient surgical procedures on an upper extremity."
-What potential side effect did the study observe in patients treated with valproate?,"Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate."
-What was the effect of increasing doses of flecainide acetate on the occurrence of tachycardia in patients with paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation?,"Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group. The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2)."
-How did hydroxyzine affect histamine release and clinical symptoms in patients with chronic urticaria compared to terfenadine and placebo?,"Effects of H1-antihistamine drug regimen on histamine release by nonlesional skin mast cells of patients with chronic urticaria. Profiles of compound 48/80-induced histamine release (HR) from mast cells of uninvolved skin from patients with chronic urticaria (CU) and from a normal control (NC) group were compared, and the effects of anti-H1 medications were assessed versus placebo. Then, patients with CU (15) and NC subjects (10) were randomly assigned to take either hydroxyzine (100 mg/day), terfenadine (120 mg/day), or placebo for 28 days. The effects of such treatment on the clinical response and on the profile of compound 48/80-induced HR during a 4-hour period were analyzed. Treatment with hydroxyzine in patients with CU improved the clinical symptoms and modified the profile of HR; more histamine was recovered at 1 hour (p less than 0.05) and 2 hours (p less than 0.05), as compared with baseline. Terfenadine and placebo had no effect on the clinical response or on the profiles of HR. In the NC group, the amounts of histamine recovered at 1 hour after challenge with compound 48/80 were lower than amounts of the pretherapy values (p less than 0.01). It could be concluded that (1) the profile of HR in patients with CU is reproducible during a period of 28 days, (2) only hydroxyzine modifies both the clinical response and the profile of HR, and (3) anti-H1 compounds decrease the HR in the NC group."
-What treatment was used to resolve the intraventricular hematoma in this case report?,"Lysis of intraventricular hematoma with tissue plasminogen activator. Case report. A 42-year-old woman suffered a severe intracerebral and intraventricular hemorrhage from a ruptured anterior cerebral artery aneurysm. Evacuation of the frontal hematoma and clipping of the aneurysm was performed but the intraventricular blood clot persisted, causing ventricular dilatation and high intracranial pressure (ICP) 24 hours after surgery despite external ventricular drainage. Over this period of time the patient's clinical condition improved from Grade V to Grade IVb (World Federation of Neurological Surgeons classification). The intraventricular hematoma was lysed with a total of 8 mg recombinant tissue plasminogen activator injected directly into the ventricles on the 1st and 2nd postoperative days, resulting in rapid normalization of ventricular size and ICP. The patient has since made a substantial recovery and has been able to return home."
-How does botulinum toxin treatment affect the neurophysiological characteristics of patients with dystonic blepharospasm?,"Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm."
-What are the key diagnostic criteria for quadrilateral space syndrome according to the context?,"Quadrilateral space syndrome: diagnosis and operative decompression technique. We present a series of five patients with quadrilateral space syndrome. All patients had the diagnosis made on the basis of (1) tenderness over the quadrilateral space, (2) paresthesia over the lateral shoulder and upper posterior arm, and (3) deltoid weakness associated with decreased shoulder abduction. A history of trauma was present in each patient. The operative technique described utilizes a cosmetically acceptable incision and is without the need to divide the deltoid from its origin on the scapular spine. The technique minimizes postoperative bleeding and facilities rehabilitation. Arteriography of the posterior circumflex humeral artery was not found necessary to make the diagnosis of axillary nerve entrapment in the quadrilateral space."
-What were the observed effects of the TRH analogue (RX77368) on patients with motor neuron disease?,"Comparative efficacy and safety of intravenous and oral administration of a TRH analogue (RX77368) in motor neuron disease. Ten consecutive patients with motor neuron disease (MND) who had bulbar symptoms received one or two intravenous doses followed by increasing oral doses of a TRH analogue (RX77368). Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. The initial time course of improvement correlated with increasing plasma levels of the drug, but most clinical effects persisted when the levels decreased and became undetectable after 24 hours. The oral solution was tasteless and had no, or minimal, side effects."
-What is the purpose of the clinical trial involving Cronassial in patients with Chagas' disease?,"Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo."
-What were the two methods compared in this study for preventing bone reunion after midline craniectomy for sagittal suture synostosis?,"Midline craniectomy for sagittal suture synostosis: comparative efficacy of two barriers to calvarial reclosure. This report quantitatively compares long-term head remolding achieved by two methods for retarding bone reunion after midline craniectomy for sagittal suture synostosis. In one group of six children the adjacent bone edges were overlayed with 1.0-cm-wide U-channel silicone strips, and in the other group, composed of seven patients, a considerably larger extent of the adjacent cranium was covered with silicone sheets. Mean percent change in the cephalic indices of the former group 18 months postoperatively was 9.1% +/- S.D. = 6.7, and of the latter group 23.7% +/- S.D. = 6.0 (p congruent to 0.01). These results indicate that the use of large silicone sheets lead to a significantly greater normalization of cranial proportions."
-What are the potential consequences of prolonged hiccups that may require medical intervention?,"Hiccups (singultus): review and approach to management. Hiccups are a common, and fortunately usually transient, benign malady. Occasionally, however, hiccups fail to resolve spontaneously, resulting in patient fatigue and incapacitation and the need for the affected individual to seek medical care for resolution of the problem. The approach to the management of these patients consists of the identification and treatment of serious underlying causes of the episode as well as therapeutic interventions to achieve hiccup resolution."
-Where was corticotropin-releasing hormone (CRH) immunoreactivity found in the human placenta and fetal membranes during gestation?,"The localization and distribution of corticotropin-releasing hormone in the human placenta and fetal membranes throughout gestation. Using immunohistochemical techniques, we have determined the localization and distribution of CRH immunoreactivity (CRH-IR) in the human placenta, fetal membranes, decidua, and umbilical cord. Tissues were obtained at 6-8 weeks of pregnancy, at term, in association with premature birth, and from patients with pregnancy-induced hypertension or diabetes mellitus. A polyclonal antibody to the epithelial cell marker cytokeratin was used to identify trophoblast cells. CRH-IR was not detected in placenta or decidua at 6-8 weeks gestation. In tissues obtained after idiopathic premature delivery after 21 weeks gestation, positive CRH staining was found in placenta in syncytiotrophoblast and intermediate trophoblast, but not cytotrophoblast. CRH-IR was present in intermediate trophoblast cells that had invaded maternal blood vessels in decidua basalis. In the fetal membranes, CRH-IR was localized in the epithelium and subepithelial cells of amnion, in the trophoblast layer, in some cells of the reticular and cellular layers of chorion, and in some stromal cells and invasive trophoblast cells of decidua. CRH-IR was found in the amniotic epithelium of the umbilical cord and in the musculature of the umbilical vessels. This pattern of distribution of CRH-IR was found in tissues from 21 weeks gestation to term and postterm, and was similar in tissues examined from patients with pregnancy-induced hypertension and diabetes mellitus. These results show clearly that in placenta and membranes, CRH is localized primarily to syncytiotrophoblast and intermediate trophoblast, but not to cytotrophoblast cells. We suggest that the localization of CRH-IR is consistent with CRH affecting paracrine/autocrine interactions within the placenta, fetal membranes, and decidua that may be involved in the maturation of the fetal hypothalamic-pituitary-adrenal axis and in the stimulus and maintainance of labor."
-How does brain temperature affect the cerebral metabolic rate of oxygen consumption (CMRO2) in dogs during hypothermia?,"The relationship among canine brain temperature, metabolism, and function during hypothermia. Cerebral protection by hypothermia is commonly attributed to cerebral metabolic suppression. However, at temperatures below 28 degrees C, the relationship of temperature to cerebral metabolic rate of oxygen consumption (CMRO2) has not been well characterized. Accordingly, the relationship between brain temperature and CMRO2 was determined in eight dogs during cooling from 37 to 14 degrees C while the EEG was continuously monitored. Cardiopulmonary bypass was initiated and control measurements were made at 37 degrees C during anesthesia with nitrous oxide 50-60% inspired and morphine sulfate 2 mg.kg-1 intravenously (iv). Upon cooling to 27 degrees C, the nitrous oxide was discontinued and the morphine was antagonized with naloxone 2 mg iv. Measurements were repeated at 27, 22, 18, and 14 degrees C and in four dogs again at 37 degrees C after nitrous oxide 50-60% had been reestablished at 27 degrees C along with administration of morphine sulfate 2 mg.kg-1. For each temperature interval, the temperature coefficient (Q10) for CMRO2 was calculated (Q10 = CMRO2 at x degrees C divided by CMRO2 at [x - 10] degrees C). Between 37 and 27 degrees C the Q10 was 2.23, but between 27 and 14 degrees C the mean Q10 was doubled to 4.53. With rewarming to 37 degrees C, CBF and CMRO2 returned to control levels, and brain biopsies revealed a normal brain energy state. During cooling, the EEG developed burst suppression at or below 22 degrees C. With further cooling, the periods of suppression increased; however, burst activity continued in seven of eight dogs even at 14 degrees C."
-What was the most significant prognostic factor for local recurrence in breast cancer patients treated with conservative surgery and radiation therapy?,"Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data. Between 1962 and 1984, a total of 433 patients were treated at Yale-New Haven Hospital with conservative surgery and radiation therapy (CS + RT) to the intact breast. As of January 1990, with a minimum assessable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Of all clinical factors tested, young age was the most significant prognostic factor for local recurrence (P less than .03). In addition, patients with pathologically involved lymph nodes were noted to have a lower local recurrence rate than patients with pathologically negative axillae (P less than .05). These findings were especially notable given the fact that the node-positive group had a higher percentage of T2 tumors and a higher percentage of patients in the young age group. These paradoxical findings, however, may be explained by the fact that 88% of the node-positive patients underwent adjuvant systemic therapy in the form of either systemic chemotherapy or hormonal therapy, while only 8% of node-negative patients underwent any adjuvant systemic therapy. When analyzed as a function of adjuvant therapy, those patients receiving adjuvant therapy had a lower local recurrence rate than those patients not receiving adjuvant therapy (P less than .08). We conclude that adjuvant systemic therapy impacts on the ipsilateral breast recurrence rate in patients treated with CS + RT. The implications of this study in light of the widespread use of adjuvant systemic therapy are discussed."
-What are the primary pathophysiologic mechanisms believed to cause sciatica?,"Pathophysiology of sciatica. The exact pathophysiologic mechanisms behind sciatica are incompletely known; however, compression of spinal nerve roots is known to be correlated to both pain and neural dysfunction in a segmental distribution of that specific nerve root. Compression per se may impair the transport of nutrients to the nerve tissue in such a way that affects the nerve root function. There also might be a local affect on nerve roots or root sleeves by substances leaking from the degenerated intervertebral discs."
-What were the main indications for surgical management of extracranial vertebral artery occlusive disease in this study?,"Surgical management of extracranial vertebral artery occlusive disease. Thirty-seven consecutive patients underwent vertebral artery (VA) reconstruction over a 6 years period (1983-1989). Detailed neurologic, medical, and angiographic information was obtained for all patients. Indications for surgery were as follows: (1) stenosis of VA with symptoms of vertebrobasilar insufficiency; (2) very tight stenosis (greater than 75%) of the dominant VA with stenosis or occlusion of the contralateral VA; (3) very tight stenosis of VA with bilateral occlusion of the internal carotid artery (ICA); (4) very tight stenosis of VA with homolateral ICA lesion eligible for simultaneous repair; (5) very tight stenosis of VA and very tight stenosis of the homo or contralateral carotid siphon. There were 15 isolated vertebral lesions (group I), and 22 were VA lesions associated with lesions of the supraaortic trunks which were simultaneously treated (group II). The reconstructions of the first portion of the VA were 30 (12 of group I and 18 of group II) and reimplantation of the VA into the common carotid artery was the procedure of choice. There were 7 revascularizations of the third portion of the VA at C1-C2 level (3 of group I and 4 of group II): carotid-vertebral bypass, using an autogenous vein graft, was the procedure of choice. Three patients in group II died in the immediate postoperative period from myocardial infarction but no patient presented immediate postoperative neurologic deficits. All symptomatic patients but one were relieved of their symptoms in a median follow-up of 31 months. No postoperative complications were observed. Long-term results were satisfactory in all the 28 patients at their last follow-up visit."
-What did the study reveal about transesophageal echocardiography's sensitivity in detecting mitral regurgitation in St. Jude Medical mitral valve prostheses?,"Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis. Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component."
-What factors have contributed to the recent reductions in liver cirrhosis deaths in Western countries?,"Factors in recent reductions in liver cirrhosis deaths. Since the mid-1970s, there have been substantial declines in liver cirrhosis deaths in many Western countries following a long period of increases. There is variability in the pattern of changes observed: in a sample of 29 countries between 1974 and 1982-83, seven countries showed a significant linear decline, three revealed a curvilinear pattern, increases were observed in six and the rest (13) showed no notable changes. Although reductions in per capita consumption of alcohol may be a contributing factor, these reductions do not seem to account for all of the decreases in cirrhosis deaths that have been observed. Among other factors that might contribute, changes or increases in treatment for alcohol abuse and AA membership have been most strongly linked to these declines; changes in patterns of consumption, dietary habits, prevention efforts and reduced exposure to predisposing factors may also be involved. In view of the importance of these declines for the understanding and prevention of alcohol problems, further research on this issue, perhaps involving international collaborative studies, is needed."
-"What are the key ultrastructural differences observed between adenomyotic glandular epithelium, proliferative endometrium, and well-differentiated endometrial cancer?",Ultrastructural study of glandular epithelium in adenomyosis in comparison with those of proliferative endometrium and well-differentiated endometrial cancer. Adenomyotic glandular tissue from five patients underwent electron microscopic investigation to observe its ultrastructural characteristics. The adenomyotic epithelium was compared with that of proliferative normal epithelium (two patients) and well-differentiated endometrial adenocarcinoma (two patients). The results revealed that morphologically the adenomyotic glandular epithelium is somewhat less differentiated than proliferative endometrium and that its cytoplasmic organelles have some similarities with those of endometrial cancer. Whether these similarities predispose the adenomyotic glandular tissue to malignant degeneration remains to be elucidated.
-What advantages did the 48 by 48 element biplane transesophageal probe offer compared to single-plane probes?,"Initial clinical experience with a 48 by 48 element biplane transesophageal probe. Recent technologic advances in ultrasound have resulted in the capability of transesophageal echocardiographic imaging in both transverse and longitudinal planes. Previous biplane probes suffered from inferior images because of reduced scan elements. We evaluated the utility of a prototype 48 X 48 element biplane transesophageal probe in 23 consecutive patients. Examinations were well tolerated with no side effects. In comparison to the single transverse plane, imaging with the longitudinal plane gave superior information on prosthetic valve pathology, atrial septal abnormalities, and pathoanatomy of the ascending aorta and mitral valve. Complementary information was provided by the longitudinal plane in patients with endocarditis and vegetations and in mitral protheses. Images obtained with this 48 X 48 element biplane probe along with color and spectral Doppler information were not perceptibly inferior to those obtained by single-plane probes. In conclusion, biplane transesophageal echocardiography with a 48 X 48 element probe indicates a great potential for enhanced three-dimensional understanding of cardiac pathology and diagnostic yield in specific pathologies."
-What is Klippel-Trenaunay syndrome (KTS) and what are its primary clinical characteristics?,"Klippel-Trenaunay syndrome: the risks and benefits of vascular interventions. Our experience with Klippel-Trenaunay syndrome (KTS), a rare congenital malformation, has increased considerably in recent years and now includes 144 patients (65 male and 79 female patients). Hemangioma was present in 137 patients (95.1%), varicosity in 110 (76.4%), and hypertrophy of the soft tissues or bones in 134 (93.1%). In most patients (71.5%) the disease involved one lower extremity. Diagnostic workup included roentgenogram to document limb length discrepancy, noninvasive arterial and venous evaluation, contrast venography, and nuclear magnetic resonance imaging. Most patients did well without treatment or with elastic compression only. Surgical treatment for the vascular malformation in KTS is rarely needed and it continues to be controversial. To evaluate the risks and benefits of vascular interventions, we examined in detail the clinical histories of nine patients who in the last decade underwent operation for a vascular malformation of the lower extremity. In seven patients we removed varicose veins or resected hemangioma of the lower extremity. Although none was cured, all five who underwent resection of varicose veins and one of the two patients who underwent resection of a hemangioma improved. Two additional patients, however, who underwent resection of varicose veins in another institution had worsening of the symptoms. In one patient we performed deep venous reconstruction for atresia of the superficial femoral vein, using the contralateral saphenous vein. Such operation in KTS has not been reported previously. The patient has a patent graft with a competent valve and clinical improvement 6 months after the operation. Although patients with severe chronic venous insufficiency, disturbing cosmetic appearance, or complications of hemangioma may benefit from surgical treatment, detailed preoperative imaging of the extremity and pelvis with magnetic resonance imaging and contrast venography is needed to decrease complications. Rarely, reconstruction for atresia or hypoplasia of the deep veins may be needed."
-How does platelet function change in patients with symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage?,"Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage."
-What technique was used to minimize postoperative hypotony in Molteno glaucoma implant procedures?,"The use of releasable sutures in Molteno glaucoma implant procedures to reduce postoperative hypotony. We used releasable sutures to minimize immediate postoperative hypotony and flat anterior chamber in 19 cases of refractory glaucoma requiring insertion of a single-plate Molteno implant in a one-stage procedure. A slip knot using 7-0 nylon suture was fashioned around the Molteno tube under a lamellar scleral flap. In 18 of the 19 eyes, anterior chamber depth was normal immediately after surgery."
-What was the purpose of using tissue-type plasminogen activator (tPA) in this study on subarachnoid hemorrhage patients?,"Prevention of vasospasm by clot removal and intrathecal bolus injection of tissue-type plasminogen activator: preliminary report. In this study, we evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in cases with a diffuse severe subarachnoid hemorrhage. All 10 cases were graded Group 3 according to the classification of Fisher and associates, and the CT number (Hounsfield number) of the subarachnoid clot was over 75. After clipping the aneurysm and removing the clot, three cisternal drainage catheters were inserted into both sylvian cisterns and the prepontine cistern, and continuous ventricular drainage was performed routinely. Postoperatively, tPA (0.5 mg/2.5 ml) was infused as a bolus into both basal cisterns and the lateral ventricle twice daily for about 6 days. Angiography and cerebral blood flow studies using single photon emission computed tomography were performed on Day 4 or 5 and between Days 7 and 10 after onset of the hemorrhage. To date, there have been no cases that have shown angiographic vasospasm or delayed ischemic neurological deficits. This preliminary study indicates that the intrathecal bolus injection of tPA produces a marked effect on vasospasm."
-What were the two most important independent prognostic factors for survival in this study of vulvar carcinoma?,"Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study). Analysis of 588 patients with vulvar carcinoma delineated four risk groups by the proportional hazards model. Groin node status (laterality and number positive) and lesion diameter were the only two important independent prognostic factors. The 5-year relative survival rates were 98%, 87%, 75%, and 29% for the risk group categories of minimal (negative groin nodes and lesion diameter less than or equal to 2 cm), low (one positive groin node and lesion diameter less than or equal to 2 cm or negative groin nodes and fewer than two lesions less than or equal to 8 cm diameter), intermediate (negative groin nodes and lesion diameter greater than 8 cm diameter, one positive groin node and lesion diameter greater than 2 cm, or two unilaterally positive groin nodes and lesion diameter less than or equal to 8 cm), and high (three or more positive groin nodes or two bilaterally positive groin nodes), respectively. Applying the International Federation of Gynecology and Obstetrics staging (1988) to these data discriminated risk of death (caused by recurrent vulvar cancer); the 5-year rates were 98%, 85%, 74%, and 31% for stages I, II, III, and IV, respectively. However, within International Federation of Gynecology and Obstetrics stage III there were 47 low-, 95 intermediate-, and 28 high-risk patients with relative survivals of 95%, 74%, and 34%, respectively. Overall, this assessment validates current International Federation of Gynecology and Obstetrics vulvar carcinoma staging, but further refinements are warranted in stage III."
-What diagnostic technique was used to study regional cerebral blood flow in a patient with alternating hemiplegia?,"Ictal 99mTc-HMPAO SPECT in alternating hemiplegia. 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) was performed in a patient with alternating hemiplegia during 2 episodes of the disease. The regional cerebral blood flow patterns correlated with the clinical manifestations during both episodes. Hyperperfusion of the contralateral hemisphere was suggested by asymmetric 99mTc-HMPAO uptake, whereas symmetric 123I-N-isopropyl-p-iodoamphetamine uptake was detected during the interictal period. The results suggested that alternating hemiplegia in infants represents an atypical manifestation of epilepsy, despite the lack of paroxysmal electroencephalographic abnormalities during the episodes. 99mTc-HMPAO SPECT appears to be a useful method for detecting transient regional cerebral blood flow alterations during paroxysmal events because the tracer is rapidly available for emergencies and retains a fixed distribution for 5-8 hours, sufficient time to allow for SPECT acquisition."
-What are the distinctive clinical characteristics of native valve endocarditis caused by Staphylococcus epidermidis compared to endocarditis caused by other organisms?,"Native valve Staphylococcus epidermidis endocarditis: report of seven cases and review of the literature. This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermidis. The literature on endocarditis caused by S. epidermidis is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and skin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis."
-What was the maximum hypothermic preservation time for skeletal muscle in rat hindlimbs using Euro-Collins solution?,"Preservation of skeletal muscle in tissue transfers using rat hindlimbs. Replantation of major extremities after long periods of ischemia can lead to viable replants in many cases, but functional restoration is often poor owing to fibrosis of the muscle. In this study, maximum hypothermic time in tissue transfers containing skeletal muscle using hindlimbs of Lewis rats preserved in 4 degrees C Euro-Collins solution was investigated. After preserving midthigh amputated legs in this solution for 6, 9, and 12 hours, the legs were transplanted to other inbred rats using microsurgical technique, and 1 week later, gastrocnemii were obtained to analyze ATP, ADP, and AMP using high-performance liquid chromatography. The values were compared with those for healthy legs, nonischemic operated control legs, and legs preserved in the same manner for 6, 9, and 12 hours. Histologic and serologic examinations were conducted. ATP values of the 9-hour preservation group resumed those of the nonischemic operated control group, with the values of the 12-hour preservation group remaining at 61 percent. Histologically, focal necrosis, hyaline degeneration, and regeneration processes were the most characteristic manifestations in the muscles transplanted after cold ischemia of 12 hours. It was concluded that skeletal muscle could be preserved for 9 hours in 4 degrees C Euro-Collins solution."
-What is Henoch-Schonlein purpura and how does it affect children according to the surgical evaluation in this study?,"Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived."
-How did chronic hypoxia affect the cardiovascular parameters of spontaneously hypertensive rats in the study?,"Effects of atrial natriuretic factor in chronic hypoxic spontaneously hypertensive rats. The present study was designed first to investigate the pulmonary hypertensive effects of chronic hypoxia in spontaneously hypertensive rats and second to compare the cardiovascular effects of atrial natriuretic factor on rats exposed to hypoxia and on control rats kept at sea level. Catheters were placed in the femoral and pulmonary arteries for measurement of mean systemic arterial pressure and mean pulmonary arterial pressure. The cardiac output was measured by thermodilution method. It was found that 4 weeks of simulated 18,000-foot hypoxia led to polycythemia, right ventricular hypertrophy, and pulmonary hypertension, which resulted from an increased pulmonary vascular resistance. However, systemic arterial pressure was not significantly different between the two groups of rats. Atrial natriuretic factor administration decreased systemic arterial pressure and pulmonary arterial pressure to a lesser extent in the hypoxic group compared with the sea level control group. It is concluded that these animals showed an impaired response to atrial natriuretic factor after long-term exposure to hypoxia."
-How did the second cerebrovascular accident affect the patient's long-standing hyperpathia in the right upper extremity?,"Disappearance of thalamic pain after parietal subcortical stroke. A hypertensive man had a long standing history of contumacious hyperpathia in the right upper extremity, resistant to medical therapy, secondary to a lacunar infarct in the left thalamus. A second cerebrovascular accident caused a small lesion in the left corona radiata, interrupting the thalamoparietal interconnections, and terminated the pain instantly. Interruption of the subcortical parietal white matter may more effectively control pain than cortical lesions. A few surgeons have successfully treated rebellious chronic pain with stereotaxic operations in the corona radiata, resulting in lesions very similar to our patient's. This overlooked and nearly forgotten technique may still have value in treating selected cases."
-What percentage of unselected blood donors were found to have antibodies to hepatitis C virus in the United Kingdom study?,"Hepatitis C virus antibodies in subjects with and without liver disease in the United Kingdom. The prevalence of antibody to hepatitis C virus, evidence of previous or current infection with this agent of parenterally transmitted non-A, non-B hepatitis, was determined in 340 subjects residing in the United Kingdom. The antibody was detected in 3 per cent of unselected blood donors and in 60 per cent of patients with chronic post-transfusion non-A, non-B hepatitis. Evidence for infection was also found in 30 per cent of intravenous drug abusers, and in 75 per cent of haemophiliacs receiving commercial factor VIII concentrate. The infection is uncommon in renal units and amongst sexually promiscuous groups attending sexually-transmitted disease clinics. Although the seropositivity rate in primary biliary cirrhosis and chronic B and delta hepatitis was very low (0-2 per cent), in patients with autoimmune and alcoholic liver disease it was 14-16 per cent which, although lower than that quoted in studies from Spain and Italy, is considerably higher than would be expected by chance. The reason for the high incidence of non-A, non-B hepatitis in this latter group of patients is unclear."
-What medical interventions were used to control blood pressure in the patient with severe hypertension after renal artery injury?,"Severe hypertension with segmental renal infarction following surgical removal of a retroperitoneal malignant hemangiopericytoma: a case report. Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed."
-What were the predialysis atrial natriuretic peptide (ANP) levels in the three patient groups studied?,"Atrial natriuretic peptide in dialysis patients under various conditions of volume homeostasis. Atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were studied in 19 patients with end-stage renal disease (ESRD) under haemodialysis (HD). On the basis of clinical findings, patients were divided into three groups: group A, 6 patients, of mean age 41 +/- 15 years, without heart failure and in need of ultrafiltration (658 +/- 282 ml h-1); group B, 6 patients, of mean age 54 +/- 15 years, without heart failure under isovolaemic HD; group C, 7 patients, of mean age 60 +/- 3 years, with heart failure (NYHA III-IV) and in need of ultrafiltration (607 +/- 120 ml h-1). The highest predialysis ANP levels were found in group C (1534 +/- 471 pg ml-1) followed by group A (476 +/- 168 pg ml-1) and group B (236 +/- 138 pg ml-1) (normal range 62 +/- 27 pg ml-1). Systolic and diastolic blood pressure and heart rate did not correlate with ANP levels in either of the groups. However, iso-osmotic reduction of the body weight by ultrafiltration was correlated with decreasing ANP levels during HD (for groups A and C, r = 0.88 and 0.98, respectively). Isovolaemic HD did not alter ANP concentrations (group B). All patients received a volume bolus at the end of HD, and they responded with an instant increase in ANP concentration, which was most pronounced in patients with concomitant heart failure. PRA was not significantly correlated with ANP levels during HD. In conclusion, the results of this study indicate that there is a sensitive response of ANP levels to changes in body fluid status in ESRD."
-What were the key findings of the Early Treatment Diabetic Retinopathy Study (ETDRS) regarding aspirin treatment for diabetic retinopathy?,"Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Aspirin treatment did not alter the course of diabetic retinopathy in patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). In this randomized clinical trial supported by the National Eye Institute, 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy were assigned randomly to either aspirin (650 mg per day) or placebo. Aspirin did not prevent the development of high-risk proliferative retinopathy and did not reduce the risk of visual loss, nor did it increase the risk of vitreous hemorrhage. This was true both for eyes assigned randomly to deferral of photocoagulation and for eyes assigned randomly to early argon laser photocoagulation. The ETDRS results indicate that for patients with mild-to-severe non-proliferative or early proliferative diabetic retinopathy, it is likely that aspirin has no clinically important beneficial effects on the progression of retinopathy. The data also show that aspirin 650 mg per day had no clinically important harmful effects for diabetic patients with retinopathy. These findings suggest there are no ocular contraindications to aspirin when required for cardiovascular disease or other medical indications."
-What were the key findings of the Medical Research Council European trial comparing chorion villus sampling and amniocentesis for prenatal diagnosis?,"Medical Research Council European trial of chorion villus sampling. MRC working party on the evaluation of chorion villus sampling. First-trimester chorion villus sampling has the advantage over second-trimester amniocentesis of allowing earlier prenatal diagnosis of various genetic and cytogenetic disorders in the fetus (and therefore earlier termination in affected pregnancies) but the relative safety and diagnostic accuracy remain unclear. Between 1985 and 1989, 3248 women seeking prenatal diagnosis, principally because of their age, were recruited to an international, multicentre, randomised comparison of the safety and diagnostic accuracy of the two techniques--5% of women allocated chorion villus sampling and 8% of those allocated amniocentesis were not tested, usually because of spontaneous miscarriage. 6% and 2% were retested, in most because of sampling failure. The endpoint of a liveborn infant who survived was achieved by 86% of women allocated chorion villus sampling and 91% of those allocated amniocentesis; statistical analysis, after appropriate weighting for a centre's contribution, showed that the typical difference between the groups was 4.6% (95% confidence interval 1.6-7.5%; p less than 0.01). This difference reflected more spontaneous fetal deaths before 28 weeks' gestation (2.9% [0.6-5.3%]); more terminations of pregnancy for chromosomal anomalies (1.0% [0.0-2.1%]); and more neonatal deaths (0.3% [-0.1 to 0.7%]). The difference in neonatal deaths was due to a preponderance of very immature liveborn infants in the chorion villus sampling group, and this factor also explained that group's longer mean stay in hospital. More abnormal diagnoses followed chorion villus than amniotic fluid analyses (5.6% vs 3.9%). This difference was largely due to diagnoses of trisomy 18 and of (usually mosaic) abnormalities known to be confined to the placenta. 3 terminated pregnancies were false positives, 1 tested by chorion villus sampling and 2 by amniocentesis, and 2 other mosaic cases diagnosed by chorion villus sampling may have been false positives. There was 1 false-negative result in the chorion villus sampling group. The possibility of earlier exclusion or diagnosis of some fetal disorders afforded by first-trimester chorion villus sampling must be set against its clinical risks."
-What were the key findings of the Ontario Child Health Study regarding the psychosocial characteristics of parents with children who have chronic health problems?,"Children with chronic illness: family and parent demographic characteristics and psychosocial adjustment. This paper presents the results of an epidemiologic study that compares and contrasts psychosocial characteristics of parents and family units of children with chronic illness or physical disability (chronic health problems) with those of healthy children. Data were derived from the Ontario Child Health Study of 1869 randomly selected families, with 3294 children aged 4 to 16 years. In the absence of significant differences between parents and families of children with chronic illness alone and those with physical disability, these groups were combined for analysis, for which odds ratios (OR) or t tests were used. Significant positive findings included increased rates of parental treatment for ""nerves"" (mothers' OR = 2.1, fathers' OR = 1.9) and increased maternal negative affect scores (Bradburn Affect Balance Scale) (P less than .001) among parents of children with chronic health problems. Important negative findings (95% confidence interval of the OR included 1) included no increase in single-parent families (OR = 1.2), social isolation (OR = 1.0), or alcohol problems (OR = 1.2) among parents of children with chronic health problems. Categorically defined family dysfunction did not differ between the two groups (OR = 1.1). These data contrast with several clinic-based studies and suggest that, in a widely generalizable population survey, families of children with chronic health problems including physical disability do not suffer a marked excess of dysfunction, although some indicators of individual parent psychosocial problems were modestly elevated."
-What was the key finding regarding IL-4 and IL-2 mRNA levels in mice infected with Schistosoma mansoni?,"In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. Using Northern Blot analysis, the endogenous levels of IL-4 and IL-2 mRNA in the spleens, mesenteric lymph nodes, and granulomatous livers of male CBA/J mice in the acute phase of infection with Schistosoma mansoni have been quantified. High levels of IL-4 mRNA were detected in all three tissues from infected mice, whereas none was detected in tissues from normal, uninfected, age-matched mice. Isolation of the granulomas from the livers of infected mice and subsequent extraction of total RNA from these lesions resulted in a 70-fold enrichment of IL-4 message compared with the whole, unseparated granulomatous liver tissue. Hence, the predominant source of the IL-4 mRNA detected in livers from infected mice appears to be the schistosome egg-induced granulomas within these livers. In contrast, IL-2 mRNA was never detected in any of these tissues from either infected or normal mice. Control experiments were performed that ruled out the possibility that this inability to detect IL-2 mRNA was due to a difference in the efficacy of the IL-4 and IL-2 probes or due to a selective lability of IL-2 message. These data imply that IL-4-producing, Th2 lymphocytes are active in and possibly integral to the granulomatous, delayed-type hypersensitivity response characteristic of this infection, and directly challenges the current hypothesis that delayed-type hypersensitivity responses are exclusively mediated by Th1 lymphocytes."
-What cardiac disturbances were observed in patients receiving taxol during clinical trials?,"Cardiac disturbances during the administration of taxol. The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined."
-What was the cause of subarachnoid hemorrhage in the seventy-one-year-old Japanese man?,"Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery."
-What was the overall 5-year actuarial disease-free survival rate after salvage surgery for patients with carcinoma of the buccal mucosa?,"Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05)."
-What percentage of patients achieved complete thrombolysis based on the duration of their limb ischaemia symptoms?,"Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected."
-What were the key findings of the study comparing different ventilation methods during single-operator cardiopulmonary resuscitation in an ambulance?,"Single operator cardiopulmonary resuscitation in ambulances. Which ventilation device? Cardiopulmonary resuscitation en route to hospital is performed by a single-handed operator in many British ambulances. In this study, three emergency ventilation devices, and mouth-to-mouth breathing, were compared for effectiveness in unintubated patients. Seventeen paramedics used each method on a Laerdal manikin in a randomised order, under identical conditions. Three experienced cardiopulmonary resuscitation instructors repeated the tests in a moving ambulance. There were significant differences in minute volume (p less than 0.01) and number of effective chest compressions (p less than 0.05); mouth-to-mouth breathing produced the best overall results and the simplest device was a close second. The value of automatic ventilators for single-operator cardiopulmonary resuscitation in unintubated patients is questioned."
-What is the significance of the first reported case of HTLV-1 associated T cell lymphoma in South East Asia?,"HTLV-1 associated T cell lymphoma in South East Asia: case report and family study. Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives."
-What is the key finding in this case study regarding neutrophil function and protein abnormalities?,"An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins. A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs."
-What was the purpose of studying programmed ventricular stimulation at different time points after acute myocardial infarction?,"Usefulness of early versus late programmed ventricular stimulation in acute myocardial infarction. To determine the influence of timing on the prognostic value of programmed ventricular stimulation after acute myocardial infarction (AMI), 32 patients were studied on day 19 (early study) and again on day 36 (late study) after AMI using up to 3 extrastimuli. At the early study, sustained monomorphic ventricular tachycardia (VT) was induced in 12 patients (38%), sustained polymorphic VT in 8 (25%), nonsustained monomorphic VT in 1 (3%), nonsustained polymorphic VT in 1 (3%) and no inducible arrhythmia in 10 (31%). At the late study, sustained monomorphic VT, nonsustained monomorphic VT and nonsustained polymorphic VT were induced in 8 patients (25%) each, and no inducible arrhythmia in 8 (25%). Of the 12 patients who had inducible sustained monomorphic VT at the early study, 7 had noninducibility of sustained monomorphic VT at the late study. Of the 20 patients who had noninducibility of sustained monomorphic VT at the early study, 3 had inducible sustained monomorphic VT at the late study. During the follow-up period (mean +/- standard deviation 21 +/- 8 months), there were 2 sudden cardiac deaths and 3 occurrences of sustained VT. Univariate analysis revealed both inducibilities of sustained monomorphic VT at the early study (p = 0.045) and at the late study (p less than 0.001) to be predictive of sudden cardiac death or clinical occurrence of sustained VT. However, inducibility of sustained monomorphic VT at the late study had a higher sensitivity (100%), specificity (89%), positive predictive value (63%) and negative predictive value (100%) than at the early study (80, 70, 33 and 95%, respectively)."
-What is the difference between allochiria and allesthesia according to the original descriptions by Obersteiner and Stewart?,"Allochiria vs allesthesia. Is there a misperception? Allochiria is the mislocation of sensory stimuli to the corresponding opposite half of the body or space. Obersteiner (1882) introduced the term allochiria (Greek allos = other + chiria = hand), and more than 20 authors employed it in this context over the next 25 years. Stewart (1894) described a related phenomenon in which stimuli are displaced to a different point on the same extremity. He noted that the displacements were different than allochiria and coined the term allachaesthesia (ie, allesthesia) (Greek allache = elsewhere + aisthesis = perception). Despite this historical background, Jones (1907) redefined both terms in an attempt to increase diagnostic specificity and attributed allochiria to hysteria. Jones' reinterpretation does not appear to be justified historically, etymologically, or scientifically and has resulted in contradictory definitions of allochiria and allesthesia in present-day medical dictionaries and neurologic textbooks. We advocate a return to usage consistent with the original descriptions and word derivations."
-What was the purpose of the study on autologous fat injection in the canine larynx?,"Autologous fat injection for vocal cord medialization in the canine larynx. This study examined the use of autologous fat as an alternative to Teflon and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show mode-rate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation."
-What percentage of age-matched elderly subjects made omissions on at least one visuo-spatial neglect test?,"Performance of age-matched controls on a battery of visuo-spatial neglect tests. Examination of 47 independent elderly subjects, matched with a population of patients with acute stroke, found that 55% made at least one omission on a battery of neglect tests. Up to 43% made omissions on any one test. Increasing age and other evidence of cognitive impairment were associated with impaired performance on the battery. Omissions were attributed to an age-related decline in visuo-spatial function. Cut-off points are provided to distinguish between such age-related impairment and visuospatial neglect. The importance of age-matched control studies in developing tests of cognitive impairment in stroke research is highlighted."
-What unique characteristics were observed in the hepatoid adenocarcinoma of the renal pelvis in this case study?,"Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. A right renal pelvic mass in a 72-year-old man was resected. The histologic appearance of the tumor was a mixture of tubular adenocarcinoma cells and hepatoid neoplastic cells, and there was a resemblance to hepatoid adenocarcinoma. The intraoperative level of serum alpha-fetoprotein (AFP) was calculated to be 2246 ng/ml, and the postoperative level ranges from 183.6 to 285.6 ng/ml. Lectin binding assays showed that the serum AFP was the hepatic carcinoma type. In a hepatoid portion, an iron-negative, brown to green pigment was positive for bile. Alpha-fetoprotein was immunohistochemically evident in the neoplastic cells. In addition to the hepatic differentiation, the tumor had differentiated into intestinal absorptive or pancreatobiliary tract cells, as deduced from the frequent presence of spicular bodies, a unique light microscopic feature equivalent to microvilli with an actin core. The hepatoid adenocarcinoma is a distinct type of AFP-producing carcinoma present in the organs with epithelium of endodermal origin. Hepatoid adenocarcinoma in the renal pelvis may arise from a metaplasia of neoplastic mesonephric cells into endodermal cells."
-How did the study evaluate the effects of oral magnesium on premenstrual syndrome symptoms?,"Oral magnesium successfully relieves premenstrual mood changes. Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster ""pain"" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster ""negative affect."" In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes."
-What were the key findings regarding the long-term quality of life for childhood and adolescent CNS tumor survivors in this study?,"Quality of life in long-term survivors of CNS tumors of childhood and adolescence. Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or their proxies) who had CNS tumors diagnosed before the age of 20 between 1945 and 1974, survived at least 5 years, and reached 21 years of age. Survivors were 32 years old on average at follow-up. When compared with 479 matched siblings as controls. CNS tumor survivors were more likely to have died or to have become mentally incompetent sometime during the follow-up period. They were more likely to be at risk for such adverse outcomes as unemployment (odds ratio [OR], 10.8; 95% confidence interval [CI], 4.6 to 25.7], to have a health condition that affected their ability to work (OR, 5.9; CI, 3.7 to 9.4), to be unable to drive (OR, 28.8; CI, 6.9 to 119.9), or to describe their current health as poor (OR, 7.8; CI, 1.7 to 35.7). Unfavorable outcomes were more frequent in male survivors than in females, in those with supratentorial tumors compared with infratentorial ones, and in those who received radiation therapy. As clinicians consider improving therapies, they should anticipate late effects, such as those we observed, and attempt to target subgroups for interventions that may improve subsequent quality of life."
-What was the gender distribution of children who were victims of dog bites in the study?,"Dog bites in urban children. As a result of a perceived increase in pit bull injuries, all children who presented to The Children's Hospital of Philadelphia during 1989 for evaluation of dog bite injuries were prospectively studied. Epidemiologic information was collected from parents, either at the time of visit or by phone on the following day. A total of 168 children were enrolled; the mean age was 8 years. Males outnumbered females 1.5:1. Most (61%) injuries occurred in or around the home and involved dogs known to the patient (77%). Types of injuries included abrasions (33%), punctures (29%), and lacerations (38%). Thirteen bites had associated complications; nine developed infection. Twelve (7%) children required admission to the hospital. More than 12 different purebreeds or cross-breeds were identified as perpetrators, including German shepherds (n = 35), pit bulls (n = 33), rottweilers (n = 9), and Dobermans (n = 7). Most (54%) animals were contained (ie, leashed, fenced, in-house) at the time of injury. Fewer (46%) were provoked prior to biting. Significantly more pit bull injuries (94% vs 43%, P less than .001) were the consequence of unprovoked attacks and involved freely roaming animals (67% vs 41%, P less than .01). Children aged 5 or younger were more likely to provoke animals prior to injury than were older children (69% vs 36%, P less than .001). It is recommended that families with young children be the target of pet safety education and that measures be sought that would lead to early identification of a potentially dangerous dog and restrict ownership."
-What medical condition did the 29-year-old man develop that led to the management of megaduodenum through duodenoplasty and feeding jejunostomy?,"Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy. A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo-obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum."
-How did the fentanyl consumption differ between the epidural and intravenous groups in this postoperative pain management study?,"Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. A prospective, open, clinical trial is described in which 20 patients having upper abdominal surgery were randomly allocated to receive fentanyl for postoperative analgesia by patient-controlled demand analgesic computer by either the epidural or intravenous route. Hourly pain, sedation and nausea scores were very similar in the two groups during the first 24 hours after surgery. What few differences there were favoured the epidural group. There was a highly significant difference in fentanyl consumption between the two groups, with the intravenous group demanding consistently more than twice as much as the epidural group."
-What were the most common viral and bacterial pathogens causing lower respiratory infections in children in this tropical southern Indian study?,"Etiology of acute respiratory infections in children in tropical southern India. Nasopharyngeal secretions and throat-swab specimens from 809 children less than 6 years old with acute respiratory infection were examined by culture and indirect immunofluorescence for the presence of virus or viral antigen. Blood was cultured for the presence of bacteria in selected cases of lower respiratory infection (LRI); pleural fluid also was cultured in cases of empyema. Viruses were detected in 163 (49%) of 331 children with LRI. Respiratory syncytial virus (RSV) was the commonest agent isolated (106 children). Other viruses isolated included parainfluenza viruses (36 children), adenoviruses (12), and influenza viruses (five). Outbreaks of infection due to RSV occurred during August through October. Pneumonia was the commonest LRI encountered (178 children). Among children with pneumonia, viruses were detected in 65 (37%) of 178 children, and bacteria were isolated from 27 (18%) of the 147 children for whom blood cultures were done. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the common bacterial pathogens isolated. In cases of empyema and pyopneumothorax, S. aureus was the commonest organism isolated. There were 116 children with bronchiolitis, 83 (72%) of whom had viral infections; the majority of these children (81%) had RSV infection. Croup was uncommon (eight cases) and was caused mainly by parainfluenza viruses."
-What were the two treatment methods compared in this study for managing refractory ascites in patients with cirrhosis?,"Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. BACKGROUND. There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS. We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS. During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS. The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved."
-How does a fish oil-enriched diet affect the microcirculatory manifestations of ischemia-reperfusion injury in hamsters?,"Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters. Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the break-down of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesion-promoting leukotriene (LT) B4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB5, emphasizing the mediator role of LTB4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury."
-How does the external anal sphincter function differ between spinal cord injury patients and healthy volunteers?,"External anal sphincter function in spinal patients. Electromyographic and manometric study. Six patients with complete transection of the spinal cord and six healthy volunteers were examined by using anorectal manometry together with electromyographic (EMG) recording of the external anal sphincter composed of striated muscle. Anal pressure and EMG activity of the external anal sphincter were continuously recorded at rest and during gradual rectal distention (10, 20, 30, 40, and 50 ml) by means of an air-filled balloon eliciting a rectoanal inhibitory reflex (RAIR) at the upper part, and an inflation reflex (IR) at the lower part of the anal canal. All patients and controls had a RAIR for each rectal distention volume. A relationship between the duration of the RAIR and the rectal distention volume was present in controls only. In controls the IR was present for each rectal distention volume, whereas it was present in only one patient for a 40-ml volume. During the resting period, all controls showed continuous tonic EMG activity of the external anal sphincter, but after 30 minutes all the patients showed a decrease and ultimately in five cases a disappearance of the tonic EMG activity of the external anal sphincter. In spinal patients, the presence or absence of EMG activity of the external anal sphincter did not modify the anal canal pressure. These results indicate that: 1) the tonic EMG activity of the external anal sphincter seems to be under the control of supraspinal structures, because in spinal patients it disappears in the absence of sensitive inputs toward the spinal cord; 2) the absence of EMG activity at rest indicates that the external anal sphincter is not implicated in the RAIR disturbances observed in spinal patients; 3) the IR is not a spinal reflex but is under voluntary control, because it is not present in spinal humans; 4) in spinal humans the tonic EMG activity of the external anal sphincter does not play a role in the maintenance of the anal pressure at rest."
-How can the expression of ABO(H) antigens and beta-2 microglobulin help predict the response to intravesical BCG treatment in superficial transitional cell carcinoma of the bladder?,"ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin. The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone."
-How does allopurinol (ALLO) mitigate norepinephrine-induced cardiac damage in rabbits?,"Modulation of catecholamine cardiomyopathy by allopurinol. It has been suggested that cardiac injury by catecholamines may be the result of coronary constriction leading to ischemic damage. Allopurinol (ALLO) has been shown to reduce the extent of myocardial necrosis in various systems. Hence the possibility that ALLO might limit norepinephrine (NE) injury was tested. Rabbit hearts were infused with NE (3 micrograms/min/kg) for 90 minutes, with or without ALLO (50 micrograms/min/kg). Control specimens infused with saline solution plus ALLO were also prepared. Hearts were excised 48 hours later and studied as isovolumic isolated heart preparations. Peak systolic pressure, coronary flow, and myocardial oxygen consumption were significantly reduced in the hearts infused with NE but not in the NE + ALLO hearts. Myocardial adenosine triphosphate and glycogen concentrations were 29% and 26% lower in the NE hearts compared with control hearts. These reductions were absent in the NE + ALLO group. Moreover, rates of creatine phosphokinase and lactic dehydrogenase release were sharply elevated in the NE hearts but not in those also given ALLO. These findings are consistent with the changes observed histologically. The amount of myocardial damage was less in the ALLO + NE group compared with the NE group (p less than 0.02). This appears to be the first report to demonstrate that ALLO reduces myocyte damage by NE. Possible mechanisms include decreased free radical production, scavenging of free radicals, and preservation of the adenine nucleotide pool. Because xanthine oxidase activity is absent in the rabbit, the latter two mechanisms are more likely explanations for the findings."
-What is autoerotic asphyxia and how can it lead to fatal consequences?,"A case of autoerotic asphyxia associated with multiplex paraphilia. During the past 20 years, the sensational aspects of autoerotic fatalities have captured the attention of medical examiners, psychiatrists, law enforcement agents, and the public, as well as the individuals themselves who engage in these dangerous practices. Reports of deaths related to sexual asphyxia have been presented numerous times at national and international meetings and have been the topic of discussion on television talk shows and in the press. Autoerotic fatalities and all the sexual curiosities related to these activities have prompted death scene investigators to publish case reports, and even textbooks, on the subject. The case presented herein is one of a multicomponent paraphilia in which self-asphyxiation (autoasphyxiophilia) led to a fatal autoerotic event."
-What was the unusual presentation of the child with a biopterin synthesis defect?,"Paroxysmal tremor and orofacial dyskinesia secondary to a biopterin synthesis defect. We report a child with a systemic biopterin synthesis defect due to an absence of 6-pyruvoyl-tetrahydropterin synthase who had an unusual presentation, with three episodes of coarse ""rubral-like"" tremor in arms and legs orofacial dyskinesia between the ages of 3 and 6 months. Response to levodopa therapy and CSF neurotransmitter metabolite concentrations before and after therapy suggests that his clinical syndrome resulted from a secondary dopamine deficiency."
-How do Quechua highlanders from the Andes demonstrate metabolic efficiency during exercise at high altitudes compared to lowlanders?,"Metabolic and work efficiencies during exercise in Andean natives. Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms."
-What changes in coronary diameter were observed 4 hours after percutaneous transluminal coronary angioplasty (PTCA)?,"Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course. BACKGROUND. To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA. METHODS AND RESULTS. All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments. CONCLUSIONS. Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA."
-What challenges did the study identify with laser cone biopsy specimens that could interfere with reliable histologic diagnosis?,"The histologic reliability of laser cone biopsy of the cervix. Laser conization of the cervix has been advocated as the technique of choice for the treatment of cervical intraepithelial neoplasia (CIN) in preference to ablative techniques, because it provides a specimen for histologic diagnosis while retaining the advantages of an outpatient procedure with minimal short- and long-term morbidity. To determine whether specimens so obtained are adequate for reliable histologic diagnosis, we reviewed 77 laser conizations performed for lesions confirmed to contain CIN in a colposcopically directed biopsy and satisfying the criteria for local ablation and scored the cones for the presence of epithelial denudation and laser coagulation artifact that interfered with the diagnosis of CIN or the assessment of the margins of excision. Thirty specimens (39%) were negative for CIN. Twenty-eight (36%) showed extensive epithelial denudation, ten (13%) contained coagulation artifact that made recognition of CIN extremely difficult or impossible, and in 11 (14%), assessment of margins was extremely difficult or impossible because of laser coagulation artifact. We conclude that these difficulties with the histologic interpretation of laser cone specimens make it an unsuitable excisional technique when reliable histologic diagnosis of cervical lesions is required."
-What did the study reveal about the relationship between alpha 1 antitrypsin phenotypes and alcoholic pancreatitis?,"Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis. Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis."
-What was the main objective of the study regarding ovarian hyperstimulation in patients treated with human menopausal gonadotropin?,"Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer. OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle."
-How do the plasma and saliva levels of PGI2 and TXA2 differ in classical migraine patients during an attack-free period?,"Plasma and saliva levels of PGI2 and TXA2 in the headache-free period of classical migraine patients. The effects of nicardipine. The levels of Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were assayed simultaneously (RIA) in the plasma and saliva of 9 patients suffering from classical migraine attacks. The assays were done during an attack-free period. In relation to the control group we observed a significant decrease in the plasma levels of PGI2 together with a sharp increase in TXA2 in saliva. When the patients were treated with nicardipine, a calcium antagonist, the TXA2 increase in saliva did not occur. These results suggest both a systemic and local effect in the classical migraine attacks. We explain and discuss our results by referring to the PGI2: TXA2 equilibrium system. Nicardipine action might be related to its ability to reduce the calcium entry into the cell induced by thromboxane."
-What type of rare neural tumor was observed within the mandibular bone in this case study?,"Unusual intramandibular neural tumor. Neural tumors within the jaw bones are exceptional. We present the histologic observation of a central mandibular tumor of neural origin. Immunohistochemistry confirmed the neural nature of the tumor, which had features of a schwannoma (neurilemmoma) together with ganglion cells as seen in ganglioneuroma. Moreover, the association with an intracranial tumor, possibly a meningioma, is emphasized."
-What percentage of reflux events were simultaneously detected by both scintigraphy and pH monitoring in patients with severe reflux esophagitis?,"Simultaneous esophageal pH monitoring and scintigraphy during the postprandial period in patients with severe reflux esophagitis. To compare reflux events detected by intraesophageal pH monitoring with that of scintigraphy, we simultaneously performed both techniques along with esophageal manometry in nine patients with severe reflux esophagitis. Two hundred eighteen reflux events were detected in the recumbent posture after a meal during a 40-min interval. Both techniques simultaneously detected only 23% of all reflux events. Scintigraphy alone detected 61% of all reflux events as opposed to 16% for pH monitoring. Of those reflux events diagnosed only by scintigraphy, more occurred while the intraesophageal pH was less than 4 (ie, during an acid-clearing interval) than while the intraesophageal pH was greater than 4 (ie, when intragastric contents were neutralized by the meal). Most reflux events occurred during periods of stable, but low LES pressure. While reflux events diagnosed by scintigraphy significantly decreased during the second of two 20-min postprandial intervals, those by pH monitoring tended to increase. That simultaneous scintigraphy and pH monitoring agreed on less than 1/3 of all reflux events not only underscores the fact that both techniques measured different physical components of the esophageal refluxate (ie, volume vs acid concentration, respectively), but also were influenced by different physiologic events such as the ingestion of a meal, gastric emptying, and esophageal acid clearance."
-"What approach do comprehensive multidisciplinary pain centers use to help patients with chronic, disabling pain?","Pain centers--organization and outcome. Pain treatment centers have evolved at a rapid rate, but they differ in their complexity and services provided. Patients, as well as primary care physicians, have difficulty in identifying the appropriate center for a specific problem. Guidelines for pain centers have recently been proposed by the International Association for the Study of Pain, along with an attempt at their accreditation. Outcome studies from pain centers have proliferated, with a wide range of treatment programs being reported. Comprehensive multidisciplinary pain centers using the rehabilitation medicine approach are effective in decreasing disability and increasing the productivity of patients with chronic, disabling pain."
-What differences were observed in motor fiber degeneration and conduction block between the extensor digitorum brevis (EDB) and anterior lateral (AL) compartment muscles in peroneal nerve palsies?,"Quantitation of axon loss and conduction block in peroneal nerve palsies. We compared conduction in motor fibers supplying the extensor digitorum brevis (EDB) and anterior lateral compartment (AL) muscles. The object was to determine whether there were any differences in the relative proportions of degenerated and blocked nerve fibers between the longer EDB and shorter AL fibers. In almost every case the percentage of motor fibers undergoing axonal degeneration was greatest in EDB fibers. Conversely, the percentage of conduction block was greatest in the AL motor fibers. As clinical recovery is dependent on AL muscles rather than EDB, electrophysiological study of the relative proportions of degenerated and blocked fibers in the former should provide a more reliable measure of outcome than similar studies of EDB. Conduction velocity distal to the fibular head was not slowed despite the large loss of EDB motor fibers. Evidence for selective involvement of the larger myelinated fibers is, therefore, lacking. The location of the major conduction abnormalities was in almost every case between the mid-fibular head and popliteal fossa."
-"How are depression, chronic fatigue, and chronic pain interconnected in terms of their psychological and neurobiological factors?","Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery."
-How do DNA methylation patterns change during embryonic development in mice?,"Demethylation of CpG islands in embryonic cells. DNA in differentiated somatic cells has a fixed pattern of methylation, which is faithfully copied after replication. By contrast, the methylation patterns of many tissue-specific and some housekeeping genes are altered during normal development. This modification of DNA methylation in the embryo has also been observed in transgenic mice and in transfection experiments. Here we report the fate in mice of an in vitro-methylated adenine phosphoribosyltransferase transgene. The entire 5' CpG island region became demethylated, whereas the 3' end of the gene remained modified and was even methylated de novo at additional sites. Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences. This suggests that gene sequences can be recognized in the early embryo and imprinted with the correct methylation pattern through a combination of demethylation and de novo methylation."
-What distinguishes Neisseria lactamica from Neisseria meningitidis in laboratory testing?,"Neisseria lactamica meningitis following skull trauma. A woman developed meningitis due to Neisseria lactamica in association with a cribriform plate fracture. Cerebrospinal fluid antigen tests for Neisseria meningitidis were negative. The patient recovered with intravenous penicillin therapy. N. lactamica can be rapidly distinguished from N. meningitidis by the hydrolysis of ONPG (o-nitrophenyl-beta-D-galactopyranoside). In contrast to N. meningitidis and Neisseria gonorrhoeae, N. lactamica lacks virulence properties. As 100% of N. lactamica strains are susceptible to penicillin and all three previously described patients with N. lactamica meningitis have recovered with penicillin treatment, the reason for distinguishing the organisms in this context is primarily to prevent unnecessary anxiety and prophylaxis among contacts."
-How might exclusion criteria in hypertension trials potentially impact the generalizability and statistical power of research findings?,"Potential impact of exclusion criteria on results of hypertension trials. Recent trials of antihypertensive therapy, including the Veterans Administration trials, the Hypertension Detection and Follow-up Program, the Multiple Risk Factor Intervention Trial, the Australian Mild Hypertension Trial, and the British Medical Research Council Trial, are reviewed with a particular emphasis on the criteria leading to the exclusion of potentially eligible participants. The observation of all-cause and cause-specific mortality rates in the group ultimately selected to participate in the trial is suggested as an index to the general applicability of trial results. Because end-point rates are fundamental for determining sample size, substantial reduction in these end-point rates by patient exclusion should be taken into account by the trial design. Some recent trials may have generated end-point-event rates so low that the power of the trial to detect reasonable treatment effects was substantially reduced. Future trials should attempt to take this important factor into account at the design stage."
-What is the association between adult polycystic kidney disease (APKD) and seminal vesicle cysts?,"Seminal vesicle cysts: association with adult polycystic kidney disease. Adult polycystic kidney disease (APKD) is associated with cyst formation in the kidney, liver, pancreas, esophagus, ovary, uterus, and brain. Four patients with APKD (aged 45-65 years) with computed tomographic evidence of seminal vesicle cysts are described. All seminal vesicles contained cystic masses with attenuation values of 0-30 HU. Seminal vesicle thickness was 3-4 cm (normal, 1.5 cm). High-attenuation walls separated the cysts, which were 3-35 mm in diameter. All patients had typical renal stigmata of APKD. None had cysts elsewhere, except one patient with hepatic cysts. Postmortem examination in one patient confirmed the seminal vesicle cysts as well as APKD. It is likely that a basement membrane defect allows cyst formation in multiple organs, presumably including the seminal vesicles. Because of the association of seminal vesicle cysts with ipsilateral urogenital anomalies, and because only 60% of patients with APKD have a relevant familial history, the kidneys of patients with cross-sectional imaging evidence of seminal vesicle cysts should also be studied."
-What treatment method was used to control bleeding from a penetrating atherosclerotic aortic ulcer in this case report?,"Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization. A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention."
-How does hypoxic exercise affect the levels of atrial natriuretic factor (ANF) and aldosterone in untrained men?,"Effect of hypoxic exercise on atrial natriuretic factor and aldosterone regulation. To evaluate the possible physiologic role of atrial natriuretic factor (ANF) in the observed dissociation of aldosterone secretion from the renin-angiotensin system during hypoxic exercise, 12 untrained men, ages 18 to 24, were studied on two separate days for 30 min during hypoxic (16% O2) and normoxic (room air) exercise on a bicycle ergometer. Workloads were adjusted to produce individual heart rates that remained within 70 to 75% of their previously measured maximum. Hemoglobin saturation decreased during hypoxia from 98 +/- 0.1% to 90 +/- 0.4% (P less than .01). Plasma aldosterone levels increased significantly (P less than .01) under both breathing conditions, yet were on average 36% lower during hypoxia than during normoxia (P less than .001). Plasma ANF levels increased during exercise under both conditions (P less than .01), yet levels were 45% greater during hypoxia than during normoxia (P less than .001). Plasma renin activity, adrenocorticotropic hormone, cortisol, potassium, and systolic blood pressure increased during exercise on both study days (P less than .01, compared to basal level), and showed no difference between normoxic and hypoxic conditions. Plasma pH was slightly higher during hypoxic exercise (P less than .05, compared to normoxia). We conclude that acute hypoxemia is a potent enhancing stimulus for ANF release during dynamic exercise and that ANF is probably a contributing factor in the dissociation of aldosterone secretion from the renin-angiotensin system under these conditions."
-How does technetium-HMPAO SPECT help in evaluating the effectiveness of carotid endarterectomy in patients with internal carotid artery stenosis?,"Use of technetium-HMPAO to demonstrate changes in cerebral blood flow reserve following carotid endarterectomy. Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy."
-What were the key findings regarding survival times between black and white patients with metastatic breast cancer in the Piedmont Oncology Association study?,"A comparison of treatment outcomes for black patients and white patients with metastatic breast cancer. The Piedmont Oncology Association experience. Prior studies have shown that black patients with breast cancer have poorer survival times compared with white patients even when adjusted for stage. Seventy-four black patients treated on six Piedmont Oncology Association (POA) protocols were compared with 74 randomly selected white patients treated with the same protocols to determine if race had any independent effect on response, time to progression, or survival time. Patients were evenly matched for pretreatment characteristics with the exception that white patients had a significantly higher percentage of bone metastases and significantly less skin involvement. Response rates and median time to progression were similar for black patients and white patients at 31% and 25%, and 9.3 and 9.1 months, respectively. Black patients had poorer survival times even when adjusting for covariables; median survival time was 14.3 months for black patients and 20.3 months for white patients (P less than 0.05). The reason for this survival difference in Stage IV patients is unclear, but is unlikely to be related to treatment. Additional research in this area will be necessary to resolve this issue."
-How does the type of muscle contraction (concentric vs eccentric) and exercise intensity affect exercise-induced muscle soreness?,"Exercise-induced muscle soreness after concentric and eccentric isokinetic contractions. The purpose of this two-part study was to determine whether the amount of exercise-induced muscle soreness differs between subjects who perform concentric and eccentric isokinetic contractions of their quadriceps femoris muscles. In experiment 1, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised at the same power level. In experiment 2, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised with maximal effort. Muscle soreness ratings, obtained by using a visual analogue scale, were taken immediately before exercise and at 24 and 48 hours postexercise. Changes in muscle soreness ratings between exercise groups from preexercise to postexercise periods were compared in both experiments, using a one-way between-subjects analysis of variance. There was no difference in the change in muscle soreness from preexercise to post-exercise periods between groups exercising at equal power levels. Subjects who exercised using eccentric contractions with maximal effort demonstrated greater increases in muscle soreness than those who performed concentric contractions. The results suggest that exercise intensity, rather than contraction type, may be the dependent factor in producing exercise-induced muscle soreness."
-How can ultrafast MR imaging help differentiate between liver hemangiomas and hepatic metastases?,"Differentiation between hemangiomas and metastases of the liver with ultrafast MR imaging: preliminary results with T2 calculations. We studied the efficacy of T2 measurements at high field strength in distinguishing between liver hemangiomas and hepatic metastases when an ultrafast (single-excitation) MR imaging technique is used. Fourteen patients with known liver tumors were imaged in a 2.0-T prototype ultrafast MR scanner with a spin-echo (infinite TR and TE of 30-340 msec) pulse sequence. Each image was obtained with a total data acquisition time of 20 msec. T2 calculations for hepatic metastases (n = 6) showed a mean of 79.3 +/- 13.5 msec, whereas hemangiomas (n = 8) showed a T2 of 139.8 +/- 18.8 msec (p less than .0001). T2 values of lesions had a smaller relative standard deviation than previously reported, and the range of T2 values of hemangiomas (119-181 msec) and metastases (68-103 msec) did not overlap. Our preliminary results suggest that T2 calculations with ultrafast MR imaging may be useful for differentiating hemangiomas from metastases. We hypothesize that T2 values obtained from ultrafast MR images are more reliable than those obtained from conventional MR images, primarily because of the elimination of T1 information and effects of motion on image signal intensity."
-What is the current status of thrombolytic treatment for patients with unstable angina according to the context?,"Thrombolysis in unstable angina: results of clinical studies. Ample evidence exists to support the major role of intracoronary thrombosis superimposed on a disrupted plaque in unstable angina. Consequently, thrombolytic treatment, already established to be highly beneficial in patients with acute myocardial infarction, might also be indicated in patients with unstable angina. The clinical response to thrombolytic treatment has been evaluated in several small-sized studies with inconsistent and somewhat deceiving results. Thus, the role of thrombolysis in the treatment of unstable angina is still controversial. Two ongoing large-scale, randomized, controlled trials, the Third Thrombolysis in Myocardial Infarction (TIMI III) in the United States testing recombinant tissue-type plasminogen activator and UNASEM in Europe testing anisoylated plasminogen-streptokinase activator complex will, it is hoped, solve the debate. At present, early thrombolysis might be considered for the treatment of the subset of patients with severe rest angina associated with transient ST-T ischemic changes."
-How does oximetry help in detecting sleep apnea syndrome (SAS) and quantifying apneic events?,"Does oximetry contribute to the detection of apneic events? Mathematical processing of the SaO2 signal. The purpose of this study was to assess the ability of continuous nocturnal oximetry to detect sleep apnea syndrome (SAS) and to recognize nonapneic oxyhemoglobin desaturations. Oxygen saturation oscillations, related to successive apneas in SAS or to apneic episodes in COPD or restrictive patients, were quantified using a new index: delta = 1/n sigma 1 n magnitude of delta(SaO2)/delta(t)(12-s intervals) Twenty-six patients (15 SAS, 8 COPD, and 3 restrictive patients) were included in a prospective study comparing nocturnal oximetry and polysomnography over 34 nights. In apneic patients, we found a strong correlation (r2 = 0.73, p less than 0.01) between time spent in apnea and the delta index. In COPD, the number of apneas was also correlated to the delta index (r2 = 0.92, p less than 0.01). A lower threshold for delta of 1.5 is accurate enough to detect apneas if initial SaO2 is greater than 93 percent. If initial SaO2 is greater than 93 percent, the delta threshold should be 0.8 (sensitivity 95 percent). Such a method could contribute to the accurate selection of patients for polysomnography."
-How did antibiotic treatment affect food intake and nutrient absorption in children with Shigella infection during the acute stage of the disease?,"Effect of antibiotics on food intake and absorption of nutrients for children with diarrhea due to Shigella. The effect of antibiotic therapy on intake of food and absorption of nutrients for 19 male children aged 1-5 years with suspected shigella infection was studied. The children were admitted to the hospital with acute diarrhea, high fever, abdominal pain, and greater than or equal to 25 red blood cells and white blood cells per high-power field in the stool. Microbiologic diagnosis was made within 48 hours of admission. On the basis of clinical and microbiologic criteria, children were classified as having mild or severe infection. Ten children with mild infection did not receive antibiotics, whereas nine children with severe infection were treated with ampicillin. After the children were rehydrated, a 72-hour balance study was carried out during the acute stage of infection with Shigella and was repeated 2 weeks after recovery. The levels of consumption of food and absorption of nutrients were estimated. During the acute stage of infection, such levels were higher for the children treated with antibiotics than for the untreated group. During the recovery phase, the levels of intake of food and absorption of nutrients were equal for both groups. Thus, children who are treated with appropriate antibiotics not only may recover from infection with Shigella more rapidly, but they also may be able to absorb nutrients more efficiently."
-How does bronchoscopy via the laryngeal mask provide advantages in assessing patients with malignant tracheal tumors and vocal cord paralysis?,Flexible bronchoscopy via the laryngeal mask: a new technique. Malignant tracheal tumours often cause airway obstruction and this may be aggravated by vocal cord paralysis due to invasion of the recurrent laryngeal nerve. Conventional endoscopic techniques performed under general anaesthesia do not give a simultaneous view of vocal cord function and the distal airways. The technique of bronchoscopy via the laryngeal mask allowed full assessment of the cause of stridor in a patient with a malignant tracheal tumour that was causing airways obstruction and vocal cord paralysis.
-What is the primary factor believed to be responsible for the development of diabetic retinopathy?,"On the pathogenesis of diabetic retinopathy. A 1990 update. Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane."
-What characteristic appearance did normal urethras demonstrate on T2-weighted MR images?,"Female urethra: MR imaging. The potential of magnetic resonance (MR) imaging in the evaluation of the female urethra was studied in 64 patients. Spin-echo T1- and T2-weighted images were obtained in all 64 patients, and contrast-enhanced T1-weighted images were also obtained in 27 patients. Urethral pathologic conditions, established with urethroscopy or histologic examination, or both, included urethral diverticula, inflammatory granuloma, and primary and metastatic neoplasms. On T2-weighted images, all normal urethras demonstrated a characteristic targetlike appearance with differentiation among the outer ring of low signal intensity, the middle zone of higher signal intensity, and the center of low signal intensity. After injection of gadopentetate dimeglumine, the targetlike appearance of the normal urethra was seen on the T1-weighted images. Urethral diverticula were detected with MR imaging in all nine patients with that diagnosis, and in each, MR imaging demonstrated urethral expansion, distortion of the zonal anatomy, and presence of fluid in the middle zone. Primary or metastatic urethral neoplasms were also detected with MR imaging in every patient with the diagnosis, but differentiation between benign and malignant disease was not possible. Local staging of primary or metastatic malignant disease was correct in eight of the 11 patients. In three patients, the inflammatory changes could not be differentiated from tumor invasion, resulting in overestimation of tumor extent."
-What is purpura fulminans and how is it related to meningococcemia in this case study?,"Purpura fulminans and adrenal hemorrhage due to group Y meningococcemia in an elderly woman. A 70-year-old previously healthy woman was admitted with a 1-day history of malaise, sore throat, nausea, vomiting, rigors, and confusion. She was found to be in septic shock with purpura fulminans and disseminated intravascular coagulation. She died within 36 hours of admission. Blood cultures grew Neisseria meningitidis group Y. Necropsy revealed evidence of shock and bilateral adrenal hemorrhage."
-What was the relationship between D-dimer plasma concentrations and intracardiac thrombus in patients with mitral stenosis?,"Intracardiac mobile thrombus and D-dimer fragment of fibrin in patients with mitral stenosis. OBJECTIVE--To investigate the relation between intracardiac thrombus and blood coagulability in patients with mitral stenosis. DESIGN--Prospective study. Cross sectional echocardiography and plasma concentrations of the D-dimer fragment of fibrin were used concurrently to detect intracardiac thrombus in patients with mitral stenosis. SETTING--Department of Medicine, National Cardiovascular Centre, Osaka, Japan. PATIENTS--63 patients with mitral stenosis. None of them had been receiving any anticoagulants or antiplatelet agents. MAIN OUTCOME MEASURES--Plasma concentrations of D-dimer in patients with a mobile intracardiac thrombus, those in patients with a non-mobile intracardiac thrombus, and those in patients without an intracardiac thrombus. RESULTS--A mobile intracardiac thrombus was found in 10 patients and a non-mobile thrombus in eight. The remaining 45 patients had no intracardiac thrombi. Plasma concentrations of D-dimer in the 10 patients with a mobile thrombus were all greater than 300 ng/ml (mean 983.3, 95% confidence interval 498.9 to 1467.7 ng/ml) and they were significantly higher than those in the patients with a non-mobile thrombus (226.2, 33.6 to 418.8 ng/ml) and the patients without an intracardiac thrombus (147.2, 110.4 to 184 ng/ml). CONCLUSIONS--A high plasma concentration of D-dimer seemed to reflect a hypercoagulable intracardiac state and may be a helpful indicator of the possible presence of mobile intracardiac thrombus in patients with mitral stenosis."
-What were the two treatment methods compared in this study for managing oesophageal achalasia?,Prospective clinical and manometric study comparing pneumatic dilatation and sublingual nifedipine in the treatment of oesophageal achalasia. A study was carried out in 30 patients affected by a mild or moderate degree of oesophageal achalasia to compare the clinical and manometric effects of sublingual nifedipine and pneumatic dilatation. Sixteen patients were dilated twice with Rider-Moeller dilators and 14 were treated with sublingual nifedipine 10-20 mg 30 minutes before meals. A manometric evaluation was performed before and six months after starting treatment. The clinical evaluation (according to Vantrappen's criteria) was performed every three months for a mean follow up of 21 months. In both groups of patients a significant (p less than 0.001) fall in lower oesophageal sphincter pressure was observed after treatment and excellent or good clinical results were observed in 75% of dilated patients and in 77% of patients treated with nifedipine. One patient could not tolerate nifedipine. No complications were observed after dilatation. It is concluded that longterm treatment with sublingual nifedipine and pneumatic dilatation are equally effective in the treatment of oesophageal achalasia of mild or moderate degree.
-How do p53 gene mutations potentially contribute to the development of lymphoid leukemias?,"Mutations of the p53 gene in lymphoid leukemia. p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase-polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias."
-How did the use of energy-weighted acquisition affect the quantitative analysis of SPECT thallium-201 images?,"Changes in quantitative SPECT thallium-201 results associated with the use of energy-weighted acquisition. The effect of utilizing energy-weighted acquisition on quantitative analysis of SPECT thallium-201 images was evaluated by simultaneously acquiring energy-weighted and windowed projection images in ten patients. The paired image sets were processed identically and evaluated by probability analysis of defect magnitude as indicated by a commercially available software analysis package. It was predicted that defect magnitude would increase as a result of improved image contrast. This was confirmed experimentally. One should be cautious in relying on strict quantitative criteria in cardiac studies with thallium-201, especially when major changes in the imaging system or technique are introduced."
-"What clinical and laboratory features characterize the ""lymphoma syndrome"" in childhood acute lymphoblastic leukemia?","Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the ""lymphoma syndrome"" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL."
-How does chronic xerostomia affect esophageal acid exposure and potential injury?,"Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency."
-How do insulin and glucagon contribute to liver recovery and cell proliferation in rats with acute hepatic failure?,"Insulin and glucagon therapy of acute hepatic failure. When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst of DNA synthesis reaches a maximum earlier than that seen in controls. Both hormones enhance the increment of hepatic putrescine essential for DNA synthesis through activation of ornithine decaroxylase and/or spermidine-N1-acetyltransferase. The enhancement of putrescine content by each hormone is additive. Putrescine supplementation promotes hepatic DNA synthesis after hepatectomy. Based on these data, we conclude that a combination of insulin and glucagon is effective in the therapy of acute hepatic failure in rats. The restoration of liver function as well as the stimulation of liver cell proliferation via putrescine production may contribute to this effect."
-What are the four common final pathways involved in understanding different types of obesity according to the MONA LISA hypothesis?,"Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis. The mechanisms underlying different types of obesity have been gradually clarified. Animal models with hypothalamic, genetic or dietary obesity have been examined with a feedback model. Four common final pathways are involved in this model. One of these final common pathways is the sympathetic nervous system. Most Obesities kNown Are Low In Sympathetic Activity states the MONA LISA Hypothesis. A second common pathway is the endocrine system involving adrenal glucocorticosteroids. The third common pathway is hyperphagia. Although not essential for most obesities, hyperphagia may be essential in animals with injury to the hypothalamic paraventricular nucleus. The final pathway is reduced physical activity. The tonic activity of these systems and their response to changes in the diet affect nutrient partitioning between fat and protein. This framework has been used to review genetic obesity, hypothalamic obesity and dietary obesity."
-"What was the main finding of the double-blind, placebo-controlled trial investigating topical PUVA treatment for persistent palmoplantar pustulosis?","A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis. The effect of topical PUVA was investigated in the treatment of patients with persistent palmoplantar pustulosis (PPP). In this double-blind, placebo-controlled trial of 27 patients with PPP there was an overall improvement of the hands and feet in both the active and placebo-treated areas and little difference between them."
-What was the operative mortality rate and 1-year actual survival rate in the Oregon Liver Transplantation Program during its initial two years?,"Initial two-year results of the Oregon Liver Transplantation Program. During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B."
-How do glomerular hypertrophy and sclerosis contribute to the progression of kidney disease?,"Evidence for a pathogenic linkage between glomerular hypertrophy and sclerosis. Primary renal disease of immunologic or nonimmunologic mechanisms induces loss of substantial nephron population. It is presumed that the initial loss of functioning nephrons causes alterations of function and metabolism in remnant nephrons, which per se are self-inflictive, leading to further loss of nephrons. The ultimate outcome of this vicious cycle is the end-stage kidney. The potential role of various pathophysiologic mechanisms has been explored. These studies have shown a tight link between glomerular hypertrophy and sclerosis. Analysis of individual glomeruli show a biphasic pattern of these two parameters. Early development of glomerular sclerosis takes place along with the hypertrophy of the glomerulus, and further advancement of sclerosis occurs with shrinkage in glomerular size. Thus, we propose that, after initial nephron loss, the remnant glomeruli are exposed to increased growth-promoting factors, which are self-inflictive in nature due to their capacity to produce excessive amounts of extracellular matrix in the mesangial area. When the excessive matrix obliterates the glomerular capillary lumen, a typical sclerotic lesion appears. This is a vicious and accelerating process, since sclerosis induces further reduction in the nephron population, thereby imposing greater influence of growth-promoting factors even on glomeruli that are initially resistant."
-What is endorectal sonography and what diseases can it be used to evaluate?,"Endorectal sonography in the evaluation of rectal and perirectal disease. Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases."
-How can quantitative motor performance tests help in early detection of Parkinson's disease?,"Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are ""at risk for"" Parkinson's disease and other related disorders."
-What was the average number of previous operations per joint in the study of elbow replacements for post-traumatic arthritis?,"Total replacement for post-traumatic arthritis of the elbow. Fifty-three of 55 consecutive elbow replacements for post-traumatic arthritis were followed for a minimum of two years (mean 6.3, range 2 to 14.4). The patients presented difficult management problems, having undergone an average of two previous operations per joint; 22 joints had suffered prior complications; 18 had less than 50 degrees of flexion and six were flail. One of three versions of the Coonrad prosthesis was employed in all. During the follow-up period, 10 patients underwent 14 revision procedures for aseptic loosening; 38 elbows are currently without progressive radiolucent lines. In two patients an elbow had to be resected, one for deep infection and the other for bone resorption following a foreign-body reaction to titanium. The current design of the Coonrad prosthesis offers a reliable option for the treatment of post-traumatic arthritis but should be used only in carefully selected patients over the age of 60 years."
-What were the key findings regarding treatment approaches for aortic graft infection in this study?,"Total excision and extra-anatomic bypass for aortic graft infection. Reports of high mortality and amputation rates following total excision and extra-anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared."
-"What type of cancer did the 77-year-old male develop in his gastric remnant, and how long after his initial gastric resection was it discovered?","Primary squamous cell carcinoma of a gastric remnant. A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting."
-How has the introduction of gadolinium-enhanced magnetic resonance imaging (MRI) impacted the diagnosis and treatment of acoustic neuromas?,"Acoustic neuroma: a cost-effective approach. A cost-effective approach to the diagnosis and treatment of acoustic neuromas continues to evolve as diagnostic methods improve. In the past 7 months, since gadolinium-enhanced magnetic resonance imaging (MRI) has become available in our practice, our screening and presurgical workup has changed. The purpose of this article is to outline the current philosophy of the senior authors in relation to acoustic neuroma management on the basis of 72 patients diagnosed from July 1988 to February 1989. With more sensitive diagnostic means, older less sensitive studies may be eliminated from the routine workup, thus maintaining cost-effectiveness while preserving the highest standard of patient care. The body of this article will review our current use of the many available diagnostic options and emphasize a cost-effective approach."
-What were the 4-year actuarial survival rates for patients who underwent aortic valve replacement with Omniscience and Omnicarbon valves?,"Aortic valve replacement with omniscience and omnicarbon valves. Clinical results achieved in 100 cases of aortic valve replacement with the Omniscience (O-S) valve during the period from 1980 to 1985 as well as 100 cases of aortic valve replacement with the Omnicarbon (O-C) valve during the period from 1985 to 1989 were studied. Concomitant surgical procedures including mitral valve replacement were performed in 63 patients in the O-S group and 67 patients in the O-C group. Cumulative follow-up in the two groups was carried out for a total of 559 and 273 patient-years, respectively. The overall 4-year actuarial survival rate was 82% +/- 3.8% in the O-S group and 89.5% +/- 3.2% in the O-C group, the corresponding rates for patients undergoing isolated aortic valve replacement being 82.9% +/- 4.2% in the O-S group and 91.9% +/- 3.5% in the O-C group. The overall 4-year actuarial event-free rate with respect to thromboembolic complications was 88.8% +/- 3.3% in the O-S group and 94.4% +/- 2.8% in the O-C group, as compared with the corresponding rates of 89.2% +/- 3.6% in the O-S group and 95.9% +/- 2.8% in the O-C group for patients undergoing isolated aortic valve replacement. The overall rate of valve-related complications, including thromboembolism, anticoagulant-related hemorrhage, perivalvular leak, infection, and structural failure, was 78.8% +/- 4.2% in the O-S group and 89.3% +/- 3.5% in the O-C group (p less than 0.05), and for isolated aortic valve replacement, 79.7% +/- 4.5% in the O-S group and 89.6% +/- 4.1% in the O-C group."
-What modifications were made to the titanium Greenfield filter to improve its performance compared to the original stainless steel version?,"Results of a multicenter study of the modified hook-titanium Greenfield filter. Initial efforts to modify the stainless steel Greenfield filter for percutaneous insertion led to development of a titanium Greenfield filter, which could be inserted by use of a 12F carrier. This device functioned well as a filter but had an unacceptable 30% rate of migration, tilting, and penetration. Therefore a titanium Greenfield filter with modified hooks was developed and has been tested in 186 patients at 10 institutions. Successful placement occurred in 181 (97%); placement of the remainder was precluded by unfavorable anatomy. A contraindication to anticoagulation was the most frequent indication for insertion (75%). All but two were inserted percutaneously, predominantly via the right femoral vein (70%). Initial incomplete opening was seen in four patients (2%), which was corrected by guide wire manipulation and asymmetry of the legs in 10 (5.4%). Insertion site hematoma occurred in one patient, and apical penetration of the cava during insertion occurred in a second patient. Both events were without sequelae. Follow-up examinations were performed at 30 days at which time 35 deaths had occurred. Recurrent embolism was suspected in six patients (3%) and two of three deaths were confirmed by autopsy. Filter movement greater than 9 mm was seen in 13 patients, (11%) and increase in base diameter greater than or equal to 5 mm was seen in 17 patients (14%). CT scanning showed evidence of caval penetration in only one patient (0.8%). Insertion site venous thrombosis was seen in 4/46 (8.7%) patients screened. The modified hook titanium Greenfield filter is inserted percutaneously or operatively through a sheath, eliminating concern for misplacement from premature discharge."
-What serious medical complications can arise from the use of traditional tribal enemas containing harmful substances like potassium dichromate?,"Colonic complications after toxic tribal enemas. Tribal enemas obtained from traditional healers are used widely in Southern Africa for a variety of indications. Inclusion of injurious substances such as potassium dichromate may cause serious colonic and renal complications. Nine such patients, in seven of whom chromate use was confirmed, presented after a mean delay of 7.3 days. All patients had bloody diarrhoea and vomiting and three underwent major colonic resection, requiring a total of ten procedures. One patient suffered mechanical perforation of the rectum, with subsequent necrotizing fasciitis, necessitating rectal excision. Eight patients had acute renal failure and seven required dialysis. One patient died. At follow-up one patient has chronic renal failure and only three are completely well. Although local medical practitioners are aware of the problem, the challenge of preventing harmful cultural practices remains."
-What are the potential advantages and limitations of intradermal hepatitis B vaccination compared to traditional intramuscular vaccination?,"Intradermal hepatitis B vaccination. The availability of vaccine since 1982 for immunization against hepatitis B virus (HBV) has had minimal impact on the disease; mass immunization has been suggested. Intradermal vaccination, which has precedent in prophylaxis of other infectious diseases, has been investigated as a low-cost alternative to traditional intramuscular HBV vaccination. Results of open and comparative trials indicate similar seroconversion rates for intradermal and intramuscular HBV vaccination routes in healthy adults. However, antibody titers and, presumably, duration of antibody protection appear to be decreased with intradermal HBV vaccination. Limited data suggest that demographic factors such as age and gender may affect vaccine responsiveness to intradermal HBV vaccine. Adverse skin reactions are common but do not represent a deterrent to continued intradermal HBV vaccination. There is a need for large-scale prospective comparative trials to substantiate the value of intradermal HBV vaccination. Nevertheless, the potential economic and epidemiologic benefit of intradermal vaccination justifies continued investigation for prevention of HBV infection."
-What novel diagnostic approach did the authors describe for obtaining tissue samples from Meckel cave lesions?,"Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology. The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction."
-What was the main objective of the study on outpatient pain clinics?,"Audit of outpatients: entering the loop. OBJECTIVE--To develop and test a method for routine data collection to observe current practice in outpatient pain clinics. DESIGN--Prospective questionnaire survey completed by consultants on each patient seen during October 1989 to May 1990. SETTING--Outpatient pain clinics of five teaching and five district general hospitals in Scotland and northern England. MAIN OUTCOME MEASURES--Number of new referrals and their source, and characteristics of pain at presentation. RESULTS--4354 forms were completed by 21 consultants over 29 weeks, corresponding to 2241 patients, of whom 981 were new referrals. The proportion of consultations at which new referrals were seen varied among the 10 clinics from 15% to 34%. The difference could not be accounted for by type of hospital. Sources of new referrals varied widely between the clinics (for example, range 22% to 78% for general practitioner referrals), as did new referrals by the type of pain (range 10.8% to 55.2% for low back pain, 10.5% to 32.5% for pain associated with surgery). However, these differences in types of patients seen could not be accounted for by variations in referral patterns among clinics. Problems identified in performing an audit of outpatients included the difficulty of obtaining firm diagnoses, the need for a method to link successive patient contacts, and the complexity of the presenting problem in many patients. CONCLUSIONS--It is possible to collect data for audit routinely in outpatient clinics. Observation of current practice in the clinics suggested possible unmet need or inappropriate management, which may require changes in practice."
-What were the two techniques used for aortic valve reconstruction in this study?,"Indications and limitations of aortic valve reconstruction. To elucidate the value of conservative operation for aortic regurgitation, all consecutive patients operated on between July 1988 and July 1990 were reviewed. Of 251 patients with aortic regurgitation, 107 (42.6%) had nonprosthetic operation. The mean age was 23 years, and 90 patients (84.1%) were rheumatic. Two techniques were used: repair (annular and leaflet plasties, 69 cases) and cusp extension with glutaraldehyde-treated pericardium (25 bovine, 13 autologous). There were two hospital deaths (1.8%), both in the repair group, and no late deaths or embolic events. Only 5 patients (4.7%) were anticoagulated. In the repair group there were 12 reoperations, four (5.9%) due to aortic and eight to mitral dysfunction. In the cusp extension group there were two reoperations due to mitral dysfunction. Echocardiographic follow-up showed better results with cusp extension. In conclusion, conservative operation for aortic regurgitation is possible in a high percentage of young rheumatic patients and does not require anticoagulation. Cusp extension is more reliable than repair in terms of early results, although its long-term durability is not yet known."
-How does HIV infection impact cell-mediated immunity in patients with chronic D hepatitis?,"Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis. To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication."
-What are the key anatomical features of the infrahyoid portion of the neck that make it suitable for axial imaging and differential diagnosis?,"Differential diagnosis of head and neck lesions based on their space of origin. 2. The infrahyoid portion of the neck. The infrahyoid portion of the neck can be considered as a series of contiguous fascial planes and intervening spaces that lend themselves well to axial imaging. These spaces can serve as a basis on which to formulate differential diagnoses for diseases in this region. This pictorial essay describes the fascia and fascial spaces of the infrahyoid portion of the neck. The contents of each space, the common abnormalities affecting the space, and the characteristic displacements produced by disease in each space are reviewed."
-What were the independent predictors of mortality identified in the multivariate analysis of patients with congestive heart failure?,"Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically."
-What were the primary prognostic factors identified in this study of carcinoid tumours in the gastrointestinal tract?,"Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome. This study represents retrospective analysis of 87 patients with a carcinoid tumour of the gastrointestinal tract seen and followed in the British Columbia Cancer Agency (BCCA) from 1960 to 1986. In 49 cases, the primary site was the small bowel. The rest of the cases were distributed as follows: 11 appendix, 10 rectum, 5 stomach, and 7 undetermined. We extrapolated the Dukes' and modified Astler-Coller surgicopathological classifications used for colorectal cancer for use in our cases of carcinoid tumour of the gastrointestinal tract. A strong correlation was found, using this staging, with disease-specific survival. Other prognostic factors included histologic differentiation, the presence of macroscopic residual disease after initial surgery, and level of 5-hydroxyindoleacetic acid (5-HIAA) in urine. Among 51 patients with surgically grossly removed disease, there was a tendency for the development of distant and distant/locoregional recurrence more often than locoregional recurrence alone. The liver was the commonest site of distant recurrence. Analysis of the effect of radiotherapy or chemotherapy on carcinoid tumour of the gastrointestinal tract proved unsuccessful because only a small portion of the patients had this treatment, and it was used mainly for palliation."
-What are the key characteristics and management strategies for neurofibromatosis-2?,"Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described."
-What were the most common tumor types observed in the study of children treated for brain tumors?,"Growth hormone deficiency following radiation therapy of primary brain tumors in children. The medical records of 123 patients treated for brain tumors at Children's Hospital and Medical Center, Seattle, Washington, between 1985 and 1987 were reviewed. The endocrinological complications of radiation therapy and the effectiveness of growth hormone (GH) replacement therapy were assessed. These were the first 2 years after synthetic GH became available. The disease pathology was confirmed at craniotomy or biopsy in 108 patients. Ninety-five children completed radiation therapy and 65 of these were alive at the time of review; these 65 children represent the study population. The most common tumor types were medulloblastoma, craniopharyngioma, and ependymoma. Endocrine evaluation was initiated with changes in the patients' growth velocity. Patient workup included skeletal x-ray films for determination of bone and analysis of thyroxin, thyroid-stimulating hormone, and somatomedin-C levels. Following 1-dopa and clonidine stimulation, provocative studies of GH levels were performed. Growth hormone failure and short stature were observed in 26 children, most commonly in the 2nd year after tumor treatment. Eight patients with GH failure were also hypothyroid. Hormone replacement therapy was initiated with recombinant GH, 0.05 mg/kg/day, and all children so treated showed an increase in height, with eight patients experiencing catch-up growth. There were no complications of therapy or tumor recurrence. Studies of baseline bone age and somatomedin-C levels on completion of radiation therapy are recommended. Comprehensive endocrine studies should follow changes in the patients' growth velocity. With early GH replacement, catch-up growth is possible and normal adult heights may be achieved."
-What is the prevalence and characteristics of subarachnoid hemorrhage (SAH) in patients with sickle-cell disease based on the University of Illinois study?,"Subarachnoid hemorrhage in sickle-cell disease. The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed."
-What defines the abnormal B-cell population in peripheral blood from multiple myeloma patients?,"Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage."
-What was the most effective body-support system for preventing heel ulcers in bedridden patients according to the study?,"Preventing heel ulcers: a comparison of prophylactic body-support systems. Five commercially available body-support systems used in the prevention of decubitus heel ulcers were objectively compared for their capacity to dissipate or decrease pressure concentration at the most prominent posterior aspect of the heel in bedridden, insensate patients. The Foot Drop Stop, a foam heel suspender, completely eliminated contact between the heel and the bed, and it was the most successful in decreasing pressure concentration. The space boot and foam heel protectors were far more successful than sheepskin rugs or polyester heel protectors, which provided little protection to the prominent heel."
-What are the potential causes of unilateral hydrocephalus identified in this prenatal sonographic study?,"Unilateral hydrocephalus: prenatal sonographic diagnosis. We studied six cases of unilateral hydrocephalus detected prenatally to analyze the sonographic features of the abnormality and to determine the cause and clinical outcome. In all cases, third-trimester sonograms showed marked unilateral lateral ventriculomegaly (mean atrial width, 4.4 cm) and normal contralateral lateral, third, and fourth ventricles. Five of the six cases had marked thinning of the cortical mantle on the affected side and shift of midline structures to the contralateral side. The causes of unilateral hydrocephalus were agenesis or stenosis of the foramen of Monro in three cases, transient obstruction of the foramen in one fetus with an intraventricular hematoma, underlying brain dysplasia in one fetus with a variant of holoprosencephaly, and undetermined in one case. All six neonates had placement of a ventriculoperitoneal shunt catheter; four of these have had normal cognitive development at follow-up. The remaining two infants have moderate to severe developmental impairment. Unilateral hydrocephalus is a rare anomaly that can be recognized by prenatal sonography. Even though unilateral ventriculomegaly may be marked, early diagnosis and treatment may result in a favorable clinical outcome."
-What is ankle arthrodesis and when should it be considered as a treatment option?,"An overview of ankle arthrodesis. Arthrodesis of the ankle can result in a painless, normal walking gait. However, complications in ankle arthrodesis can be major, and can occur when anatomy, deformity, or bony deficiency is not properly addressed. Nonoperative treatment should always be considered first, and, if possible, an open or arthroscopic ankle debridement can provide significant pain relief. Arthrodesis should be considered after conservative treatment fails. Infections, deformity, sensory deficiencies, and bony defects require special consideration. The use of bone graft and internal or external compression will enhance the likelihood of a successful arthrodesis."
-What is a glandular odontogenic cyst and when was it first described?,"Glandular odontogenic cyst: clinicopathologic analysis of three cases. The glandular odontogenic cyst is a rare cyst of odontogenic origin, first described in 1988 by Gardner et al. Three previously unreported glandular odontogenic cysts are presented; none recurred after the initial surgical treatment, and one example was associated with a squamous odontogenic tumor-like proliferation in the wall. Ten similar cases were found in the literature, and their clinical and roentgenographic features, and follow-up, have been compared with the present cases."
-What are the different clinical categories of scleral inflammation and their progression based on the study?,"Progression of scleral disease. The clinical features of 290 patients with scleral inflammation were reviewed to determine whether a classification based on the anatomical site and clinical appearance of the disease at presentation reflected its natural history. The authors' results confirm that the majority of patients remain in the same clinical category throughout the course of their disease. Of the 104 (35.9%) patients who experienced a recurrence of their disease, only 12 had progressed from diffuse to nodular disease, and 10 patients who originally had nodular disease developed scleral necrosis. Patients with necrotizing scleritis were older than patients in the other groups and more frequently had an associated systemic disease than patients with either diffuse or nodular disease; necrotizing scleritis was the most difficult disease to treat. Diffuse anterior scleritis had a lower incidence of visual loss (9%) than either nodular scleritis (26%) or necrotizing disease (74%), and, therefore, the authors consider nodular scleritis a disease of intermediate severity between diffuse scleritis and necrotizing disease. In this series, 12% of patients presented with posterior scleritis, and visual loss was most frequent in this group (84%)."
-How does a prolonged difference in diastolic blood pressure affect the risks of stroke and coronary heart disease?,"Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease. The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both."
-How do soluble and diffusible gases like helium and nitrous oxide affect the size of air emboli in pulmonary arterioles?,"Effect of ventilation with soluble and diffusible gases on the size of air emboli. Pulmonary hypertension resulting from venous air embolism is known to increase after ventilation with highly soluble and diffusible gases. Exacerbation of the hypertension could be due to further blockage of the circulation if the bubbles enlarge as a result of ingress of gas by diffusion. This mechanism has been frequently cited but lacks direct proof. To determine directly whether intravascular air bubbles actually enlarge when highly soluble and diffusible gases are inspired, we used microscopy to measure the size of gas emboli in vivo. When air bubbles were injected into the right atrium, the bubbles that appeared in pulmonary arterioles were larger during ventilation with helium or nitrous oxide than with air. Air bubbles injected into the pulmonary artery enlarged when the inspired gas was changed to helium or nitrous oxide. The direction, magnitude, and timing of changes in bubble size were consistent with a net diffusion of gas into the bubbles. These data support the idea that venous air emboli enlarge during ventilation with soluble and diffusible gases and thereby cause further vascular obstruction."
-How do platelets contribute to the resistance of thrombi to lysis in unstable angina?,"Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants."
-What are the different types of viruses that can cause hepatitis?,"Viral hepatitis. The new ABC's. Hepatitis may be caused by hepatitis A virus, hepatitis B virus, hepatitis C virus (classic non-A non-B viral hepatitis), hepatitis D virus (delta agent), and hepatitis E virus (epidemic non-A non-B viral hepatitis). Cytomegalovirus, Epstein-Barr virus, and herpes simplex virus may also occasionally cause hepatitis. Some forms of hepatitis carry the risks of chronic infection, cirrhosis, or hepatocellular carcinoma. Treatment options for viral hepatitis are limited and, in many cases, still under investigation. Prophylaxis is available for many forms of hepatitis and should be offered to those at risk."
-How did antibiotic therapy affect vitamin B12 absorption in subjects with atrophic gastritis?,"Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria."
-What is telangiectatic osteosarcoma and how has its prognosis changed over time?,"Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy."
-What medical complications can arise from large vessel occlusion in patients with systemic lupus erythematosus (SLE)?,"Large vessel occlusion with vasculitis in systemic lupus erythematosus. Patients with SLE may have acute large vessel occlusion due to vasculitis and/or circulating antiphospholipid antibodies, as illustrated by the case we have reported. Unfortunately, delayed medical attention led to gangrene of the foot and amputation. Early recognition and appropriate treatment may significantly decrease morbidity and mortality. Medical treatment may include corticosteroids, thrombolysis, anticoagulation, or immunosuppression."
-What are the key hemodynamic effects of ACE inhibitors in treating hypertension?,"Angiotensin converting enzyme inhibitors. Present and future. The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the ""more local"" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents."
-How does the Valsalva maneuver help in detecting left ventricular diastolic function abnormalities in patients with coronary artery disease or systemic hypertension?,"Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension. It has been suggested that changes in left atrial pressure may mask or mimic left ventricular diastolic function abnormalities detected by Doppler echocardiography. The effect of the Valsalva maneuver on the transmitral flow velocity profile was therefore studied in 28 patients without evidence of coronary artery disease (group 1, mean age +/- standard deviation 50 +/- 8 years) and in 94 patients with evidence of coronary artery disease or systemic hypertension (group 2, mean age 54 +/- 10 years). At baseline, group 2 patients had higher peak late diastolic filling velocity (A), lower peak early (E) to late diastolic filling velocity (E/A) ratio and longer isovolumic relaxation time than group 1, whereas heart rate, E velocity and E deceleration time were similar in both groups. During Valsalva, both groups had similar increases in heart rate and similar decreases in E velocity but E/A ratio decreased significantly only in group 2 because of a lesser decrease in A velocity. The E/A ratio was greater than or equal to 1.0 both before and during Valsalva in all but 1 patient in group 1, whereas in group 2, 32 patients had E/A greater than or equal to 1.0 at rest and during Valsalva, 33 patients had E/A greater than or equal to 1.0 at rest but less than 1.0 both at rest and during Valsalva. Using group 1 as controls, prevalence, specificity and positive predictive value of E/A less than 1.0 in group 2 were 31, 100 and 100% at rest and 66, 96 and 98% during Valsalva."
-How does the lipid membrane composition differ in the cerebral tissue of Rett syndrome patients compared to age-matched controls?,"Membrane cerebral lipids in Rett syndrome. The lipid membrane composition of cerebral tissue from 5 patients with classic Rett syndrome, ages 12-30 years, and from 14 age-matched controls was studied. The results demonstrated a selective loss of myelin-associated lipids and an enrichment of gangliosides in temporal white matter. The ganglioside pattern revealed an increase of astroglial cell-associated gangliosides and reduced proportions of gangliosides GD1a and GT1b. This latter finding may be crucial in synaptic function. The fatty acid compositions of ethanolamine phosphoglyceride, choline phosphoglyceride, and galactosylceramide were normal."
-How does inspiratory muscle fatigue affect subsequent high-intensity exercise performance?,"Effect of respiratory muscle fatigue on subsequent exercise performance. The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled to volitional exhaustion at 90% of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise."
-Does temporary occlusion of hypogastric arteries reduce blood loss during radical retropubic prostatectomy?,"Effect of temporary occlusion of hypogastric arteries on blood loss during radical retropubic prostatectomy. We report on a prospective, partially randomized study of 130 patients, examining the effect of temporary occlusion of the hypogastric arteries on intraoperative blood loss, perioperative blood replacement and change in preoperative to postoperative hematocrit. We observed no significant difference in any of these parameters when comparing patients who did and did not undergo intraoperative occlusion of the hypogastric arteries. These findings suggest that temporary occlusion of the hypogastric arteries during radical prostatectomy does not have a major effect on the blood loss associated with this operation. Extensive collateral circulation to the prostate and a substantial venous component of blood loss may explain these findings. Banking of 3 units of autologous blood preoperatively would have decreased the need for homologous transfusions in the majority of patients."
-What cross-resistance patterns were observed in the ACNU-resistant glioma sublines?,"Cross-resistance patterns in ACNU-resistant glioma sublines in culture. Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance."
-What are the key differences in management and recurrence rates between suprahyoid and infrahyoid cystic hygromas?,"Cervicofacial cystic hygroma. Patterns of recurrence and management of the difficult case. Cystic hygromas usually present in infancy or early childhood as compressible masses that may rapidly and intermittently enlarge. While they may arise in any anatomic location, hygromas of the head and neck are especially difficult to manage since enlargement may cause serious sequela such as airway obstruction, feeding difficulties, and speech pathology. Complete extirpation of these lesions is often impossible, and recurrence rates are accordingly high. We reviewed our 10-year experience in treating cervicofacial cystic hygromas. Of 34 patients, 21 had lesions cephalad to the hyoid and 13 had lesions caudal to the hyoid. While none of the 13 children with infrahyoid lesions demonstrated feeding or respiratory difficulties, eight of 21 children with suprahyoid involvement presented with dysphagia or airway compromise. The recurrence rates for infrahyoid and suprahyoid lesions were 15% and 81%, respectively. Those children with suprahyoid hygromas also experienced an increased operative complication rate compared with patients with infrahyoid involvement. Principles of management for suprahyoid and infrahyoid lesions are described, including the specific management of lingual, submandibular, parotid, and parotofacial hygromas."
-What is the primary goal of studying the mechanisms behind essential hypertension?,"Can essential hypertension be subclassified with respect to mechanism? Hypertension may result from a variety of abnormalities. The rise in blood pressure may trigger other secondary events that further influence cardiovascular homeostasis. The ability to measure some markers associated with hypertension or the responsiveness of blood pressure to nutritional interventions or to specific therapeutic agents may also have pathogenetic implications. The ultimate goal of further knowledge in this area should be to understand the fundamental abnormalities responsible for hypertension. Such insight would permit more effective treatment and, perhaps, primary prevention of this ubiquitous and multifaceted disorder."
-What was the primary objective of the study on imazodan for treating chronic congestive heart failure?,"Effectiveness of imazodan for treatment of chronic congestive heart failure. The Imazodan Research Group. A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo."
-What is the median weartime for the optimum anal continence plug design in the study?,"The anal continence plug: a disposable device for patients with anorectal incontinence. Anorectal incontinence is most commonly found in the elderly, but colorectal surgeons now see an increasing number of younger patients with this condition. Although medical and surgical treatments are available, a proportion of patients remain refractory to therapy. We investigated the efficacy of three designs of anal continence plug. 8 women and 2 men (mean age, 52 years) who were incontinent to both liquid and solid stool tested each plug for three consecutive weeks. 1 patients withdrew from the study. The median weartime for the optimum plug design was 12 h, and there were no episodes of incontinence in 82% of the periods during which the plug was in place. Patients required a median of eleven plugs per week, and in 82% of cases insertion was as easy as with a suppository. Plugs may have a place in the management of patients with anorectal incontinence."
-What were the survival rates for different stages of cervical cancer when treated with californium-252 neutron brachytherapy?,"A review of californium-252 neutron brachytherapy for cervical cancer. Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals."
-What were the key findings of the study comparing polyamide and polypropylene membranes for plasma separation?,Comparison of polyamide and polypropylene membranes for plasma separation. Plasma separation experiments were made with polyamide experimental prototype hollow-fiber plasma filters with surface areas between 0.025 m2 and 0.1090 m2 using bovine blood collected in acid citrate dextrose (ACD). The maximum filtration velocity rose with the wall shear rate gamma w as gamma w 0.72 +/- 0.02 and decreased with the length of fiber L as L-0.41 with a correlation coefficient of 0.97 +/- 0.02. The results were similar to those with polypropylene fibers. We also investigated the occurrence of hemolysis as a function of shear rate and transmembrane pressure. The free hemoglobin concentration of filtered plasma was checked using a U.V. spectrophotometer. It was concluded that polyamide membrane filters can be safely used for plasma separation from blood.
-How does chemotherapy affect natural killer (NK) cell activity in breast cancer patients?,"The relationship of chemotherapeutic and endocrine intervention on natural killer cell activity in human breast cancer. Peripheral blood natural killer (NK) activity against K562 target tumor cells was monitored in patients with breast cancer receiving no treatment, combination chemotherapy, and/or endocrine therapy. NK activity in untreated Stage I patients with no evidence of disease (ned) was significantly higher than in healthy controls. NK activity was shown to decline in individuals with cytotoxic drug therapy (P equals 0.036). There also were reduction in lymphocyte recoveries concomitant with chemotherapeutic intervention (P less than 0.001). Lymphocyte counts were incorporated in a calculation of absolute NK activity that more accurately reflected the significant reduction in NK activity that occurred in patients with localized and systemic disease on chemotherapy. Different chemotherapeutic agents were found to selectively affect NK activity. Stage II patients on phenylalanine mustard (P)/5-fluorouracil (F) (PF) and cyclophosphamide (C)/methotrexate (M)/5-fluorouracil (F) (CMF) protocols showed significant reductions in overall NK activity relative to healthy controls and Stage I patients with ned. Patients on P/doxorubicin (A)/F/tamoxifen (Tx) (PAFT) protocols showed reduced NK activity relative to Stage I patients. Patients on the short-dose C/A (CA) protocol showed normal levels of overall NK activity. High-risk Stage I patients on methotrexate (M)/F (MF)with sequential leucovorin rescue and patients with metastatic disease on endocrine therapy, i.e., Tx or megestrol acetate (Meg) showed overall NK activities in the range of healthy controls. Patients with systemic disease on CMF, CMF/vincristine/prednisone (CMFVP), vinblastine/A/thiotepa/fluoxymesterone (VATH), mitomycin/mitoxantrone (MtMx), and A regimens showed overall levels of absolute NK that were significantly less than either healthy controls or metastatic patients undergoing endocrine therapy. NK cytolytic data, monitored at multiple effector to target ratios, were subjected to exponential regression analysis. The elevation of NK cell responses in Stage I patients with ned and the decline of NK cell responses with cytotoxic chemotherapy were due to alterations in the maximal plateau levels of NK cell cytotoxicity represented by the A (asymptote) values. The k values obtained on regression analysis and indices of the relative killing capacities of individual NK cells remained unaltered in all populations. These results suggest that the cytolytic lymphocyte NK pool, elevated in Stage I patients with cancer, selectively declines as a result of cytotoxic therapy."
-How does the atrial natriuretic factor (ANF) hormonal system contribute to sodium excretion in dogs with experimental heart failure?,"The atrial natriuretic factor hormonal system in the regulation of sodium excretion in dogs with experimental heart failure. In response to a meat meal containing 125 mEq of sodium, conscious dogs (n = 5) with an arteriovenous (AV) fistula and chronic compensated heart failure exhibited temporally related increases in postprandial plasma immunoreactive atrial natriuretic factor (iANF), right atrial pressure, and sodium excretion. In separate experiments, two weeks of dietary sodium restriction produced similar marked stimulation of renin and aldosterone both in normal dogs (n = 5), and in AV fistula dogs (n = 5) with chronic high circulating levels of ANF. Plasma iANF did not change (P greater than .05) in either group. These results suggest that the ANF system is involved in the postprandial regulation of sodium excretion in the AV fistula dogs with compensated heart failure. In the postabsorptive state, however, the activity of the renin-aldosterone axis is closely related to dietary sodium intake and appears to function independently of the ANF system for the prevention of sodium loss."
-What are the key histologic and clinical characteristics of malignant blue nevus based on the analysis of 12 cases?,"Malignant blue nevus. To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm."
-What paraneoplastic syndrome was observed in the patient with pheochromocytoma and how was it potentially related to interleukin-6?,"Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production. Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome."
-What was the average cost of averting death or severe disability through neurosurgical intervention in this study?,"Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community."
-How was HLA class I antigen expression evaluated in patients with chronic hepatitis B?,"HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy."
-What factors were found to potentially delay malaria diagnosis in this urban emergency department study?,"Malaria in an urban emergency department: epidemiology and diagnostic features of 25 cases. This article presents a retrospective study of 25 patients diagnosed with malaria in an urban emergency department (ED) between June 1986 and June 1989. The mean annual case rate of malaria in this study group was more than three times the national rate. This may be ascribed to the notable ethnic diversity of the population. A history of travel to an area endemic for malaria was eventually elicited from all patients. The most common chief complaint was fever (56%) followed by abdominal pain (12%). Temperatures were elevated in 70% of the patients, with a mean temperature of 102.9 degrees F (39 degrees C). Gender was found to play a role in delaying diagnosis, with women accounting for 83% of a group of patients requiring multiple ED visits before diagnosis. The authors conclude that malaria must be considered when diagnosing patients in ethnically diverse populations. Gender may be associated with a delay in diagnosis. A careful travel history and a peripheral smear are aids in rapid diagnosis."
-What did the study reveal about interferon-alpha production in acute versus chronic hepatitis B virus infection?,"Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection. In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus."
-What factors were associated with the embolization of the prosthetic aortic valve in the young woman described in this case report?,"Death by embolization of prosthetic aortic valve. This report describes a case in which a young woman died from embolization of her prosthetic aortic valve. The discussion includes the embolization's association with chronic intravenous narcotism, recurrent bacterial endocarditis, and acute cocaine toxicity."
-What makes flunarizine unique among calcium antagonists in terms of its effects on the brain?,"Flunarizine in migraine: a minireview. Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena."
-What was the primary purpose of this study comparing ondansetron and metoclopramide?,"A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy."
-What was the outcome of thrombolytic therapy in patients with unstable angina in this study?,"Thrombosis and thrombolysis in unstable angina. Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures."
-"What is the relationship between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension?","Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system. An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based."
-What was the primary diagnostic challenge in identifying the cause of neurological deterioration in this 1-year-old male infant?,"Intracranial arteriovenous fistula manifesting as progressive neurological deterioration in an infant: case report. This 1-year-old male infant had been diagnosed with cerebral degenerative disease because he developed psychomotor regression, and brain atrophy was demonstrated on computed tomography. He underwent magnetic resonance imaging, which suggested a cerebrovascular malformation. Cerebral angiography disclosed an arteriovenous fistula, fed by an anterior cerebral artery and directly draining into a cortical vein. The occlusion of the feeding artery was followed by a satisfactory recovery. The mechanism of the neurological symptoms in this patient is thought to be caused by a steal phenomenon and compression of the brain stem by venous engorgement in the posterior fossa."
-What was the main finding of the study regarding low power laser biostimulation for chronic oro-facial pain?,Low power laser biostimulation of chronic oro-facial pain. A double-blind placebo controlled cross-over study in 40 patients. The efficacy of low power laser stimulation in the treatment of chronic oro-facial pain conditions was investigated in a double-blind placebo controlled modified cross-over study in 40 patients. The laser was an invisible infrared (IR) diode laser with an emission at 904 nanometer (nm). Treatment effect was evaluated by means of VAS-scales and global assessment of pain. Outcome of treatment was correlated to changes in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). The clinical impression was that placebo was superior to laser stimulation. No statistically significant difference between the analgesic effect of the laser and placebo irradiation was found on VAS-scales. A significant (P = 0.05) increase in 5-HIAA excretion was found in the placebo group. It is concluded that the possibility of a substantial placebo response should be taken into consideration using 904 nm (IR) lasers for pain treatment in patients with this type of chronic oro-facial pain.
-What was the frequency of dysplasia or cancer found in this colonoscopic screening of ulcerative colitis patients with more than 15 years of disease duration?,"Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question."
-What types of melanocytic nevi in children and adolescents may indicate an increased risk of malignant melanoma?,"Important melanocytic lesions in childhood and adolescence. Melanocytic nevi are common in children and adolescents, and the preponderance of these lesions are benign. Congenital melanocytic nevi, dysplastic nevi, and large numbers of common acquired nevi, however, may indicate an increased risk of malignant melanoma. With the exception, possibly, of giant congenital nevi, melanoma associated with these lesions generally occurs in adulthood. Nonetheless, some patients can be identified as being at increased risk for the development of melanoma during childhood. The poor prognosis associated with advanced melanoma and the curability of early lesions underscore the importance of prompt recognition of melanoma when it does occur in children. Furthermore, physicians who care for children are in a key position to decrease risk of melanoma throughout the lifespan by encouraging avoidance of excessive sun exposure during childhood."
-What was the dosage and administration method of metoclopramide used in this study for treating gastroparesis?,"Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. We investigated the safety and efficacy of short-term s.c. administration of metoclopramide in the treatment of symptomatic gastric stasis. Ten patients with gastroparesis, documented by abnormal solid phase radionuclide gastric emptying study, were treated with 10 mg (2 ml) of s.c. metoclopramide every 6 hr for 3 days. Patients gave themselves the injections as outpatients. Questionnaires were then completed concerning symptom relief, local side effects and adverse reactions. A repeat gastric emptying study was obtained immediately after the last dose of metoclopramide. Serum metoclopramide concentrations were obtained at trough, 1, 2, 3, 4 and 5 hr postadministration and serum prolactin levels at trough, 1 and 3 hr. Pharmacokinetic analysis showed mean peak metoclopramide concentration at 30 min of 99.7 +/- 47.1 ng/ml with measured levels of 93.9 +/- 106.83 ng/ml at 60 min and return to trough values by 4 hr; trough prolactins remained elevated above normal values. Gastric stasis improved from a base-line retention of 78.7% of radioisotope at 2 hr to 72.5% after 3 days of therapy (P = .65). Eight patients reported significant improvement in symptomology and two patients reported lessening of symptoms such as nausea, vomiting, bloating, abdominal pain, heartburn and vomiting. The side effects were minimal and did not interfere with completion of the protocol. We demonstrated that s.c. administration of metoclopramide was well accepted by patients and resulted in subjective and objective improvement of gastric stasis. In addition, serum metoclopramide concentrations were comparable with other parenteral routes of administration. Furthermore, serum prolactin levels may provide both a bioassay of efficacy and a marker for monitoring compliance."
-"How does 1,25-dihydroxyvitamin D3 affect the interferon-gamma-induced expression of MHC class II antigens on HEp-2 cells?","Differential enhancement of interferon-gamma-induced MHC class II expression of HEp-2 cells by 1,25-dihydroxyvitamin D3. Interferon-gamma (IFN-gamma) induces the expression of MHC class II antigens on non-lymphoid cells. In this study we investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the most active metabolite of vitamin D3, on the IFN-gamma-induced expression of MHC class II antigens on HEp-2 cells. We found that 1,25(OH)2D3 enhanced the IFN-gamma-induced expression of HLA-DR on these cells. Differential effects on the MHC class II antigens HLA-DR, -DQ and -DP were also observed."
-What were the most common late complications following abdominal aortic operation in this study?,"Reoperations for late complications following abdominal aortic operation. Fifty patients were identified who, following abdominal aortic operation, developed late complications affecting the vascular graft or endarterectomy and who underwent their first reoperation between 1979 and 1989. Thrombosis was the commonest complication affecting 28 (56 per cent) patients, followed by false aneurysm in 11 (22 per cent), enteric fistula in nine (18 per cent) and graft infection in two (4 per cent). The 30-day mortality rate for reoperation was 8 per cent; longer follow-up revealed mortality rates of 22, 50 and 63 per cent at 1, 3 and 5 years respectively. Thirty-four complications required reoperation within 5 years of the original surgery. Reoperation was needed for 35 patients whose original pathology was occlusive disease and for 15 whose original pathology was aneurysm. The nature of the complication was related to initial pathology; thrombosis was far commoner in those with occlusive disease, and enteric fistula and false aneurysm were commoner in those with aneurysmal disease."
-What was the cumulative percentage of patients free of arrhythmia after serial drug treatment in this study?,"Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events."
-How does the p53 gene mutation correlate with the progression of chronic myelocytic leukemia (CML) in this patient's case study?,Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
-What percentage of radiologic modalities showed inaccuracies in assessing lumbar spine fusions in this study?,"Correlation of radiologic assessment of lumbar spine fusions with surgical exploration. Although inspection of posterolateral lumbar fusion is the best method of determining its solidity, routine exploration of the fusion is somewhat impractical because of the morbidity and expense involved. Removal of internal fixation devices or implantable batteries or reoperation for failed back surgery enabled the exploration and assessment of lumbar spine fusions in 214 operations on 175 patients. The preoperative radiologic assessment (plain roentgenographs, polytomography, bending films, and computed tomographic scans) were correlated with surgical findings. This study indicated a significant percentage of inaccuracy of all radiologic modalities used. Noncorrelations were present in 36% of plain roentgenographs, 41% of polytomograms, 38% of bending films, and 43% of computed tomographic scans. Radiologic inaccuracy was manifest on both the positive and negative sides. Computed tomographic scanning presented the lowest percentage of inaccuracy (22%) and bending films the highest percentage (27%). Based on these findings, there exists the need for more accurate noninvasive methods to determine the solidity of spine fusions."
-What are the typical clinical features associated with cervicocranial arterial dissection?,"Cervicocranial arterial dissection. Dissection of the cervicocranial arteries is becoming more frequently recognized as a cause of neurological disorders. Typical clinical features seen with dissection include unilateral headache, oculosympathetic palsy, amaurosis fugax, and symptoms of focal brain ischemia. The diagnosis of carotid or intracranial dissection is usually best confirmed by angiography, although magnetic resonance imaging and computed tomography have been shown to visualize intimal dissection. The prognosis in cases of spontaneous dissection is generally benign unless the initial manifestation involves infarction with substantial deficit. The best approach to treatment appears to be the administration of the anticoagulant, heparin, followed by warfarin or antiplatelet therapy. Surgical intervention is reserved for cases of progressive or recurrent ischemic complication that occurs despite the administration of adequate doses of anticoagulants."
-What factors were significantly associated with an increased risk of cholelithiasis in childhood cancer patients after treatment?,"Cholelithiasis after treatment for childhood cancer. The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones."
-What were the key findings of the comparison between digital examination and anal endosonography in evaluating anal fistulae?,"Comparison between anal endosonography and digital examination in the evaluation of anal fistulae. A prospective trial was performed comparing the accuracy of digital examination and anal endosonography in defining the anatomy of anal fistulae. Before operation 38 consecutive patients were assessed by the consultant in charge of the case, by a research fellow and by anal endosonography involving two radiologists. These findings were compared with the operative findings. Consultants correctly identified 26 of 33 internal openings, 29 of 34 primary tracks and 15 of 21 secondary tracks. The research fellow correctly identified 26 internal openings, 24 primary tracks and 10 secondary tracks. There was no significant difference between the accuracy of consultants and the research fellow. Anal endosonography identified 10 internal openings based on initial criteria. This rose to 24 when revised ultrasonographic criteria were applied. There was no statistical difference between consultant assessment and anal ultrasonography in correctly identifying intersphincteric and transphincteric tracks. Ultrasonography is unable to assess primary superficial, suprasphincteric and extrasphincteric tracks or secondary supralevator and infralevator tracks. Consultant assessment of secondary supralevator and infralevator tracks was correct in 78 per cent of cases."
-What was the aim of the study in developing a test for gastric emptying and small bowel transit?,"Towards a less costly but accurate test of gastric emptying and small bowel transit. Our aim is to develop a less costly but accurate test of stomach emptying and small bowel transit by utilizing selected scintigraphic observations 1-6 hr after ingestion of a radiolabeled solid meal. These selected data were compared with more detailed analyses that require multiple scans and labor-intensive technical support. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected summaries of scintigraphic transit measurements. We studied 14 patients with motility disorders (eight neuropathic and six myopathic, confirmed by standard gastrointestinal manometry) and 37 healthy subjects. The patient group had abnormal gastric emptying (GE) and small bowel transit time (SBTT). The proportion of radiolabel retained in the stomach from 2 to 4 hr (GE 2 hr, GE 3 hr, GE 4 hr), as well as the proportion filling the colon at 4 and 6 hr (CF 4 hr, CF 6 hr) were individually able to differentiate health from disease (P less than 0.05 for each). From the logistic discriminant model, an estimated sensitivity of 93% resulted in similar specificities for detailed and selected transit parameters for gastric emptying (range: 62-70%). Similarly, combining selected observations, such as GE 4 hr with CF 6 hr, had a specificity of 76%, which was similar to the specificity of combinations of more detailed analyses. Based on the present studies and future confirmation in a larger number of patients, including those with less severe motility disorders, the 2-, 4-, and 6-hr scans with quantitation of proportions of counts in stomach and colon should provide a useful, relatively inexpensive strategy to identify and monitor motility disorders in clinical and epidemiologic studies."
-What was the 10- and 15-year actuarial survival rate for medulloblastoma patients in this study?,"Medulloblastoma: freedom from relapse longer than 8 years--a therapeutic cure? Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (greater than or equal to 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately."
-What was the treatment regimen used for patients with locally advanced paranasal sinus and nasopharynx tumors in this study?,"Locally advanced paranasal sinus and nasopharynx tumors treated with hyperfractionated radiation and concomitant infusion cisplatin. Fourteen patients with paranasal sinus complex and nasopharynx tumors were treated at State University of New York Health Science Center at Brooklyn (Brooklyn, NY) with a regimen of split-course hyperfractionated radiation (120 cGy/fraction) and concomitant cisplatin infusion (5 to 7 mg/m2/24 hours). All of the patients had T4 tumors or massively recurrent disease with base of skull or facial bone involvement. Twelve patients were treated with curative intent receiving total doses of 6000 to 6960 cGy (modal 6750 cGy), whereas two patients were treated with less than 5000 cGy as palliation. Eleven of the 12 patients (92%) achieved a complete response, and 7 of 12 (58%) are alive at 35 to 72 months (mean, 47 months). Five patients are alive with no evidence of disease, and two with a local recurrence. Three patients died of distant disease, and two died from a local recurrence. When the response to treatment was analyzed based on tumor volume and radiation dose, only two of nine lesions measuring between 4 to 10 cm failed locally. The two palliative patients had almost complete local clearance of the disease but died at 2 and 8 months, respectively. In nine patients, the eye or optic nerve was included in the treatment field and received between 2000 to 6960 cGy. Only one of these nine patients had ophthalmic complication and this was confined to the cornea."
-How does iloprost affect microvascular permeability in skeletal muscle after ischemia and reperfusion?,"Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion. Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified."
-How might exercise training potentially influence coronary collateral circulation?,"Exercise training and coronary collateral circulation. This review examines the potential for an exercise-induced increase in coronary collateral circulation, with specific reference to the role and functional significance of collateral vessels, highlighting animal and human studies in particular, and their inherent methodological limitations. Exercise training may enhance myocardial oxygen supply by promoting transient periods of myocardial ischemia, a potent trigger of collateral growth. Some human studies have shown that moderate-to-high intensity training can result in a higher double product at the onset of angina and/or ischemic ST-segment depression, suggesting that myocardial oxygen supply has increased. Attempts to use thallium-201 exercise scintigraphy to assess myocardial perfusion before and after a physical training program have produced conflicting data, whereas angiographic studies in group trials have, without exception, yielded disappointing results. Thus, direct evidence that exercise stimulates collateralization in humans is lacking."
-What percentage of bladder tumors showed positive signals for HPV type 16/18 DNA in this study?,"Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation. The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain."
-What is the significance of monosomy 7 in the reported case of erythroleukemia?,"Erythroleukemia in a child associated with monosomy 7. A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm."
-What rare condition can cause hypertension with increased renin concentrations in infants?,"Hypertension associated with increased renin concentrations in nephroblastoma. An infant with severe hypertension who had a nephroblastoma which was secreting active renin is described. Nephroblastoma must be included in the differential diagnosis of hypertension associated with increased renin concentrations, even in the absence of an abdominal mass."
-How do the hemodynamic effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) differ in experimental heart failure?,"Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure. S-nitrosothiols are potent in vitro vasodilators, but little is known about their in vivo action. In this study, we compared the effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) on left ventricular (LV) hemodynamics in congestive heart failure rats. By using a twoday crossover design, stepwise i.v. infusions of SNAP or NTG at 3, 5 and 8 micrograms/min were administered for 30 min each, followed by a dose of 10 micrograms/min over the next 10 h. LV end-diastolic and peak-systolic pressures (LVEDP and LVPSP, respectively) were measured at selected intervals. SNAP and NTG produced maximal LVEDP reductions of 46 and 44%, respectively, at the highest infusion rate. However, at the lower doses, greater reductions of LVEDP were seen with SNAP. NTG had a smaller effect on LVPSP (maximum 6% reduction) than SNAP (maximum reduction of 15%). During the 10-h infusion of NTG, LVEDP gradually returned to base-line values, indicating the development of tolerance, despite relatively constant plasma levels of NTG over the infusion period. Tolerance in LVEDP effects was not observed during the 10-h infusion of SNAP. In the presence of NTG tolerance, rats were still responsive to SNAP (mean reduction of LVEDP 24%), suggesting the absence of cross-tolerance between these two nitrovasodilators. These results suggest that SNAP is a more potent in vivo vasodilator than NTG, has more arterial action than NTG and is less prone to produce LV hemodynamic tolerance."
-What is the main focus of the case reports discussed in the context?,"Pattern of arterial involvement of the head, neck, and eyes in giant cell arteritis: three case reports. The findings of two post-mortem examinations and one CT scan of patients with biopsy proved giant cell arteritis (GCA) are presented. The presence or absence of intracranial involvement in GCA is discussed."
-What are coronary artery aneurysms and how are they typically detected?,"Coronary artery aneurysms--a case study and literature review. Coronary artery aneurysms are detected with increasing frequency owing to the advent of coronary angiographies. Although most patients with coronary artery aneurysms are asymptomatic, manifestations of myocardial ischemia may occur. The case described herein serves as a basis for a discussion of the pathogenesis, clinical manifestations, detection, and treatment of coronary artery aneurysms."
-What ethical considerations do physicians face when deciding whether to treat hypercalcemia in patients with advanced malignancy?,"Hypercalcemia of advanced malignancy: decision making and the quality of death. Hypercalcemia is a common complication of certain advanced malignancies and although not therapeutically difficult, its presence raises complex ethical issues. Treatment of this condition is most easily justified when the patient is not terminal, the benefits are tangible, and the patient agrees with therapy. Withholding treatment is defensible medically, legally, and morally when a terminal situation is present, when drawbacks exceed the benefits, and when an informed patient declines therapy. Hypercalcemia is one of a number of conditions of dying that can be controlled by the physician. The physician's decision to treat such a condition, in part, depends upon his or her view of a good death. Further study is needed to clarify and avoid those situations of dying which involve suffering. Physicians must begin this difficult analysis and dialogue if they are to fulfill their obligation to minimize suffering in all patients."
-What evidence suggests that interferon-alpha therapy can cause persistent neurotoxicity in cancer patients?,"Persistent neurotoxicity of systemically administered interferon-alpha. Fourteen cancer patients had evidence of persistent neurotoxicity of interferon-alpha therapy long after their treatment was discontinued. Although most of the cognitive symptoms were mild to moderate in severity, they were incapacitating to these individuals in their usual work. The neuropsychological test abnormalities were not attributable to subsequent therapy, disease status, or other medical problems. The pattern of deficits was consistent with frontal-subcortical dysfunction. Of the four patients who had follow-up assessment, two had improved and two had deteriorated. These findings suggest that in some cases interferon neurotoxicity is not reversible."
-What surgical procedure is described for treating lateral nasal wall neoplasms and what are its key characteristics?,"'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and ""medial maxillectomy,"" an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora."
-What was the overall prevalence of dementia in individuals 65 years and older in the East Baltimore Mental Health Survey?,"Dementia: case ascertainment in a community survey. The three-stage East Baltimore Mental Health Survey, conducted in 1981 as part of the Epidemiological Catchment Area Program, provided an opportunity to assess the prevalence of dementia and specific dementing disorders in a community-based, cross-sectional sample of the population. From the 3,841 households originally sampled, 810 individuals were selected for clinical psychiatric evaluation. Forty-one individuals were given a provisional diagnosis and referred to Stage 3 for differential diagnosis, with 32 individuals completing this evaluation. Thorough clinical evaluation of these cases resulted in an overall prevalence of dementia of 4.5% in those 65 years of age and older. The prevalence of specific dementing disorders was Alzheimer's disease (AD) (2.0%), Multi-Infarct Dementia (MID) (2.0%) and Mixed Dementia (MD) (0.5%). Prevalence increased with age for all dementias: Non-Whites had higher rates of dementia than Whites; females had higher rates of AD while males had higher rates of MID; and the prevalence of AD increased with increasing education, whereas the prevalence of MID decreased with increased education. Although this study includes only a small number of cases, necessitating some caution in interpreting the results, these figures do represent an estimate of the prevalence of severe dementing disorders and provide a basis for further community study."
-What is the key histological finding in the papular mucinosis associated with L-tryptophan-induced eosinophilia-myalgia syndrome?,"Papular mucinosis in L-tryptophan-induced eosinophilia-myalgia syndrome. Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses."
-What is fludarabine and in which types of leukemia has it shown potential effectiveness?,"Fludarabine: a review. The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels."
-What were the outcomes of endovascular treatment for brain arteriovenous malformations in this study?,"Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases. The authors report the results of treatment in 49 consecutive patients with brain arteriovenous malformations (AVM's) who underwent therapeutic embolization with liquid adhesive agents between 1984 and 1988 at the Toronto Western Hospital. Thirty-three patients had no other treatment and were followed up with angiography at 2 years and clinically from 2 to 6 years. Of the other 16 patients, 10 had adjunctive radiosurgery and six underwent surgical resection following embolization. Seven (14%) of the 49 patients had a morphological cure effected by embolization as evidenced on their 2-year follow-up angiograms: these have remained clinically stable. Twelve patients developed neurological deficits after embolization; eight (16% of the series) were transient and four (8%) were permanent. Two patients (4%) had a delayed hemorrhage after incomplete obliteration of their malformations. Endovascular treatment resulted in clinical improvement in 15 (33%) of the other 46 patients. None of the patients who initially presented with hemorrhage had a rebleed following embolization. It is concluded that endovascular treatment with liquid embolic material can be an integral part of the multidisciplinary treatment protocol for patients with brain AVM's."
-How does nonsteroidal anti-inflammatory drug (NSAID) usage impact upper gastrointestinal lesions in elderly patients?,"Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage. The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer."
-What were the key findings comparing restorative proctocolectomy with and without a covering ileostomy in patients with ulcerative colitis?,"Comparison of restorative proctocolectomy with and without covering ileostomy in ulcerative colitis. The experience of restorative proctocolectomy for ulcerative colitis is reported in 16 consecutive patients with no covering ileostomy (group 2) in comparison with 15 patients with a covering stoma (group 1); in each group a J pouch was constructed. All patients had pre- and postoperative clinical and manometric evaluations of the functional result up to 12 months. There were no deaths or permanent failures. The number of early complications was four in each group. Re-ileostomy was needed in one patient of group 1, and an ileostomy was constructed in three patients of group 2. At 1 year after operation the functional results did not differ between groups 1 and 2 in terms of daily frequency of defaecation (mean 5.6 and 5.4 in 24 h respectively), or in terms of anal basal or maximal squeeze pressures. There was a significant (P less than 0.01) saving in total hospital stay (median 11 days) and in operating theatre time (mean 41 min) in patients with no covering ileostomy. It is concluded that a covering ileostomy may be unnecessary in restorative proctocolectomy, at least in suitable cases with no technical difficulty at the time of operation."
-What percentage of severely hearing impaired adults in the audiology clinic had a mixed hearing impairment in their better hearing ear?,"Characterization of severely and profoundly hearing impaired adults attending an audiology clinic. Despite the fact that around 12 per cent of adult patients attending an audiology department will be severely hearing impaired (pure tone averages of 0.5, 1, 2 and 4 kHz of 70 dB HL or worse in the better hearing ear), their clinical and audiometric characteristics have not been well documented. These characteristics were collected prospectively in 132 adult patients attending a Severe Impairment Clinic, set up to manage their specific problems. The inability to provide sufficient masking makes audiometric assessment of the severity of the impairment uncertain in the poorer hearing ear in 52 per cent of these patients. In addition, the limited bone conduction output makes it almost invariably impossible to assess the masked bone conduction thresholds and hence the air-bone gap in the poorer ear. Hence, accurate characterization is only practical of the better hearing ear in such patients. In 67 per cent of the better hearing ears, there was a mixed hearing impairment, the air-bone gap being 20 dB or greater. The aetiology of the conductive component was almost equally otosclerosis and chronic otitis media. In only 19 per cent was the impairment of a pure sensorineural type, broken down as 6 per cent congenitally acquired, 5 per cent due to meningitis and 9 per cent being adult in onset. In the remaining 14 per cent of patients the type of impairment could not be classified as the bone conductive thresholds were off scale. Having had experience of managing these patients at a special clinic and knowing the workload involved, it is argued that consideration be given to setting up such clinics in most departments."
-What potential complication can cold-reacting autoantibodies cause during cardiac operations?,Agglutination of blood cardioplegia by cold-reacting autoantibodies. Cold-reacting autoantibodies occasionally occur in patients requiring cardiac operations. This report describes the clinical course of 1 patient with cold-reacting autoantibodies and intracoronary agglutination of the blood cardioplegia solution. Observations made in vivo and in vitro are considered in discussing recommendations for the management of extracorporeal circulation and cardioplegic arrest in patients with clinically silent cold-reacting autoantibodies.
-What are the key characteristics of Fibromyalgia Syndrome (FS) according to the context?,"Toward an integrated understanding of fibromyalgia syndrome. I. Medical and pathophysiological aspects. Fibromyalgia syndrome (FS) is a chronic pain disorder characterized by diffuse musculoskeletal soreness, stiffness, non-restorative sleep and psychological disturbance. At present, much about the etiology, pathological mechanisms and course of FS are unknown. Indeed, standardized diagnostic criteria have only been recently agreed upon. The present paper is the first of a two-part series which reviews the extant empirical literature concerning FS, with a view to arriving at an integrated understanding of the syndrome. The present paper describes the clinical presentation of FS and historical conceptualizations of the disorder. Available research on pathophysiological mechanisms in FS is then presented. In this section we have included literature concerning histology of muscle, sleep architecture, neurotransmitter anomalies and neuropeptide involvement in FS symptomatology."
-What is a peripheral ameloblastoma and how rare is this odontogenic tumor?,"Peripheral ameloblastoma: a clinical and histologic study of 11 cases. Peripheral ameloblastoma (PA) is a rare odontogenic tumor. Previously, only 39 cases of PA had been reported in the English literature. In this article 11 additional cases of PA are presented. Concordance with previous cases was evident with regard to race, clinical appearance, and site of predilection. However, differences were observed with regard to age, sex distribution, and predominant histologic pattern. The average age in the current cases is younger, there is no male bias, and the most common histologic pattern is plexiform rather than follicular or acanthomatous. Recurrence following simple excision is rare, but has been reported. Long-term postoperative follow-up is recommended."
-What is primary breast lymphoma (PBL) and how was it treated in the described cases?,"Primary breast lymphoma. Primary breast lymphoma (PBL) is a rare tumor of the breast. Three cases of PBL are being described. All three cases achieved remission following biopsy, chemotherapy, and/or radiotherapy. The literature is extensively reviewed with emphasis on true incidence of PBL and survival rates."
-What are some potential causes of high-attenuation mediastinal masses on unenhanced CT scans?,"High-attenuation mediastinal masses on unenhanced CT. On unenhanced CT scans, a variety of mediastinal masses contain areas with attenuation values higher than the attenuation value of the chest wall musculature. The increased attenuation may be diffuse or focal and may be a result of calcium deposition, high iodine content, or areas of acute hemorrhage. This report illustrates the gamut of high-attenuation mediastinal masses seen on unenhanced CT. Masses that are of high attenuation only on IV contrast-enhanced images (e.g., aberrant vessels) are not included."
-How does subeschar tissue fluid (STF) impact cell-mediated immune function in patients with severe thermal injury?,"Subeschar tissue fluid: a source of cell-mediated immune suppression in victims of severe thermal injury. Thermal injury results in pronounced physiologic alterations in microcirculation at the site of tissue damage. The consequence of these changes is an increase in microvascular permeability, leading to the accumulation of tissue edema, or subeschar tissue fluid (STF). One of the adverse properties of edema is its capacity in vitro to inhibit cell-mediated immune function. Since previous studies evaluated STF collected 5 to 7 days after thermal injury, the present study was designed to determine the time frame during which STF demonstrates its immune suppressive nature. Seven patients with severe thermal injury (30% to 100% total body surface area) were entered into the study. STF was collected in serial fashion, beginning as early as 9 hours after injury and continuing until fascial excision or patient death (maximum of 139 hours after injury). The addition of STF to cultures of lymphocytes obtained from healthy donors resulted in complete inhibition of mitogen-induced lymphocyte proliferation (MILP). Serum collected concomitantly from this group of patients was also capable of inhibiting MILP. From its inception, STF possesses the ability to inhibit MILP; this suppressive nature is stable, persisting for prolonged periods of time. The gradual absorption of STF likely contributes to the serologic evidence of cell-mediated immune suppression documented in victims of severe thermal injury."
-How do TGF alpha and TGF beta influence liver regeneration and hepatocyte proliferation?,"Protooncogenes and growth factors associated with normal and abnormal liver growth. Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF alpha, an autocrine, stimulatory growth factor, and TGF beta, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The expression of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF alpha and other growth factors and enter a proliferative phase. It is possible that TGF beta 1 serves as a stop signal for liver regeneration but the mechanisms by which TGF beta inhibits hepatocyte DNA synthesis are still unknown."
-How did psychopathology levels impact hospital stay length and medical service costs for inpatients in this study?,"Relation of psychopathology in general medical inpatients to use and cost of services. The authors investigated the relation between psychopathology in medically ill inpatients and use and cost of medical care services. Of 455 medical inpatients, the Medical Inpatient Screening Test identified 27.9% as very depressed, 27.5% as very anxious, 20.2% as having cognitive dysfunction, and 8.6% as having high pain levels. Overall, the test identified 51% of the patients as having high levels of psychopathology or pain. These subjects had a 40% longer median length of hospital stay and 35% greater mean hospital costs than those with low levels of psychopathology or pain. Patients with greater psychopathology also had higher hospital charges, more procedures during hospitalization, and more discharge diagnoses but did not differ from the other patients in sex, race, age, diagnosis-related group (DRG) major diagnostic category, or DRG weight."
-How does the presence of blood medium affect the pulsed-dye laser ablation of normal and atherosclerotic human aorta tissues?,"Enhancement of pulsed-dye laser ablation of arterial tissues with blood medium: effects of laser-induced shock waves. The influence of blood medium on tissue ablation by a pulsed dye laser and its selectivity for atheroma were investigated. The role of shock waves on tissue ablation was also evaluated. Normal and atherosclerotic human aortas were irradiated by a 480 nm pulsed dye laser activated at 5 Hz. The laser was coupled with a single 0.2 mm fiber (Uni-guide) (40 mjoules/pulse) or a multifiber catheter (14 x 150 microns) (100 mjoules/pulse). Shock waves were measured using a fluid-filled catheter connected to a strain gauge manometer. With the Uni-guide, pulse-dye lasing resulted in greater ablation of atheroma in blood (11.6 x 10(-3) mm3/joule, p less than 0.001 versus atheroma measured in saline and normal tissue in blood) followed by normal tissue in blood (2.5 x 10(-3)mm3/joule), atheroma in saline (1.71 x 10(-3)mm3/joule, p less than 0.05 versus normal tissue in saline), and normal tissue in saline (0.54 x 10(-3) mm3/joule). With the multifiber catheter, laser ablation was the greatest in atheroma in blood (0.55 +/- 0.26 mm3/joule p less than 0.001 versus atheroma in saline and normal tissue in blood), followed by normal tissue in blood (0.27 +/- 0.12 mm3/joule), atheroma in saline (0.14 +/- 0.15 mm3/joule, p less than 0.001 versus normal tissue in saline), and normal tissue in saline (0 mm3/joule). The ablation efficiency of the multifiber catheter was greater than that of the Uni-guide (p less than 0.0001)."
-What is the significance of the two case studies involving isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma?,Isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma. Two women developed apparently isolated recurrences of ovarian carcinoma involving prior incisions after receiving intraperitoneal radioactive chromic phosphate (P-32) adjuvant therapy for early epithelial ovarian carcinoma. Both are alive without evidence of disease at second-look laparotomy after surgical resection of the abdominal wall metastases and cisplatin-based combination chemotherapy. Mechanisms of cutaneous and incisional implantation metastases are discussed. Adjuvant therapy with intraperitoneal P-32 is unable to provide systemic therapy for occult metastatic disease. The favorable outcome in these cases probably reflects limited tumor burden at the time of recurrence and stands in stark contrast to other cases of soft tissue recurrences of ovarian carcinoma reported previously.
-How does blockade of ATP-sensitive potassium channels affect reactive hyperemia in the canine coronary circulation?,"Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 +/- 41%. After low-dose (0.8 mumol/min) and high-dose (3.7 mumol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 +/- 14% and 50 +/- 8%, respectively (p less than 0.05 compared with control for both). The decline in flow debt repayment was due to a significant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon."
-What are the key findings of the study regarding volume tests for chronic venous insufficiency?,"Volume tests for chronic venous insufficiency: an appraisal. Chronic venous disease is increasingly treated surgically with a variety of experimental procedures. Noninvasive volume tests are commonly used before surgery to select patients and after surgery to assess results. Rapid volume changes are considered to indicate regurgitation. Rigorous statistical validation of tests and the confounding nature of unmeasured arterial inflow are seldom considered. Volume changes were measured in 29 control limbs and 35 limbs with venous disease, with mercury-in-silicone rubber strain gauges, for both exercise and elevation. Normalization for arterial flow permitted calculation of the regurgitation rate. Normal (95% confidence) limits for measured and calculated parameters were determined. Specificity was shown by the percent of normal parameter values for control limbs and sensitivity by the percent of abnormal values for extremities with venous disease. Arterial flow significantly altered volume curves. Normalization increased specificity and sensitivity significantly. Calf exercise tests, even normalized, were too insensitive to be reliable. Elevation tests were significantly more sensitive for determining regurgitation. However, exercise tests were useful and supplied important information about the calf muscle pump. We conclude that, as currently used, many limb volume test procedures are unsuitable but could be improved significantly by normalization to reduce the confounding effect of regional arterial flow and use of an elevation test to measure regurgitation."
-What is the significance of the mutation in the porcine ryanodine receptor gene in relation to malignant hyperthermia in swine?,"Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs."
-What was the main objective of the study on phenytoin overdose?,"Severe oral phenytoin overdose does not cause cardiovascular morbidity. STUDY OBJECTIVE: To evaluate the potential for cardiovascular toxicity from severe oral phenytoin overdose. STUDY POPULATION: Fifty-seven patients admitted during a two-year period to an inner-city hospital for severe oral phenytoin overdose, which is defined as a peak level of 40 micrograms/mL or more. METHODS: Case records were reviewed retrospectively for symptoms and signs of phenytoin toxicity, especially circulatory effects. Baseline and toxic 12-lead ECGs, when available, were reviewed in detail. Continuous variables were compared using either paired or unpaired t tests, as appropriate. Significance was taken as P less than or equal to .05. RESULTS: Mean peak phenytoin level was 49.4 +/- 7.7 micrograms/mL. Continuous single-lead ECG monitoring in 36 patients (63%) for a mean of 26.5 +/- 21.6 hours revealed no incidents of dysrhythmia requiring treatment. ECGs recorded during toxicity in 52 cases (91%) revealed no clinically significant abnormalities attributable to phenytoin. ECGs during toxic and baseline states were available for detailed analysis in 15 cases. Ten patients exhibited an increase in PR interval (mean, 19 +/- 10 ms) when toxic, whereas five had a decrease (mean, 18 +/- 11 ms) compared with nontoxic records. No change in heart rate, QRS duration, or corrected QT interval was observed. There were no circulatory complications and no deaths. CONCLUSION: Cardiovascular toxicity is rarely a manifestation of oral phenytoin overdose. Routine management of stable patients with severe phenytoin overdose in a monitored setting is not mandatory."
-What neurotoxic effects were observed in patients treated with intraventricular alpha-interferon for leptomeningeal disease?,"Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease. Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment."
-How does positive end-expiratory pressure (PEEP) affect splanchnic circulation in experimental peritonitis?,"Effects of positive end-expiratory pressure on splanchnic circulation and function in experimental peritonitis. Splanchnic and central hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in anesthetized pigs using mechanical ventilatory assistance, with or without sepsis (fecal peritonitis). One hour after sepsis, PEEP (10 cm H2O) was applied (n = 6). Another group (n = 6) had sepsis without PEEP. In one group (n = 6) without sepsis, PEEP was applied after 1 hour, while a fourth group (n = 5), without sepsis or PEEP, served as a control. The group with PEEP and sepsis had reduced cardiac index, portal venous blood flow, and liver surface blood flow. The group with PEEP alone had reduced splanchnic circulation by increasing gastrointestinal vascular resistance, while the group with sepsis alone had increased portal vascular resistance. In a separate series with sepsis, intermittent PEEP, and vigorous fluid resuscitation, it was demonstrated that avoiding hypovolemia did not seem to protect from the PEEP effects on the splanchnic circulation. The combination of sepsis and PEEP was not additive on portal blood flow reduction but reduced bile production."
-What factors were associated with higher mortality rates in patients with ruptured abdominal aortic aneurysms in this study?,"Factors affecting survival of patients with ruptured abdominal aortic aneurysm in a West Virginia community. The hospital records for patients treated for ruptured abdominal aortic aneurysms in southern West Virginia during a recent five year period were reviewed. The over-all mortality rate was 62 per cent. Patients with intraperitoneal rupture had a higher mortality rate (97 per cent) than patients with retroperitoneal rupture (25 per cent). Patients at increased risk were more than 80 years of age, presented with syncope, experienced a short duration of symptoms before seeking medical attention, had preoperative systolic blood pressure levels of less than 90 millimeters of mercury and had a preoperative hemoglobin level of less than 8. Other factors associated with death were a delay in beginning surgical treatment, a larger total blood loss and amount of blood transfused. The results of multivariate analysis demonstrated that preoperative blood pressure, preoperative hemoglobin, presence of syncope and the amount of blood loss were, in large part, reflections of the type of rupture and had only slight independent relationship to mortality. The most effective method of preventing fatal outcome is elective resection of the aneurysms before rupture occurs."
-What were the anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A compared to other antiepileptic drugs?,"Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats. The anticonvulsant profiles of two potent and orally active gamma-aminobutyric acid (GABA) uptake inhibitors, 1-(4,4-diphenyl-3-butenyl)-3-piperidine-carboxylic acid hydrochloride (SK&F 89976-A) and 1-(4,4-diphenyl-3-butenyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (SK&F 100330-A), were determined with a battery of well-standardized tests in mice and rats and compared with the profiles of phenytoin (PHT), carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) when subjected to the same tests. ED50 values were calculated and compared with TD50 values for minimal motor impairment to provide protective indexes (PI = TD50/ED50). The anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A were similar and suggest that these compounds raise the threshold for seizure initiation rather than inhibit seizure spread. Like intraperitoneal (i.p.) PHT, CBZ, VPA, and CZP, SK&F 89976-A and SK&F 100330-A inhibited seizures in corneally kindled rats. The profiles of SK&F 89976-A and SK&F 100330-A were most similar to that of CZP and virtually opposite to that of PHT. Intraperitoneal SK&F 100330-A provided complete protection against pentylenetetrazol-induced seizures [subcutaneous (s.c.) PTZ] in mice but was ineffective against seizures induced by maximal electroshock (MES) at doses slightly greater than its TD50. SK&F 100330-A provided complete protection against picrotoxin-induced seizures (s.c. Pic) and against both clonus and forelimb tonic extension induced by NMDA N-methyl-D-aspartate [intracerebral ventricular (i.c.v.)-NMDA] in mice; however, SK&F 100330-A was ineffective against seizures induced by bicuculline (s.c. Bic) and strychnine (s.c. Strych) at doses slightly greater than its TD50. SK&F 89976-A was similar but provided partial protection against NMDA-induced clonus."
-How does substance P protect against the neurodegenerative effects of beta amyloid in the brain?,"An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P. Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta amyloid. Immunoblot analysis showed that beta amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta amyloid. Thus, beta amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P."
-How did technetium-99m-HMPAO labeled leukocyte imaging help in detecting the chronic prosthetic vascular graft infection in the 77-year-old patient?,Chronic prosthetic vascular graft infection visualized with technetium-99m-hexamethylpropyleneamine oxime-labeled leukocytes Technetium-99m-HMPAO labeled leukocytes demonstrated chronic femoro-femoral prosthetic vascular graft infection several times during an 18-mo period in a 77-yr-old man. The intensity and distribution of the uptake in the graft were fluctuating in different imaging occasions possibly indicating the strength and location of the infection. Gallium-67-citrate imaging showed negative results twice. The reason for negative 67Ga results remained obscure. The infected graft was removed and the patient did well 5 mo postoperatively.
-Does zidovudine have an effect on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection?,"No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection. Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity."
-How accurate is pneumothorax CT in evaluating chest wall and mediastinal invasion in lung cancer patients?,"Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT. For preoperative evaluation of chest wall and mediastinal invasion by lung cancer, computed tomography (CT), combined with artificial pneumothorax (pneumothorax CT), was performed in 43 patients with lung cancer in whom conventional CT scans showed that the mass was contiguous to the chest wall (n = 30) and/or mediastinum (n = 25) but without evidence of definite tumor invasion. Invasion was diagnosed on the basis of whether an air space existed between the mass and the adjacent structures. In three patients pneumothorax was not produced. After the procedure, four patients developed symptomatic pneumothorax, and one, subcutaneous emphysema. Comparison of diagnoses based on findings at pneumothorax CT, surgery, and pathologic examination showed that pneumothorax CT is 100% accurate for chest wall invasion and 76% accurate for mediastinal invasion. The authors conclude that this procedure is helpful in accurate evaluation of the T criterion in lung cancer, especially for patients in whom findings at conventional CT suggest tumor invasion of the chest wall and mediastinum."
-What is the relationship between alpha 2 macroglobulin complexes and the severity of acute pancreatitis?,"Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks. Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis."
-How does the depletion of factor XII-dependent fibrinolytic activity relate to the risk of early myocardial reinfarction after rt-PA therapy?,"Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction."
-What is the success rate of arthroscopic stapling for treating superior labral tears in young athletes?,"Arthroscopic stapling for detached superior glenoid labrum. Superior labral tears of the shoulder involve the biceps tendon and labrum complex which may be detached, displaced inferiorly, and interposed between the glenoid and the humeral head. We have treated ten young athletes with painful shoulders due to this lesion by arthroscopic stapling. Arthroscopy at the time of staple removal, after three to six months, showed that all the lesions had been stabilised. Clinical review at over 24 months showed an excellent or good result in 80%. The two relative failures were due in one to residual subacromial bursitis, and the other to multidirectional shoulder instability. Arthroscopic stapling can restore the shoulder anatomy, and it is recommended for active adolescent athletes with this lesion."
-What was the complication rate for intra-aortic balloon pump (IABP) insertion in different clinical scenarios according to the study?,"Percutaneous intra-aortic balloon pump: emphasis on complications. In a review of our 5-year experience with intra-aortic balloon pump (IABP) insertion I examined the complications of percutaneous IABP placement in 93 patients, and compared them with those reported in other studies in the literature. I analyzed several variables that may affect the complication rate. Of 78 patients in our series who had percutaneous IABP cardiac assist, 15 (19%) had complications, which falls into the acceptable range reported by others. Among 15 patients who had surgical placement of an IABP, the complication rate was similar at 20%. The complication rate after IABP insertions done by surgeons primarily in the operating room was compared with that from insertions done by cardiologists in the catheterization laboratory. The overall complication rate was found to be higher in the second group, 28.0% compared with 12.8%. The application of the IABP in cardiogenic shock was associated with a high complication rate (46%). On the other hand, its insertion before cardiac surgery was associated with a relatively low complication rate (9.5%)."
-What were the clinical outcomes for patients who underwent mitral prosthesis insertion with native leaflets left intact?,"Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: adverse clinical outcome in seven patients. Left ventricular (LV) outflow obstruction may result from retaining the anterior mitral leaflet when a mitral prosthesis is inserted in the mitral anulus. We retrospectively reviewed the echocardiograms (two-dimensional Doppler and Doppler color flow imaging, or transesophageal with color flow imaging) obtained in seven patients with preoperative mitral regurgitation who had a prosthesis implanted with the native mitral leaflets left intact. Systolic anterior motion of the native anterior mitral leaflet, as seen in dynamic LV outflow tract obstruction, was observed in six of seven patients. LV fractional shortening preoperatively was less than or equal to 0.25 in all (mean 0.20 +/- 0.04) and did not significantly (p = ns) increase postoperatively (mean 0.27 +/- 0.12). Color flow imaging revealed disturbed systolic flow in the LV outflow tract in five patients, and all had systolic anterior motion of the native anterior mitral leaflet. Continuous wave Doppler detected significant systolic LV outflow tract jets in five patients averaging 4.1 +/- 0.9 m/sec. Mitral prosthetic function was normal (pressure half-time of 81 +/- 25 msec and mean gradient of 7 +/- 3 mm Hg +/- SD) in five patients. Clinical follow-up revealed that all had died, six of them within 2 months of their operation. Thus systolic anterior motion of the native anterior mitral leaflet occurs commonly after prosthetic mitral valve insertion with the native leaflets left intact. Continuous wave Doppler often demonstrates increased systolic LV outflow tract velocities consistent with dynamic LV outflow obstruction."
-What was the treatment and outcome for the 40-year-old woman with periorbital necrobiotic xanthogranuloma and stage I multiple myeloma?,"Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma."
-What percentage of patients with failed back surgery syndrome experienced successful outcomes after spinal cord stimulator implantation at 2.2 and 5.0 years follow-up?,"Failed back surgery syndrome: 5-year follow-up after spinal cord stimulator implantation. Spinal cord stimulation, in use for more than 20 years, has evolved into an easily implemented technique, with percutaneous methods for electrode placement. We have reviewed our experience with this technique in treating ""failed back surgery syndrome,"" and have assessed patient and treatment characteristics as predictors of long-term outcome. A series of 50 patients with failed back surgery syndrome (averaging 3.1 previous operations), who underwent spinal cord stimulator implantation, was interviewed by impartial third parties, at mean follow-up intervals of 2.2 years and 5.0 years. Successful outcome (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in 53% of patients at 2.2 years and in 47% of patients at 5.0 years postoperatively. Ten of 40 patients who were disabled preoperatively returned to work. Improvements in activities of daily living were recorded in most patients for most activities; loss of function was rare. Most patients reduced or eliminated analgesic intake. Statistical analysis (including univariate and multivariate logistic regression) of patient characteristics as prognostic factors showed significant advantages for female patients and for those with programmable multi-contact implanted devices. These results, in patients with postsurgical lumbar arachnoid and epidural fibrosis and without surgically remediable lesions, compare favorably with the results in two separate series of patients with failed back surgery syndrome, in whom 1) surgical lesions were diagnosed and repeated operation performed; and 2) monoradicular pain syndromes were diagnosed and dorsal root ganglionectomies performed at our institution. This suggests the need for further assessment of selection criteria, critical analysis of treatment outcome, and prospective study of spinal cord stimulation and alternative approaches to failed back surgery syndrome."
-What clinical benefits did aspirin and heparin demonstrate in the treatment of unstable angina according to the clinical trials?,"Antiplatelet and antithrombotic therapy in unstable angina. In 4 well-controlled clinical trials, aspirin reduced the incidence of coronary events in unstable angina. The benefits were present during the acute, subacute and more chronic phases of the disease and were independent of the doses and of other protocol differences. This benefit of aspirin can be extended to some, but not all, other antiplatelet drugs. In 4 clinical trials, heparin used acutely added substantial benefit to the management of unstable angina, reducing the event rate and also the incidence of refractory angina more than aspirin. The long-term benefit of antithrombin therapy remains to be more thoroughly investigated. Despite these successes, the failure rate of aspirin and of heparin remains high, justifying a continuing search for more potent and safe antiplatelet and antithrombotic drugs."
-What was the primary purpose of using carbon dioxide laser ablation in treating cutaneous metastases from malignant melanoma?,"Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma. Multiple cutaneous and superficial subcutaneous metastases from malignant melanoma in 30 patients were treated palliatively by carbon dioxide laser ablation when lesions were to numerous, too large or recurring too rapidly for multiple local excisions. The number of lesions per patient ranged from three to 250 (median 30). Patients were treated under local or general anaesthetic and as day cases or inpatients. After a median follow-up interval of 8 months fewer than 1 per cent of lasered metastases have recurred locally. Sixteen patients have developed cutaneous metastases at other sites requiring further treatment. Approximately 2000 lesions have been treated on 64 occasions. Patients reported little or no pain after the operation and required only simple dry dressings. Wounds were completely healed in 2-6 weeks with good cosmetic results. This simple and effective treatment is becoming an alternative to isolated limb perfusion."
-How has endoscopy improved the diagnosis and treatment of peptic ulcer disease?,"Use of endoscopy in peptic ulcer disease. The diagnosis and treatment of acute bleeding caused by peptic ulcer disease has been greatly facilitated by fiberoptic endoscopy. The basic differentiation between malignant and benign gastric ulcer requires endoscopic confirmation with biopsy. The management of bleeding from peptic ulceration can be enhanced by endoscopic examination as can the prediction of risk for recurrent bleeding or need for surgical intervention. Various therapeutic maneuvers can be performed endoscopically, including monopolar and multipolar cautery, laser and heater probe therapy, and injection of vasoconstrictors to control bleeding. Endoscopic balloon dilation for the management of gastric outlet obstruction is often effective."
-What is the relationship between optic chiasmal neuritis and multiple sclerosis according to the given context?,"Optic chiasmal neuritis. In four of six patients with clinical optic chiasmal neuritis, MRI demonstrated abnormalities of the chiasm. Optic chiasmal neuritis may be the initial manifestation of multiple sclerosis, a reflection of established CNS demyelination, or an isolated clinical finding."
-What was the overall accuracy of MR imaging in staging endometrial carcinoma according to the NCI cooperative study?,"MR imaging evaluation of endometrial carcinoma: results of an NCI cooperative study. A prospective study to assess the usefulness of magnetic resonance (MR) imaging in the evaluation of endometrial carcinoma was undertaken by five institutions under the auspices of the National Cancer Institute. Six different MR imagers were used, ranging in magnetic field strength from 0.15 T to 1.5 T. For each unit, appropriate T1- and T2-weighted sequences in the transverse plane and T2-weighted sequences in the sagittal plane were used. Initially, 107 patients were entered in the study, but only 88 fulfilled all the criteria and provide the basis for this study. The abnormality within the endometrial cavity was demonstrated with MR imaging in 81% of the patients. The overall accuracy with MR imaging for staging endometrial carcinoma was 85%. In the evaluation of depth of myometrial invasion for stage I disease, overall accuracy with MR imaging was 74%. The accuracy of MR imaging in assessing tumors confined to endometrium or tumor with superficial myometrial invasion was 89% and decreased to 54% in assessing deep myometrial invasion. The results of this prospective study performed by multiple examiners with vastly different equipment demonstrate the inherent value of MR imaging in the evaluation of this neoplasm."
-"How did prazosin treatment affect blood pressure, HDL-cholesterol concentration, and apoprotein-AI/HDL kinetics in patients with mild hypertension?","Effect of prazosin treatment on HDL kinetics in patients with hypertension. The effect of prazosin treatment on blood pressure, plasma HDL-cholesterol concentration, and apoprotein-AI/HDL (apoAI/HDL) kinetics was studied in 11 patients with mild hypertension. Blood pressure (mean +/- SEM) fell from 143 +/- 1/96 +/- 1 to 134 +/- 1/86 +/- 1 mm Hg after 4 to 5 months of prazosin treatment (P less than .001), associated with an increase in plasma HDL-cholesterol concentration from 38 +/- 2 to 46 +/- 2 mg/dL (P less than .001). Both the fractional catabolic rate (FCR) and total synthetic rate of apoAI/HDL, which were higher than previous reported values for normal individuals, decreased from 0.36 +/- 0.02 to 0.30 +/- 0.02 L/day and 17.4 +/- 1.1 to 13.8 +/- 1.1 mg/kg/min, respectively. These changes were statistically significant, and the post-treatment values for both variables were now within the normal range. When the decay curve was further analyzed by nonlinear curve fitting, it was shown that the return to normal of the FCR of apoAI/HDL in patients treated with prazosin was accounted for by the decrease of the decay constants of the second [p(2)] and third [p(3)] components of the 125I-AI/HDL disappearance curve. In conclusion, abnormalities in HDL concentration and HDL kinetics exist in patients with very mild hypertension. These defects were significantly improved with prazosin treatment, and this may render the compound of particular clinical benefit in the treatment of patients with mild hypertension."
-What role does radiotherapy play in the treatment of paediatric haemangiomas?,"Paediatric haemangiomas: the role of radiotherapy. Radiotherapy currently maintains an occasional place in the therapy of complicated haemangiomas of childhood. Eight such childhood benign lesions have been so treated at St Bartholomew's Hospital in the last 10 years. The case histories are presented before being discussed in the context of other therapies available (no treatment, steroids, embolism and surgery), radiation technique used and radiation dose prescription advised."
-What is Human Cyclical Neutropenia and what are its key clinical characteristics?,"Fatal human cyclical neutropenia with unresolving tonsillitis and bilateral cervical abscesses. Human Cyclical Neutropenia is a rare haematological disorder, characterized by periodic oscillations in peripheral neutrophil levels from normal to neutropenic, during which patients experience ulcerative stomatitis, fever, malaise and occasional cutaneous and subcutaneous infections. We present our experience with a fatal case of Human Cyclical Neutropenia together with a brief review of the literature and diagnostic criteria. The paper aims to heighten the clinical awareness of the otolaryngologist to the condition. Close co-operation with the haematologist is essential both for diagnosis and management."
-What surgical procedure is described for treating lateral nasal wall neoplasms and what are its key characteristics?,"'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and ""medial maxillectomy,"" an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora."
-What was the primary purpose of the study on slow-release nifedipine in patients with variant angina?,"Efficacy of slow-release nifedipine on myocardial ischemic episodes in variant angina pectoris. To evaluate the efficacy of slow-release nifedipine (a single dose of 20 mg given at 10 P.M. or 2 doses of 20 mg at 10 P.M. and 6 A.M.) on ischemic episodes in patients with variant angina, a single-blind crossover study with ambulatory electrocardiographic monitoring was performed in 15 patients (13 men and 2 women, mean age 63 years). In all, there were 646 ischemic episodes detected with ambulatory electrocardiographic monitoring during the study period, and 618 episodes of them occurred during placebo periods with a circadian variation. Sixty-nine percent of the episodes in placebo periods were asymptomatic. The number of anginal attacks, nitroglycerin tablets taken, ST-segment elevation and the total ischemic duration significantly decreased during nifedipine therapy compared with results after the placebo therapy period, respectively (p less than 0.01 or 0.05). Twenty-eight ischemic episodes occurred during nifedipine therapy when the plasma level of nifedipine was low. Thus, asymptomatic ischemic episodes more frequently occur than symptomatic episodes and the administration of slow-release nifedipine is highly effective in suppressing not only symptomatic but also asymptomatic myocardial ischemia in patients with variant angina. The timing of the administration of slow-release nifedipine is an important factor in suppressing ischemic episodes."
-What is the main finding of this study regarding the natural course of hepatic haemangiomas in adults?,"Natural history of hepatic haemangiomas: clinical and ultrasound study. Hepatic haemangiomas are the most common benign tumours of the liver and commonly present as incidental findings on sonographic examination of the abdomen. Since little is known of the natural course of these tumours, we performed a clinical and sonographic follow up of 123 haemangioma patients. Our prospective study investigated clinical and sonographic findings in 158 haemangiomas for periods of 12 to 60 months. Ninety nine haemangiomas measured less than 2 cm and had an echogenic pattern; 40 were between 2 cm and 5 cm with a mainly echogenic structure; 19 measured greater than 5 cm and showed a mixed echo pattern. At the first examination only eight patients, all with giant haemangiomas, presented symptoms which could be attributed to the tumour. During follow up only one haemangioma changed in shape and size. One patient who was symptom free at the first examination experienced right upper abdominal quadrant pain during follow up. No deterioration occurred in any of the patients with symptoms at the first examination, and all had a satisfactory quality of life. No complications arose during the follow up period. This study shows that in adults haemangiomas remain stable in size and echo patterns rarely change. Only haemangiomas greater than 5 cm may cause symptoms. Prolonged clinical and sonographic follow up of small and medium sized haemangiomas is not warranted."
-What recent advances have been made in the treatment of breast cancer?,"Recent advances in the treatment of breast cancer. Multidisciplinary efforts have defined a number of prognostic factors and newer strategies to improve the outcome of patients with breast cancer. Conservative surgery has led to improved functional and cosmetic results. The development of a number of effective adjuvant regimens has led to improved survival. In patients with stage I disease, several biological characteristics of tumor have been identified that are associated with increased risk of relapse. A multimodality approach to patients with locally advanced disease and inflammatory cancer has resulted in improved survival. A number of hormonal and cytotoxic drug contaminations can palliate metastatic disease, with a small fraction of patients remaining in extended remission. Dose-intensive programs may lead to further improvements in survival of selected patients with this disease."
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_1.md b/agentic-apps/agentic_rag_milvus/knowledge/user_1.md
deleted file mode 100644
index b2700a36..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_1.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Leanne Graham
-
-- **Username**: Bret
-- **Email**: Sincere@april.biz
-- **Address**: 
-  - Street: Kulas Light
-  - Suite: Apt. 556
-  - City: Gwenborough
-  - Zipcode: 92998-3874
-  - Geo: 
-    - Latitude: -37.3159
-    - Longitude: 81.1496
-- **Phone**: 1-770-736-8031 x56442
-- **Website**: hildegard.org
-- **Company**: 
-  - Name: Romaguera-Crona
-  - Catchphrase: Multi-layered client-server neural-net
-  - BS: harness real-time e-markets
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_10.md b/agentic-apps/agentic_rag_milvus/knowledge/user_10.md
deleted file mode 100644
index f130a331..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_10.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Clementina DuBuque
-
-- **Username**: Moriah.Stanton
-- **Email**: Rey.Padberg@karina.biz
-- **Address**: 
-  - Street: Kattie Turnpike
-  - Suite: Suite 198
-  - City: Lebsackbury
-  - Zipcode: 31428-2261
-  - Geo: 
-    - Latitude: -38.2386
-    - Longitude: 57.2232
-- **Phone**: 024-648-3804
-- **Website**: ambrose.net
-- **Company**: 
-  - Name: Hoeger LLC
-  - Catchphrase: Centralized empowering task-force
-  - BS: target end-to-end models
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_2.md b/agentic-apps/agentic_rag_milvus/knowledge/user_2.md
deleted file mode 100644
index 55588f3d..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_2.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Ervin Howell
-
-- **Username**: Antonette
-- **Email**: Shanna@melissa.tv
-- **Address**: 
-  - Street: Victor Plains
-  - Suite: Suite 879
-  - City: Wisokyburgh
-  - Zipcode: 90566-7771
-  - Geo: 
-    - Latitude: -43.9509
-    - Longitude: -34.4618
-- **Phone**: 010-692-6593 x09125
-- **Website**: anastasia.net
-- **Company**: 
-  - Name: Deckow-Crist
-  - Catchphrase: Proactive didactic contingency
-  - BS: synergize scalable supply-chains
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_3.md b/agentic-apps/agentic_rag_milvus/knowledge/user_3.md
deleted file mode 100644
index afb163af..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_3.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Clementine Bauch
-
-- **Username**: Samantha
-- **Email**: Nathan@yesenia.net
-- **Address**: 
-  - Street: Douglas Extension
-  - Suite: Suite 847
-  - City: McKenziehaven
-  - Zipcode: 59590-4157
-  - Geo: 
-    - Latitude: -68.6102
-    - Longitude: -47.0653
-- **Phone**: 1-463-123-4447
-- **Website**: ramiro.info
-- **Company**: 
-  - Name: Romaguera-Jacobson
-  - Catchphrase: Face to face bifurcated interface
-  - BS: e-enable strategic applications
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_4.md b/agentic-apps/agentic_rag_milvus/knowledge/user_4.md
deleted file mode 100644
index c72606d7..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_4.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Patricia Lebsack
-
-- **Username**: Karianne
-- **Email**: Julianne.OConner@kory.org
-- **Address**: 
-  - Street: Hoeger Mall
-  - Suite: Apt. 692
-  - City: South Elvis
-  - Zipcode: 53919-4257
-  - Geo: 
-    - Latitude: 29.4572
-    - Longitude: -164.2990
-- **Phone**: 493-170-9623 x156
-- **Website**: kale.biz
-- **Company**: 
-  - Name: Robel-Corkery
-  - Catchphrase: Multi-tiered zero tolerance productivity
-  - BS: transition cutting-edge web services
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_5.md b/agentic-apps/agentic_rag_milvus/knowledge/user_5.md
deleted file mode 100644
index 4504e219..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_5.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Chelsey Dietrich
-
-- **Username**: Kamren
-- **Email**: Lucio_Hettinger@annie.ca
-- **Address**: 
-  - Street: Skiles Walks
-  - Suite: Suite 351
-  - City: Roscoeview
-  - Zipcode: 33263
-  - Geo: 
-    - Latitude: -31.8129
-    - Longitude: 62.5342
-- **Phone**: (254)954-1289
-- **Website**: demarco.info
-- **Company**: 
-  - Name: Keebler LLC
-  - Catchphrase: User-centric fault-tolerant solution
-  - BS: revolutionize end-to-end systems
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_6.md b/agentic-apps/agentic_rag_milvus/knowledge/user_6.md
deleted file mode 100644
index 6dca38d2..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_6.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Mrs. Dennis Schulist
-
-- **Username**: Leopoldo_Corkery
-- **Email**: Karley_Dach@jasper.info
-- **Address**: 
-  - Street: Norberto Crossing
-  - Suite: Apt. 950
-  - City: South Christy
-  - Zipcode: 23505-1337
-  - Geo: 
-    - Latitude: -71.4197
-    - Longitude: 71.7478
-- **Phone**: 1-477-935-8478 x6430
-- **Website**: ola.org
-- **Company**: 
-  - Name: Considine-Lockman
-  - Catchphrase: Synchronised bottom-line interface
-  - BS: e-enable innovative applications
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_7.md b/agentic-apps/agentic_rag_milvus/knowledge/user_7.md
deleted file mode 100644
index 5ff50017..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_7.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Kurtis Weissnat
-
-- **Username**: Elwyn.Skiles
-- **Email**: Telly.Hoeger@billy.biz
-- **Address**: 
-  - Street: Rex Trail
-  - Suite: Suite 280
-  - City: Howemouth
-  - Zipcode: 58804-1099
-  - Geo: 
-    - Latitude: 24.8918
-    - Longitude: 21.8984
-- **Phone**: 210.067.6132
-- **Website**: elvis.io
-- **Company**: 
-  - Name: Johns Group
-  - Catchphrase: Configurable multimedia task-force
-  - BS: generate enterprise e-tailers
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_8.md b/agentic-apps/agentic_rag_milvus/knowledge/user_8.md
deleted file mode 100644
index 3e8a9680..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_8.md
+++ /dev/null
@@ -1,18 +0,0 @@
-# Nicholas Runolfsdottir V
-
-- **Username**: Maxime_Nienow
-- **Email**: Sherwood@rosamond.me
-- **Address**: 
-  - Street: Ellsworth Summit
-  - Suite: Suite 729
-  - City: Aliyaview
-  - Zipcode: 45169
-  - Geo: 
-    - Latitude: -14.3990
-    - Longitude: -120.7677
-- **Phone**: 586.493.6943 x140
-- **Website**: jacynthe.com
-- **Company**: 
-  - Name: Abernathy Group
-  - Catchphrase: Implemented secondary concept
-  - BS: e-enable extensible e-tailers
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/knowledge/user_9.md b/agentic-apps/agentic_rag_milvus/knowledge/user_9.md
deleted file mode 100644
index 9f7b26a7..00000000
--- a/agentic-apps/agentic_rag_milvus/knowledge/user_9.md
+++ /dev/null
@@ -1,17 +0,0 @@
-# Glenna Reichert
-
-- **Username**: Delphine
-- **Email**: Chaim_McDermott@dana.io
-- **Address**: 
-  - Street: Dayna Park
-  - Suite: Suite 449
-  - City: Bartholomebury
-  - Zipcode: 76495-3109
-  - Geo: 
-    - Latitude: 24.6463
-    - Longitude: -168.8889
-- **Phone**: (775)976-6794 x41206
-- **Website**: conrad.com
-- **Company**: 
-  - Name: Yost and Sons
-  - Catchphrase: Switchable contextual benchmark
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/list_collections.py b/agentic-apps/agentic_rag_milvus/list_collections.py
deleted file mode 100644
index d7b8bb3d..00000000
--- a/agentic-apps/agentic_rag_milvus/list_collections.py
+++ /dev/null
@@ -1,31 +0,0 @@
-import os
-from dotenv import load_dotenv
-from pymilvus import connections, utility
-
-# Load environment variables
-load_dotenv()
-
-# Get Milvus address from environment
-milvus_address = os.getenv("MILVUS_ADDRESS", "localhost:19530")
-milvus_host, milvus_port = milvus_address.split(":")
-
-# Connect to Milvus
-print(f"Connecting to Milvus at {milvus_host}:{milvus_port}...")
-try:
-    connections.connect(
-        alias="default", 
-        host=milvus_host,
-        port=milvus_port
-    )
-    
-    # List all collections
-    collections = utility.list_collections()
-    print("Available collections:")
-    for collection in collections:
-        print(f"- {collection}")
-        
-    # Close connection
-    connections.disconnect("default")
-    
-except Exception as e:
-    print(f"Error connecting to Milvus: {e}")
diff --git a/agentic-apps/agentic_rag_milvus/output/antonette.md b/agentic-apps/agentic_rag_milvus/output/antonette.md
deleted file mode 100644
index 7753c59c..00000000
--- a/agentic-apps/agentic_rag_milvus/output/antonette.md
+++ /dev/null
@@ -1,47 +0,0 @@
-Okay, let's see what the user is asking here. They want the primary advantage of using an uncemented porous-coated anatomic (PCA) hip system in total hip arthroplasty, a summary, and a story saved to a file called "Bell's palsy.md". Wait, the file name mentions Bell's palsy, which is a facial nerve disorder, not related to hip replacements. That seems like a mistake. The user probably meant to name the file related to the hip system topic. But maybe they just made a typo.
-
-Looking at the previous interaction, the assistant tried to use the write_file tool but got an error because there's no MCP client for that tool. The tools listed include undefined___write_file, but maybe the system isn't set up to handle that function. The error message says "No MCP client found for tool: undefined___write_file (client: undefined, tool: write_file)". So perhaps the function isn't properly registered or there's a configuration issue.
-
-The user's main request is to get the answer, summarize it, create a story, and save it. The first part is straightforward: the primary advantage from the context provided is biologic fixation via bone ingrowth. The summary and story can be crafted using the details from the given records.
-
-But the error indicates the write_file tool isn't available. The assistant might need to inform the user that the file couldn't be saved due to a tool issue and offer to provide the content instead. Alternatively, check if there's another way to save the file, but according to the tools provided, undefined___write_file is the only option. Since that's not working, the assistant should respond accordingly.
-
-Also, the file name "Bell's palsy.md" is likely incorrect. The user might have intended something like "PCA_hip_system.md". But since they specified that name, perhaps they want it that way, but it's conflicting with the content. Maybe they made a mistake, so pointing that out would be helpful.
-
-Putting this together, the response should first answer the question correctly, summarize the info, create the story, then mention the error in saving the file and offer to provide the content instead. Also, note the possible typo in the filename.
-</think>
-
-It seems there was an issue saving the file due to a tool configuration error. Let me provide the content here instead, and clarify the answer to your question first:
-
----
-
-**Primary Advantage of Uncemented PCA Hip Systems**:  
-The main advantage is **biologic fixation**, achieved through porous coatings that allow bone ingrowth, eliminating reliance on cement. This reduces risks of cement-related complications (e.g., loosening, fractures, or migration) and provides long-term stability. Studies show:  
-- No acetabular component failures or reoperations for instability.  
-- High Harris hip scores (average 90.5 post-surgery).  
-- Low revision rates (only 2 femoral components failed in 35 cases).  
-
----
-
-### Story: The Stability Revolution in Hip Replacement  
-**The Challenge**:  
-For decades, cemented hip implants faced risks of loosening over time. But in 1984, a new approach emerged: the uncemented PCA hip system, designed to fuse with the body’s own bone.  
-
-**The Science**:  
-The system’s porous surface, resembling a microscopic lattice, encouraged bone cells to grow into the gaps. This natural integration created a牢靠锚定 without cement, promising durability even in active patients.  
-
-**A Patient’s Journey**:  
-Take *James*, a 58-year-old construction worker with severe osteoarthritis. His surgeon implanted a PCA acetabular component and a cemented femoral stem (a hybrid approach). Over 3 years, James’ Harris hip score soared from 45 to 92. He returned to lifting heavy materials, his hip stable and pain-free.  
-
-**The Data**:  
-- In a study of 44 patients with PCA acetabular components, no loosening or migration occurred.  
-- Thigh pain (a common early side effect) resolved in most cases within 2 years.  
-- Only 2 femoral components needed revision—proof that biologic fixation works when initial stability is achieved.  
-
-**The Future**:  
-The PCA system’s success paved the way for cementless implants, now preferred for younger, active patients. For older adults, hybrid approaches balance cement’s immediate stability with the long-term benefits of bone integration.  
-
----
-
-### Note:  
-The file "Bell's palsy.md" was not saved due to a tool error. If you’d like to proceed, clarify the desired filename (it appears unrelated to hip systems) or ask me to resend the content for manual copying. Let me know how to assist further!
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/output/test.md b/agentic-apps/agentic_rag_milvus/output/test.md
deleted file mode 100644
index 21749c3f..00000000
--- a/agentic-apps/agentic_rag_milvus/output/test.md
+++ /dev/null
@@ -1,3 +0,0 @@
-# Test File
-
-This is a test.
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/package.json b/agentic-apps/agentic_rag_milvus/package.json
deleted file mode 100644
index 8956f53e..00000000
--- a/agentic-apps/agentic_rag_milvus/package.json
+++ /dev/null
@@ -1,36 +0,0 @@
-{
-  "name": "agentic-rag-opensearch",
-  "version": "1.0.0",
-  "description": "Agentic RAG system with MCP and custom embedding",
-  "main": "index.js",
-  "type": "module",
-  "scripts": {
-    "dev": "tsx src/index.ts",
-    "embed-knowledge": "tsx src/embedKnowledge.ts",
-    "embed-csv": "tsx src/embedCSV.ts",
-    "update-rag": "tsx src/updateRAG.ts",
-    "rebuild-collection": "tsx src/rebuildCollection.ts",
-    "test": "echo \"Error: no test specified\" && exit 1"
-  },
-  "keywords": [
-    "rag",
-    "mcp",
-    "llm",
-    "agent"
-  ],
-  "author": "",
-  "license": "ISC",
-  "dependencies": {
-    "@aws-sdk/client-bedrock-runtime": "^3.525.0",
-    "@modelcontextprotocol/sdk": "^1.10.1",
-    "@modelcontextprotocol/server-filesystem": "^2025.3.28",
-    "@zilliz/milvus2-sdk-node": "^2.5.8",
-    "chalk": "^5.4.1",
-    "csv-parse": "^5.5.5",
-    "dotenv": "^16.4.5",
-    "node-fetch": "^3.3.2",
-    "openai": "^4.28.4",
-    "tsx": "^4.7.1",
-    "typescript": "^5.3.3"
-  }
-}
diff --git a/agentic-apps/agentic_rag_milvus/pnpm-lock.yaml b/agentic-apps/agentic_rag_milvus/pnpm-lock.yaml
deleted file mode 100644
index f9ffb084..00000000
--- a/agentic-apps/agentic_rag_milvus/pnpm-lock.yaml
+++ /dev/null
@@ -1,2937 +0,0 @@
-lockfileVersion: '9.0'
-
-settings:
-  autoInstallPeers: true
-  excludeLinksFromLockfile: false
-
-importers:
-
-  .:
-    dependencies:
-      '@aws-sdk/client-bedrock-runtime':
-        specifier: ^3.525.0
-        version: 3.787.0
-      '@modelcontextprotocol/sdk':
-        specifier: ^1.10.1
-        version: 1.10.2
-      '@modelcontextprotocol/server-filesystem':
-        specifier: ^2025.3.28
-        version: 2025.3.28(zod@3.24.2)
-      '@zilliz/milvus2-sdk-node':
-        specifier: ^2.5.8
-        version: 2.5.8
-      chalk:
-        specifier: ^5.4.1
-        version: 5.4.1
-      csv-parse:
-        specifier: ^5.5.5
-        version: 5.6.0
-      dotenv:
-        specifier: ^16.4.5
-        version: 16.4.7
-      node-fetch:
-        specifier: ^3.3.2
-        version: 3.3.2
-      openai:
-        specifier: ^4.28.4
-        version: 4.91.1(zod@3.24.2)
-      tsx:
-        specifier: ^4.7.1
-        version: 4.19.3
-      typescript:
-        specifier: ^5.3.3
-        version: 5.8.2
-
-packages:
-
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diff --git a/agentic-apps/agentic_rag_milvus/src/Agent.ts b/agentic-apps/agentic_rag_milvus/src/Agent.ts
deleted file mode 100644
index e4b3a563..00000000
--- a/agentic-apps/agentic_rag_milvus/src/Agent.ts
+++ /dev/null
@@ -1,172 +0,0 @@
-import MCPClient from "./MCPClient";
-import ChatOpenAI from "./ChatOpenAI";
-import { logTitle } from "./utils";
-import { ToolCall } from "./ChatOpenAI";
-
-export default class Agent {
-    private mcpClients: MCPClient[];
-    private llm: ChatOpenAI | null = null;
-    private model: string;
-    private systemPrompt: string;
-    private context: string;
-
-    constructor(model: string, mcpClients: MCPClient[], systemPrompt: string = '', context: string = '') {
-        this.mcpClients = mcpClients;
-        this.model = model;
-        this.systemPrompt = systemPrompt;
-        this.context = context;
-    }
-
-    async init() {
-        logTitle('TOOLS');
-        for await (const client of this.mcpClients) {
-            await client.init();
-        }
-        const tools = this.mcpClients.flatMap(client => client.getTools());
-        this.llm = new ChatOpenAI(this.model, this.systemPrompt, tools, this.context);
-    }
-
-    async close() {
-        for await (const client of this.mcpClients) {
-            await client.close();
-        }
-    }
-
-    async invoke(prompt: string) {
-        if (!this.llm) throw new Error('Agent not initialized');
-        
-        try {
-            logTitle('AGENT EXECUTION');
-            console.log("Invoking LLM with tools...");
-            
-            // Start the conversation with the user prompt
-            let response = await this.llm.chat(prompt);
-            
-            // Continue the conversation until no more tool calls are needed
-            while (response.toolCalls && response.toolCalls.length > 0) {
-                logTitle('TOOL CALLS');
-                console.log(`Processing ${response.toolCalls.length} tool calls`);
-                
-                // Process each tool call
-                for (const toolCall of response.toolCalls) {
-                    await this.processToolCall(toolCall);
-                }
-                
-                // Continue the conversation with the tool results
-                response = await this.llm.chat();
-            }
-            
-            logTitle('FINAL RESPONSE');
-            console.log("Successfully completed request");
-            return response.content;
-        } catch (error) {
-            console.error("Error in agent execution:", error);
-            throw error;
-        }
-    }
-    
-    private async processToolCall(toolCall: ToolCall) {
-        try {
-            const { id, function: { name, arguments: argsString } } = toolCall;
-            console.log(`Executing tool call: ${name}`);
-            
-            // Parse the arguments
-            const args = JSON.parse(argsString);
-            
-            // Find the MCP client that can handle this tool
-            let clientName = name.split('___')[0];
-            let toolName = name.split('___')[1] || name;
-            
-            // If no client name in the tool name, try to find a client that has this tool
-            if (!toolName || toolName === name) {
-                console.log(`No client prefix found in tool name: ${name}. Trying to find a matching client...`);
-                toolName = name;
-                
-                // Try to find a client with this tool
-                for (const client of this.mcpClients) {
-                    const hasMatchingTool = client.getTools().some(tool => 
-                        tool.name === name || tool.name.endsWith(`___${name}`)
-                    );
-                    
-                    if (hasMatchingTool) {
-                        clientName = client.mcp.name;
-                        console.log(`Found matching client: ${clientName} for tool: ${name}`);
-                        break;
-                    }
-                }
-            }
-            
-            // Find the appropriate client
-            const client = this.mcpClients.find(c => c.mcp.name === clientName);
-            
-            if (!client) {
-                throw new Error(`No MCP client found for tool: ${name} (client: ${clientName}, tool: ${toolName})`);
-            }
-            
-            console.log(`Using client: ${clientName} to call tool: ${toolName}`);
-            
-            // Special handling for write_file tool
-            if (toolName === 'write_file') {
-                try {
-                    // Call the tool and get the result
-                    const result = await client.callTool(toolName, args);
-                    console.log(`Tool result: ${JSON.stringify(result).substring(0, 100)}...`);
-                    
-                    // Append the tool result to the conversation
-                    this.llm?.appendToolResult(id, JSON.stringify(result));
-                } catch (mcpError) {
-                    console.error(`MCP tool call failed: ${mcpError}`);
-                    
-                    // Try fallback direct file writing
-                    console.log("Attempting fallback file writing...");
-                    try {
-                        const fs = await import('fs');
-                        const path = await import('path');
-                        
-                        // Get the output directory from the first client's args
-                        const outPath = this.mcpClients[0]?.args[2] || process.cwd();
-                        
-                        // Construct the file path
-                        const filePath = path.join(outPath, args.path);
-                        
-                        // Write the file
-                        fs.writeFileSync(filePath, args.content);
-                        
-                        const result = { success: true, path: filePath };
-                        console.log(`Fallback file writing succeeded: ${filePath}`);
-                        
-                        // Append the success result to the conversation
-                        this.llm?.appendToolResult(id, JSON.stringify(result));
-                    } catch (fsError) {
-                        console.error(`Fallback file writing failed: ${fsError}`);
-                        
-                        // Append the error as the tool result
-                        this.llm?.appendToolResult(id, JSON.stringify({ 
-                            error: `Both MCP and fallback file writing failed: ${fsError.message}` 
-                        }));
-                    }
-                }
-            } else {
-                // For other tools, proceed normally
-                try {
-                    // Call the tool and get the result
-                    const result = await client.callTool(toolName, args);
-                    console.log(`Tool result: ${JSON.stringify(result).substring(0, 100)}...`);
-                    
-                    // Append the tool result to the conversation
-                    this.llm?.appendToolResult(id, JSON.stringify(result));
-                } catch (error) {
-                    console.error(`Error calling tool: ${error}`);
-                    
-                    // Append the error as the tool result
-                    this.llm?.appendToolResult(id, JSON.stringify({ error: error.message }));
-                }
-            }
-        } catch (error) {
-            console.error(`Error processing tool call: ${error}`);
-            console.error(`Error details:`, error);
-            // Append the error as the tool result
-            this.llm?.appendToolResult(toolCall.id, JSON.stringify({ error: error.message }));
-        }
-    }
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/src/ChatOpenAI.ts b/agentic-apps/agentic_rag_milvus/src/ChatOpenAI.ts
deleted file mode 100644
index 7d0ad90d..00000000
--- a/agentic-apps/agentic_rag_milvus/src/ChatOpenAI.ts
+++ /dev/null
@@ -1,151 +0,0 @@
-import OpenAI from "openai";
-import { Tool } from "@modelcontextprotocol/sdk/types.js";
-import 'dotenv/config'
-import { logTitle } from "./utils";
-
-export interface ToolCall {
-    id: string;
-    function: {
-        name: string;
-        arguments: string;
-    };
-}
-
-export default class ChatOpenAI {
-    private llm: OpenAI;
-    private model: string;
-    private messages: OpenAI.Chat.ChatCompletionMessageParam[] = [];
-    private tools: Tool[];
-
-    constructor(model: string, systemPrompt: string = '', tools: Tool[] = [], context: string = '') {
-        this.llm = new OpenAI({
-            apiKey: process.env.OPENAI_API_KEY,
-            baseURL: process.env.OPENAI_BASE_URL,
-            defaultHeaders: {
-                // Use only one authentication method to avoid conflicts
-                "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-                // Removed "api-key" header to prevent double authentication
-            }
-        });
-        this.model = model;
-        this.tools = tools;
-        if (systemPrompt) this.messages.push({ role: "system", content: systemPrompt });
-        if (context) this.messages.push({ role: "user", content: `Here is some context that might be helpful: \n\n${context}` });
-    }
-
-    async chat(prompt?: string): Promise<{ content: string, toolCalls: ToolCall[] }> {
-        logTitle('CHAT');
-        if (prompt) {
-            this.messages.push({ role: "user", content: prompt });
-        }
-        
-        // Debug the request
-        console.log('Sending request to model:', this.model);
-        console.log('Messages count:', this.messages.length);
-        console.log('Tools count:', this.tools.length);
-        
-        try {
-            // Create request options with tools if available
-            const requestOptions: OpenAI.Chat.ChatCompletionCreateParams = {
-                model: this.model,
-                messages: this.messages,
-                stream: false,
-            };
-            
-            // Add tools if available
-            if (this.tools.length > 0) {
-                requestOptions.tools = this.getToolsDefinition();
-                requestOptions.tool_choice = "auto";
-            }
-            
-            console.log('Sending request with options:', JSON.stringify({
-                ...requestOptions,
-                messages: `[${requestOptions.messages.length} messages]` // Don't log full messages
-            }, null, 2));
-            
-            const completion = await this.llm.chat.completions.create(requestOptions);
-            
-            // Extract the response content and tool calls
-            const message = completion.choices[0]?.message;
-            const content = message?.content || "";
-            const toolCalls = message?.tool_calls?.map(tc => ({
-                id: tc.id,
-                function: {
-                    name: tc.function.name,
-                    arguments: tc.function.arguments
-                }
-            })) || [];
-            
-            // Add the response to messages
-            this.messages.push({
-                role: "assistant",
-                content: content,
-                tool_calls: message?.tool_calls
-            });
-            
-            // Log the response
-            if (toolCalls.length > 0) {
-                console.log(`Response includes ${toolCalls.length} tool calls`);
-                toolCalls.forEach(tc => console.log(`- Tool: ${tc.function.name}`));
-            } else {
-                console.log('Response content:', content.substring(0, 100) + (content.length > 100 ? '...' : ''));
-            }
-            
-            return {
-                content: content,
-                toolCalls: toolCalls,
-            };
-        } catch (error) {
-            console.error('Error details:', error);
-            
-            // Enhanced error logging
-            console.error('Full error object:', JSON.stringify(error, null, 2));
-            
-            if (error.response) {
-                console.error('Response status:', error.response.status);
-                console.error('Response headers:', error.response.headers);
-                try {
-                    const responseText = await error.response.text();
-                    console.error('Response data:', responseText);
-                    try {
-                        // Try to parse as JSON for better readability
-                        const responseJson = JSON.parse(responseText);
-                        console.error('Response JSON:', JSON.stringify(responseJson, null, 2));
-                    } catch (parseError) {
-                        // If not valid JSON, the text version is already logged
-                    }
-                } catch (e) {
-                    console.error('Could not read response data:', e);
-                }
-            }
-            
-            // Log the exact request that was sent
-            console.error('Request that caused the error:');
-            console.error('- URL:', process.env.OPENAI_BASE_URL + '/chat/completions');
-            console.error('- Model:', this.model);
-            console.error('- Messages count:', this.messages.length);
-            console.error('- Tools count:', this.tools.length);
-            
-            throw error;
-        }
-    }
-
-    public appendToolResult(toolCallId: string, toolOutput: string) {
-        this.messages.push({
-            role: "tool",
-            content: toolOutput,
-            tool_call_id: toolCallId
-        });
-    }
-
-    private getToolsDefinition(): OpenAI.Chat.Completions.ChatCompletionTool[] {
-        return this.tools.map((tool) => ({
-            type: "function",
-            function: {
-                name: tool.name,
-                description: tool.description,
-                parameters: tool.inputSchema,
-            },
-        }));
-    }
-}
diff --git a/agentic-apps/agentic_rag_milvus/src/EmbeddingRetriever.ts b/agentic-apps/agentic_rag_milvus/src/EmbeddingRetriever.ts
deleted file mode 100644
index d7487345..00000000
--- a/agentic-apps/agentic_rag_milvus/src/EmbeddingRetriever.ts
+++ /dev/null
@@ -1,95 +0,0 @@
-import { logTitle } from "./utils";
-import MilvusVectorStore from "./MilvusVectorStore";
-import 'dotenv/config';
-import fetch from 'node-fetch';
-
-export default class EmbeddingRetriever {
-    private embeddingModel: string;
-    private vectorStore: MilvusVectorStore;
-    private embeddingEndpoint: string;
-
-    constructor(embeddingModel: string) {
-        this.embeddingModel = embeddingModel;
-        this.vectorStore = new MilvusVectorStore();
-        this.embeddingEndpoint = 'http://18.232.167.163:8080/v1/embeddings';
-    }
-
-    async embedDocument(document: string) {
-        logTitle('EMBEDDING DOCUMENT');
-        const embedding = await this.embed(document);
-        this.vectorStore.addEmbedding(embedding, document);
-        return embedding;
-    }
-
-    async embedQuery(query: string) {
-        logTitle('EMBEDDING QUERY');
-        const embedding = await this.embed(query);
-        return embedding;
-    }
-
-    private async embed(document: string): Promise<number[]> {
-        try {
-            console.log(`Sending embedding request to custom endpoint: ${this.embeddingEndpoint}`);
-            console.log(`Document length: ${document.length} characters`);
-            
-            const response = await fetch(this.embeddingEndpoint, {
-                method: 'POST',
-                headers: {
-                    'Content-Type': 'application/json',
-                },
-                body: JSON.stringify({
-                    content: document
-                }),
-            });
-            
-            if (!response.ok) {
-                throw new Error(`HTTP error! Status: ${response.status}`);
-            }
-            
-            const responseBody = await response.json();
-            
-            // Check if we got a valid embedding
-            // The response format is an array with objects containing the embedding
-            if (Array.isArray(responseBody) && responseBody.length > 0 && responseBody[0].embedding) {
-                // Extract the embedding from the first item in the array
-                const embedding = responseBody[0].embedding;
-                
-                // Check if the embedding is a nested array and flatten it if needed
-                const flatEmbedding = Array.isArray(embedding[0]) ? embedding[0] : embedding;
-                
-                console.log(`Successfully received embedding with ${flatEmbedding.length} dimensions`);
-                return flatEmbedding;
-            } else {
-                console.log("Warning: Embedding API didn't return a valid embedding");
-                console.log("Response:", JSON.stringify(responseBody, null, 2));
-                // Return a small random embedding vector for testing purposes
-                return Array(1536).fill(0).map(() => Math.random());
-            }
-        } catch (error) {
-            console.error("Error fetching embedding from custom endpoint:", error);
-            // Return a mock embedding in case of error
-            return Array(1536).fill(0).map(() => Math.random());
-        }
-    }
-
-    async retrieve(query: string, topK: number = 3): Promise<string[]> {
-        console.log(`Starting retrieval for query: "${query.substring(0, 50)}..."`);
-        
-        const queryEmbedding = await this.embedQuery(query);
-        console.log(`Generated query embedding with ${queryEmbedding.length} dimensions`);
-        
-        // Log a few values from the embedding to check consistency
-        console.log(`Embedding sample values: [${queryEmbedding.slice(0, 5).join(', ')}]`);
-        
-        const results = await this.vectorStore.search(queryEmbedding, topK);
-        console.log(`Search returned ${results.length} results`);
-        
-        if (results.length === 0) {
-            console.log(`WARNING: No results found for query: "${query.substring(0, 50)}..."`);
-        } else {
-            console.log(`First result preview: "${results[0].substring(0, 100)}..."`);
-        }
-        
-        return results;
-    }
-}
diff --git a/agentic-apps/agentic_rag_milvus/src/MCPClient.ts b/agentic-apps/agentic_rag_milvus/src/MCPClient.ts
deleted file mode 100644
index ec51a76f..00000000
--- a/agentic-apps/agentic_rag_milvus/src/MCPClient.ts
+++ /dev/null
@@ -1,98 +0,0 @@
-import { Client } from "@modelcontextprotocol/sdk/client/index.js";
-import { StdioClientTransport } from "@modelcontextprotocol/sdk/client/stdio.js";
-import { Tool } from "@modelcontextprotocol/sdk/types.js";
-
-export default class MCPClient {
-    public mcp: Client;
-    private command: string;
-    private args: string[]
-    private transport: StdioClientTransport | null = null;
-    private tools: Tool[] = [];
-
-    constructor(name: string, command: string, args: string[], version?: string) {
-        this.mcp = new Client({ name, version: version || "0.0.1" });
-        this.command = command;
-        this.args = args;
-    }
-
-    public async init() {
-        await this.connectToServer();
-    }
-
-    public async close() {
-        await this.mcp.close();
-    }
-
-    public getTools() {
-        return this.tools;
-    }
-
-    public callTool(name: string, params: Record<string, any>) {
-        return this.mcp.callTool({
-            name,
-            arguments: params,
-        });
-    }
-
-    private async connectToServer() {
-        try {
-            this.transport = new StdioClientTransport({
-                command: this.command,
-                args: this.args,
-            });
-            await this.mcp.connect(this.transport);
-
-            try {
-                const toolsResult = await this.mcp.listTools();
-                this.tools = toolsResult.tools.map((tool) => {
-                    // Prefix tool names with the client name to ensure proper routing
-                    const prefixedName = `${this.mcp.name}___${tool.name}`;
-                    return {
-                        name: prefixedName,
-                        description: tool.description,
-                        inputSchema: tool.inputSchema,
-                    };
-                });
-                console.log(
-                    "Connected to server with tools:",
-                    this.tools.map(({ name }) => name)
-                );
-            } catch (toolError) {
-                console.error("Failed to list tools from MCP server: ", toolError);
-                console.log("Adding fallback write_file tool manually");
-                
-                // Add a fallback write_file tool manually
-                this.tools = [{
-                    name: `${this.mcp.name}___write_file`,
-                    description: "Write content to a file",
-                    inputSchema: {
-                        type: "object",
-                        properties: {
-                            path: { type: "string", description: "Path to the file" },
-                            content: { type: "string", description: "Content to write" }
-                        },
-                        required: ["path", "content"]
-                    }
-                }];
-            }
-        } catch (e) {
-            console.error("Failed to connect to MCP server: ", e);
-            console.error("Error details:", e);
-            console.log("Will continue without MCP tools and rely on fallback methods");
-            
-            // Add a dummy tool so the agent can still make tool calls
-            this.tools = [{
-                name: `${this.mcp.name}___write_file`,
-                description: "Write content to a file (fallback)",
-                inputSchema: {
-                    type: "object",
-                    properties: {
-                        path: { type: "string", description: "Path to the file" },
-                        content: { type: "string", description: "Content to write" }
-                    },
-                    required: ["path", "content"]
-                }
-            }];
-        }
-    }
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/src/MilvusVectorStore.ts b/agentic-apps/agentic_rag_milvus/src/MilvusVectorStore.ts
deleted file mode 100644
index 47aca140..00000000
--- a/agentic-apps/agentic_rag_milvus/src/MilvusVectorStore.ts
+++ /dev/null
@@ -1,145 +0,0 @@
-import { MilvusClient, DataType, InsertReq, SearchParam } from '@zilliz/milvus2-sdk-node';
-import { VectorStoreItem } from './VectorStore';
-import 'dotenv/config';
-
-export default class MilvusVectorStore {
-    private client: MilvusClient;
-    private collectionName: string = 'rag_documents_384d';
-    private dimension: number = 384; // Changed to match the custom embedding endpoint dimensions
-
-    constructor() {
-        // Connect to Milvus service through NLB
-        this.client = new MilvusClient({
-            address: process.env.MILVUS_ADDRESS || 'k8s-default-milvusnl-fd87300847-5fa4d28f059626c9.elb.us-east-1.amazonaws.com:19530',
-            username: process.env.MILVUS_USERNAME || '',
-            password: process.env.MILVUS_PASSWORD || '',
-        });
-        this.initCollection();
-    }
-
-    private async initCollection() {
-        try {
-            // Check if collection exists
-            const hasCollection = await this.client.hasCollection({
-                collection_name: this.collectionName,
-            });
-
-            if (!hasCollection.value) {
-                // Create collection if it doesn't exist
-                await this.client.createCollection({
-                    collection_name: this.collectionName,
-                    fields: [
-                        {
-                            name: 'id',
-                            data_type: DataType.Int64,
-                            is_primary_key: true,
-                            autoID: true,
-                        },
-                        {
-                            name: 'embedding',
-                            data_type: DataType.FloatVector,
-                            dim: this.dimension,
-                        },
-                        {
-                            name: 'document',
-                            data_type: DataType.VarChar,
-                            max_length: 65535,
-                        },
-                    ],
-                });
-
-                // Create index for vector search
-                await this.client.createIndex({
-                    collection_name: this.collectionName,
-                    field_name: 'embedding',
-                    index_type: 'HNSW',
-                    metric_type: 'COSINE',
-                    params: { M: 8, efConstruction: 64 },
-                });
-
-                // Load collection into memory
-                await this.client.loadCollection({
-                    collection_name: this.collectionName,
-                });
-            }
-        } catch (error) {
-            console.error('Error initializing Milvus collection:', error);
-        }
-    }
-
-    async addEmbedding(embedding: number[], document: string) {
-        try {
-            // Create a new client for each insertion to avoid pool draining issues
-            const insertClient = new MilvusClient({
-                address: process.env.MILVUS_ADDRESS || 'k8s-default-milvusnl-fd87300847-5fa4d28f059626c9.elb.us-east-1.amazonaws.com:19530',
-                username: process.env.MILVUS_USERNAME || '',
-                password: process.env.MILVUS_PASSWORD || '',
-            });
-            
-            const insertData: InsertReq = {
-                collection_name: this.collectionName,
-                fields_data: [{
-                    embedding: embedding,
-                    document: document,
-                }],
-            };
-            
-            await insertClient.insert(insertData);
-            
-            // Close the client after insertion
-            await insertClient.closeConnection();
-        } catch (error) {
-            console.error('Error adding embedding to Milvus:', error);
-        }
-    }
-
-    async search(queryEmbedding: number[], topK: number = 3): Promise<string[]> {
-        try {
-            console.log(`Searching Milvus with topK=${topK}`);
-            
-            // Verify the embedding dimensions
-            console.log(`Query embedding dimensions: ${queryEmbedding.length}`);
-            if (queryEmbedding.length !== this.dimension) {
-                console.error(`Dimension mismatch: Query embedding has ${queryEmbedding.length} dimensions, but collection expects ${this.dimension}`);
-            }
-            
-            const searchParams: SearchParam = {
-                collection_name: this.collectionName,
-                vector: queryEmbedding,
-                output_fields: ['document'],
-                limit: topK,
-                params: { ef: 64 },
-            };
-            
-            console.log(`Executing search with params: ${JSON.stringify({
-                collection_name: searchParams.collection_name,
-                limit: searchParams.limit,
-                params: searchParams.params
-            })}`);
-            
-            const searchResult = await this.client.search(searchParams);
-            
-            console.log(`Search completed. Results: ${searchResult?.results?.length || 0}`);
-            
-            if (searchResult && searchResult.results && searchResult.results.length > 0) {
-                console.log(`Found ${searchResult.results.length} matching documents`);
-                return searchResult.results.map(item => item.document as string);
-            } else {
-                console.log(`No matching documents found. Search result: ${JSON.stringify(searchResult)}`);
-                return [];
-            }
-        } catch (error) {
-            console.error('Error searching in Milvus:', error);
-            console.error('Error details:', JSON.stringify(error, null, 2));
-            return [];
-        }
-    }
-
-    async close() {
-        try {
-            await this.client.closeConnection();
-        } catch (error) {
-            console.error('Error closing Milvus connection:', error);
-        }
-    }
-}
diff --git a/agentic-apps/agentic_rag_milvus/src/README.md b/agentic-apps/agentic_rag_milvus/src/README.md
deleted file mode 100644
index e1fbc9aa..00000000
--- a/agentic-apps/agentic_rag_milvus/src/README.md
+++ /dev/null
@@ -1,56 +0,0 @@
-# RAG System with Custom Embedding Model
-
-This project implements a Retrieval-Augmented Generation (RAG) system using a custom embedding model and Milvus vector database.
-
-## Setup
-
-1. Install dependencies:
-```bash
-npm install
-```
-
-2. Create a `.env` file with the following variables:
-```
-MILVUS_ADDRESS=your_milvus_address
-MILVUS_USERNAME=your_milvus_username
-MILVUS_PASSWORD=your_milvus_password
-AWS_REGION=your_aws_region
-```
-
-## Embedding the CSV Data
-
-To embed the `q_c_data.csv` file from the knowledge folder:
-
-```bash
-npm run embed-csv
-```
-
-This will process the CSV file, extract question-context pairs, and embed them using the custom embedding endpoint.
-
-## Running the Application
-
-To run the main application:
-
-```bash
-npm start
-```
-
-## Files
-
-- `index.ts`: Main application entry point
-- `EmbeddingRetriever.ts`: Handles embedding generation using the custom endpoint
-- `MilvusVectorStore.ts`: Manages vector storage and retrieval in Milvus
-- `Agent.ts`: Implements the agent that uses the RAG system
-- `updateRAG.ts`: Script to process and embed the CSV data
-
-## Custom Embedding Endpoint
-
-The system uses a custom embedding endpoint at http://18.232.167.163:8080/v1/embeddings instead of AWS Bedrock.
-
-Example request:
-```bash
-curl --request POST \
-    --url http://18.232.167.163:8080/v1/embeddings \
-    --header "Content-Type: application/json" \
-    --data '{"content": "Your text here"}'
-```
diff --git a/agentic-apps/agentic_rag_milvus/src/VectorStore.ts b/agentic-apps/agentic_rag_milvus/src/VectorStore.ts
deleted file mode 100644
index 506339ea..00000000
--- a/agentic-apps/agentic_rag_milvus/src/VectorStore.ts
+++ /dev/null
@@ -1,10 +0,0 @@
-export interface VectorStoreItem {
-    embedding: number[];
-    document: string;
-}
-
-export interface VectorStore {
-    addEmbedding(embedding: number[], document: string): Promise<void>;
-    search(queryEmbedding: number[], topK: number): Promise<string[]>;
-    close?(): Promise<void>;
-}
diff --git a/agentic-apps/agentic_rag_milvus/src/embedCSV.ts b/agentic-apps/agentic_rag_milvus/src/embedCSV.ts
deleted file mode 100644
index 467f5289..00000000
--- a/agentic-apps/agentic_rag_milvus/src/embedCSV.ts
+++ /dev/null
@@ -1,85 +0,0 @@
-import fs from "fs";
-import path from "path";
-import { parse } from "csv-parse/sync";
-import EmbeddingRetriever from "./EmbeddingRetriever";
-import { logTitle } from "./utils";
-
-// Function to process and embed CSV data
-async function embedCSVData() {
-    logTitle('EMBEDDING CSV DATA');
-    
-    const csvPath = path.join(process.cwd(), 'knowledge');
-    
-    if (!fs.existsSync(csvPath)) {
-        console.error(`CSV data directory not found: ${csvPath}`);
-        return false;
-    }
-    
-    try {
-        // Get all CSV files in the data directory
-        const files = fs.readdirSync(csvPath)
-            .filter(file => file.endsWith('.csv'));
-        
-        console.log(`Found ${files.length} CSV files in the data directory`);
-        
-        // Initialize the embedding retriever
-        const embeddingRetriever = new EmbeddingRetriever("custom-embedding-model");
-        
-        // Process each file
-        for (const file of files) {
-            const filePath = path.join(csvPath, file);
-            console.log(`Processing file: ${file}`);
-            
-            // Read the file content
-            const content = fs.readFileSync(filePath, 'utf-8');
-            
-            // Parse CSV
-            const records = parse(content, {
-                columns: true,
-                skip_empty_lines: true
-            });
-            
-            console.log(`Found ${records.length} records in ${file}`);
-            
-            // Process each record
-            for (const record of records) {
-                // Convert record to a string representation
-                const recordString = Object.entries(record)
-                    .map(([key, value]) => `${key}: ${value}`)
-                    .join('\n');
-                
-                // Create a document with metadata
-                const document = `# ${record.name || record.title || record.id || 'Record'}\n\n${recordString}`;
-                
-                // Embed the document
-                await embeddingRetriever.embedDocument(document);
-            }
-            
-            console.log(`Successfully embedded ${records.length} records from ${file}`);
-        }
-        
-        // Close Milvus connection when done
-        // @ts-ignore - Access private property for cleanup
-        if (embeddingRetriever.vectorStore && typeof embeddingRetriever.vectorStore.close === 'function') {
-            // @ts-ignore
-            await embeddingRetriever.vectorStore.close();
-        }
-        
-        return true;
-    } catch (error) {
-        console.error("Error embedding CSV data:", error);
-        return false;
-    }
-}
-
-// Main function
-(async () => {
-    const success = await embedCSVData();
-    
-    if (success) {
-        console.log("CSV data embedding completed successfully");
-    } else {
-        console.error("CSV data embedding failed");
-        process.exit(1);
-    }
-})();
diff --git a/agentic-apps/agentic_rag_milvus/src/embedKnowledge.ts b/agentic-apps/agentic_rag_milvus/src/embedKnowledge.ts
deleted file mode 100644
index fb7c3d12..00000000
--- a/agentic-apps/agentic_rag_milvus/src/embedKnowledge.ts
+++ /dev/null
@@ -1,65 +0,0 @@
-import fs from "fs";
-import path from "path";
-import EmbeddingRetriever from "./EmbeddingRetriever";
-import { logTitle } from "./utils";
-
-// Function to process and embed knowledge files
-async function embedKnowledgeFiles() {
-    logTitle('EMBEDDING KNOWLEDGE FILES');
-    
-    const knowledgePath = path.join(process.cwd(), 'knowledge');
-    
-    if (!fs.existsSync(knowledgePath)) {
-        console.error(`Knowledge directory not found: ${knowledgePath}`);
-        return false;
-    }
-    
-    try {
-        // Get all markdown files in the knowledge directory
-        const files = fs.readdirSync(knowledgePath)
-            .filter(file => file.endsWith('.md'));
-        
-        console.log(`Found ${files.length} markdown files in the knowledge directory`);
-        
-        // Initialize the embedding retriever
-        const embeddingRetriever = new EmbeddingRetriever("custom-embedding-model");
-        
-        // Process each file
-        for (const file of files) {
-            const filePath = path.join(knowledgePath, file);
-            console.log(`Processing file: ${file}`);
-            
-            // Read the file content
-            const content = fs.readFileSync(filePath, 'utf-8');
-            
-            // Embed the document
-            await embeddingRetriever.embedDocument(content);
-        }
-        
-        console.log(`Successfully embedded ${files.length} knowledge files`);
-        
-        // Close Milvus connection when done
-        // @ts-ignore - Access private property for cleanup
-        if (embeddingRetriever.vectorStore && typeof embeddingRetriever.vectorStore.close === 'function') {
-            // @ts-ignore
-            await embeddingRetriever.vectorStore.close();
-        }
-        
-        return true;
-    } catch (error) {
-        console.error("Error embedding knowledge files:", error);
-        return false;
-    }
-}
-
-// Main function
-(async () => {
-    const success = await embedKnowledgeFiles();
-    
-    if (success) {
-        console.log("Knowledge embedding completed successfully");
-    } else {
-        console.error("Knowledge embedding failed");
-        process.exit(1);
-    }
-})();
diff --git a/agentic-apps/agentic_rag_milvus/src/index.ts b/agentic-apps/agentic_rag_milvus/src/index.ts
deleted file mode 100644
index 8b305e29..00000000
--- a/agentic-apps/agentic_rag_milvus/src/index.ts
+++ /dev/null
@@ -1,174 +0,0 @@
-import MCPClient from "./MCPClient";
-import Agent from "./Agent";
-import path from "path";
-import EmbeddingRetriever from "./EmbeddingRetriever";
-import fs from "fs";
-import { logTitle } from "./utils";
-
-// Use the parent directory (where the command is run) instead of src directory
-const outPath = path.resolve(process.cwd(), 'output');
-const TASK = `
-Give me the answer about What is the primary advantage of using an uncemented porous-coated anatomic (PCA) hip system in total hip arthroplasty? 
-Summarize this information and create a story about it.
-Save the story to a file named "Bell's palsy.md" in the output directory as a beautiful markdown file.
-`
-
-// Make sure output directory exists
-if (!fs.existsSync(outPath)) {
-  fs.mkdirSync(outPath, { recursive: true });
-}
-
-// Add test function for Milvus search
-async function testMilvusSearch() {
-  console.log('Testing Milvus search functionality...');
-  
-  const embeddingRetriever = new EmbeddingRetriever("custom-embedding-model");
-  
-  // Generate a test embedding (random values)
-  const testEmbedding = Array(1536).fill(0).map(() => Math.random());
-  
-  // Try a direct search with the test embedding
-  // @ts-ignore - Access private property for testing
-  const results = await embeddingRetriever.vectorStore.search(testEmbedding, 5);
-  
-  console.log(`Test search returned ${results.length} results`);
-  if (results.length > 0) {
-    console.log('First result preview:', results[0].substring(0, 100) + '...');
-  } else {
-    console.log('No results found in test search');
-  }
-  
-  // Try a simple query that should match something
-  const simpleQuery = "surgical complications";
-  console.log(`Testing simple query: "${simpleQuery}"`);
-  const queryResults = await embeddingRetriever.retrieve(simpleQuery, 5);
-  
-  console.log(`Simple query returned ${queryResults.length} results`);
-  if (queryResults.length > 0) {
-    console.log('First result preview:', queryResults[0].substring(0, 100) + '...');
-  } else {
-    console.log('No results found for simple query');
-  }
-}
-
-// Start the application immediately
-(async () => {
-  try {
-    logTitle('INITIALIZING AGENTIC RAG SYSTEM');
-    
-    // Run test search first
-    await testMilvusSearch();
-    
-    // Initialize the filesystem MCP client
-    const fileMCP = new MCPClient("mcp-server-file", "npx", ['-y', '@modelcontextprotocol/server-filesystem', outPath]);
-    
-    // Add a fallback method to write files directly if MCP fails
-    const fallbackWriteFile = async (filename: string, content: string) => {
-      try {
-        const filePath = path.join(outPath, filename);
-        fs.writeFileSync(filePath, content);
-        console.log(`Fallback: Successfully wrote file to ${filePath}`);
-        return { success: true, path: filePath };
-      } catch (error) {
-        console.error(`Fallback: Failed to write file: ${error}`);
-        return { success: false, error: error.message };
-      }
-    };
-    
-    await main(fileMCP, fallbackWriteFile);
-  } catch (error) {
-    console.error("Error in main:", error);
-  }
-})();
-
-async function main(fileMCP: MCPClient, fallbackWriteFile?: (filename: string, content: string) => Promise<any>) {
-  // Step 1: Retrieve relevant context using RAG
-  const context = await retrieveContext("What is the primary advantage of using an uncemented porous-coated anatomic (PCA) hip system in total hip arthroplasty?");
-  
-  // Step 2: Initialize the agent with the context and MCP client
-  logTitle('INITIALIZING AGENT');
-  const systemPrompt = `You are a helpful assistant that can retrieve information and create stories.
-You have access to tools that can help you complete tasks.
-When asked to save files, always use the filesystem tool to write the content.
-Specifically, use the mcp-server-file___write_file tool to save files.
-The output path is ${outPath}.`;
-
-  const agent = new Agent('Qwen/QwQ-32B-AWQ', [fileMCP], systemPrompt, context);
-  await agent.init();
-  
-  // Step 3: Execute the task with the agent
-  logTitle('EXECUTING TASK');
-  console.log(TASK);
-  
-  try {
-    const response = await agent.invoke(TASK);
-    
-    // Step 4: Close connections
-    logTitle('TASK COMPLETED');
-    console.log(response);
-    
-    // Always use the fallback method to save the file
-    logTitle('USING FALLBACK METHOD TO SAVE FILE');
-    
-    // Extract the content from the response - try different patterns
-    let content = null;
-    
-    // Try to extract markdown content
-    const markdownMatch = response.match(/```markdown\n([\s\S]*?)\n```/);
-    if (markdownMatch && markdownMatch[1]) {
-      content = markdownMatch[1];
-    } else {
-      // Try to extract any code block content
-      const codeBlockMatch = response.match(/```(?:\w+)?\n([\s\S]*?)\n```/);
-      if (codeBlockMatch && codeBlockMatch[1]) {
-        content = codeBlockMatch[1];
-      } else {
-        // If no code blocks, use the entire response
-        content = response;
-      }
-    }
-    
-    if (content && fallbackWriteFile) {
-      console.log("Extracted content for file writing:", content.substring(0, 100) + "...");
-      const result = await fallbackWriteFile("antonette.md", content);
-      if (result.success) {
-        console.log(`Successfully saved file using fallback method to ${result.path}`);
-      } else {
-        console.error(`Failed to save file using fallback method: ${result.error}`);
-      }
-    } else {
-      console.error("Could not extract content from response or fallback method not available");
-    }
-  } catch (error) {
-    console.error("Error during task execution:", error);
-  } finally {
-    await agent.close();
-    
-    // Close Milvus connection when done
-    const embeddingRetriever = new EmbeddingRetriever("custom-embedding-model");
-    // @ts-ignore - Access private property for cleanup
-    if (embeddingRetriever.vectorStore && typeof embeddingRetriever.vectorStore.close === 'function') {
-      // @ts-ignore
-      await embeddingRetriever.vectorStore.close();
-    }
-  }
-}
-
-async function retrieveContext(query: string) {
-    logTitle('RETRIEVING CONTEXT');
-    console.log(`Query: ${query}`);
-    
-    // Initialize the embedding retriever
-    const embeddingRetriever = new EmbeddingRetriever("custom-embedding-model");
-    
-    // Retrieve relevant documents
-    const documents = await embeddingRetriever.retrieve(query, 5);
-    
-    // Combine documents into context
-    const context = documents.join('\n\n');
-    
-    console.log(`Retrieved ${documents.length} relevant documents`);
-    console.log('Context preview:', context.substring(0, 200) + '...');
-    
-    return context;
-}
diff --git a/agentic-apps/agentic_rag_milvus/src/package.json b/agentic-apps/agentic_rag_milvus/src/package.json
deleted file mode 100644
index 6f2cd313..00000000
--- a/agentic-apps/agentic_rag_milvus/src/package.json
+++ /dev/null
@@ -1,35 +0,0 @@
-{
-  "name": "agentic-rag-opensearch",
-  "version": "1.0.0",
-  "description": "Agentic RAG system with MCP and custom embedding",
-  "main": "index.js",
-  "type": "module",
-  "scripts": {
-    "dev": "tsx index.ts",
-    "embed-knowledge": "tsx embedKnowledge.ts",
-    "embed-csv": "tsx embedCSV.ts",
-    "update-rag": "tsx updateRAG.ts",
-    "test": "echo \"Error: no test specified\" && exit 1"
-  },
-  "keywords": [
-    "rag",
-    "mcp",
-    "llm",
-    "agent"
-  ],
-  "author": "",
-  "license": "ISC",
-  "dependencies": {
-    "@aws-sdk/client-bedrock-runtime": "^3.525.0",
-    "@modelcontextprotocol/sdk": "^1.10.1",
-    "@modelcontextprotocol/server-filesystem": "^2025.3.28",
-    "@zilliz/milvus2-sdk-node": "^2.5.8",
-    "chalk": "^5.4.1",
-    "csv-parse": "^5.5.5",
-    "dotenv": "^16.4.5",
-    "node-fetch": "^3.3.2",
-    "openai": "^4.28.4",
-    "tsx": "^4.7.1",
-    "typescript": "^5.3.3"
-  }
-}
diff --git a/agentic-apps/agentic_rag_milvus/src/rebuildCollection.ts b/agentic-apps/agentic_rag_milvus/src/rebuildCollection.ts
deleted file mode 100644
index 893d5054..00000000
--- a/agentic-apps/agentic_rag_milvus/src/rebuildCollection.ts
+++ /dev/null
@@ -1,96 +0,0 @@
-import { MilvusClient, DataType } from '@zilliz/milvus2-sdk-node';
-import { logTitle } from "./utils";
-import 'dotenv/config';
-
-// Function to rebuild the Milvus collection with 384 dimensions
-async function rebuildCollection() {
-    logTitle('REBUILDING MILVUS COLLECTION');
-    
-    const collectionName = 'rag_documents_384d';
-    const dimension = 384; // New dimension to match the custom embedding endpoint
-    
-    try {
-        // Connect to Milvus
-        const client = new MilvusClient({
-            address: process.env.MILVUS_ADDRESS || 'k8s-default-milvusnl-fd87300847-5fa4d28f059626c9.elb.us-east-1.amazonaws.com:19530',
-            username: process.env.MILVUS_USERNAME || '',
-            password: process.env.MILVUS_PASSWORD || '',
-        });
-        
-        // Check if collection exists and drop it if it does
-        const hasCollection = await client.hasCollection({
-            collection_name: collectionName,
-        });
-        
-        if (hasCollection.value) {
-            console.log(`Collection ${collectionName} already exists. Dropping it...`);
-            await client.dropCollection({
-                collection_name: collectionName,
-            });
-            console.log(`Collection ${collectionName} dropped successfully.`);
-        }
-        
-        // Create new collection with 384 dimensions
-        console.log(`Creating new collection ${collectionName} with ${dimension} dimensions...`);
-        await client.createCollection({
-            collection_name: collectionName,
-            fields: [
-                {
-                    name: 'id',
-                    data_type: DataType.Int64,
-                    is_primary_key: true,
-                    autoID: true,
-                },
-                {
-                    name: 'embedding',
-                    data_type: DataType.FloatVector,
-                    dim: dimension,
-                },
-                {
-                    name: 'document',
-                    data_type: DataType.VarChar,
-                    max_length: 65535,
-                },
-            ],
-        });
-        
-        // Create index for vector search
-        console.log(`Creating index for collection ${collectionName}...`);
-        await client.createIndex({
-            collection_name: collectionName,
-            field_name: 'embedding',
-            index_type: 'HNSW',
-            metric_type: 'COSINE',
-            params: { M: 8, efConstruction: 64 },
-        });
-        
-        // Load collection into memory
-        console.log(`Loading collection ${collectionName} into memory...`);
-        await client.loadCollection({
-            collection_name: collectionName,
-        });
-        
-        console.log(`Collection ${collectionName} created and indexed successfully.`);
-        
-        // Close connection
-        await client.closeConnection();
-        
-        return true;
-    } catch (error) {
-        console.error("Error rebuilding Milvus collection:", error);
-        return false;
-    }
-}
-
-// Main function
-(async () => {
-    const success = await rebuildCollection();
-    
-    if (success) {
-        console.log("Collection rebuild completed successfully. Now you need to re-embed your documents.");
-        console.log("Run 'pnpm embed-knowledge' and 'pnpm embed-csv' to populate the new collection.");
-    } else {
-        console.error("Collection rebuild failed");
-        process.exit(1);
-    }
-})();
diff --git a/agentic-apps/agentic_rag_milvus/src/updateRAG.ts b/agentic-apps/agentic_rag_milvus/src/updateRAG.ts
deleted file mode 100644
index f5afef35..00000000
--- a/agentic-apps/agentic_rag_milvus/src/updateRAG.ts
+++ /dev/null
@@ -1,79 +0,0 @@
-import fs from "fs";
-import path from "path";
-import { parse } from "csv-parse/sync";
-import EmbeddingRetriever from "./EmbeddingRetriever";
-import { logTitle } from "./utils";
-
-// Function to update the RAG process with CSV data
-async function updateRAGWithCSV() {
-    logTitle('UPDATING RAG WITH CSV DATA');
-    
-    const csvFilePath = path.join(process.cwd(), '..', 'knowledge', 'q_c_data.csv');
-    
-    if (!fs.existsSync(csvFilePath)) {
-        console.error(`File not found: ${csvFilePath}`);
-        return false;
-    }
-    
-    try {
-        // Read the CSV file
-        const fileContent = fs.readFileSync(csvFilePath, 'utf-8');
-        
-        // Parse the CSV content
-        const records = parse(fileContent, {
-            columns: true,
-            skip_empty_lines: true
-        });
-        
-        console.log(`Found ${records.length} records in the CSV file`);
-        
-        // Initialize the embedding retriever
-        const embeddingRetriever = new EmbeddingRetriever("custom-embedding-model");
-        
-        // Process each record in batches to avoid overwhelming the system
-        const batchSize = 50;
-        let processedCount = 0;
-        
-        for (let i = 0; i < records.length; i += batchSize) {
-            const batch = records.slice(i, i + batchSize);
-            
-            // Process batch in parallel
-            await Promise.all(batch.map(async (record) => {
-                // Combine question and context for better retrieval
-                const documentText = `Question: ${record.question}\nContext: ${record.context}`;
-                
-                // Embed the document
-                await embeddingRetriever.embedDocument(documentText);
-            }));
-            
-            processedCount += batch.length;
-            console.log(`Processed ${processedCount}/${records.length} records`);
-        }
-        
-        console.log(`Successfully embedded ${processedCount} records from the CSV file`);
-        
-        // Close Milvus connection when done
-        // @ts-ignore - Access private property for cleanup
-        if (embeddingRetriever.vectorStore && typeof embeddingRetriever.vectorStore.close === 'function') {
-            // @ts-ignore
-            await embeddingRetriever.vectorStore.close();
-        }
-        
-        return true;
-    } catch (error) {
-        console.error("Error updating RAG with CSV data:", error);
-        return false;
-    }
-}
-
-// Main function
-(async () => {
-    const success = await updateRAGWithCSV();
-    
-    if (success) {
-        console.log("RAG update completed successfully");
-    } else {
-        console.error("RAG update failed");
-        process.exit(1);
-    }
-})();
diff --git a/agentic-apps/agentic_rag_milvus/src/utils.ts b/agentic-apps/agentic_rag_milvus/src/utils.ts
deleted file mode 100644
index 660eca95..00000000
--- a/agentic-apps/agentic_rag_milvus/src/utils.ts
+++ /dev/null
@@ -1,9 +0,0 @@
-import chalk from "chalk";
-
-export function logTitle(message: string) {
-    const totalLength = 80;
-    const messageLength = message.length;
-    const padding = Math.max(0, totalLength - messageLength - 4); // 4 for the "=="
-    const paddedMessage = `${'='.repeat(Math.floor(padding / 2))} ${message} ${'='.repeat(Math.ceil(padding / 2))}`;
-    console.log(chalk.bold.cyanBright(paddedMessage));
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_milvus/test-endpoint-with-tools.js b/agentic-apps/agentic_rag_milvus/test-endpoint-with-tools.js
deleted file mode 100644
index 7a52387c..00000000
--- a/agentic-apps/agentic_rag_milvus/test-endpoint-with-tools.js
+++ /dev/null
@@ -1,90 +0,0 @@
-// Test script to check LLM endpoint with tools
-import 'dotenv/config';
-import { OpenAI } from 'openai';
-
-async function testEndpointWithTools() {
-  console.log('Testing LLM endpoint with tools');
-  console.log('Base URL:', process.env.OPENAI_BASE_URL);
-  
-  // Create OpenAI client with simplified configuration
-  const openai = new OpenAI({
-    apiKey: process.env.OPENAI_API_KEY,
-    baseURL: process.env.OPENAI_BASE_URL,
-    defaultHeaders: {
-      // Using only one authentication method
-      "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-    }
-  });
-
-  // Simple message with tools
-  const messages = [
-    { role: "user", content: "What's the weather like in Seattle?" }
-  ];
-
-  // Define a simple tool
-  const tools = [
-    {
-      type: "function",
-      function: {
-        name: "get_weather",
-        description: "Get the current weather in a location",
-        parameters: {
-          type: "object",
-          properties: {
-            location: {
-              type: "string",
-              description: "The city and state, e.g. San Francisco, CA"
-            }
-          },
-          required: ["location"]
-        }
-      }
-    }
-  ];
-
-  try {
-    console.log('Sending request with tools...');
-    
-    // Use the original model name format that worked in the simple test
-    const modelName = 'Qwen/QwQ-32B-AWQ';
-    console.log('Using model:', modelName);
-    
-    const response = await openai.chat.completions.create({
-      model: modelName,
-      messages: messages,
-      tools: tools,
-      tool_choice: "auto",
-      stream: false
-    });
-    
-    console.log('Success! Response:');
-    console.log(JSON.stringify(response, null, 2));
-    return response;
-  } catch (error) {
-    console.error('Error occurred:');
-    console.error('Status:', error.status);
-    console.error('Headers:', error.headers);
-    
-    if (error.response) {
-      try {
-        const responseText = await error.response.text();
-        console.error('Response body:', responseText);
-        try {
-          const responseJson = JSON.parse(responseText);
-          console.error('Response JSON:', JSON.stringify(responseJson, null, 2));
-        } catch (parseError) {
-          // If not valid JSON, the text version is already logged
-        }
-      } catch (e) {
-        console.error('Could not read response data:', e);
-      }
-    }
-    
-    throw error;
-  }
-}
-
-// Run the test
-testEndpointWithTools()
-  .then(() => console.log('Test completed successfully'))
-  .catch(err => console.error('Test failed:', err.message));
diff --git a/agentic-apps/agentic_rag_milvus/test-endpoint.js b/agentic-apps/agentic_rag_milvus/test-endpoint.js
deleted file mode 100644
index 53b03e5a..00000000
--- a/agentic-apps/agentic_rag_milvus/test-endpoint.js
+++ /dev/null
@@ -1,67 +0,0 @@
-// Simple test script to check LLM endpoint connectivity
-import 'dotenv/config';
-import { OpenAI } from 'openai';
-
-async function testEndpoint() {
-  console.log('Testing LLM endpoint with a simple request');
-  console.log('Base URL:', process.env.OPENAI_BASE_URL);
-  
-  // Create OpenAI client with simplified configuration
-  const openai = new OpenAI({
-    apiKey: process.env.OPENAI_API_KEY,
-    baseURL: process.env.OPENAI_BASE_URL,
-    defaultHeaders: {
-      // Using only one authentication method
-      "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-    }
-  });
-
-  // Simple message without tools
-  const messages = [
-    { role: "user", content: "Hello, can you respond with a simple greeting?" }
-  ];
-
-  try {
-    console.log('Sending request...');
-    
-    // Try with the original model name format
-    const modelName = 'Qwen/QwQ-32B-AWQ';
-    console.log('Using model:', modelName);
-    
-    const response = await openai.chat.completions.create({
-      model: modelName,
-      messages: messages,
-      stream: false
-    });
-    
-    console.log('Success! Response:');
-    console.log(JSON.stringify(response, null, 2));
-    return response;
-  } catch (error) {
-    console.error('Error occurred:');
-    console.error('Status:', error.status);
-    console.error('Headers:', error.headers);
-    
-    if (error.response) {
-      try {
-        const responseText = await error.response.text();
-        console.error('Response body:', responseText);
-        try {
-          const responseJson = JSON.parse(responseText);
-          console.error('Response JSON:', JSON.stringify(responseJson, null, 2));
-        } catch (parseError) {
-          // If not valid JSON, the text version is already logged
-        }
-      } catch (e) {
-        console.error('Could not read response data:', e);
-      }
-    }
-    
-    throw error;
-  }
-}
-
-// Run the test
-testEndpoint()
-  .then(() => console.log('Test completed successfully'))
-  .catch(err => console.error('Test failed:', err.message));
diff --git a/agentic-apps/agentic_rag_milvus/test-file-write.js b/agentic-apps/agentic_rag_milvus/test-file-write.js
deleted file mode 100644
index 31f67447..00000000
--- a/agentic-apps/agentic_rag_milvus/test-file-write.js
+++ /dev/null
@@ -1,16 +0,0 @@
-// Simple test script to verify file writing works
-import fs from 'fs';
-import path from 'path';
-
-const outPath = path.resolve(process.cwd(), 'output');
-const filePath = path.join(outPath, 'test.md');
-
-console.log(`Attempting to write to: ${filePath}`);
-console.log(`Output directory exists: ${fs.existsSync(outPath)}`);
-
-try {
-  fs.writeFileSync(filePath, '# Test File\n\nThis is a test.');
-  console.log(`Successfully wrote file to ${filePath}`);
-} catch (error) {
-  console.error(`Failed to write file: ${error}`);
-}
diff --git a/agentic-apps/agentic_rag_milvus/test-mcp-server.js b/agentic-apps/agentic_rag_milvus/test-mcp-server.js
deleted file mode 100644
index 1b0444ec..00000000
--- a/agentic-apps/agentic_rag_milvus/test-mcp-server.js
+++ /dev/null
@@ -1,65 +0,0 @@
-// Test script to check MCP server functionality
-import { spawn } from 'child_process';
-import path from 'path';
-
-const outPath = path.resolve(process.cwd(), 'output');
-console.log(`Testing MCP server with output path: ${outPath}`);
-
-// Start the MCP server process
-const mcpProcess = spawn('npx', ['-y', '@modelcontextprotocol/server-filesystem', outPath], {
-  stdio: ['pipe', 'pipe', 'pipe']
-});
-
-// Log server output
-mcpProcess.stdout.on('data', (data) => {
-  console.log(`MCP Server stdout: ${data}`);
-});
-
-mcpProcess.stderr.on('data', (data) => {
-  console.error(`MCP Server stderr: ${data}`);
-});
-
-// Send a test message to the server after it starts
-setTimeout(() => {
-  try {
-    console.log('Sending test message to MCP server...');
-    const message = {
-      jsonrpc: '2.0',
-      id: '1',
-      method: 'listTools',
-      params: {}
-    };
-    
-    mcpProcess.stdin.write(JSON.stringify(message) + '\n');
-    
-    // Wait for response and then try to call the write_file tool
-    setTimeout(() => {
-      console.log('Attempting to call write_file tool...');
-      const writeFileMessage = {
-        jsonrpc: '2.0',
-        id: '2',
-        method: 'callTool',
-        params: {
-          name: 'write_file',
-          arguments: {
-            path: 'mcp-test.md',
-            content: '# MCP Test\n\nThis file was created using the MCP server.'
-          }
-        }
-      };
-      
-      mcpProcess.stdin.write(JSON.stringify(writeFileMessage) + '\n');
-      
-      // Close the server after testing
-      setTimeout(() => {
-        console.log('Closing MCP server...');
-        mcpProcess.kill();
-        process.exit(0);
-      }, 2000);
-    }, 1000);
-  } catch (error) {
-    console.error(`Error sending message to MCP server: ${error}`);
-    mcpProcess.kill();
-    process.exit(1);
-  }
-}, 2000);
diff --git a/agentic-apps/agentic_rag_milvus/tsconfig.json b/agentic-apps/agentic_rag_milvus/tsconfig.json
deleted file mode 100644
index e5f25ec9..00000000
--- a/agentic-apps/agentic_rag_milvus/tsconfig.json
+++ /dev/null
@@ -1,17 +0,0 @@
-{
-  "compilerOptions": {
-    "target": "ES2020",
-    "module": "ESNext",
-    "moduleResolution": "Bundler",
-    "esModuleInterop": true,
-    "outDir": "./dist",
-    "rootDir": "./src",
-    "strict": true
-  },
-  "include": [
-    "src/**/*"
-  ],
-  "exclude": [
-    "node_modules"
-  ]
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_opensearch/.env.example b/agentic-apps/agentic_rag_opensearch/.env.example
deleted file mode 100644
index 83402d24..00000000
--- a/agentic-apps/agentic_rag_opensearch/.env.example
+++ /dev/null
@@ -1,29 +0,0 @@
-# OpenAI API Configuration
-# API key for accessing the LLM model
-# This should match the key configured in your LiteLLM gateway
-OPENAI_API_KEY=your-openai-api-key
-
-# Base URL for the OpenAI-compatible API
-# This should be the URL of your model hosting service (Ray service or LiteLLM gateway)
-OPENAI_BASE_URL=http://your-model-endpoint/v1
-
-# OpenSearch Configuration
-# Endpoint URL of your OpenSearch cluster
-# This will be automatically set by the setup-opensearch.sh script
-OPENSEARCH_ENDPOINT=https://your-opensearch-domain-endpoint
-
-# AWS region where your OpenSearch cluster is deployed
-AWS_REGION=us-east-1
-
-# Langfuse Configuration for LLM Observability
-# URL of the Langfuse service deployed in your EKS cluster
-# This should be the load balancer URL from your model-observability deployment
-LANGFUSE_HOST=http://your-langfuse-host-url
-
-# Langfuse public key for authentication
-# Get this from your Langfuse dashboard after creating a project
-LANGFUSE_PUBLIC_KEY=pk-lf-your-public-key
-
-# Langfuse secret key for authentication
-# Get this from your Langfuse dashboard after creating a project
-LANGFUSE_SECRET_KEY=sk-lf-your-secret-key
diff --git a/agentic-apps/agentic_rag_opensearch/AmazonQ.md b/agentic-apps/agentic_rag_opensearch/AmazonQ.md
deleted file mode 100644
index 7505747b..00000000
--- a/agentic-apps/agentic_rag_opensearch/AmazonQ.md
+++ /dev/null
@@ -1,72 +0,0 @@
-# Augmented LLM with MCP and RAG
-
-This project demonstrates a framework-independent implementation of an augmented Large Language Model (LLM) system that combines Model Context Protocol (MCP) for tool usage and Retrieval Augmented Generation (RAG) for enhanced context awareness.
-
-## Project Overview
-
-This application creates an AI agent that can:
-1. Retrieve relevant information from a knowledge base using vector embeddings
-2. Interact with external tools through the Model Context Protocol (MCP)
-3. Generate responses based on both the retrieved context and tool interactions
-4. Complete tasks like summarizing content and saving results to files
-
-## Architecture
-
-The system is built with a modular architecture consisting of these key components:
-
-```
-Agent → Manages the overall workflow and coordinates components
-  ├── ChatOpenAI → Handles LLM interactions and tool calling
-  ├── MCPClient(s) → Connects to MCP servers for tool access
-  └── EmbeddingRetriever → Performs vector search for relevant context
-      └── VectorStore → Stores and searches document embeddings
-```
-
-## Workflow Explanation
-
-1. **Initialization**:
-   - The system loads knowledge documents and creates embeddings using AWS Bedrock
-   - Embeddings are stored in an in-memory vector store
-   - MCP clients are initialized to connect to tool servers
-
-2. **RAG Process**:
-   - When a query is received, it's converted to an embedding
-   - The system searches for the most relevant documents using cosine similarity
-   - Retrieved documents are combined to form context for the LLM
-
-3. **Agent Execution**:
-   - The agent initializes with the LLM, MCP clients, and retrieved context
-   - The user query is sent to the LLM along with the context
-   - The LLM generates responses and may request tool calls
-
-4. **Tool Usage**:
-   - When the LLM requests a tool, the agent routes the call to the appropriate MCP client
-   - The MCP client executes the tool and returns results
-   - Results are fed back to the LLM to continue the conversation
-
-5. **Output Generation**:
-   - The LLM generates a final response incorporating tool results and context
-   - In the example task, it creates a markdown file with information about "Antonette"
-
-## Key Technologies
-
-- **LLM Integration**: Uses OpenAI API for language model capabilities
-- **MCP Implementation**: Connects to MCP servers for filesystem operations
-- **Vector Embeddings**: Uses AWS Bedrock for generating embeddings
-- **Vector Search**: Implements cosine similarity for finding relevant documents
-
-## Implementation Details
-
-- **Framework Independence**: Built without relying on frameworks like LangChain or LlamaIndex
-- **Modular Design**: Components are separated for easy maintenance and extension
-- **AWS Integration**: Uses AWS Bedrock for embedding generation
-- **Tool Orchestration**: Manages tool calls and responses through MCP protocol
-
-## Example Use Case
-
-The current implementation demonstrates a task where the agent:
-1. Retrieves information about a user named "Antonette" from the knowledge base
-2. Summarizes the information and creates a story about her
-3. Saves the output to a markdown file using the filesystem MCP tool
-
-This architecture can be extended to support various tasks requiring context-aware responses and tool usage.
diff --git a/agentic-apps/agentic_rag_opensearch/MULTI_AGENT_GUIDE.md b/agentic-apps/agentic_rag_opensearch/MULTI_AGENT_GUIDE.md
deleted file mode 100644
index 3aed245a..00000000
--- a/agentic-apps/agentic_rag_opensearch/MULTI_AGENT_GUIDE.md
+++ /dev/null
@@ -1,95 +0,0 @@
-# Multi-Agent System Guide
-
-## Overview
-
-This guide explains how to use the multi-agent RAG system that has been implemented to replace the single-agent architecture.
-
-## Architecture Changes
-
-### Before (Single Agent)
-- Single `Agent` class handling all responsibilities
-- Direct embedding and retrieval in main flow
-- Simple workflow execution
-
-### After (Multi-Agent)
-- **SupervisorAgent**: Orchestrates the entire workflow
-- **KnowledgeAgent**: Manages knowledge embedding and change detection
-- **RAGAgent**: Handles context retrieval and semantic search
-- **MCPAgent**: Manages tool interactions and LLM communication
-
-## Usage
-
-### 1. Running the Multi-Agent System
-```bash
-pnpm dev
-```
-
-### 2. Embedding Knowledge (Standalone)
-```bash
-# Embed all knowledge files (markdown, text, JSON, and CSV) with change detection
-pnpm embed-knowledge
-```
-
-### 3. Testing the System
-```bash
-pnpm test-agents
-```
-
-## Key Features
-
-### Automatic Change Detection
-- The KnowledgeAgent monitors file changes using hashes
-- Only processes modified files for efficiency
-- Maintains metadata across runs
-
-### Intelligent Workflow
-1. **Knowledge Check**: Automatically detects and embeds new/changed files
-2. **Context Retrieval**: Uses RAG to find relevant information
-3. **Task Execution**: Leverages MCP tools to complete tasks
-
-### Error Handling
-- Each agent handles its own errors gracefully
-- Supervisor provides comprehensive error reporting
-- Resource cleanup is handled properly
-
-## Agent Responsibilities
-
-### SupervisorAgent
-- Initializes and coordinates all sub-agents
-- Manages the complete workflow execution
-- Provides task tracking and result summaries
-- Handles cleanup and resource management
-
-### KnowledgeAgent
-- Scans knowledge directory for changes
-- Embeds new or modified documents
-- Supports multiple file formats (MD, TXT, JSON, CSV) in a unified process
-- Maintains change detection metadata
-
-### RAGAgent
-- Performs semantic search using embeddings
-- Retrieves relevant context for queries
-- Supports advanced features like reranking
-- Optimizes context for LLM consumption
-
-### MCPAgent
-- Manages LLM interactions with tool support
-- Handles multi-turn conversations
-- Processes tool calls through MCP protocol
-- Maintains conversation context
-
-## Configuration
-
-The system uses the same environment variables as before:
-- `OPENAI_API_KEY`: Your OpenAI API key
-- `OPENAI_BASE_URL`: Your model hosting endpoint
-- `OPENSEARCH_ENDPOINT`: Your OpenSearch endpoint
-- `AWS_REGION`: Your AWS region
-
-## Benefits
-
-1. **Modularity**: Each agent has a specific purpose
-2. **Maintainability**: Easier to modify individual components
-3. **Scalability**: Agents can be scaled independently
-4. **Reliability**: Better error isolation and handling
-5. **Extensibility**: Easy to add new agent types
diff --git a/agentic-apps/agentic_rag_opensearch/README.md b/agentic-apps/agentic_rag_opensearch/README.md
deleted file mode 100644
index 591db125..00000000
--- a/agentic-apps/agentic_rag_opensearch/README.md
+++ /dev/null
@@ -1,207 +0,0 @@
-# Multi-Agent RAG with MCP and OpenSearch
-
-This project implements a multi-agent Large Language Model (LLM) system that combines Model Context Protocol (MCP) for tool usage and Retrieval Augmented Generation (RAG) for enhanced context awareness, using OpenSearch as the vector database.
-
-## Architecture
-![Architecture Diagram](images/arch.png)
-
-## Project Overview
-
-This application creates a multi-agent AI system that can:
-1. **Automatically detect and embed knowledge changes** using a Knowledge Agent
-2. **Retrieve relevant information** from a knowledge base using vector embeddings stored in OpenSearch via a RAG Agent
-3. **Interact with external tools** through the Model Context Protocol (MCP) via an MCP Agent
-4. **Coordinate the entire workflow** through a Supervisor Agent
-5. **Complete complex tasks** like summarizing content and saving results to files
-
-## Multi-Agent Architecture
-
-The system is built with a modular multi-agent architecture consisting of these key components:
-
-```
-SupervisorAgent → Manages the overall workflow and coordinates all agents
-  ├── KnowledgeAgent → Monitors knowledge changes and handles embedding
-  │   └── EmbeddingRetriever → Creates and manages document embeddings
-  │       └── OpenSearchVectorStore → Stores and searches document embeddings
-  ├── RAGAgent → Handles context retrieval and semantic search
-  │   └── EmbeddingRetriever → Performs vector search for relevant context
-  └── MCPAgent → Manages tool interactions and LLM communication
-      ├── ChatOpenAI → Handles LLM interactions and tool calling
-      └── MCPClient(s) → Connects to MCP servers for tool access
-```
-
-## Multi-Agent Workflow
-
-1. **Supervisor Initialization**:
-   - The SupervisorAgent initializes all sub-agents
-   - Each agent sets up its required resources and connections
-
-2. **Knowledge Management (KnowledgeAgent)**:
-   - Scans the knowledge directory for file changes
-   - Compares file hashes and modification times
-   - Automatically embeds new or modified documents
-   - Supports both markdown/text files and CSV files
-   - Maintains metadata to track changes efficiently
-
-3. **Context Retrieval (RAGAgent)**:
-   - Converts user queries to embeddings
-   - Searches for the most relevant documents using cosine similarity in OpenSearch
-   - Supports advanced features like reranking and hybrid search
-   - Returns structured context for the LLM
-
-4. **Task Execution (MCPAgent)**:
-   - Receives the user query and retrieved context
-   - Initializes the LLM with appropriate system prompts
-   - Manages tool calls through MCP protocol
-   - Handles multi-turn conversations with tool interactions
-
-5. **Workflow Coordination (SupervisorAgent)**:
-   - Orchestrates the entire process from start to finish
-   - Manages task queues and results
-   - Provides comprehensive workflow summaries
-   - Handles error recovery and cleanup
-
-## Key Components
-
-### SupervisorAgent
-- **Purpose**: Orchestrates the entire multi-agent workflow
-- **Responsibilities**: Task management, agent coordination, result aggregation
-- **Features**: Task queuing, result tracking, workflow summaries
-
-### KnowledgeAgent
-- **Purpose**: Manages knowledge base updates and embeddings
-- **Responsibilities**: Change detection, document embedding, metadata management
-- **Features**: File monitoring, hash-based change detection, CSV support
-
-### RAGAgent
-- **Purpose**: Handles context retrieval and semantic search
-- **Responsibilities**: Vector search, document ranking, context preparation
-- **Features**: Semantic search, hybrid search, document reranking
-
-### MCPAgent
-- **Purpose**: Manages LLM interactions and tool usage
-- **Responsibilities**: Tool orchestration, conversation management, task execution
-- **Features**: Multi-tool support, conversation history, error handling
-
-## Getting Started
-
-### Prerequisites
-
-- Node.js 18+
-- pnpm or npm
-- OpenAI API key
-- AWS OpenSearch Domain
-- AWS credentials configured
-
-### Installation
-
-```bash
-# Clone the repository
-git clone <repository-url>
-
-# Go to the right path
-cd agentic-apps/agentic_rag_opensearch
-
-# Install dependencies
-pnpm install
-
-# Set up environment variables
-# Create a .env file with:
-OPENAI_API_KEY=your-api-key
-OPENAI_BASE_URL=your-model-hosting-endpoint
-OPENSEARCH_ENDPOINT=your-opensearch-endpoint
-AWS_REGION=your-aws-region
-LANGFUSE_HOST=
-LANGFUSE_PUBLIC_KEY=
-LANGFUSE_SECRET_KEY=
-```
-
-### Usage
-
-```bash
-# Embed all knowledge documents (markdown, text, JSON, and CSV files with change detection)
-pnpm embed-knowledge
-
-# Run the multi-agent application
-pnpm dev
-
-# Test the multi-agent system
-pnpm test-agents
-```
-
-## Multi-Agent Features
-
-### Intelligent Knowledge Management
-- **Automatic Change Detection**: Monitors file modifications using hashes and timestamps
-- **Incremental Updates**: Only processes changed files to improve efficiency
-- **Multi-format Support**: Handles markdown, text, JSON, and CSV files in a unified workflow
-- **Metadata Persistence**: Maintains state across application restarts
-
-### Advanced RAG Capabilities
-- **Semantic Search**: Vector-based similarity search using OpenSearch
-- **Hybrid Search**: Combines keyword and semantic search (extensible)
-- **Document Reranking**: Improves relevance of retrieved documents
-- **Context Optimization**: Structures context for optimal LLM performance
-
-### Robust Tool Integration
-- **MCP Protocol**: Standardized tool communication
-- **Multi-tool Support**: Can integrate multiple MCP servers
-- **Error Handling**: Graceful handling of tool failures
-- **Conversation Management**: Maintains context across tool interactions
-
-### Workflow Orchestration
-- **Task Queuing**: Manages complex multi-step workflows
-- **Result Tracking**: Comprehensive logging of all agent activities
-- **Error Recovery**: Handles failures gracefully with detailed reporting
-- **Resource Management**: Proper cleanup and connection management
-
-## Example Use Case
-
-The current implementation demonstrates a comprehensive workflow where the system:
-1. **Automatically checks** for knowledge base changes and updates embeddings if needed
-2. **Retrieves relevant information** about Bell's palsy treatment from the knowledge base
-3. **Generates a comprehensive report** with multiple sections and detailed information
-4. **Saves the output** to a markdown file using the filesystem MCP tool
-5. **Provides detailed workflow summaries** and task results
-
-## Extending the Multi-Agent System
-
-This modular architecture can be easily extended:
-
-### Adding New Agents
-- Create specialized agents for specific domains (e.g., WebSearchAgent, DatabaseAgent)
-- Implement the common agent interface for seamless integration
-- Register with the SupervisorAgent for workflow coordination
-
-### Enhanced Knowledge Management
-- Add support for more file formats (PDF, DOCX, etc.)
-- Implement intelligent chunking strategies
-- Add knowledge graph capabilities
-- Integrate with external knowledge sources
-
-### Advanced RAG Features
-- Implement query expansion and refinement
-- Add multi-modal search capabilities
-- Integrate with specialized embedding models
-- Implement adaptive retrieval strategies
-
-### Tool Ecosystem Expansion
-- Add more MCP servers for different tool categories
-- Implement custom tool validation and security
-- Add tool usage analytics and optimization
-- Create tool recommendation systems
-
-### Production Deployment
-- Add comprehensive monitoring and logging
-- Implement horizontal scaling capabilities
-- Add authentication and authorization
-- Deploy as microservices with API gateways
-
-## Architecture Benefits
-
-1. **Modularity**: Each agent has a specific responsibility, making the system maintainable
-2. **Scalability**: Agents can be scaled independently based on workload
-3. **Reliability**: Isolated failures don't bring down the entire system
-4. **Extensibility**: New capabilities can be added without modifying existing agents
-5. **Testability**: Each agent can be tested in isolation
-6. **Observability**: Detailed tracking of all agent interactions and results
diff --git a/agentic-apps/agentic_rag_opensearch/cleanup-opensearch.sh b/agentic-apps/agentic_rag_opensearch/cleanup-opensearch.sh
deleted file mode 100755
index 882ba3c1..00000000
--- a/agentic-apps/agentic_rag_opensearch/cleanup-opensearch.sh
+++ /dev/null
@@ -1,166 +0,0 @@
-#!/bin/bash
-
-# Script to cleanup OpenSearch cluster and related resources
-
-set -e
-
-# Color codes for better readability
-GREEN='\033[0;32m'
-BLUE='\033[0;34m'
-RED='\033[0;31m'
-YELLOW='\033[0;33m'
-NC='\033[0m' # No Color
-
-# Function to display messages with timestamp
-log() {
-  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
-}
-
-warn() {
-  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
-}
-
-error() {
-  echo -e "${RED}[$(date '+%Y-%m-%d %H:%M:%S')] ERROR:${NC} $1"
-  exit 1
-}
-
-success() {
-  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
-}
-
-# Configuration variables
-DOMAIN_NAME="agentic-rag-opensearch"
-REGION="us-east-1"
-SECURITY_GROUP_NAME="opensearch-sg"
-
-# Check prerequisites
-check_prerequisites() {
-  log "Checking prerequisites..."
-  
-  # Check AWS CLI
-  if ! command -v aws &> /dev/null; then
-    error "AWS CLI is not installed. Please install it first."
-  fi
-  
-  # Check AWS credentials
-  if ! aws sts get-caller-identity &> /dev/null; then
-    error "AWS credentials not configured or invalid. Please configure AWS CLI."
-  fi
-  
-  success "All prerequisites satisfied."
-}
-
-# Delete OpenSearch domain
-delete_opensearch_domain() {
-  log "Checking for OpenSearch domain: $DOMAIN_NAME"
-  
-  EXISTING_DOMAIN=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION 2>/dev/null || echo "")
-  
-  if [ -n "$EXISTING_DOMAIN" ]; then
-    log "Deleting OpenSearch domain: $DOMAIN_NAME"
-    
-    aws opensearch delete-domain \
-      --domain-name $DOMAIN_NAME \
-      --region $REGION
-    
-    log "OpenSearch domain deletion initiated. This may take several minutes..."
-    
-    # Wait for deletion to complete
-    local max_attempts=30  # 15 minutes
-    local attempt=1
-    
-    while [ $attempt -le $max_attempts ]; do
-      log "Attempt $attempt/$max_attempts: Checking if domain is deleted..."
-      
-      DOMAIN_CHECK=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION 2>/dev/null || echo "DELETED")
-      
-      if [ "$DOMAIN_CHECK" = "DELETED" ]; then
-        success "OpenSearch domain deleted successfully!"
-        break
-      fi
-      
-      log "Domain still exists. Waiting 30 seconds..."
-      sleep 30
-      ((attempt++))
-    done
-    
-    if [ $attempt -gt $max_attempts ]; then
-      warn "Domain deletion is taking longer than expected. Please check AWS console."
-    fi
-  else
-    log "OpenSearch domain '$DOMAIN_NAME' not found. Skipping deletion."
-  fi
-}
-
-# Delete security group
-delete_security_group() {
-  log "Checking for security group: $SECURITY_GROUP_NAME"
-  
-  # Get default VPC
-  DEFAULT_VPC=$(aws ec2 describe-vpcs --filters "Name=is-default,Values=true" --query "Vpcs[0].VpcId" --output text --region $REGION)
-  
-  if [ "$DEFAULT_VPC" = "None" ] || [ -z "$DEFAULT_VPC" ]; then
-    log "No default VPC found. Skipping security group deletion."
-    return
-  fi
-  
-  EXISTING_SG=$(aws ec2 describe-security-groups --filters "Name=group-name,Values=$SECURITY_GROUP_NAME" "Name=vpc-id,Values=$DEFAULT_VPC" --query "SecurityGroups[0].GroupId" --output text --region $REGION 2>/dev/null || echo "None")
-  
-  if [ "$EXISTING_SG" != "None" ] && [ -n "$EXISTING_SG" ]; then
-    log "Deleting security group: $EXISTING_SG"
-    
-    # Try to delete the security group
-    if aws ec2 delete-security-group --group-id $EXISTING_SG --region $REGION 2>/dev/null; then
-      success "Security group deleted successfully!"
-    else
-      warn "Failed to delete security group. It may still be in use or have dependencies."
-      log "You may need to delete it manually from the AWS console."
-    fi
-  else
-    log "Security group '$SECURITY_GROUP_NAME' not found. Skipping deletion."
-  fi
-}
-
-# Clean up .env file
-cleanup_env_file() {
-  log "Cleaning up .env file..."
-  
-  if [ -f ".env" ]; then
-    # Remove or comment out OPENSEARCH_ENDPOINT
-    if grep -q "OPENSEARCH_ENDPOINT=" .env; then
-      sed -i.bak 's/^OPENSEARCH_ENDPOINT=/#OPENSEARCH_ENDPOINT=/' .env
-      success ".env file updated (OPENSEARCH_ENDPOINT commented out)."
-    else
-      log "OPENSEARCH_ENDPOINT not found in .env file."
-    fi
-  else
-    log ".env file not found. Nothing to clean up."
-  fi
-}
-
-# Main execution
-main() {
-  log "Starting OpenSearch cluster cleanup..."
-  
-  warn "This will delete the OpenSearch domain and related resources."
-  read -p "Are you sure you want to continue? (y/N): " -n 1 -r
-  echo
-  
-  if [[ ! $REPLY =~ ^[Yy]$ ]]; then
-    log "Cleanup cancelled."
-    exit 0
-  fi
-  
-  check_prerequisites
-  delete_opensearch_domain
-  delete_security_group
-  cleanup_env_file
-  
-  success "OpenSearch cluster cleanup completed!"
-  log "All resources have been cleaned up."
-  log "Note: It may take a few minutes for all AWS resources to be fully removed."
-}
-
-# Execute main function
-main
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@@ -1,2003 +0,0 @@
-question,context
-What were the surgical complications observed in patients who underwent excision of limbal dermoids?,"Excision of limbal dermoids. We reviewed the clinical files of 10 patients who had undergone excision of unilateral epibulbar limbal dermoids. Preoperatively, all of the affected eyes had worse visual acuity (P less than .02) and more astigmatism (P less than .01) than the contralateral eyes. Postoperatively, every patient was cosmetically improved. Of the eight patients for whom both preoperative and postoperative visual acuity measurements had been obtained, in six it had changed minimally (less than or equal to 1 line), and in two it had improved (less than or equal to 2 lines). Surgical complications included persistent epithelial defects (40%) and peripheral corneal vascularization and opacity (70%). These complications do not outweigh the cosmetic and visual benefits of dermoid excision in selected patients."
-What is the most important aspect of initial treatment for Bell's palsy?,"Bell's palsy. A diagnosis of exclusion. In cases of acute unilateral facial weakness, a careful and systematic evaluation is necessary to identify the cause. Idiopathic facial paralysis (Bell's palsy) is a diagnosis of exclusion. It is also the most common cause of unilateral facial weakness seen by primary care physicians. The most important aspect of initial treatment is eye protection. Administration of systemic oral corticosteroids may lessen severity and duration of symptoms."
-How did steroid therapy help in the removal of the retained foreign body in the endobronchial region?,"Retained endobronchial foreign body removal facilitated by steroid therapy of an obstructing, inflammatory polyp. Oral and topical steroids were used to induce regression in an inflammatory, obstructing endobronchial polyp caused by a retained foreign body. The FB (a peanut half), which had been present for over six months, was then able to be easily and bloodlessly retrieved with fiberoptic bronchoscopy."
-What unusual complication of Crohn's disease was observed in the patient described in this case report?,"Recurrent buccal space abscesses: a complication of Crohn's disease. A patient is described with generalized gastrointestinal involvement by Crohn's disease. Symptoms of recurrent ulceration and mucosal tags are well-described oral manifestations of Crohn's disease; however, in our patient recurrent facial abscesses, which required extraoral drainage, also developed. This complication has not previously been reported."
-What are the key characteristics and management recommendations for intracranial fibromatosis based on the given context?,"Intracranial fibromatosis. Fibromatoses are uncommon infiltrative lesions affecting musculoaponeurotic structures, most often of the limbs and trunk. Lesions involving the cranial cavity are rare and require the same aggressive surgical management as elsewhere in the body. This case illustrates their clinical and neuroradiological features and underscores the necessity for aggressive resection to avoid recurrence. The literature is reviewed."
-What was the effect of intrathecally administered morphine sulfate on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) in awake patients?,"The effect of intrathecal morphine on somatosensory evoked potentials in awake humans. Although the effect of systemic opioids on somatosensory evoked potentials has been well described, little is known about the interaction between intrathecally administered opioid analgesics and somatosensory evoked potentials. Accordingly, the influence of intrathecally administered morphine on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) was investigated in 22 unpremedicated, awake, neurologically normal patients scheduled to undergo elective abdominal or pelvic procedures. Patients were randomly assigned to receive either preservation-free intrathecal morphine sulfate (ITMS) or placebo. After baseline PTSCEP, heart rate and, mean blood pressure were recorded, ITMS (15 micrograms.kg-1) was injected via standard dural puncture with the patient in the lateral position. PTSCEPs, heart rate, and mean blood pressure were recorded again at 5, 10, 20, 30, 60, 90, and 120 min. Control patients were treated identically (including position, sterile preparation, and subcutaneous tissue infiltration with local anesthetic), except for lumbar puncture, and were unaware of their randomization. Before administration of ITMS, PTSCEP P1, N1, P2, N2, and P3 latencies were 39.4 +/- 3.2, 47.6 +/- 3.9, 59.2 +/- 3.2, 70.4 +/- 3.7, and 84.6 +/- 5.5 ms, (mean +/- standard deviation), respectively. The corresponding P1-N1, N1-P2, and P2-N2 amplitudes were 2.4 +/- 1.1, 2.4 +/- 1.1, and 2.3 +/- 0.9 microV, respectively. There were no significant changes over time between the control and ITMS groups. PTSCEPs resulting from left-sided stimulation were not different from those elicited by right-sided stimulation. All ITMS patients had intense postoperative analgesia for at least 24 h. It is concluded that ITMS does not affect PTSCEP waveforms in the 35-90 ms latency range during the awake state."
-What is the key message of the 29th Rovenstine lecture regarding the ongoing education and approach of anesthesiologists?,"The 29th Rovenstine lecture: clinical challenges for the anesthesiologist. In conclusion, I hope that my comments have reaffirmed your biases or, even more importantly, stimulated you to think in a different way about the information explosion in our specialty and medicine in general. I believe our specialty is in a golden era that will benefit from the past and be nourished by new discoveries and understanding. We as clinicians must accept the challenge of recognizing what new information deserves incorporation into our practice, what old information deserves to be sustained, and what merits new scrutiny and perhaps should be discarded. If I had one wish, it would be that anesthesiologists would never lose their zeal to be students--their thirst for new information--as the continuum of anesthesia education is indeed a life-long process. That wish, ladies and gentlemen, is my challenge to all anesthesiologists."
-What was the purpose of the study on encainide and flecainide in patients with supraventricular arrhythmias?,"Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias. In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias."
-How do lymphokines contribute to the potential immunotherapy of cancer?,"Approaches to immunotherapy of cancer: characterization of lymphokines as second signals for cytotoxic T-cell generation. Lymphokines, the soluble molecules produced by cells of the immune system, regulate cell-cell interactions and, consequently, the functional status of the immune system. Altering immunoregulatory pathways with lymphokines in vivo may provide a mechanism for controlling a variety of immunologic disorders. Although normally produced in vivo in very small quantities, the widespread availability of recombinant lymphokines has made it possible to study the molecular signals involved in production of lymphocyte effectors with activity against tumor. For example, interleukin-2-based cancer immunotherapy programs have, in certain clinical situations, suggested that immunologic intervention can influence the regression of metastatic cancer. Ultimately the successful application of these biologic agents requires an understanding of the interaction between the immune system and tumor on a molecular level. To induce a given biologic effect, it is necessary both to classify the required lymphokines and to identify the relevant effector cell populations. This review will examine the progress made in identifying the requirements for lymphokine-induced cytotoxic T-lymphocyte function."
-What was the clinical progression and outcome of the 71-year-old woman's retinal condition associated with non-Hodgkin's large cell lymphoma?,"Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma). A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma."
-How did morphine and naloxone affect pain-related behaviors in rats with peripheral mononeuropathy?,"The 'tonic' pain-related behaviour seen in mononeuropathic rats is modulated by morphine and naloxone. This study investigated the sensitivity to pharmacological manipulations of a rating method, adapted from the formalin test, to measure the tonic component of the pain-related behaviour induced by creating a peripheral mononeuropathy with 4 loose ligatures around the common sciatic nerve. Although the adequacy of opioid substances in alleviating neuropathic pain is highly controversial, the effects of morphine (1 mg/kg i.v.) and naloxone (1 mg/and 3 micrograms/kg i.v.) were tested 1-2 weeks after the nerve ligatures were established, when pain-related behaviours were well developed. Morphine (1 mg/kg i.v.) induced a potent and prolonged decrease in the pain-rating score at week 2 after surgery. Either at week 1 or week 2, naloxone elicited a bidirectional dose-dependent action: a further increase in the pain-rating score with the high dose (1 mg/kg i.v.), and a paradoxical decrease in the score with the low dose of 3 micrograms/kg i.v. These effects are comparable to those already described in several rat models of inflammatory pain and, in the same model of neuropathy, using a phasic nociceptive test, the measure of the vocalization to paw pressure. A few differences in the effects of naloxone on tonic and phasic pain are noted and discussed."
-What cardiovascular changes were observed in patients during upper gastrointestinal endoscopy with deep sedation?,"Examination of cardiorespiratory changes during upper gastrointestinal endoscopy. Comparison of monitoring of arterial oxygen saturation, arterial pressure and the electrocardiogram. Critical events including hypoxaemia, arrhythmias and myocardial ischaemia may occur more frequently during endoscopic procedures than during anaesthesia. A study was undertaken to assess the cardiovascular changes and to evaluate suitable monitoring techniques to detect critical events during sedation and endoscopy. Twenty patients scheduled to undergo a prolonged endoscopic procedure which required deep sedation were studied. Continuous recordings of electrocardiogram, heart rate and arterial oxygen saturation were made and arterial pressure was recorded at one-minute intervals. The study commenced immediately before administration of sedatives, continued for the duration of the examination and for one hour following the examination. Oxygen saturation decreased in all patients during the examination to a mean of 82.9% (SD 11.9), and remained below baseline for the duration of the examination and into the recovery period. Statistically significant increases and reductions of systolic arterial pressure and rate-pressure product were found during the procedures compared with baseline values recorded before administration of sedatives. Sixteen of the 20 patients developed tachycardia during the examination. Ten patients developed ectopic foci which were supraventricular, ventricular or both in origin. Electrocardiogram changes resolved during the recovery period. Myocardial ischaemia was assessed by S-T segment depression and a significant correlation was found between S-T segment depression and hypoxaemia, although the magnitude of the S-T depression was small and may not have been detected clinically. No correlation was found between S-T segment depression and arterial pressure, heart rate or rate-pressure product."
-How did the presence of 4-methylpyrazole affect blood alcohol levels and methionine metabolism in the experimental groups of Golden Syrian hamsters?,"Hepatic transmethylation and blood alcohol levels. Golden Syrian hamsters that have elevated hepatic alcohol dehydrogenase activity were divided into four groups and group-fed on four different liquid diets for five weeks. Group I was fed a control diet formulated for hamsters. Group II was fed the control diet containing 20 micrograms of 4 methylpyrazole per litre. Group III was fed the hamster ethanol liquid diet (ethanol amounting to 36% of total calories). Group IV was fed the ethanol diet to which 4-methylpyrazole (20 micrograms/litre) was added. Groups I, II and III were group-fed the amount consumed by Group IV on a daily basis. Upon killing the animals, blood alcohol levels were found to be elevated in Group IV but not in Group III. Hepatic methionine synthetase (MS) was inhibited in Group IV. Betaine-homocysteine methyltransferase was induced in this group to compensate for the MS inhibition and liver betaine was lowered reflecting this induction. None of these changes were seen in Group III. Since none of the animals showed an aversion to their respective diets and gained weight normally, these data indicate that it was the elevated blood levels of ethanol rather than nutritional factors that were related to the changes in methionine metabolism."
-What are the key characteristics of memory T cells in liver inflammation?,"Memory T cells represent the predominant lymphocyte subset in acute and chronic liver inflammation. T cells can be divided into two main phenotypic subpopulations-i.e., the CD45RA-positive (2H4-positive) ""naive"" subset and the CD45RO-positive (UCHL1-positive) ""memory"" subset. In light of this recent functional reinterpretation of T-lymphocyte subpopulations, we reinvestigated the composition of the inflammatory infiltrate in liver biopsy specimens from patients with acute and chronic hepatitis. In normal liver, the few scattered mononuclear cells present in portal tracts and in the intralobular parenchyma consisted of both CD45RA-positive (2H4-positive) naive and CD45RO-positive (UCHL1-positive) memory T cells. In inflammatory liver diseases, portal tract and periportal and intralobular areas of inflammation consisted virtually only of CD45RO-positive (UCHL1-positive) memory T cells, which strongly expressed the CDw29 (4B4) antigen, and the adhesion molecules LFA-1, CD2, LFA-3, CD44 and VLA-4 and the activation marker human leukocyte antigen-DR. These results indicate that activated memory T cells represent the predominant subpopulation of lymphocytes in areas of liver inflammation. Memory T cells strongly express various homing receptors and adhesion molecules, which probably allow them to accumulate at inflammatory sites and to strengthen interaction with target cells. Furthermore, the increased number of memory T cells with enhanced interferon-gamma production in areas of liver inflammation may contribute to the maintenance and up-regulation of immune responses occurring in inflammatory liver diseases."
-What ultrastructural changes were observed in endothelial cells after intracutaneous injection of NAP-1/IL-8?,"Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study. Neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, was injected intracutaneously into human skin. Sequential biopsy specimens were taken in order to investigate the sequence of ultrastructural changes induced by the cytokine. Whereas intracutaneous injection of 100 ng of NAP-1/IL-8 per site caused no macroscopic changes, by histology infiltration with polymorphonuclear leukocytes (PMN) and monocytes was present within 1 h and increased at 3 and 5 h. No lymphocyte infiltration was noted. The first ultrastructural changes (30 min) consisted of the presence of cytoplasmic 7-nm microfilament bundles, as well as numerous protrusions of the luminal plasma membrane of endothelial cells (EC). As a striking feature, multiple 100- to 160-nm electron lucent vesicles could be observed in the EC cytoplasm. These structures differed from plasmalemmal vesicles and suggest secretory activity. When PMN and monocytes appeared in the vascular lumen (1 h and later), the number of 100-160-nm electron-lucent vesicles had decreased significantly. In contrast to C5a-injected skin sites, mast cell degranulation was absent."
-What percentage of patients in the study had squamous cell carcinoma?,"Bronchogenic carcinoma with chest wall invasion. Bronchogenic carcinoma with chest wall involvement continues to present a major clinical challenge. We have treated 52 patients since 1973, excluding those with superior sulcus tumors. There were 37 male and 15 female patients with an average age of 62.9 years. Chest pain was an initial symptom in 37%. All patients had negative mediastinoscopy results. Squamous cell carcinoma was present in 53% and adenocarcinoma in 35%. The median number of ribs resected was two (range, one to six), and only 2 patients required chest wall reconstruction. Pathologic staging was T3 N0 M0 in 83% and T3 N1 M0 in 17%. Operative mortality was 3.8%. Absolute 5-year survival was 26.3%. Patients who had N1 disease had a 5-year survival of only 11%. Radiation therapy was employed in 46% for positive nodes or close margins. Bronchogenic carcinoma with chest wall invasion remains potentially curable if N2 nodes are not involved. The role of radiation therapy has not been clearly defined. Morbidity and mortality should be minimal."
-What are the two most common electronic weapons discussed in the context?,"Electronic weaponry--a question of safety [published erratum appears in Ann Emerg Med 1991 Sep;20(9):1031] Electronic weapons represent a new class of weapon available to law enforcement and the lay public. Although these weapons have been available for several years, there is inadequate research to document their safety or efficacy. Two of the most common, the TASER and the stun gun, are reviewed. The electronic weapon was initially and still is approved by the US Consumer Product Safety Commission; its approval was based on theoretical calculations of the physical effects of damped sinusoidal pulses, not on the basis of animal or human studies. These devices are widely available and heavily promoted, despite limited research into their safety or efficiency and despite recent animal studies documenting their potential for lethality."
-What was the primary objective of surgical management for acoustic tumors in this study?,"Operative management of acoustic neuromas: the priority of neurologic function over complete resection. The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post-operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity."
-What is the potential drug interaction described in the context that may lead to cardiotoxicity?,"Torsades de pointes occurring in association with terfenadine use. Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although found in many clinical settings, torsades de pointes is most often drug induced. This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone. Measured serum concentrations of terfenadine and its main metabolite showed excessive levels of parent terfenadine and proportionately reduced concentrations of metabolite, suggesting inhibition of terfenadine metabolism. We believe that a drug interaction between terfenadine and ketoconazole resulted in the elevated terfenadine levels in plasma and in the cardiotoxicity previously seen only in cases of terfenadine overdose."
-What is the prevalence of celiac or superior mesenteric artery stenoses among male veterans evaluated for peripheral vascular disease?,"Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients."
-What were the key findings of the brain-stem auditory evoked responses (BAER's) analysis in patients with acoustic neurinoma?,"Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma. The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors. Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p less than 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p less than 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p less than 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression. Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve."
-What was the first successful heterotransplantation of a human carcinoid tumor into nude mice?,"First heterotransplantation of a human carcinoid tumor into nude mice. The first successful heterotransplantation of a human carcinoid tumor into nude mice is reported. CSH, a voluminous hepatic metastasis of a primary bronchial carcinoid tumor (CSB) was resected and transplanted into three irradiated nude (Swiss-nu/nu) mice both by subcutaneous (SC) and intramuscular (IM) routes; the success rate was five of six. Heterotransplanted tumors took 4 to 5 months to appear in the mice and 1 month to attain a width of 0.5 cm. Both human and mouse tumors (named CSH-SC and CSH-IM) were studied by light and electron microscopy. They were Grimelius-positive, neuron-specific enolase-positive, and bombesin-negative by immunocytochemistry. Furthermore, CSH-SC cells presented characteristic (pear-shaped, rod-shaped, or tadpole-shaped) neurosecretory granules. Although CSB and CSH were slightly serotonin positive by immunocytochemistry, only a few serotonin-positive cells were found in CSH-SC and none in CSH-IM, suggesting partial loss of differentiation or an increase in serotonin catabolism during transplantation."
-What was the purpose of the study on signal-averaged electrocardiogram (SAECG) reproducibility?,"A prospective evaluation of the immediate reproducibility of the signal-averaged ECG. The purpose of this investigation was to prospectively evaluate the immediate reproducibility of the signal-averaged electrocardiogram (SAECG). A total of 114 patients undergoing evaluation for ventricular arrhythmias were enrolled in this protocol. Two consecutive SAECG's (40 Hz bidirectional high-pass filtering with a computer-automated system) were performed 10 minutes apart. Abnormal SAECG parameters were defined as (1) vector QRS duration more than 120 msec, (2) terminal root mean square (RMS) voltage less than 20 microV, and (3) low-amplitude signal (LAS) duration more than 40 msec. An SAECG was defined as abnormal if at least one vector parameter was abnormal. There was close correlation between vector parameters during the two SAECG observations: QRS duration had the highest reproducibility (r2 = 0.97, p less than 0.001) followed by terminal RMS voltage (r2 = 0.92, p less than 0.001), and LAS duration (r2 = 0.90, p less than 0.001). The mean (+/- SD) percentage of change between the two recordings was 2% +/- 2% of the QRS duration, 13% +/- 22% for terminal RMS voltage, and 7% +/- 11% for LAS duration. The reproducibility of an initially normal SAECG was 92% and of an initially abnormal SAECG, 96%. Seventeen patients (15%) had a change in one of the three vector parameters between the two recordings. There were no clinically significant differences between the 17 patients in whom the SAECG was nonreproducible and the 97 patients in whom the SAECG was reproducible. However, reproducibility was significantly higher in patients with an initially normal versus an initially abnormal SAECG (92% vs 76%, p = 0.03)."
-What were the independent risk factors for stroke identified in this Chinese population study?,"Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke."
-What percentage of lung cancers showed an air bronchogram or air bronchiologram on CT scans and histologic sections in this study?,"Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors. Despite improved techniques--such as bronchoscopy and percutaneous needle biopsy--to evaluate pulmonary nodules, there are still many cases in which surgical resection is necessary before carcinoma can be differentiated from benign lesions. The present study was undertaken to determine if the presence of an air bronchogram or air bronchiologram (patent visible bronchus or bronchiole) is useful in distinguishing small lung cancers from benign nodules. Thin-section chest CT scans were obtained in patients with 20 peripheral lung cancers less than 2 cm in diameter (18 adenocarcinomas, one squamous cell carcinoma, and one large cell carcinoma) and 20 small benign nodules (eight hamartomas, seven tuberculomas, two foci of aspergillosis, one focus of cryptococcosis, one chronic focal interstitial pneumonitis, and one plasma cell granuloma). The images were compared with regard to the patency of any bronchus or bronchiole within the lesions. After surgical resection, the specimens were inflated with agar and sectioned transversely to correlate gross morphology and low-power histologic sections with the CT appearance. An air bronchogram or air bronchiologram was seen in the tumors on 65% of CT scans and 70% of histologic sections. Benign nodules had a patent bronchus or bronchiole on CT scans and histologic sections in only one case (5%). These findings suggest that the presence of an air bronchogram in a lung nodule is a useful finding to help differentiate adenocarcinomas from benign lesions."
-What were the most frequent complications observed in patients receiving long-term spinal morphine administration via Port-A-Cath?,"Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study. Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases)."
-How accurate is real-time ultrasound in detecting deep venous thrombosis (DVT) compared to contrast venography?,"Real-time ultrasound for the detection of deep venous thrombosis. PURPOSE: Accurate diagnosis of deep venous thrombosis (DVT) is a clinical problem in emergency practice. A prospective trial was conducted comparing real-time ultrasound with contrast venography in the diagnosis of proximal DVT. METHODS: Seventy patients whose clinical presentations mandated diagnostic evaluation for DVT had real-time ultrasound of the involved leg followed by contrast venography. Initial readings of ultrasound and venography were compared with each other and with final readings to assess reliability of interpretation. RESULTS: Final ultrasound readings agreed with final venogram readings in all patients. Negative initial ultrasound readings agreed with final venogram readings in 56 of 56 patients (negative predictive value, 100%; 95% confidence interval, 94 to 100). Eighteen patients had positive initial ultrasound readings compared with 14 who had positive final venogram readings (positive predictive value, 78%; 95% confidence interval, 55 to 91). CONCLUSION: Negative real-time ultrasonography reliably excludes proximal DVT. Positive ultrasound reliably diagnoses proximal DVT only in experienced hands."
-How does dual-chamber sensor-driven pacing compare to single-chamber pacing in terms of cardiac output for patients with chronotropic incompetence?,"Single- versus dual-chamber sensor-driven pacing: comparison of cardiac outputs. Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long-term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 +/- 0.3 L/min and 4.68 +/- 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 +/- 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 +/- 0.6 L/min and 7.41 +/- 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise (p less than 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value (p less than 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence."
-How does D-dimer affect the secretion of interleukin and other substances in the NOMO-1 human promonocytic leukemia cell line?,"FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line. We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation."
-What factors predict the success of stereotactic aspiration for colloid cysts?,"Stereotactic management of colloid cysts: factors predicting success. Stereotactic aspiration is a valuable surgical alternative for colloid cysts when used alone or in conjunction with microsurgical resection. Since 1981, the authors have performed computerized tomography (CT)-guided stereotactic aspiration as the initial procedure in 22 patients with colloid cysts; stereotactic aspiration alone was successful in 11 patients (50%). Of the 11 patients in whom aspiration failed, stereotactic endoscopic resection was attempted in three and was successful in one. Seven patients required a craniotomy and microsurgical removal of the cyst performed via a transcortical approach. The preoperative CT appearance in eight cases of a hypodense or isodense cyst correlated favorably with successful aspiration of the cyst in six patients. A hyperdense appearance on the preoperative CT scan in 14 cases was associated with subtotal aspiration in 13 patients; five required craniotomy for removal. Preoperative magnetic resonance (MR) imaging in eight patients provided excellent anatomical definition of the cyst and its relationship to other structures of the third ventricle, but it was not possible to correlate successful aspiration with cyst appearance on MR images with short or long relaxation time sequences. The authors' 9-year experience suggests that preoperative CT studies accurately determine size, predict viscosity, and help to define a group of colloid cyst patients for whom stereotactic cyst aspiration will likely be successful. Unsuccessful stereotactic aspiration was related to two features: the high viscosity of the intracystic colloid material (nine patients), or deviation of the cyst away from the aspiration needle due to small cyst volume (two patients). Because of its simplicity and low risk, stereotactic surgery can be offered to selected patients as the initial procedure of choice. Craniotomy can be reserved for those whose imaging studies predict failure or for those whose cyst cannot be aspirated."
-What percentage of patients with chronic demyelinating polyneuropathy showed MRI changes suggestive of demyelination?,"Cranial magnetic resonance imaging in chronic demyelinating polyneuropathy. Twenty one patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and five patients with chronic demyelinating polyneuropathy associated with benign monoclonal paraproteinaemia none of whom had signs or symptoms of central nervous system disease, had cranial magnetic resonance imaging (MRI) on a 1.5 Tesla unit. Areas of increased white matter signal intensity were seen in one of 10 patients aged less than 50 years and in five of 16 patients aged more than 50 years. In only two of the patients (8%), neither of whom had paraproteinaemia, did the appearance strongly suggest demyelination. The only clinical variable that predicted MRI changes was age (p less than 0.01)."
-How did the bleeding patterns differ between postmenopausal women receiving estradiol and norethisterone acetate versus estradiol and cyproterone acetate?,"Bleeding patterns during continuous combined estrogen-progestogen therapy. Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding."
-How does liver cirrhosis affect the metabolism and processing of lysophosphatidylcholine in rats?,"Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis. Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance."
-How many additional metastatic lymph nodes were found through serial sectioning in this study?,"The value of single versus multiple sections for detection of lymph node metastasis. This study was undertaken to determine the value of serial sectioning of lymph nodes as an aid in optimally examining cervical specimens for metastasis. The presence or absence of lymph node metastasis in 802 lymph nodes obtained from 51 consecutive neck dissection specimens were initially determined by the routine method, examination of one section from each node. This examination revealed 40 lymph nodes with metastatic involvement. Further study of the 716 lymph nodes that were initially interpreted as free of tumor by serial sectioning added only two positive nodes. Thus, serial sectioning did not contribute significantly to the detection of lymph node metastasis."
-What was the observed difference in hemolytic activity between plasma from ALS patients and normal controls?,"Cytotoxic activity in plasma from patients with amyotrophic lateral sclerosis. The present study evaluates an assay of cytotoxic effect of plasma from patients with amyotrophic lateral sclerosis. Plasma from 20 recently diagnosed ALS patients induced hemolysis of normal red blood cells with a significantly greater intensity than that of normal controls. After at least 1 month of treatment with prednisone and azathioprine, the hemolytic activity of ALS plasma was reduced but was still higher than that of control plasma."
-What are the MR imaging characteristics of giant cell tumors in patients with Paget disease of bone?,"Multiple giant cell tumors and Paget disease of bone: radiographic and clinical correlations. The clinical and radiographic findings of four patients with multicentric giant cell tumor (GCT) of bone and Paget disease were retrospectively reviewed. Three patients underwent magnetic resonance (MR) imaging evaluation; all patients underwent computed tomography (CT). The MR characteristics of the bone component in pagetic GCT appeared to reflect the pagetic phase; a sclerotic pattern was largely represented by hypointense marrow signal intensity on images obtained with both long and short repetition times (TRs) and echo times (TEs). Conversely, a tumor appearing in a mixed pagetic phase demonstrated more heterogeneous signal intensity with all pulse sequences. Extensive soft-tissue components, noted in all cases, showed largely intermediate signal intensity on short TR/TE images and foci of increased signal intensity on longer TR/TE images. In most cases, dramatic reduction in tumor bulk was noted with the use of steroids alone. An awareness of this entity is important because the appearance of lytic lesions with soft-tissue extension in patients with Paget disease does not necessarily imply a grave prognosis. Serial CT or MR imaging is helpful in monitoring the remissions and exacerbations that reflect response to therapy in Paget disease and GCT."
-What are the key MRI findings and considerations when assessing the postoperative spine in patients with degenerative disc disease?,"Magnetic resonance assessment of the postoperative spine. Degenerative disc disease. The magnetic resonance (MR) imaging findings in patients after surgery for degenerative disc disease in the lumbar and cervical spine are discussed. In the lumbar spine, changes seen in the immediate postoperative period, use of Gd-DTPA in distinguishing scar and disc and postoperative complications are reviewed. In the cervical spine, operative approaches and types, the appearance of bony stenosis, and disc herniations are demonstrated."
-What are the advantages and outcomes of using the pedicled island flap technique for repairing complicated urethral strictures?,"Urethroplasty using the pedicled island flap technique in complicated urethral strictures. Many techniques have been described for the repair of recurrent urethral strictures. Experience with 1-stage correction of hypospadias and epispadias, using a vascularized island flap technique, has led to its increased application for complicated adult urethral strictures. The advantage of the vascularized island flap technique is that reconstruction can be completed with only 1 operation, and it provides good subjective and objective results. Analysis of 50 consecutive cases treated by this approach has proved its validity. Of the 50 cases fistulas occurred in 20%, of which 12% required surgical correction, and stricture recurred in 32%. The largest proportion of recurrence was noted in patients who were primarily treated with 3 or more urethrotomies within a short time. Therefore, we recommend open surgical repair when 1 or 2 internal urethrotomies fail to produce a good result."
-What percentage of HIV-seropositive patients were found to have bullous pemphigoid (BP)-type autoantibodies in the study?,"Bullous pemphigoid autoantibodies, HIV-1 infection and pruritic papular eruption. Bullous pemphigoid (BP)-type autoantibodies were found by Western blot (WB) analysis of epidermal extracts in the serum of 38% of HIV-seropositive patients compared with 21% of HIV-seronegative patients with chronic pruritus and 76% of patients with BP. They were further identified as BP autoantibodies (BPab) by immunoprecipitation and immunoelectron microscopy. Their incidence increased from 21% in HIV infection stage II to 37% and 43% in stages III and IV, respectively. Of the patients suffering from HIV-related chronic pruritic papulovesicular eruption. 75% showed circulating BPab as compared with 29% in those without skin problems (P = 0.0066) and, among them, 30% met the diagnostic criteria for BP when histology, WB, immunofluorescence and immunoelectron microscopy techniques were used. In conclusion, this study identifies an autoimmune skin reaction that may account for, or be related to, the distressing pruritic eruptions occurring in HIV-infected patients."
-What is the significance of the DNA segment isolated from the agouti locus in mice?,Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse. Molecular characterization of a radiation-induced agouti (a)-locus mutation has resulted in the isolation of a segment of DNA that maps at or near the a locus on chromosome 2 in the mouse. This region of DNA is deleted in several radiation- or chemical-induced homozygous-lethal a-locus mutations and is associated with specific DNA structural alterations in two viable a-locus mutations. We propose that DNA probes from this region of chromosome 2 will be useful for ultimately characterizing the individual gene or genes associated with a-locus function.
-How do fish oils (EPA and DHA) affect platelet aggregation induced by nitrogen microbubbles?,"Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles. Platelet aggregation induced by N2 microbubbles (simulating microbubbles developed during deep diving) was measured in seven volunteers before and after intake of ethyl-eicosapentaenoate (-EPA, 3.5 g/day) and ethyl-docosahexaenoate (-DHA, 2.5 g/day) for 2 wk. The relative content of arachidonic acid (AA) decreased in platelets from all individuals, whereas the content of EPA and DHA increased. The decrease of AA was almost identical with the increase of EPA plus DHA. In plasma the AA content was unchanged, while EPA and DHA increased. The N2 microbubble-induced aggregation showed a significant negative correlation with the DHA content both in platelets and in plasma. Less aggregation was also observed with high EPA content in platelets or plasma. A significant correlation between AA content in platelets and aggregation was seen. Intake of marine oils may be beneficial to divers under deep diving and to patients during extracorporeal circulation, because this may reduce the microbubble-induced aggregation."
-What is midventricular obstruction and how does it relate to chronic systemic hypertension?,"Midventricular obstruction associated with chronic systemic hypertension and severe left ventricular hypertrophy. Midventricular obstruction is an uncommon finding previously defined by catheterization and angiographic techniques in patients with hypertrophic cardiomyopathy. This study describes the clinical and echocardiographic findings of 10 consecutive patients (mean age 73 years) with severe concentric left ventricular (LV) hypertrophy and the unusual finding of a dynamic systolic obstruction located in the midportion of the left ventricle. All patients were known to have chronic hypertension, and none had a history or family history of hypertrophic cardiomyopathy. In each case, a well-defined, high velocity, turbulent jet was identified by Doppler color flow imaging and subsequently confirmed with conventional Doppler techniques. Septal and posterior wall thickness averaged 1.67 and 1.57 cm, respectively. Mean LV mass index was 199 g/m2 and ejection fraction averaged 78%. Peak systolic velocity obtained by continuous-wave Doppler averaged 2.7 m/s and appeared as either a ""late-peaking"" or a ""spike and dome"" configuration. Seven of 10 patients gave a history of syncope or severe presyncope at the time of echocardiographic examination. At a mean follow-up of 1 year, syncope or presyncope had resolved in 5 patients in whom medication was adjusted based on the ultrasound study, but persisted in 2 patients in whom diuretic therapy was continued. It is concluded that obstruction to systolic flow can occur at the mid-LV level in some patients with severe concentric LV hypertrophy and avoidance of medication known to lower LV volume may relieve symptoms of transient inadequate cardiac output."
-How do blood type differences impact waiting times and graft survival in cadaveric renal transplantation?,"The impact of nonidentical ABO cadaveric renal transplantation on waiting times and graft survival. Blood type O recipients of cadaveric renal transplants have longer pretransplant waiting periods than blood type A, B, and AB recipients. To evaluate reasons for and consequences of this discrepancy, we studied both the frequency of various donor and recipient blood type combinations and their outcomes. Among 37,659 cadaveric renal transplants performed during 1983 through 1989, there were 2,625 transplants (7%) received by patients of compatible but nonidentical blood types. Of 18,575 type O donor organs, 16,784 were received by type O patients for a recipient to donor ratio of 0.9. The corresponding ratios were greater than 1.0 for all other blood types (1.02 for blood type A, 1.14 for type B, and 2.18 for type AB). This causes blood type O patients to have a lower access to transplantation and to have significantly longer waiting times than patients of all other blood types. This inequality of access diminished significantly (P less than 0.001) over the years, but did not resolve by 1989. Analysis of relative risk for first graft loss by multiple regression (Cox) showed that transplantation across compatible blood types had a 9.1% higher risk (P less than 0.1) than that of transplantation among identical blood types. Cadaveric renal transplantation within identical blood types optimizes access to transplantation and avoids further aggravating past disadvantages for blood type O recipients."
-What were the key findings of the study comparing streptokinase and recombinant tissue plasminogen activator (rTPA) in treating acute lower limb ischaemia?,"Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia. Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase."
-What rare cardiac condition did the woman present with due to metastatic melanoma?,"Metastatic melanoma to the heart presenting with ventricular tachycardia. Intraventricular tumors in adults are uncommon, and the association of these with ventricular tachycardia is even more rare. We report a case of an intracardiac metastatic melanoma in a woman who presented with syncope due to ventricular tachycardia."
-What clinical methods are used for risk stratification in patients after a myocardial infarction?,"Risk stratification after myocardial infarction. Clinical overview. Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification."
-What is the clinical significance of recurrent pericarditis in hypocomplementemic urticarial vasculitis syndrome?,"Recurrent pericarditis and cardiac tamponade in a patient with hypocomplementemic urticarial vasculitis syndrome. We describe a patient with hypocomplementemic urticarial vasculitis syndrome complicated by recurrent pericarditis and cardiac tamponade. The episodes of pericarditis were associated with urticarial vasculitis, hypocomplementemia, and circulating IgG antibodies to the collagen-like region of Clq. Histopathologic examination of the skin and pericardium demonstrated vasculitis associated with immunoglobulin and complement deposition suggesting an immune complex mediated etiology. Recurrent pericarditis should be included in the clinical spectrum of hypocomplementemic urticarial vasculitis syndrome."
-How did supplemental oxygen affect breathlessness and oxygen saturation in patients with chronic obstructive airway disease (COAD) and interstitial lung disease (ILD)?,"Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease. We have compared the symptomatic benefit of air and oxygen at rest in hypoxemic patients with chronic obstructive airway disease (COAD) or interstitial lung disease (ILD). A total of 12 severely disabled patients with COAD (mean +/- SEM, PaO2, 50.3 +/- 3.7 mm Hg) and 10 with ILD (PaO2, 48.0 +/- 3.1 mm Hg) received 28% oxygen and air by Venturi face mask, each gas on two occasions, in a double-blind randomized fashion. SaO2 increased (p less than 0.01) in both groups during oxygen breathing: COAD, 85.1 +/- 2.3% versus 93.1 +/- 1.4%; ILD, 85.5 +/- 1.7% versus 94.7 +/- 0.9%. The patients with COAD stated that air helped their breathing on 15 of 24 occasions and that oxygen helped on 22 of 24 occasions (p less than 0.05). In the patients with ILD the values were 6 of 20 and 13 of 20 occasions, respectively (p less than 0.05). In both groups of patients the severity of breathlessness recorded on a 100-mm visual analog scale was significantly (p less than 0.05) lower during oxygen breathing: COAD, 29.6 +/- 4.5 versus 45.6 +/- 6.0; ILD, 30.2 +/- 5.1 versus 48.1 +/- 4.4. Ventilation measured by magnetometers was significantly lower during oxygen breathing in the patients with COAD (8.2 +/- 1.0 versus 9.3 +/- 1.1 L/min; p less than 0.05), but the difference between oxygen and air in patients with ILD was not statistically significant (9.3 +/- 1.3 versus 11.2 +/- 1.6 L/min; p greater than 0.05)."
-What was the impact of mitomycin C (MMC) as an adjuvant treatment on survival rates in patients with resected gastric cancer after a 10-year follow-up?,"Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up. Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up."
-What are the key histological and histochemical characteristics of mucin-producing tumors in the pancreas?,"Mucin-producing tumor of the pancreas. A new pancreatic tumor, called mucin-producing tumor, has received great attention in Japan. These tumors are found inside the pancreatic duct and produce large quantities of copious mucus. The authors examined 22 cases of these tumors histologically and histochemically. In 12 malignant cases, the tumors inside the ducts consisted of cancerous lesions over small areas along with papillary or atypical hyperplasia. Tumors in ten benign cases mainly consisted of papillary hyperplasia. Except for three patients with carcinoma in situ, cancerous tumors infiltrated the pancreatic parenchyma and, in some cases, were observed invading the bile duct or duodenum. A mucous histochemical study showed evidence of sialomucin in malignant cases; neutral mucin was dominant in benign cases. Characteristics of this disease were also compared with 13 cases of mucinous cystic neoplasm. From the results, it was concluded that these two diseases can be classified into the same conceptual category."
-How was acute massive hepatic injury induced in rats in this experimental model?,"A rat model of acute liver necrosis induced by a monoclonal antibody to liver-specific antigen and complement. Acute massive hepatic injury was induced in rats by a monoclonal antibody against a rat liver-specific membrane antigen, and its histological characteristics were investigated. A single intravenous injection of murine ascites containing a monoclonal antibody produced numerous hemorrhagic foci of degenerated and necrotic liver cells predominantly in zones 1 (the periportal area) and 2 (the area of transition between the periportal zone and the perivenular zone) of the liver lobule within 10 min. Massive hepatocellular necroses were observed 1 hr later, but no inflammatory cell infiltration occurred in and around the necrotic foci. Immunohistological study demonstrated marked deposition of the third component of the complement system in the necrotic area. Serum complement activity was sharply decreased immediately after the injection of the antibody, suggesting that the hepatic necrosis is ascribable to a complement-mediated immune attack on the liver cell membrane induced by the antigen-antibody reaction. The hepatic necrosis in response to monoclonal-antibody injection did not progress to a chronic disease and healed almost completely, changing to scar tissues within 2 wk. Although it is not clear whether this hepatic injury has any clinical relevance, this antibody/complement model may be useful for investigating the cause and therapy of hepatic diseases such as fulminant hepatitis."
-What unique observation was made about the lateral rectus muscle after the silicone band transection in this case report?,"Preserved action of a rectus muscle after transection by an encircling solid silicone band. We present a case of anterior migration of a solid silicone band through a lateral rectus muscle. In this patient the action of the lateral rectus was preserved, and this is demonstrated photographically. The possible reasons for this rare complication and the possible mechanism by which lateral rectus activity remained intact are explained."
-What is the primary histologic reaction pattern in Behcet's disease?,"Clinical features of Behcet's disease. Report of four cases. Behcet's disease is a multisystem inflammatory disorder of unknown etiology. The unifying histologic reaction pattern is a leukocytoclastic vasculitis that affects predominantly the skin, oral mucosa, and eyes. Many other sites of involvement have been reported but are inconsistently found in individual patients. Early recognition and treatment of Behcet's disease may help prevent devastating permanent sequelae such as blindness. Because oral involvement is often the first manifestation of this disorder, dental practitioners are in a unique position to help these patients. We report four cases of Behcet's disease in North American patients. Diagnostic criteria and treatment options are reviewed."
-How did recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) impact neutrophil recovery and patient outcomes in autologous bone marrow transplantation for lymphoid cancer?,"Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. BACKGROUND. The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS. We conducted a randomized, double-blind, placebo-controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty-eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS. No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS. In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration."
-What differences were observed between Candida tropicalis and Candida albicans fungemia in children with leukemia?,"Candida tropicalis and Candida albicans fungemia in children with leukemia. The records were reviewed for all patients hospitalized at a pediatric oncology center for complications of leukemia (n = 822) or lymphoma (n = 290) during an 8-year period. The results of surveillance cultures (throat, rectal, and urine) and blood cultures were analyzed to identify cases of Candida tropicalis and C. albicans colonization and/or fungemia. None of the patients with lymphoma who had positive surveillance cultures for C. albicans (n = 89) or C. tropicalis (n = 23) had fungemia. Among patients with leukemia, significant fungal infection was documented in 12 of 107 colonized with C. tropicalis (11.2%) versus 14 of 700 (2%) colonized with C. albicans (P less than 0.001). The two groups of children with fungemia were similar in primary diagnoses (predominantly acute lymphoblastic leukemia) and in the frequency of several known risk factors for infection, including the duration of neutropenia (absolute neutrophil counts, less than 500/microliters). Patients with C. tropicalis fungemia all had disseminated disease compared with nine of 14 patients with C. albicans fungemia. Also, subcutaneous abscesses were unique to patients with C. tropicalis in this series. Two patients in each group died of their infection; central nervous system involvement was present in both fatal cases of C. tropicalis fungemia. A high index of suspicion and the early institution of appropriate antifungal therapy are critical to the successful management of these infections in patients with leukemia."
-What was the relationship between the degree of coronary stenosis and mortality in patients who survived an anterior wall Q-wave acute myocardial infarction?,"Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05)."
-What are the contributing factors that may lead to late bleeding after rhytidectomy?,"Late bleeding after rhytidectomy from injury to the superficial temporal vessels. Five healthy, normotensive women, whose mean age was 49.8 years, developed expanding hematomas between 8 and 10 days (average 9 days) after rhytidectomy. In each patient, the bleeding vessel could be identified: In two, it was the parietal branch of the superficial temporal artery; in two, it was the parietal branch of the superficial temporal vein; and in one, it was the superficial temporal artery immediately before its branching. Contributing factors may have been sudden physical exertion in four of the five patients and in another salicylate ingestion. Several measures can help avoid late bleeding from the superficial temporal vessels or their branches; not using a too potent vasoconstrictive agent (epinephrine) in the local anesthetic so that the vessels will be easier to visualize; not injecting the local anesthetic too deeply or incising to deeply; dividing and ligating the superficial temporal vessel and its major branches if injured; using bipolar coagulation on small branches; and instructing patients repeatedly not to engage in strenuous activity or to ingest salicylates for at least 2 weeks after operation."
-What is the current understanding of dietary fiber's effectiveness in managing constipation and diarrhea in tube-fed patients?,"Dietary fiber and bowel function in tube-fed patients. In tube-fed patients, dietary fiber is often used to manage constipation/diarrhea. Dietary fiber consists of water-soluble and insoluble plant compounds that are resistant to digestion by small-bowel enzymes but are fermented to varying degrees by colonic bacteria. Many physiologic effects of fiber may be related to the degree of fermentation. Few controlled studies of fiber-containing tube feedings have been performed. These studies have limitations and are nondefinitive as to whether fiber prevents or controls constipation/diarrhea. Constipation in tube-fed patients has not been shown to respond to mixed soluble/insoluble fiber in the few studies performed to date. Likewise, fiber may be of only limited benefit in controlling diarrhea in acute illness because of such factors as stress or medication. Fiber does play a role in maintaining gut integrity in all patients, whether they have diarrhea or not. Fiber may be recommended as part of a standard tube-feeding regimen to help assure gut mucosal integrity but not specifically to treat constipation/diarrhea. Further studies are necessary before the role of fiber in the management of constipation/diarrhea in tube-fed patients is determined."
-What was the effectiveness of fluconazole in treating hepatosplenic candidiasis in patients who did not respond to previous antifungal treatments?,"Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy."
-What abnormal vascular responses were observed in patients with hypertrophic cardiomyopathy during exercise?,"Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy. BACKGROUND. Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads. METHODS AND RESULTS. To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001). CONCLUSIONS. The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy."
-What were the significant predictors of death on the first day in the Surgical Intensive Care Unit (SICU)?,"Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications. The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU."
-What potential complications can arise from percutaneous insertion of an intra-aortic balloon pump?,"Aortoiliac dissection after percutaneous insertion of an intra-aortic balloon pump. Aortic or aortoiliac dissection may complicate percutaneous intra-aortic balloon pump insertion in various ways. Thrombosis can escape clinical recognition if no major obstruction develops. Death due to perforation after dissection is not uncommon. In this case study, aortoiliac dissection led to bilateral iliac artery stenosis, an unusual complication of percutaneous femoral cannulation for insertion of a balloon pump."
-How does heart rate affect pulmonary artery acceleration time in different levels of pulmonary artery pressure?,"Effects of heart rate and pulmonary artery pressure on Doppler pulmonary artery acceleration time in experimental acute pulmonary hypertension. Chronic pulmonary hypertension in humans is characterized by shortening of the pulmonary artery acceleration time as measured by Doppler echocardiography, such that the higher the pulmonary artery pressure, the shorter the pulmonary acceleration time. Increases in heart rate are also known to produce decreases in the pulmonary artery acceleration time. To explore the relationship between mean pulmonary artery pressure, heart rate, and Doppler pulmonary artery acceleration time, experimental acute pulmonary hypertension was created in nine Duroc swine, either by infusion of Sephadex beads with embolization of the pulmonary arterial circulation or by partially occluding the main pulmonary artery 8 to 10 cm distal to the pulmonic valve. Pulmonary artery Doppler flow velocity recordings and invasive pressure measurements were made at baseline and at paced atrial rates ranging from 60 to 160 beats per minute, in 20-beat increments. The results in this acute animal model reveal that increases in heart rate produced significant decreases in Doppler pulmonary artery acceleration time at mean pressures below 25 mm Hg. However, with mean pulmonary artery pressures greater than 25 mm Hg, both heart rate and increases in pulmonary artery pressure had no significant effect on acceleration time."
-How does hypertension and elevated cholesterol affect the fibrinolytic system?,"Hypo-fibrinolysis in patients with hypertension and elevated cholesterol. To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI."
-"How does Doppler ultrasound help in identifying a small, clinically undetectable ductus arteriosus?","Doppler ultrasound and the silent ductus arteriosus. A clinically undetectable, small ductus arteriosus was identified by Doppler ultrasonography in 21 individuals. Infants were excluded from the study and no patient had pulmonary hypertension. Persistence of the ductus arteriosus is likely to be more common than shown by less sensitive diagnostic methods. Some patients considered to have infective endocarditis with a normal heart may have a silent ductus arteriosus. Evidence of such an association would justify ligation or antibiotic cover as prophylactic measures."
-What may cause tears in the retinal pigment epithelium according to the context?,Tears of the retinal pigment epithelium: occurrence in association with choroidal effusion. Two patients developed large tears of the retinal pigment epithelium associated with choroidal effusion. One tear occurred after combined cataract/filtration surgery complicated by postoperative choroidal detachment; the second developed in a patient with idiopathic uveal effusion syndrome. Weakness of the junctions of the pigment epithelial cells secondary to the accumulation of fluid in the subretinal or suprachoroidal space may result in tearing of the retinal pigment epithelium as it is stretched.
-How did different nutritional regimens affect the cell kinetic activity of gastrointestinal tumors in this preliminary study?,"Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report. Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H-TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy."
-What was the interval between HBV infection and HCC appearance in the three reported cases?,"HBV-DNA-related hepatocellular carcinoma occurring in childhood. Report of three cases. In a series of 325 HBV chronically infected children observed over an 18-year period, three developed HCC. These three children were born in southern Italy, a region characterized by a high endemic HBV infection rate; each had been infected perinatally, developed an acute hepatitis, and became a chronic carrier. Two of the three with cirrhosis were HBsAg positive at the time their HCC was detected. The remaining case had seroconverted to HBsAb but HBV-DNA integration could be demonstrated in the absence of cirrhosis; moreover HBV antigens were not expressed in the tissue of this case. The interval between HBV infection and HCC appearance in these three cases ranged from six to 11 years. A similarity between these three Italian cases and the majority of HCC arising in chronically infected children in the Far East is noted."
-"What is the medical condition described in the context, and how long has the patient been experiencing recurrent symptoms?",Localized recurrent postoperative pernio associated with leukocytoclastic vasculitis. A patient with recurrent pernio of the right ankle for 21 years after surgery had a leukocytoclastic vasculitis localized in the area. We suggest that the various histologic descriptions of pernio in the literature and in this case represent different levels of severity of the disease.
-What advantages does the microvascular peritoneal flap offer for intraoral reconstruction?,"Intraoral reconstruction with a microvascular peritoneal flap. The microvascular peritoneal flap offers a new reconstructive option for closure of intraoral defects. The flap is easy to raise, and donor-site morbidity is low. Unlike fascial flaps, in which the raw surface may take weeks to ""mucosalize,"" the peritoneal surface heals primarily. Finally, the rectus muscle effectively covers all forms of mandibular reconstruction, and the reliable skin paddle makes possible the closure of substantial cutaneous defects."
-How does transcutaneous electrical nerve stimulation (TENS) therapy affect uterine activity in women with primary dysmenorrhea?,"Interrelation of analgesia and uterine activity in women with primary dysmenorrhea. A preliminary report. The interrelation between uterine activity and pain from primary dysmenorrhea has been of interest for many years. Objective studies of uterine activity during non-steroidal antiinflammatory drug therapy have supported the assertion that uterine activity causes pain and that reducing that activity leads to pain reduction. Unfortunately, those studies could not refute the counter-assertion that reductions in uterine activity come about because of reduced pain through central analgesia and not by direct pharmacologic action. In an effort to clarify this question, a small number of women were studied using intrauterine pressure recording and analysis to evaluate objective changes in uterine physiology during transcutaneous electrical nerve stimulation (TENS) therapy for dysmenorrhea. The preliminary studies indicated that despite successful subjective therapy with TENS, intrauterine pressure parameters remained steady or showed signs of worsening. These findings indicate that TENS provides pure analgesia by an alteration of the body's ability to receive or perceive the pain signal rather than by a direct uterine effect. It appears that the reduction in uterine activity seen in objective drug studies represents direct drug action rather than a change from reduced pain through central analgesic effects."
-What was the purpose of the laboratory study on psyllium hydrophilic mucilloid (PHM) added to enteral feeding formula?,"Flow characteristics of enteral feeding with psyllium hydrophilic mucilloid added. One therapy for managing diarrhea in patients in intensive care units who are receiving enteral nutrition is administration of psyllium hydrophilic mucilloid (PHM). This laboratory study was conducted to determine whether the addition of PHM (Metamucil) to enteral feeding formula (Entrition) adversely affected the flow characteristics of the feeding formula through a small-bore feeding tube. Descriptive data were obtained from 72 trials of feeding formula with varied infusion rates, formula osmolality and temperature, and PHM concentrations. Two thirds (n = 48) of the trials were successful (PHM did not clog the tubing and obstruct flow). The remaining one third of the trials (n = 24) were unsuccessful. Successful formula infusion was influenced by formula temperature and osmolality but not by infusion rate, PHM concentration, or flow interruption. If formula with PHM was followed by formula without PHM, the infusion was successful regardless of infusion rate or formula osmolality. Thus, the data from this laboratory study indicate that when therapeutic doses of PHM are prescribed, it is feasible for PHM to be mixed in room-temperature feeding formula and infused without clogging the feeding tube."
-How does growth hormone influence kidney growth and scarring in experimental models?,"The role of growth hormone and insulin-like growth factor-I in experimental renal growth and scarring. Recent evidence suggests a causal link between early renal/glomerular hypertrophy and late kidney scarring and glomerular sclerosis. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide likely to play a role in the development of kidney growth. We observed an increased renal IGF-I content in two experimental models of accelerated kidney growth in the rat. By contrast, diabetic renal hypertrophy is abolished in the absence of growth hormone (GH). Dietary protein manipulations affect the expression of compensatory renal growth (CRG), as well as renal IGF-I content. The renotrophic effect of a high-protein diet on CRG seems GH-dependent and IGF-I-mediated. GH also appears to have a permissive role on the development of progressive renal scarring following extensive renal ablation in rats, as dwarf rats seem somewhat resistant to the development of accelerated scarring and renal failure."
-What was the 20-year survival probability for patients with T2N0M0 stage I breast carcinoma in this long-term follow-up study?,"Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients."
-How do serum endothelin-1 (ET-1) concentrations differ between subjects with primary Raynaud's phenomenon and control subjects during cold provocation?,"Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6] degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml) than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder."
-What is the key finding of this study regarding the treatment of arteriovenous malformations with peripheral aneurysms?,"Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer. Report of three cases. The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n-butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery."
-What complication did the 36-year-old mentally retarded patient experience with his Foley catheter gastrostomy tube?,"Duodenal obstruction by a nondeflating Foley catheter gastrostomy tube. We report the case of a 36-year-old mentally retarded man who presented to our emergency department after one day of vomiting and one episode of coffee-ground emesis. The Foley catheter used as his gastrostomy tube was found to be obstructing the duodenum, and the balloon could not be deflated. Removal was accomplished by rupturing the balloon by endoscopy. Our case illustrates one of many possible complications of feeding gastrostomy tubes."
-What were the most common histologic types of soft tissue sarcomas found in the chest wall in this study?,"Soft tissue sarcomas of the chest wall. Results of surgical resection. Primary soft tissue sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. Most studies have categorized these tumors as truncal sarcomas and inferred a poor prognosis. To assess the results of surgical treatment, we reviewed our 40-year experience. Methods: Records of 189 patients admitted to our institution from 1948 to 1988 were reviewed. Pathologic material was available for review in the 149 cases (79%) that comprise this report. Survival was calculated by the Kaplan-Meier method, with comparisons by log-rank analysis and significance defined as p less than 0.05. Results: Ages ranged from 3 weeks to 86 years (median, 38 years); the ratio of male to female patients was 2:1. The initial complaint was mass or pain in 97% of the cases. Ninety sarcomas (60%) were high grade and 59 (40%) were low grade. Histologic types were as follows: desmoid tumor (n = 32, 21%); liposarcoma (n = 23, 15%); rhabdomyosarcoma (n = 18, 12%); fibrosarcoma (n = 17, 11%); embryonal rhabdomyosarcoma (n = 14, 9%); malignant peripheral nerve tumor (n = 13, 9%); malignant fibrous histiocytoma (n = 11, 7%); spindle cell sarcoma (n = 4, 3%); tenosynovial sarcoma (n = 3, 3%); hemangiopericytoma (n = 3, 3%); alveolar soft part sarcoma (n = 3, 3%); and other types (n = 12, 9%). Resection was the primary treatment in 140 cases (94%). Local recurrence developed in 27%. Metastases occurred in 52 (35%) of the cases (metachronous in 42, synchronous in 10) and were more common in patients with high-grade disease (46/90, 51%) than in those with low-grade disease (6/59, 10%). Overall 5-year survival was 66%. Five-year survival rate for those with high-grade sarcomas (49%) was significantly lower than that for low-grade sarcomas (90%, p less than 0.0001). Tumor size and age of patient were not prognostic. Conclusions: Survival of patients with primary soft tissue sarcomas of the chest wall after resection is similar to that of patients with sarcomas of the extremities. Resection alone provides acceptable survival (90% at 5 years) for those with low-grade sarcomas, but adjuvant treatment should be considered for those with high-grade sarcomas."
-"How do cephalometric measurements differ between patients with sleep apnoea, non-apnoeic snorers, and non-snoring control subjects?","Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age."
-How effective are intravascular stents in managing superior vena cava syndrome?,"Intravascular stents in the management of superior vena cava syndrome. Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome."
-"How do environmental chemicals and pollution impact public health in developing countries, particularly in relation to malnutrition and infectious diseases?","Chemicals and environmentally caused diseases in developing countries. This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of ""developing countries,"" the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries."
-What did the multivariate analysis reveal about prognostic indicators in acute spinal cord injury?,"Acute spinal cord injury: magnetic resonance imaging correlated with myelopathy. Thirty-one patients (29 males and two females, 13-87 years of age (mean, 46.7 years] with acute spinal cord injury were studied by MR (magnetic resonance) imaging and the results were correlated with neurological findings. Magnetic resonance images were obtained with a 0.5 T superconductive MR scanner (Phillips Gyroscan S5). Initial imaging was performed within 24 hours after trauma in 13 patients, 1-7 days in 13 patients and 7-14 days in five patients. Twenty-six patients underwent follow-up examinations with MR imaging. Cord abnormalities including cord compression (23 patients), cord swelling (seven patients), and abnormal signal intensities on either T1 or T2-weighted images (26 patients) were observed on initial examination. Multivariate analysis showed that cord compression and abnormal intensities on T1-weighted images were important prognostic indicators. Hyperintensity on T2-weighted images was non-specific but correlated well with clinical recovery. Magnetic resonance imaging is useful in predicting the prognosis and for planning treatment following spinal cord injuries."
-Can vitamin D deficiency cause an unusual pain syndrome with hyperesthetic characteristics?,"Can vitamin D deficiency produce an unusual pain syndrome? An unusual pain occurred in five patients in the presence of compromised vitamin D status and resolved 5 to 7 days after supplementation with vitamin D in the form of ergocalciferol. The pain had a hyperesthetic quality and did not respond to the use of analgesics, including opiate derivatives. Treatment with therapeutic levels of a tricyclic antidepressant did not bring relief of symptoms. In one case, months after treatment and subsequent improvement of vitamin D status and pain, the vitamin D status again declined and the pain recurred. The pain again resolved with vitamin D replacement and improvement of levels. There may be a pain syndrome associated with vitamin D depletion that appears as hyperesthesia worsened by light, superficial pressure or even small increments of movement. This pain restricts mobility and function and may lead to further complications, such as pressure sores."
-What was the success rate of operations for dividing atrioventricular accessory pathways in patients with Wolff-Parkinson-White syndrome?,"Operations for Wolff-Parkinson-White syndrome. Forty-six patients with symptomatic tachycardia underwent operations to divide 55 atrioventricular accessory pathways. Mean age was 29 years (range 11 to 63). Ten patients (22%) had associated cardiac disease, including two with a congenital diverticulum of the coronary sinus and six (13%) who had concomitant surgical procedures. A bipolar hand-held electrode was used in 22 operations, and simultaneous multisite mapping in the last 24 operations. Ten patients (22%) had multiple accessory pathways. A modified endocardial approach was used. The overall patient success rate was 93% with 91% to 93% of accessory pathways successfully divided. The perioperative morbidity was 17%. There were two reoperations. There were no early or late deaths. Patients have been followed up for a mean of 16 months. There were five recurrences of preexcitation (two early, three late). Two of these patients (both with a congenital diverticulum of the coronary sinus) had reoperation. One patient had late recurrence of atrial fibrillation. Operation for the Wolff-Parkinson-White syndrome has a high probability of success with a low operative risk."
-How do oral contraceptives potentially impact metabolic risk markers related to coronary heart disease?,"Oral contraceptives and coronary heart disease. In industrialized countries, coronary heart disease (CHD) is a major public health problem for both men and women. Preventive strategies for reducing the excessive mortality and morbidity associated with CHD involve the identification and modification of metabolic factors believed to be involved in the disease process. Three major areas of concern are lipid metabolism, carbohydrate metabolism and the hemostatic system. The steroid hormones contained in oral contraceptives (OCs) have been shown to interfere in all three areas. In many instances OCs have been shown to alter metabolic markers for CHD in directions associated with increased risk. Although evidence is lacking that such changes induce CHD in users of modern, low-dose OCs, it would be prudent to develop formulations with a minimal impact on metabolic risk markers. There is increasing evidence that many of the metabolic disturbances seen in CHD patients share a common origin, and the development of risk-free OCs is likely to require investigation into complex interrelationships."
-What was the purpose of this pilot study involving Fluosol and emergency coronary angioplasty in patients with anterior myocardial infarction?,"Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05)."
-What are the advantages of using the rectus abdominis free flap in head and neck reconstruction?,"The rectus abdominis free flap in head and neck reconstruction. The rectus abdominis musculocutaneous free flap, based on the deep inferior epigastric artery and vein, has been used widely in reconstruction of the breast and extremities. The number of reports on its applications in the head and neck is limited. The rectus abdominis free flap is one of the most versatile soft-tissue flaps. The deep inferior epigastric artery and vein are long, large-diameter vessels that are ideal for microvascular anastomoses. The area of skin that can be transferred is probably the largest of all flaps presently in use. The versatility of this donor site is due to the ability to transfer large areas of skin with varying thicknesses and varying amounts of underlying muscle. We have successfully used this flap in 15 consecutive patients to reconstruct defects of the neck, face, mouth, pharynx, skull base, and scalp. No major complications involving either the recipient or donor sites occurred. The literature on the use of the rectus abdominis flap in head and neck reconstruction is reviewed in detail. The advantages and disadvantages of this soft-tissue free flap are thoroughly discussed in an effort to better define its proper place among the reconstructive options available to the head and neck surgeon."
-How did the protein and fat intake affect glomerular filtration rate and urinary protein loss in patients with membranous nephropathy?,"Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome. Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake."
-How did oral ofloxacin compare to parenteral antibiotics in treating chronic osteomyelitis?,"Ofloxacin versus parenteral therapy for chronic osteomyelitis. We conducted a randomized comparison of oral ofloxacin (400 mg twice a day) and parenteral agents (cefazolin, 1.0 g intravenously every 8 h, or ceftazidime, 2.0 g intravenously every 12 h) in biopsy-confirmed, nonprosthesis osteomyelitis. A total of 19 subjects received ofloxacin for an average of 8 weeks, and 14 received parenteral antibiotics for an average of 4 weeks; both therapies were well tolerated. Infections were due to Staphylococcus aureus (40%), Enterococcus spp. (3%), Pseudomonas aeruginosa (15%), and other gram-negative organisms (42%). At the completion of therapy, one P. aeruginosa infection in the ofloxacin group persisted and the organism acquired resistance, accompanied by a resistant Acinetobacter superinfection. In the parenteral group, one S. aureus infection persisted, and there was a resolved superinfection due to S. aureus as well. Eighteen-month follow-up data have been obtained. Among those treated with ofloxacin, four subjects whose initial response to therapy was successful suffered relapses of infection, three due to S. aureus and one due to P. aeruginosa, while in the parenteral group, one subject with a P. aeruginosa infection relapsed. Long-term response to therapy was successful for 14 of 19 (74%) subjects who received ofloxacin and 12 of 14 (86%) who received parenteral antibiotics; the difference was not significant. Oral ofloxacin appears comparable to parenteral antibiotics in chronic osteomyelitis due to susceptible organisms, and oral ofloxacin offers advantages in economics and convenience."
-What are the two most common procedures used for screening hearing loss in newborns or intensive care nurseries?,"Auditory screening of infants. Within the last 20 years, infant hearing screening has progressed from a laudable goal to a state-mandated reality in many areas of the United States. The high risk register provides a means by which history and neonatal physical examination can be used to identify the infant at risk for hearing loss. Two procedures (crib-O-gram and auditory brainstem-evoked response) have been the most common methods of screening for hearing loss in the newborn or in intensive care nurseries. Evoked cochlear emissions reportedly are identifiable in 90 to 100% of normal-hearing infants. This observation has lead to the use of evoked otoacoustic emissions as a hearing screening procedure with infants."
-What was the main objective of the SWIFT trial in treating acute myocardial infarction?,"SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. OBJECTIVE--To see whether early elective angiography with a view to coronary angioplasty or bypass grafting of a stenosed infarct related vessel would improve outcome in acute myocardial infarction treated by thrombolysis with anistreplase. DESIGN--Randomised study of two treatment strategies with analysis of results over 12 months. SETTING--21 district hospitals and regional cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients presenting with clinical and electrocardiographic features of acute myocardial infarction up to three hours after the onset of major symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units followed by a standard regimen of heparin, warfarin, and timolol and (in patients so randomised) early angiography plus appropriate intervention. MAIN OUTCOME MEASURE--Death or reinfarction within 12 months. RESULTS--397 patients were randomised to receive early angiography plus appropriate intervention (coronary angioplasty in 169 cases, coronary grafting in 59) and 403 patients to receive conservative care (of these, 12 had angioplasty and seven bypass grafting during the initial admission). By 12 months mortality (5.8% (23 patients) in the intervention group v 5.0% (20) in the conservative care group; p = 0.6) and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4) were similar in the two groups. No significant differences in rates of angina or rest pain were found at 12 months. Left ventricular ejection fraction at three and 12 months was the same in both groups. Median hospital stay was longer in the intervention group (11 days v 10 days; p less than 0.0001). CONCLUSION--For most patients given thrombolytic treatment for acute myocardial infarction a strategy of angiography and intervention is appropriate only when required for clinical indications."
-What are the characteristic radiographic features of chondromyxoid fibroma that help in its identification?,"Chondromyxoid fibroma: radiographic appearance in 38 cases and in a review of the literature [published erratum appears in Radiology 1991 Aug;180(2):586] Thirty-eight cases of histologically confirmed chondromyxoid fibroma were reviewed and their radiographic features recorded. These findings, coupled with a review of the English-language medical literature, suggest that this rare, benign bone tumor has a characteristic but not specific radiographic appearance and may often mimic more common tumors. Chondromyxoid fibroma may occur anywhere in the skeleton, but almost half of the cases occur around the knee. The possibility of chondromyxoid fibroma should always be considered when a focal bone lesion is evaluated that has geographic bone destruction, a sclerotic rim, lobulated margins, and septation. The diagnosis of chondromyxoid fibroma is most likely when the patient is in the 2nd decade of life."
-How do bile acids contribute to splanchnic hemodynamics in portal hypertension?,"Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia."
-What percentage of falls resulted in a major injury in this prospective study of elderly community-dwelling persons?,"Risk factors for injurious falls: a prospective study. We conducted a prospective study of the consequences of falls in 325 elderly community-dwelling persons, all of whom had fallen in the previous year. We contacted subjects every week for one year to ascertain falls and to determine the circumstances and consequences of falls. Only 6% of 539 falls resulted in a major injury (fracture, dislocation, or laceration requiring suture), but over half (55%) resulted in minor soft tissue injury. One in ten falls left the faller unable to get up for at least 5 minutes, and one in four falls caused subjects to limit their activities. The risk of injury per fall was about the same regardless of the number of falls a person had during follow-up. The risk of major injury was increased (age- and sex-adjusted odds ratio: 5.9, 95% confidence interval: 2.3-14.9) in falls associated with loss of consciousness compared to nonsyncopal falls. In multivariate analyses of nonsyncopal falls, the risk of major injury per fall was higher in persons having a previous fall with fracture (6.7; 2.1-21.5), a slower Trail Making B time (1.9; 1.1-3.2), and in Whites (18.4; 7.5-44.6). The risk that a nonsyncopal fall would result in minor injury (versus no injury) was increased in persons with a slower hand reaction time (1.8; 1.0-3.2) decreased grip strength (1.5; 1.0-2.3), in Whites (2.0; 1.0-3.7), in falls while using stairs and steps (2.2; 1.0-5.0), and turning around or reaching (3.5; 1.7-7.3). Our findings suggest that neuromuscular and cognitive impairment, as well as the circumstances of falls, affect the risk of injury when a fall occurs."
-What was the main purpose of the study on nitroglycerin patches in patients with chronic stable angina?,"The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration. This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical."
-What were the five-year cure rates for T1 glottic squamous cell carcinoma patients who underwent laser cordectomy with and without prior radiation treatment?,"Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure."
-What is the unique aspect of the obturator foramen bypass described in this case report?,Crossover ilioprofunda reconstruction: an expanded role for obturator foramen bypass. The standard obturator foramen bypass extends from the aorta or iliac artery to the ipsilateral superficial femoral or popliteal artery. This operation has been both effective and versatile as an indirect bypass procedure for circumventing difficult vascular problems in the femoral triangle. A case is presented of a patient whose limb was salvaged by an obturator foramen bypass from the contralateral iliac artery to the profunda femoris artery. This unique case is compared to other published cases to emphasize the potential advantages of the profunda femoris as the preferred graft outflow in selected cases of arterial reconstruction through the obturator foramen.
-When is antibiotic treatment recommended for bacterial gastroenteritis?,"Antibiotic treatment of bacterial gastroenteritis. Antibiotic treatment is important in certain etiologies of bacterial gastroenteritis, both for clinical improvement and for eradication of the causative organism from stools, which is important epidemiologically. The etiology, however, is seldom known at presentation in sporadic cases of diarrhea. Thus the decision to initiate antibiotic therapy and the choice of the specific antimicrobial agents should be made on a clinical basis, before culture results are available."
-How does CD45 potentially regulate signal transduction in B cells?,"Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. CD45 is a member of a family of membrane proteins that possess phosphotyrosine phosphatase activity, and is the source of much of the tyrosine phosphatase activity in lymphocytes. In view of its enzymatic activity and high copy number, it seems likely that CD45 functions in transmembrane signal transduction by lymphocyte receptors that are coupled to activation of tyrosine kinases. The B cell antigen receptor was found to transduce a Ca(2+)-mobilizing signal only if cells expressed CD45. Also, both membrane immunoglobulin M (mIgM) and CD45 were lost from the surface of cells treated with antibody to CD45, suggesting a physical interaction between these proteins. Finally, CD45 dephosphorylated a complex of mIg-associated proteins that appears to function in signal transduction by the antigen receptor. These data indicate that CD45 occurs as a component of a complex of proteins associated with the antigen receptor, and that CD45 may regulate signal transduction by modulating the phosphorylation state of the antigen receptor subunits."
-What was the effect of isradipine on systolic and diastolic blood pressure in patients with mild-to-moderate hypertension?,"Multicenter evaluation of efficacy, tolerability and safety of a new first-line antihypertensive drug, isradipine, in a Latin-American population. Isradipine, a new antihypertensive dihydropyridine calcium antagonist, was evaluated for its efficacy, tolerability, and safety in 91 ambulatory patients who had mild-to-moderate hypertension. The design of the present study included a two-week wash-out period after confirmation of disease, followed by 12 weeks of active treatment with 2.5 mg isradipine twice daily. Patients were switched from other antihypertensive drugs, mainly diuretics and beta-blockers. The dose of isradipine remained virtually unchanged throughout the study and resulted in a mean decrease of 22 mm Hg in systolic blood pressure (SBP) (P less than .00001) and 19 mm Hg in diastolic blood pressure (DBP) (P less than .00001). Heart rate was unchanged (difference of -1 beats/min), as was the mean body weight of the study patients. Isradipine was generally well tolerated. Side effects were few and, when present, tended to diminish and eventually disappear during the treatment period. All of the clinical laboratory parameters tested and electrocardiograph intervals remained unchanged. In conclusion, these results indicate that isradipine is a novel drug which is highly effective and well tolerated in the treatment of mild to moderate hypertension in this group of patients."
-What are the potential complications for pregnancies complicated by chronic hypertension?,"Diagnosis and management of chronic hypertension in pregnancy. Pregnancies complicated by chronic hypertension are at increased risk for the development of superimposed preeclampsia, abruptio placentae, and poor perinatal outcome. The frequency of these complications is particularly increased in patients with severe hypertension and those with preexisting cardiovascular and renal disease. Such women should receive appropriate antihypertensive therapy and frequent evaluations of maternal and fetal well-being. In contrast, in patients with mild essential chronic hypertension, the maternal and perinatal benefits from antihypertensive medications are highly controversial. A review of the literature revealed two placebo-controlled studies, four trials comparing treatment versus no medication, and three comparisons of methyldopa and oxprenolol. In only one of these studies were subjects randomized in the first trimester. No differences in pregnancy outcome were found with the use of antihypertensive drugs. Evaluation of the woman with chronic hypertension who is considering pregnancy should begin before conception to establish the cause and severity of the hypertension. Appropriate management should include frequent evaluation of maternal and fetal well-being; antihypertensive medications may be useful in patients with severe disease as well as in those with target organ involvement."
-How can the relationship between gastroesophageal reflux (GER) and upper airway diseases impact patient diagnosis and treatment?,"Gastroesophageal reflux and upper airway diseases. GER can have important impacts on the upper airway passages, and in turn, upper airway obstruction can certainly aggravate reflux. This relationship should be considered in the newborn or young infant, faced with a sudden life-threatening event, and in the older child or adult presenting with chronic head and neck complaints, either unexplained or unresponsive to adequate medical therapy. A causal relationship may be difficult to establish, based first on clinical expertise as a guideline, on laboratory tests, among which pharyngeal pH monitoring could be promising, and on response to medical antireflux therapy. A better understanding of the significance of high levels of reflux and defective acid clearance, as well as a more precise knowledge of the maturation and functioning of upper airway protective mechanisms, would open the way to more accurate diagnostic procedures, to a more reliable definition of the abnormal, and to greater efficiency in the management of these patients."
-What are the potential causes and techniques for removing a Foley catheter when its balloon cannot be deflated?,"Emergency management of the nondeflating Foley catheter balloon. Inability to remove a self-retaining (Foley) catheter may result from failed attempts to deflate its balloon. In this article, the authors review the causes of inability to deflate Foley catheters as well as the various techniques for their removal."
-What was the primary finding of the study regarding the mechanism of post-prandial worsening of angina?,"Post-prandial worsening of angina: all due to changes in cardiac output? BACKGROUND--The precise mechanism leading to the post-prandial worsening of angina has yet to be adequately defined. It has been attributed to an increase in double product but is perhaps more likely to be related to an increase in cardiac output after food. This study was designed to evaluate the effects of food on patients' exercise tolerance and compare these with changes in haemodynamic variables. METHODS--23 patients with chronic stable angina who had post-prandial worsening of their angina were studied. The patients were evaluated on two occasions and at each visit they underwent two symptom limited treadmill exercise tests. They remained fasting on the first visit and were given a 1400 kcal meal 60 minutes before the second exercise test on the second visit. Time to onset of 1 mm ST segment depression, heart rate, systemic arterial blood pressure, and cardiac output were measured at rest and during exercise. RESULTS--There were no differences in any of the variables during the two exercise tests on the day the patients remained fasting. After the meal exercise tolerance fell significantly by 136 seconds and the stage at which 1 mm ST segment depression was first seen was also significantly reduced. Resting cardiac output increased significantly by 0.86 1/min with the patients sitting and by 0.89 1/min standing. The exercise times after food were significantly related to cardiac output even when fasting times were taken into account. Resting heart rate increased significantly by 8.3 beats per minute sitting and 10.4 beats per minute standing. There was little change in blood pressure and no evidence that the double product predicted the post-prandial exercise time. CONCLUSIONS--Worsening of angina was related to the increase in cardiac output after a meal and successful treatment will depend upon the prevention of this increase."
-What types of headaches were observed in patients with Arnold-Chiari malformation (ACM) in this study?,"Headache spectrum in Arnold-Chiari malformation. Exertional headaches in patients with Arnold-Chiari malformation (ACM) are well described. We report four patients with Type I ACM and recurrent headaches. These patients presented, respectively, with low spinal fluid pressure headache, migraine without aura, migraine with aura, and migraine with prolonged aura. This report suggests the need for observing patients with recurrent headaches for any physical stigmata of craniovertebral junction anomalies, and the need to exclude ACM in such patients. Possible implications of the association between ACM and different types of headaches are discussed."
-What were the key findings regarding the performance of different types of prostheses in combined mitral-aortic valve replacement after a 14-year follow-up?,"Influence of type of prosthesis on late results after combined mitral-aortic valve replacement. The influence of type of prosthesis on the late outcome of patients with combined mitral-aortic valve replacement was analyzed by comparing, at a 14-year follow-up, patients receiving two biological prostheses (group 1; n = 135), two mechanical prostheses (group 2; n = 221), or a mechanical prosthesis in the aortic position and a bioprosthesis in the mitral position (group 3; n = 97). No difference was found among the three groups in terms of actuarial survival and incidence of and freedom from valve-related deaths, thromboemboli, and hemorrhages. Patients with biological prostheses had a significantly greater incidence of structural valve deterioration, reoperations, and overall complications when compared with patients with only mechanical prostheses. The results of an extended follow-up of patients with combined mitral-aortic valve replacement indicate that mechanical prostheses perform better in the long-term owing to their superior durability when compared with biological valves. The use of bioprostheses should be confined to old patients with limited life expectancy because of their cardiac disease, provided that anticoagulants are not used. Combination of mechanical and biological prostheses in the same patient should be avoided because the advantages of each type of prosthesis are lost."
-What changes in CT scan appearance can be observed in a traumatized spleen during nonoperative management?,"CT appearance of splenic injuries managed nonoperatively. This essay illustrates the appearance of the traumatized spleen on CT scans obtained during the course of conservative treatment. Although the CT appearance of acute rupture of the spleen has been adequately described, little has been reported about the appearance of the spleen as it heals after trauma. Examples of CT studies of splenic injuries illustrate the various changes in appearance over time in the traumatized spleen that is treated nonoperatively."
-What significant legislative act was passed in 1971 that helped advance cancer research and treatment?,"Progress in cancer. Definite progress has been made against cancer since the National Cancer Act was passed in 1971. Physicians are giving increased attention to cancer prevention. The exciting changes in molecular biology provide increased knowledge about basic mechanisms in tumor growth and metastases. Detailed discussions of two common solid cancers--breast and colorectal--attest to continuing advances in cancer diagnosis and treatment. All of these augur well for further progress in oncology. Continued research, basic and clinical, is mandatory."
-What was the success rate of the percutaneous posterolateral lumbar discectomy procedure in this study?,"Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise."
-What was the overall success rate of endoprosthesis insertion for proximal malignant biliary obstruction in this study?,"Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion. For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%.Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%."
-What serious complications can occur after intravesical instillation of bacillus Calmette-Guerin (BCG)?,"Complications after intravesical instillation of bacillus Calmette-Guerin: rhabdomyolysis and metastatic infection. Two cases of adverse reaction to bacillus Calmette-Guerin (BCG) bladder instillations are reported. In both cases transient fevers and systemic symptoms developed following the instillations. After an additional instillation 1 patient had high fevers, severe myalgias and profound weakness followed by rhabdomyolysis and anuric renal failure, which required 3 weeks of hemodialysis before recovery. Extensive evaluation revealed no cause other than the BCG instillations. In the other patient a firm subcutaneous nodule gradually developed on the chest wall, which contained nonviable acid fast bacilli."
-How does the severity of prior salpingitis episodes impact the recurrence rate of ectopic pregnancy in women with a prior uterine pregnancy?,"Recurrence of ectopic pregnancy: the role of salpingitis. We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk."
-What percentage of patients reported pain relief after receiving nitrous oxide in this rural EMS system study?,"Effectiveness of nitrous oxide in a rural EMS system. Prehospital systems need a safe, effective analgesic agent for the treatment of patients suffering from pain. Recent studies have documented the efficacy of nitrous oxide in urban and rural settings. This study reviews the findings on 200 patients (157 trauma, 23 medical, 18 musculoskeletal problems) who received nitrous oxide during a 28-month period in a rural EMS system. Eighty-five percent of the patients reported pain relief. Only minor side effects were noted. Patient satisfaction was high, and there was no abuse noted among personnel."
-What is an iatrogenic epidermoid cyst and how can it occur in the parotid region following ear surgery?,Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed.
-What is an epidural blood patch and how was it used to treat subarachnoid-cutaneous fistula in the described cases?,Epidural blood patch for treatment of subarachnoid fistula in children. A subarachnoid-cutaneous fistula developed in two children after the placement of a catheter in the subarachnoid space for drainage of cerebrospinal fluid. The management of this iatrogenic complication with epidural blood patch is described.
-How does the estrogen receptor (ER) level correlate with response to tamoxifen treatment in advanced breast cancer?,"The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer."
-What were the two drugs used in the study for treating patients with Raynaud's phenomenon?,"Regional intravenous ketanserin and guanethidine therapy in Raynaud's phenomenon. The authors report the results of a study of 25 patients with Raynaud's phenomenon (primary, posttraumatic, and secondary to diffuse connective tissue diseases) treated with regional intravenous injections of guanethidine or ketanserin. These two drugs were chosen because of the different etiopathologic profiles of the conditions. All the patients showed a substantial clinical improvement with a remission of trophic lesions. Conditions secondary to connective tissue disorders did not demonstrate much improvement based on instrumental data alone, possibly because of the intrinsic limitations of the techniques used for evaluating peripheral blood flow. This specific type of pharmaceutical treatment appeared to be especially suitable for this disease owing to a combination of therapeutic efficacy and a substantial reduction in the total dosage for each patient."
-What are the two fracture patterns associated with the anteroinferior cervical vertebral body corner (teardrop) fracture?,"The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis. The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the ""teardrop"" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch."
-What were the key findings of the study comparing clinical and photographic methods for assessing facial weakness?,"Facial weakness. A comparison of clinical and photographic methods of observation. The search for an internationally acceptable facial grading system has resulted in an assessment of existing methods by several investigators. These studies were based on observations of video film taken of patients with varying degrees of facial malfunction. Although the grading systems were evaluated, the use of videotape has never been compared with clinical examination and its suitability for this type of work is, therefore, unknown. We used nine facial grading systems to compare the results of clinical observation with those of photographic methods of presentation. The latter included videotape, photographic slides, and a combination of the two. The correlation between clinical examination findings and findings of any of the photographic methods was poor, suggesting the need for a standard form of presentation when grading patients. The most consistent results were found with either clinical examination or photographic slides; videotape was the least reliable."
-How do the patterns of soft palate oscillations differ between nasal and mouth snoring?,"Pattern of simulated snoring is different through mouth and nose. Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring."
-What potential risks were identified in the study regarding self-administered sublingual nitroglycerin?,"Defining the proper role for self-administered sublingual nitroglycerin. A survey of physicians and patients. Within a half-year period, we encountered six cases of patients harmed by the adverse effects of self-administered nitroglycerin--syncope, delayed definitive medical care, and the worsening of nonischemic symptoms. We therefore surveyed 112 patients after a remote myocardial infarction, and 121 cardiologists and internists, regarding the use of sublingual nitroglycerin. Of the physicians, 84 percent routinely prescribed nitroglycerin to patients after a myocardial infarction, and 79 percent of the patients had the tablets available (83 percent of these, at all times). Most patients used the tablets less than once per month, and 37 percent of the patients who always carried nitroglycerin had not used it at all during the preceding year. Although 89 percent of the patients claimed to know when to use the drug, 57 percent had used it or would use it for symptoms such as dizziness, rapid heartbeat, or presyncope. All patients having nitroglycerin claimed it relieved their symptoms, even if the relief was only partial, the time elapsed until relief could not be specified, and the symptoms were of a type unlikely to be relieved by the drug. We suggest that the practice of routinely prescribing nitroglycerin to patients after a myocardial infarction should be reassessed."
-What was the average age of patients with osteonecrosis in the femoral condyle of the knee in this study?,"Clinical course and roentgenographic changes of osteonecrosis in the femoral condyle under conservative treatment. The history of osteonecrosis in the femoral condyle of the knee was observed in 15 knees in 14 patients, averaging 62.8 years in age (range, 23-79 years). There were nine women and five men. The average follow-up period was 4.9 years (range, one to 12 years). Spontaneous osteonecrosis was found in 11 patients and steroid-induced osteonecrosis in three. The medial femoral condyles were involved in 13 knees and the lateral femoral condyles in two. The maximum width of the lesion was measured on anteroposterior roentgenograms and an osteonecrotic lesion less than 10 mm wide was rated as small. Cases of small osteonecrotic lesions displayed no remarkable changes with respect to stages and limb alignment. The average size of the steroid-induced osteonecrotic lesions was significantly larger than that of the spontaneous type. The size of the osteonecrotic lesions at the follow-up examination was compared to that observed at the initial diagnosis in 12 knees. Eight of these lesions displayed increases in dimension of more than 18% over the initial size at diagnosis."
-What were the potential benefits of performing combined coronary angiography and angioplasty in this study?,"Safety and cost effectiveness of combined coronary angiography and angioplasty. If coronary angioplasty can be safely performed at the time of the initial diagnostic catheterization, it may result in shorter hospitalization stays and lower overall costs. Combined coronary angiography and angioplasty was performed electively on 733 patients between January 1, 1984, and September 1, 1988. These patients were divided into three major subgroups based upon their indications for angioplasty: 444 (61%) procedures were performed for restenosis; 190 (26%) procedures were performed in patients for unstable angina; and 99 (13%) procedures were performed in patients without unstable angina or previous angioplasty. A subset of 219 patients from this study who underwent elective combined coronary angiography and angioplasty during 1986 were compared with a matched population of 191 patients from the angiography and angioplasty as separate procedures). The success and complication rates were similar for both of these groups. Patients who underwent the combined procedure were hospitalized for a mean of 4.6 days with average total charges of $11,128, compared with 8.0 days and $13,160 for patients undergoing separate procedures (p less than 0.001). Significant savings were also realized with respect to total contrast dose, fluoroscopic time, and total procedural time. Thus in informed patients with suitable coronary anatomy, the strategy of combined angiography and angioplasty may present an opportunity for decreasing hospitalization stay, reducing total charges for revascularization, and reducing radiation exposure without compromising the safety or effectiveness of the procedure."
-What was the mean follow-up period for the porous-coated total hip prostheses in this study?,"Prospective study of porous-coated anatomic total hip arthroplasty. Seventy-five uncemented porous-coated total hip prostheses were implanted in 64 patients. The results were reviewed after a mean follow-up period of 47 months (range, 40-64 months). The mean preoperative rating was fair, and the mean postoperative rating was excellent. There were six dislocations. Ten patients had mild thigh pain at one year; by two years, the pain had resolved in six patients. Neither moderate nor severe limp nor significant loosening of beads was observed. Only one patient had progressive radiolucent lines. The high rate of dislocation may be related to a compromise of acetabular position to obtain bony fixation in acetabula early in the series. The clinical results were encouraging."
-How did the natriuretic response of torasemide compare to furosemide in nonazotemic cirrhotic patients with ascites?,"Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed."
-How did early thrombolytic therapy affect the incidence of ventricular late potentials in patients after acute myocardial infarction?,"Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy. Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05)."
-What was the efficacy of aztreonam in preventing urinary tract infections following transurethral resection of the prostate (TURP) in this multicenter study?,"Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study. The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure."
-What is the significance of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in Turcot syndrome and related conditions?,"Ocular findings in Turcot syndrome (glioma-polyposis). Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps."
-What is the rare complication observed in this patient with mixed connective tissue disease?,Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease.
-What was the most common symptom among patients with lower esophageal mucosal rings in this study?,"Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring."
-What is the sensitivity and specificity of duplex scanning in detecting atherosclerotic renal artery stenosis?,"Role of duplex scanning for the detection of atherosclerotic renal artery disease. To assess the accuracy of renal artery duplex scanning for the purpose of diagnosing atherosclerotic renal artery stenosis, we compared the findings of renal arteriograms to the results of duplex scanning in 41 patients. Using an increase of renal artery peak systolic flow velocity of greater than 180 cm/sec, duplex scanning was able to discriminate normal from diseased renal arteries with a sensitivity of 95% and a specificity of 90%. Using the principle that blood flow velocity across a stenosis is roughly proportional to the degree of stenosis, it appeared that a ratio of the peak velocity in the renal artery to the aorta (RAR) of greater 3.5 predicted a greater than 60% diameter reduction of that renal artery, which is felt to be a significant stenosis. Forty-eight vessels were classified as having a greater than 60% diameter reduction by arteriography. Using the RAR of greater than 3.5, duplex scanning agreed in 44 renal arteries (sensitivity 92%). In the 26 renal arteries where arteriography showed a less than 60% diameter reduction, duplex scanning agreed in 16 vessels and correctly detected a focal narrowing in nine of the remaining ten vessels. Ten of 11 occluded renal arteries were correctly identified by duplex scanning. Duplex scanning determined the location of the renal artery lesion with an accuracy of 95% (kappa 0.74). Since duplex scanning can accurately demonstrate and locate focal renal artery stenosis, we believe it may become an accurate screening test for renovascular hypertension."
-How accurate was the high frequency epicardial echocardiography in measuring coronary artery dimensions and detecting atherosclerotic lesions compared to histopathological results?,"Histopathological validation of high frequency epicardial echocardiography of the coronary arteries in vitro. The accuracy and reliability of measurement of coronary artery dimensions and detection of atherosclerotic lesions by high frequency epicardial echocardiography were compared with histopathological results. Ten pressure perfused human hearts were examined in vitro with a 10 MHz (Diasonics) transducer and a 7.5 MHz (Vingmed/Sonotron) transducer. There was close agreement between ultrasound and pathological measurements of coronary artery luminal diameter. Qualitative changes in wall structure such as diffuse wall thickening and calcification were readily identified; however, the resolution of the transducers was not high enough accurately to measure wall dimensions in normal coronary arteries. Coefficient of variation measurements for intra and inter observer variability (5.2% and 6.9% respectively) showed excellent reproducibility. The technique was accurate in identifying atherosclerotic lesions, imaging arteries distal to an occlusion, locating deeply sited arteries, and identifying complete obliteration of an artery. Intraoperative video playback and transducer miniaturisation may minimise problems caused by cardiac movement and restricted access. With these developments intraoperative assessment of coronary artery disease may become a real possibility."
-What is the typical progression and prognosis of diabetic femoral neuropathy based on this study?,"The natural history of diabetic femoral neuropathy Diabetic femoral neuropathy is an uncommon, unpleasant and sometimes disabling condition, on account of both pain and muscular atrophy, whose long-term prognosis has not previously been documented. We have reviewed a group of 27 patients up to 14 years (median 62 months) after diagnosis; 18 of these were re-examined after an average of nearly 4 years (median 45 months). The condition was more common in non-insulin-dependent diabetics (88 per cent), in men (59 per cent) and in older patients (median age at diagnosis 64 years). The neuropathy was bilateral (10 cases) or unilateral (17 cases); five patients with unilateral neuropathy developed femoral neuropathy on the opposite side, usually within a few weeks of the first episode. Recovery was apparent after 3 months and usually complete by 18 months; only two of the 27 patients had severe relapses. No patients remained disabled, although there were minor residual symptoms and signs in half of the patients (2 cm reduction in thigh circumference and diminished reflexes). The outlook for femoral neuropathy, even in its most severe form, is therefore very good: residual features are demonstrable but do not cause symptoms, and relapses after the first few weeks are very rare."
-How did participation in a cardiac rehabilitation program affect patients' psychosocial function six months after an acute cardiac event?,"Effects of a multidimensional cardiopulmonary rehabilitation program on psychosocial function. The effects of participation in a structured, outpatient cardiac rehabilitation program on psychosocial function after acute myocardial infarction or coronary artery bypass surgery, or both, were evaluated prospectively in 141 patients who were married or living with ""a significant other"" (89% men, mean [+/- standard deviation] age 63 +/- 9 years old). Forty-one patients who were participants in a 3-month cardiac rehabilitation program were compared with 100 patients who did not participate in a formal program. On average, patients in both groups were well educated, older Caucasians who had minimal cardiac dysfunction (New York Heart Association class I or II). Patients in the 2 groups were not different at baseline in sociodemographic or clinical characteristics or in any of the dependent measures of anxiety, depression, psychosocial adjustment to illness or marital adjustment. Six months after initial testing, patients who attended cardiac rehabilitation were significantly less anxious (F[1,139] = 5.09, p = 0.03), less depressed (F[1,139] = 8.39, p = 0.004), had better psychosocial adjustment (F[1,139] = 5.87, p = 0.02), and were more satisfied with their marriages (F[1,139] = 8.6, p = 0.004) than nonparticipants. The findings support the effectiveness of group cardiac rehabilitation for this subgroup of patients in facilitating their psychosocial recovery after an acute cardiac event."
-How do the adrenal glands contribute to plasma norepinephrine concentrations during cardiopulmonary resuscitation in dogs?,"Plasma norepinephrine concentrations during resuscitation in the dog. The objective of this study was to evaluate whether the adrenal glands contribute to the increase in plasma norepinephrine concentrations during cardiopulmonary resuscitation, by releasing norepinephrine and/or by secreting epinephrine that facilitates the release of norepinephrine from sympathetic nerve endings via stimulation of presynaptic beta receptors. The experiments were performed in adrenalectomized and in sham-operated dogs. In adrenalectomized dogs the increase in plasma norepinephrine concentrations during cardiopulmonary arrest and basic life support (BLS) was markedly smaller than in sham-operated dogs. Intravenous infusion of physiologic doses of epinephrine during BLS in adrenalectomized animals did not influence the plasma norepinephrine concentrations. These data indicate that, as suggested by others, the marked increase in plasma norepinephrine concentrations during BLS in dogs is mainly of adrenomedullary origin. They also suggest that presynaptic facilitation of norepinephrine release by epinephrine is not important, but further experiments using higher doses of epinephrine are necessary."
-What defects were observed in the lymphokine-activated killer (LAK) cell generation and activity among acute leukemia patients?,"Defective lymphokine-activated killer cell generation and activity in acute leukemia patients with active disease. In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease."
-What are the two unusual features of the pharyngeal pouch carcinoma cases reported in this study?,"Pharyngeal pouch carcinoma: two unusual cases. Two patients with carcinomata arising in pharyngeal pouches are reported. In one, the tumour was detected preoperatively by a contrast radiographic study. In the second the lesion was a carcinoma in situ. The English literature is reviewed with reference to these two unusual features."
-How do middle ear inflammatory mediators potentially cause sensorineural hearing loss?,"Middle ear inflammatory mediators and cochlear function. Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study."
-What percentage of patients experienced experienced cerebrospinal fluid leaks after acoustic neuroma surgery in this study?,"Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. Cerebrospinal fluid leaks and associated meningitis are the most common life-threatening complications of surgery for acoustic neuromas. This retrospective study reviews 319 patients who had surgery for 321 acoustic tumors at the Sunnybrook Health Sciences Center, University of Toronto, from April 1975 to March 1990. Cerebrospinal fluid leaks occurred after 13.4% of primary tumor operations. Surgical repair was required in 6.2% of all patients; 4.4% needed more than one operation. Meningitis occurred in 5.3% of all patients. These complications were more common in larger tumors and after the combined translabyrinthine middle fossa approach. Transnasopharyngeal eustachian tube obliteration was used to stop recurrent cerebrospinal fluid leaks in two patients."
-What restriction endonucleases were used to detect polymorphisms in the progesterone receptor gene in this study?,"Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors. We examined the progesterone receptor (PgR) gene in tissue from both primary human breast tumors and normal placentas, detecting restriction fragment length polymorphisms (RFLPs) with the restriction endonucleases Pst I/Sst I and HindIII. There was a general agreement of the Pst I and Sst I polymorphisms in any individual tumor, suggesting that they define two alleles in the human PgR locus, one being characterized by a deletion of about 300 base pairs with respect to the other. Both primary human breast tumor specimens (n = 36) and human term placentas (n = 48) displayed similar allele frequencies and typical mendelian distribution of these Pst I/Sst I alleles. The previously reported HindIII PgR RFLP was also investigated in 132 breast tumors. The HindIII PgR gene RFLP did not display typical mendelian distribution in the breast tumors; the factors affecting the HindIII allele frequencies are presently unknown. Neither the HindIII RFLP nor the deletion defined by Pst I and Sst I correlated with PgR expression as determined by a ligand-binding assay, suggesting that neither is related to the heterogeneity of PgR expression seen in breast tumors."
-What treatment is recommended when there is clinical or investigative evidence suggesting the presence of a demyelinating disease?,"Destructive lesions in demyelinating disease. Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy."
-How do T1 and T2 relaxation times change in different myocardial layers following ischemia and reperfusion?,"Transmural distribution of myocardial edema by NMR relaxometry following myocardial ischemia and reperfusion. To determine the distribution and extent of myocardial edema resulting from ischemia and reperfusion, seven open-chest dogs underwent occlusion of the left circumflex coronary artery for 2 hours (group I), and 10 underwent occlusion for 2 hours and reperfusion for 2 hours (group II). Proton nuclear magnetic resonance spectroscopy (T1 and T2 relaxation times) and percent water content were determined to quantitate the amount of edema. There was a transmural increase of the T1 relaxation time of the central ischemic zone in groups I and II, although this increase was significantly greater in group II in both the subendocardium (group I = 707.8 +/- 12.5 msec, group II = 813.2 +/- 36.2 msec; p less than 0.01) and subepicardium (group I = 641.7 +/- 20.5 msec, group II = 760.5 +/- 34.7 msec; p less than 0.01). These increases were also observed in the T2 weighted relaxation time in the subendocardium (group I = 54.7 +/- 0.8 msec, group II = 78.7 +/- 6.3 msec; p less than 0.005) and subepicardium (group I = 54.0 +/- 1.4 msec, group II = 73.1 +/- 4.0 msec; p less than 0.001). Transmural differences were evident between the myocardial layers with increased T1 relaxation times (p less than 0.01) in the subendocardium in both groups. Similar increases were noted in the percent water content of the myocardium. Thus T1 and T2 relaxation times lengthened with an increase in myocardial water content following occlusion, and these relaxation times were augmented by reperfusion. We conclude that ischemia-induced edema occurs in a transmural distribution from subendocardium to subepicardium following occlusion, and this edema is further enhanced by reperfusion."
-What potential complication can occur in the fallopian tubes following an inguinal hernia repair?,"Tubal occlusion after inguinal hernia repair. A case report. Midtubal occlusion and infertility occurred subsequent to an inguinal hernia repair. Recognition of the traumatic etiology is important because other causes of midtubal obstruction, such as endometriosis, tuberculosis and adenomatoid tumor of the oviduct, may be considered contraindications to reconstructive surgery. Once recognized, the condition is highly amendable to microsurgical reconstruction."
-How did the use of fine catheter peritoneal cytology (FCPC) and laparoscopy help improve the management of patients with acute abdominal pain in this study?,"Role of fine catheter peritoneal cytology and laparoscopy in the management of acute abdominal pain. Laparoscopy and fine catheter peritoneal cytology (FCPC) have been advocated as aids in the assessment of acute abdominal pain. In all, 411 patients admitted to a district general hospital during a 10-month period were managed using a standard protocol incorporating these techniques. After initial assessment by a surgical registrar, 151 patients were excluded from further progress through the protocol (age less than 16 years, definite diagnosis made or contraindication to FCPC. The remaining 260 patients were placed in one of four management groups: (A) urgent operation (23 patients); (B) 'look and see' (40 patients); (C) 'wait and see' (59 patients); (D) urgent operation not indicated (138 patients). Eighty-eight of 99 patients (88 per cent) in groups B and C, where the need for operation was uncertain, underwent successful FCPC and 39 patients (39 per cent) underwent laparoscopy. In these patients the initial registrar management decision proved to be incorrect in 33 cases (33 per cent), but by following the protocol the number of management errors actually made was reduced to 13 (13 per cent, P less than 0.001). This would have been reduced to 8 per cent if the protocol had not been violated in five patients. This study demonstrates the effectiveness of a protocol using FCPC and laparoscopy to improve the management of patients with acute abdominal pain."
-"What is the association between HIV infection and Salmonella typhi or Salmonella paratyphi infections in the study conducted in Lima, Peru?","Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Eight cases of typhoid and paratyphoid fever were identified during a 4-year period in a cohort of 117 patients who were positive for human immunodeficiency virus in Lima, Peru. Asymptomatic patients with human immunodeficiency virus infection and patients with the lymphadenopathy syndrome had a typical clinical presentation and response to therapy. Patients with the acquired immunodeficiency syndrome who were culture positive for Salmonella typhi or Salmonella paratyphi presented with fulminant diarrhea and/or colitis; the two patients for whom at least 2 months of follow-up were available relapsed. In our cohort there were 0.06 cases of typhoid or paratyphoid per patient year of observation; this rate is approximately 60 times that in the general population in Lima, and 25 times that in the 15- to 35-year-old age group. Our data indicate that patients who are positive for human immunodeficiency virus are at significantly increased risk for infection with S typhi and S paratyphi, and suggest that the clinical presentation of these diseases in patients with the acquired immunodeficiency syndrome differs from that seen immunocompetent hosts."
-What are the comparative outcomes of extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrostolithotomy in treating stone-containing caliceal diverticula?,"The roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in the management of pyelocaliceal diverticula. Various combinations of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy were used in the treatment of 40 stone-containing caliceal diverticula in 39 patients (16 men and 23 women). Only 1 of 26 patients (4%) treated with ESWL as a single modality became stone-free, although 9 (36%) became asymptomatic. Ten patients undergoing ESWL primarily eventually required percutaneous nephrostolithotomy due to persistence of symptoms and all became stone-free. A total of 14 patients underwent a percutaneous approach as a single modality, and the diverticula in 13 of these patients became stone-free, although 2 patients did have residual parenchymal fragments. Therefore, 21 of 24 patients (87.5%) became completely free of stones using the percutaneous approach. All patients managed with percutaneous nephrostolithotomy became free of symptoms. The complex nature of access during percutaneous nephrostolithotomy favors a 1-stage approach with direct puncture into the stone-containing diverticulum. Simultaneous fulguration of the diverticulum at percutaneous nephrostolithotomy is favored, since all 17 patients in whom this technique was used had complete obliteration of the diverticulum on followup contrast studies. These data suggest that caliceal diverticula should be managed with percutaneous nephrostolithotomy, since ESWL monotherapy is unlikely to produce a stone-free or symptom-free status."
-What was the impact of optimal debulking surgery on survival rates in patients with advanced ovarian cancer across different chemotherapy trials?,"Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery. The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin."
-What are the most common menstrual symptoms associated with pelvic endometriosis according to the study?,"Menstrual symptoms in women with pelvic endometriosis. OBJECTIVE--To investigate menstrual symptoms in relation to pelvic pathology. DESIGN--A prospective questionnaire-based study. SETTING--Aberdeen Royal Infirmary, Scotland. SUBJECTS--1250 questionnaires were sent out prior to planned admission and 1200 women (96%) brought the completed questionnaires. They comprised 598 women undergoing laparoscopic sterilization, 312 having laparoscopy because of infertility, 156 having laparoscopy because of chronic pelvic pain and 134 women undergoing abdominal hysterectomy for dysfunctional uterine bleeding. MAIN OUTCOME MEASURES--The occurrence of dysmenorrhoea, menorrhagia, menstrual regularity, premenstrual spotting, deep dyspareunia and pelvic pain in women with either endometriosis and post infective pelvic adhesions or a normal pelvis. RESULTS--Menorrhagia, menstrual irregularity and premenstrual spotting occurred with equal frequency in all groups. Deep dyspareunia, pain after intercourse and recurrent pain unrelated to menstruation or coitus was more common in women with endometriosis and those with post infective pelvic adhesions than in those with a normal pelvis. Dysmenorrhoea appears to be more prevalent among women having endometriosis. CONCLUSIONS--Menstrual symptoms, while raising a high index of suspicion for endometriosis, are not entirely reliable as indicators of disease. Dysmenorrhoea is the most common reported symptom in endometriosis sufferers. Diagnostic laparoscopy should be considered before institution of treatment in women complaining of pelvic pain and menstrual symptoms."
-How do the surface markers of monocytes change during in vitro maturation to macrophages?,"In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection. In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates."
-What was the main strategy used for managing distal ileal Crohn's disease in this study?,"Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy."
-What potential risks are associated with topical diphenhydramine administration in children with varicella-zoster infection?,"Diphenhydramine toxicity in three children with varicella-zoster infection. Diphenhydramine hydrochloride is an antihistamine with anticholinergic properties that is frequently used both orally and topically for the temporary relief of pruritus. Significant systemic absorption may occur following topical administration of diphenhydramine in patients with varicella-zoster lesions. We describe three children with varicella-zoster infection (VZI) who developed bizarre behavior as well as visual and auditory hallucinations following topical applications of large amounts of diphenhydramine to the majority of skin surfaces. In two cases, oral diphenhydramine was also administered. Serum diphenhydramine concentrations approximated or exceeded those previously reported. In each case, a complete resolution of mental status abnormalities occurred within 24 hours after discontinuation of all diphenhydramine-containing products. Pharmacists and other health professionals should be aware of the potential toxicity of topical diphenhydramine in patients with VZI."
-What medical conditions were the patients treated for before experiencing cerebral vasospasm?,Symptomatic cerebral vasospasm following tumor resection: report of two cases. The authors report two cases of symptomatic cerebral vasospasm following resection of an acoustic neuroma and a left sphenoid wing meningioma. Vascular spasm was documented by transcranial Doppler and angiography studies. Both patients responded to hypervolemic therapy. Possible mechanisms contributing to this rare complication are discussed.
-How does the posterior cricoarytenoid (PCA) muscle activity change during different breathing conditions in normal adults?,"Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation. The effect of isocapnic hypoxia and hyperoxic hypercapnia on the electrical activity of the posterior cricoarytenoid (PCA) muscle was determined in eight normal adult humans by use of standard rebreathing techniques and was compared with PCA activity during voluntary hyperventilation performed under isocapnic and hypocapnic conditions. PCA activity was recorded with intramuscular hooked-wire electrodes implanted through a fiberoptic nasopharyngoscope. During quiet breathing in all subjects, the PCA was phasically active on inspiration and tonically active throughout the respiratory cycle. At comparable increments in respiratory output, hypercapnia, hypoxia, and voluntary hyperventilation appeared to be associated with similar increases in phasic or tonic PCA activity. During quiet breathing, the onset of phasic PCA activity usually occurred before inspiratory airflow and extended beyond the start of expiratory airflow. The duration of phasic PCA preactivation and postinspiratory phasic PCA activity remained unchanged during progressive hypercapnia and progressive hypoxia. The results, in combination with recent findings for vocal cord adductors, suggest that vocal cord position throughout the respiratory cycle during hyperpnea is actively controlled by simultaneously acting and antagonistic intrinsic laryngeal muscles."
-What was the diagnostic approach and treatment for the patient with isolated adrenal cryptococcosis?,"Isolated cryptococcosis of the adrenal gland. A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination."
-What was the primary finding of the multicenter trial regarding dexamethasone therapy in neonates with chronic lung disease?,"Dexamethasone therapy in neonatal chronic lung disease: an international placebo-controlled trial. Collaborative Dexamethasone Trial Group. In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups."
-What were the hemodynamic effects of desmopressin administration in patients undergoing coronary artery bypass grafting?,"Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass. Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078)."
-What makes cutaneous metastasis from papillary thyroid carcinoma rare and challenging to diagnose?,"Cutaneous metastasis from papillary carcinoma of the thyroid gland. Cutaneous metastases from carcinoma of the thyroid gland are rare. We present the clinical, histologic, and immunohistochemical features of a solitary metastasis from papillary carcinoma of the thyroid. Our results indicate that this tumor can produce epithelial mucin and, therefore, must be differentiated from other metastatic carcinomas and from primary apocrine tumors of the skin. Positive staining for thyroglobulin confirmed the diagnosis in this case."
-What were the main findings of the histopathologic analysis of 204 fibrous gingival lesions?,"Fibrous lesions of the gingiva: a histopathologic analysis of 204 cases. Two hundred four cases of fibrous lesions of the gingiva were studied histologically for the presence of calcified tissue, the nature of the connective tissue, the type of keratinization, and the degree of epithelial thickness. Initially these lesions were subcategorized into four specific entities, namely fibrous epulis, fibroepithelial polyp, calcifying fibroblastic granuloma, and ossifying fibrous epulis. It was found that 46.5% of the lesions contained calcifications. The connective tissue was represented predominantly by either the collagenous type (50.5%) or the mixed (cellular and collagenous) type (44.6%). It was also found that 36% of the lesions were ulcerated, and, of these, 79.5% were associated with the cellular type of connective tissue and calcifications. In an attempt to subcategorize the fibrous lesions into specific entities, it was found that 32 cases (15.7%) had mixed features. This fact supports the suggestion that these lesions are stages in the spectrum of a single disease process and should collectively be termed fibroblastic gingival lesions. However, it is also suggested that the two terms, namely peripheral fibroma and fibrous epulis with and without ossification, should be retained whereas the usage of other terminologies should be avoided."
-What is the significance of ipsilateral breast tumour recurrence (IBTR) in relation to distant disease risk after breast cancer treatment?,"Significance of ipsilateral breast tumour recurrence after lumpectomy. Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy."
-What was the prevalence of peripheral neuropathy in the Parsi community of Bombay according to the survey?,"Prevalence of peripheral neuropathy in the Parsi community of Bombay. We carried out a door-to-door survey to screen for neurologic diseases, including peripheral neuropathy, in a community of 14,010 Parsis living in housing colonies in Bombay, India. The most common neurologic disorder was peripheral neuropathy with 334 cases (2,384 cases/100,000 population). The most common neuropathy was compressive, with diabetes the most common noncompressive etiology. There was no leprosy, and nutritional neuropathies were rare."
-What was the response rate to preoperative chemotherapy in patients with esophageal adenocarcinoma in this pilot study?,"A pilot study of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and postoperative radiation therapy and/or chemotherapy in adenocarcinoma of the esophagus. Fifteen patients with potentially resectable adenocarcinoma of the esophagus were treated with two cycles of preoperative chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP). Response to chemotherapy was evaluated by comparative barium swallow, computerized chest tomography, esophagoscopy, and change in clinical symptomatology. Eleven patients (73%) were resected, two (13%) were explored and found inoperable, and two (13%) were not subjected to surgery (one because of death related to toxicity and one due to progressive disease). Ten of eleven patients (91%) had gross residual tumor. One patient (9%) had residual microscopic disease only. One patient (7%) had complete clinical responses (CCR), five (33%) had partial clinical response (PCR), and nine (60%) had no response (NR). Five of 15 patients (or 45% of resected patients) remain free of disease. Median survival time was 18.47 months for all patients and 23.83 months for resected patients."
-What are the characteristic symptoms of a duodenobronchial fistula?,"Duodenobronchial fistula. Duodenobronchial fistulas are an extremely rare subgroup of abdominobronchial fistulas, which include bronchobiliary, gastrobronchial, enterobronchial, colobronchial, and splenobronchial fistulas. Only one case of a duodenobronchial fistula has been previously reported. Duodenobronchial fistulas occur as a complication of a duodenal injury. The characteristic symptoms are a cough that produces copious bilious secretions, shortness of breath, and fever. The diagnosis is made by contrast gastrointestinal studies. Treatment requires an abdominal approach with interruption of the fistula at its duodenal origin and control of the inciting inflammatory process. With prompt diagnosis and treatment, thoracic drainage or pulmonary resection should not be needed."
-What is a peritoneopericardial diaphragmatic hernia and how was it discovered in this particular case?,"Peritoneopericardial diaphragmatic hernia discovered at coronary bypass operation. A 68-year-old man was discovered to have a large peritoneopericardial hernia when operated on for coronary artery bypass. Such hernias are very unusual. The pathogenesis, clinical presentation, and management of this problem are discussed."
-What is the mortality rate and morbidity rate in the study of 23 patients with acute necrotizing pancreatitis?,"Acute necrotizing pancreatitis: management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. We reviewed our recent experience with management of 23 consecutive patients with acute necrotizing pancreatitis. All patients had documented necrotizing pancreatitis with parenchymal or peripancreatic necrosis. Our method of treatment has evolved from our previous approach of controlled open lesser sac drainage (marsupialization) to staged necrosectomy/debridement with delayed primary closure over drains. With this latter approach, hospital mortality was 4 of 23 patients (17 per cent), but significant morbidity still occurred in 12 of 23 patients (52 per cent). However, recurrent intra-abdominal abscess before discharge occurred in only one patient. We believe that this operative approach toward the severely ill patient with acute necrotizing pancreatitis who requires operative intervention will minimize the occurrence of intra-abdominal sepsis."
-What makes CT imaging of pancreatic diseases in children different from adults?,"CT of the pancreas in children. CT has become a frequently used imaging method for evaluating suspected pancreatic disease in children. Although the spectrum of CT findings in pancreatic disease is well documented in adults, there is a paucity of such information in children. Familiarity with CT patterns of pancreatic disease in childhood is important for diagnosis. In this essay, we illustrate the CT findings of pancreatic lesions in children."
-What surgical technique improvements were made in treating pectus excavatum over a 15-year period?,"Pectus excavatum: a 15-year perspective. Pectus excavatum is relatively uncommon. Our experience with 177 children during a 15-year period produced changes in our surgical technique, which now includes a small transverse incision, minimal subcutaneous flap elevation, a muscle-relaxing incision over the fifth costal cartilage, complete resection of involved cartilage, use of Adkins' strut, suspension of sternum to strut, taut reefing of intercostal muscle, no tubes or drains, epidural analgesia, a patient-controlled analgesia device postoperatively, and eventual strut removal. Use of the evolved technique gives excellent cosmetic results, good functional results with minimal discomfort, and a shorter convalescent period."
-What is a false aneurysm of the right internal mammary artery and how is it related to median sternotomy?,False aneurysm of the right internal mammary artery. False aneurysm of the internal mammary artery is an uncommon complication of median sternotomy. Clinical and radiological findings of 2 such cases are presented. At operative exploration neither was directly related to the presence of a sternal wire.
-How does the concentration of inspired CO2 (FICO2) affect cardiac resuscitation in the experimental rat model?,"Hypercarbic acidosis reduces cardiac resuscitability. BACKGROUND AND METHODS: Marked increases in myocardial hypercarbia and acidosis accompany cardiac arrest and resuscitation. To investigate whether hypercarbic acidosis independent of oxygenation is of itself detrimental to cardiac resuscitation, three groups of six Sprague-Dawley rats were ventilated with gas mixtures containing concentrations of inspired CO2 (FICO2) of 0.0, 0.3, or 0.5, with oxygen fractions held constant at 0.5. After 4 mins of ventricular fibrillation, mechanical chest compressions were initiated with a pneumatic thumper; 2 mins later, transthoracic defibrillation was attempted. RESULTS: Each animal ventilated with FICO2 of 0.0 or 0.3 was successfully resuscitated. However, none of the animals ventilated with FICO2 of 0.5, in which aortic pH was less than 6.67 and aortic PCO2 was greater than 200 torr (greater than 26.7 kPa), was resuscitated (p less than .001). This finding contrasted with a second control group of seven identically treated animals which, in the absence of cardiac arrest, demonstrated no adverse effects after ventilation with an FICO2 of 0.5. CONCLUSIONS: Increases in FICO2 to levels of 0.5 under conditions of constant arterial oxygenation and controlled coronary perfusion pressure preclude successful resuscitation in this rodent model of CPR."
-What is the effectiveness of endoscopic balloon dilatation in managing intestinal strictures caused by Crohn's disease?,"Endoscopic balloon dilatation as a therapeutic option in the management of intestinal strictures resulting from Crohn's disease. Endoscopic balloon dilatation was undertaken in seven patients who presented with obstructive symptoms resulting from Crohn's disease. Five patients had strictures from recurrent disease at the site of an ileotransverse anastomosis, one had duodenal stenosis and one a colonic stricture. The procedures were performed under intravenous sedation on one to four occasions (median 2) and were uncomplicated. Sustained improvement over an 18-24-month follow-up period was achieved in five patients, but dilatation was unsuccessful in two cases. Endoscopic balloon dilatation is a safe and effective option in selected patients with intestinal strictures resulting from Crohn's disease and may overcome the need for surgery."
-What method is considered the definitive study for evaluating the integrity of breast implants?,"Definitive diagnosis of breast implant rupture by ultrasonography. Silicone breast implantation is entering its fourth decade. Our ability to monitor the integrity of ""old"" prostheses is questioned. Clinical and mammographic examinations are reliable indicators of implant rupture only if there has been gel migration away from the implant pocket. Ultrasonography is presented as a reliable, sensitive method of evaluation of implant integrity. It should be considered the definitive study of prosthesis integrity. When sonography is added to mammographic and clinical examination, the preoperative evaluation of symptomatic augmented breasts is complete. Ultrasonography may be considered with mammography in the routine breast examination of all previously augmented patients."
-What are the key principles of managing external abdominal fistulas arising from the digestive tract?,"External fistulas arising from the digestive tract. External abdominal fistulas that arise from the digestive tract are associated with high mortality and prolonged morbidity in terms of infection, malnutrition, and skin excoriation. Such external fistulas most commonly follow anastomotic leak after gastrointestinal surgery. We identified 58 patients seen over a 5-year period at the University of Louisville Hospitals because of external abdominal fistulas that arose from the stomach (8), duodenum (4), small intestine (26), colon (14), biliary tract (9), and pancreas (7). Fifteen patients had multiple fistulas and 32 had high-output fistulas (greater than 200 mL/day). Closure was achieved in 48 patients, and eight of the 10 patients whose fistulas remained open died. Overall mortality was 19%. Principles of management include control of infection, correction of fluid and electrolyte imbalance, nutritional support, proper wound care, and often operative intervention. Multiple staged operations over many months were particularly important in managing complex wounds with large abdominal wall defects and multiple fistulas. Fistula closure is the ultimate goal, and patience is important to achieve it."
-What treatment was found to be effective in managing neurogenic pulmonary edema in a patient with subarachnoid hemorrhage?,"Neurogenic pulmonary edema: treatment with dobutamine. In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema."
-What complications did the patient develop after receiving a continuous IV infusion of vasopressin?,"Rhabdomyolysis and cutaneous necrosis following intravenous vasopressin infusion. A continuous IV infusion of vasopressin was administrated to a patient with cirrhosis of the liver and acute gastrointestinal bleeding from esophageal varices. In the first 24 hours, the patient developed rhabdomyolysis and cutaneous necrosis. Stopping vasopressin infusion resulted in relief of these lesions. The rarity of these complications suggests an idiosyncratic reaction of susceptible individuals that may be related to previous vascular disease or a failure in baroreceptor regulation."
-What are the key mental health benefits of regular aerobic exercise?,"Health benefits of aerobic exercise. Regular aerobic exercise has significant cardiovascular benefits, including a reduction in incidence of and mortality from coronary artery disease--probably because of positive effects on blood lipid levels and blood pressure. Aerobic exercise can also be an important adjunct to a weight-loss program. Many persons who continue an exercise program do so because of its positive mental benefits, including reduction in anxiety and depression and modulation of stress levels. Aerobic exercise has a place in the management of diabetes, pregnancy, and aging. The problems associated with aerobic exercise are minimal compared with its benefits."
-What makes low back pain a challenging diagnosis in emergency department settings?,"Low back pain: review of diagnosis and therapy. Low back pain is a patient complaint frequently encountered in the emergency department setting. The disease entity is often a diagnostic challenge with a subtle presentation, but can be accompanied by significant neurovascular complications. Current topics of controversy include the utility of radiologic evaluation, pharmacologic and holistic treatment strategies, as well as guidelines for urgent referral of patients with lumbar pain."
-How does Color Doppler imaging help in assessing orbital blood flow in carotid artery disease?,"Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease. Color Doppler imaging was used to evaluate the hemodynamics of the ophthalmic vasculature in a case of complete internal carotid artery occlusion. This procedure, which allows rapid, noninvasive imaging, showed a partial ophthalmic artery obstruction with absent flow in the central retinal artery, central retinal vein, and nasal posterior ciliary arteries. Although altered perfusion of the retinal vessels may be evaluated clinically, assessment of blood flow in the ophthalmic and ciliary arteries previously could be evaluated only indirectly by intravenous fluorescein angiography. The color Doppler imaging findings were confirmed by intravenous fluorescein angiography and carotid arteriography. Color Doppler imaging represents a noninvasive method to diagnose abnormal blood flow of the ophthalmic artery and its branches and to evaluate serial changes of the circulation in a noninvasive manner."
-What CT scan findings are associated with a higher probability of hypovolemia in patients with subarachnoid hemorrhage?,"Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia."
-What are the key differences in spinal nerve sheath tumors between patients with neurofibromatosis type 1 and type 2?,"Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2. Benign spinal nerve sheath tumors (neurofibromas and schwannomas) often occur on dorsal nerve roots sporadically or in neurofibromatosis types 1 and 2. These are histologically benign tumors, and distinction between them is frequently not made by clinicians. To determine if there is a correlation between the histological pattern of benign spinal nerve sheath tumors and the type of neurofibromatosis, the clinical and pathological features of these tumors (86 surgical specimens and five autopsies) in 68 patients were reviewed. The patients were classified into one of four categories: neurofibromatosis type 1, neurofibromatosis type 2, uncertain, or sporadic. The diagnostic criteria used for neurofibromatosis types 1 and 2 were established by the National Institutes of Health. Patients who did not fulfill criteria for either neurofibromatosis type 1 or 2 but who had multiple nervous system tumors or other stigmata of neurofibromatosis were designated ""uncertain."" Spinal nerve sheath tumors were considered sporadic in 42 cases (40 schwannomas and two neurofibromas). In the 14 patients with neurofibromatosis type 1, all spinal nerve sheath tumors were neurofibromas. In six of the seven patients with neurofibromatosis type 2, all spinal nerve sheath tumors were schwannomas. One patient with neurofibromatosis type 2 had a spinal nerve sheath schwannoma and a tumor with features of both tumor types. The authors conclude that spinal nerve sheath tumors in patients with neurofibromatosis type 1 are neurofibromas. In contrast, spinal nerve sheath tumors occurring in neurofibromatosis type 2 or sporadically are most frequently schwannomas. The distinct histological features of these tumors may reflect different pathogenetic mechanisms even though they arise at identical sites in neurofibromatosis types 1 and 2."
-What were the key findings comparing surgically treated and untreated patients with spinal stenosis?,"The effect of decompression on the natural course of spinal stenosis. A comparison of surgically treated and untreated patients. The clinical course of 19 untreated patients with spinal stenosis (mean age, 60 years) was compared with that of 44 patients treated surgically (mean age, 65 years). The time of follow-up was 31 and 53 months, respectively. About 80% of the patients had neurogenic intermittent claudication. In the follow-up, one third of the treated and one half of the untreated patients still had neurogenic claudication. By visual analogue-scale estimation, 60% of those treated surgically and 33% of the untreated patients felt better. Fifty-eight percent of the untreated patients were unchanged. Neurophysiologic changes showed progression in almost all cases; it was more pronounced in the treated patients. No proof of severe deterioration was found in the untreated patients, and observation for 2-3 years seems to be a good alternative to surgery."
-How does monitoring cerebral oxygenation help in managing patients with acute severe closed head trauma?,"Continuous monitoring of cerebral oxygenation in acute brain injury: injection of mannitol during hyperventilation. Global cerebral oxygenation, perfusion pressure, and expired pCO2 were continuously monitored in 10 adults with acute severe closed head trauma. Cerebral oxygenation was monitored by fiberoptic catheter oximetry, which allowed simultaneous measurements of arterial and jugular bulb oxyhemoglobin saturation. Intracranial pressure levels over 20 mm Hg were recorded several times in all patients, in spite of sedation, muscle paralysis, and profound hyperventilation. Intracranial hypertension was frequently associated with oligemic cerebral hypoxia, identified as abnormally low jugular oxygen saturation in the presence of normal arterial oxygenation. Intracranial hypertension was then managed with intravenous administration of mannitol boluses, which yielded simultaneous decreases in intracranial pressure and increases in cerebral oxygenation to highly statistically significant levels. Monitoring cerebral oxygenation was clinically useful because it allowed identification of impaired cerebral oxygenation even when cerebral perfusion pressure was normal. It is therefore proposed as a new monitoring technique, to supplement conventional monitoring of cerebral perfusion pressure."
-What were the key findings of the study on chronic neurological effects of acute organophosphate pesticide intoxication in Nicaraguan agricultural workers?,"Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group. Acute organophosphate pesticide poisonings cause substantial morbidity and mortality world wide; however, whether organophosphates cause chronic neurological sequelae has not been established. To see whether single episodes of acute unintentional organophosphate intoxication lead to chronic neuropsychological dysfunction, we carried out a retrospective study of agricultural workers in Nicaragua who had been admitted to hospital between July 1, 1986, and July 31, 1988, for occupationally related organophosphate intoxication. This ""poisoned"" group (36 men) was tested on average about two years after the episode of pesticide poisoning and compared with a matched control group. The poisoned group did much worse than the control group on all neuropsychological subtests, with significantly worse performance on five of six subtests of a World Health Organisation neuropsychological test battery and on 3 of 6 additional tests that assessed verbal and visual attention, visual memory, visuomotor speed, sequencing and problem solving, and motor steadiness and dexterity. Differences in neuropsychological performance could not be explained by other factors. The findings of a persistent decrease in neuropsychological performance among individuals with previous intoxication emphasise the importance of prevention of even single episodes of organophosphate poisoning."
-What was the accuracy of fine needle aspiration (FNA) cytology in differentiating between benign and malignant pancreatic lesions in this study?,"Preoperative and intraoperative fine needle aspiration cytology of pancreatic lesions. The aim of the present study was to describe our experience from 1976 through 1988 with fine needle aspiration (FNA) cytology of pancreatic lesions in 90 patients. Fine needle aspirations were performed preoperatively under ultrasound guidance (USG) in 46 patients, under computed tomographic guidance (CTG) in seven patients, and intraoperatively in 37 patients. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 80 patients, of whom 62 had malignant pancreatic disease (MPD) and 18 had benign pancreatic disease (BPD). The accuracy of cytologic diagnoses was verified by histologic, cytologic, and clinical findings. In 62 patients with MPD, the cytologic findings suggested malignancy in 54 patients, suspected malignancy in five, and did not reveal malignancy in three patients. Among 18 patients with BPD, all of the cytologic findings were reported as benign. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for intraoperative FNA cytologic results were 96%, 100%, 100%, 91%, and 97%, respectively, and for USG FNA cytologic results were 94%, 100%, 100%, 78%, and 95%, respectively. No complications followed the procedure. Conclusions: Both transabdominal percutaneous imaging-guided and intraoperative FNA cytology of pancreatic lesions are simple, safe, and highly accurate methods in differentiation of benign from malignant pancreatic lesions."
-What measures have been used to reduce the incidence of stress erosive gastritis in critically ill patients?,"Stress erosive gastritis. Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention."
-What were the key findings of autonomic function studies in patients with Friedreich's ataxia?,"Autonomic function in Friedreich's ataxia. Autonomic function studies were performed on 15 patients with Friedreich's ataxia, and the results compared with those of 76 healthy subjects. There was an increase in resting supine heart rate, attributed to cardiac abnormalities. Other tests of sympathetic and parasympathetic function were normal. The normal autonomic function studies are consistent with the pathological findings of degeneration predominantly of large diameter myelinated fibres with sparing of small myelinated and unmyelinated fibres."
-What was the incidence of tracheostomal stenosis in patients who underwent total laryngectomy with immediate tracheoesophageal puncture compared to the control group?,"Tracheostomal stenosis after immediate tracheoesophageal puncture. The incidence of tracheostomal stenosis in a group of patients after total laryngectomy with or without pharyngectomy plus immediate tracheoesophageal or tracheogastric puncture was compared with that of a control group without puncture. The stenosis rate of the puncture group was significantly higher than that of the control group (19% vs 6%). The other probable etiologic factors for stomal stricture were similar in both groups. Analysis of the risk factors in the puncture group suggested a higher tendency of stenosis in females (43% vs 16%) and in patients receiving postoperative radiotherapy (29% vs 14%), although the difference failed to reach statistical significance."
-What was the primary objective of the Systolic Hypertension in the Elderly Program (SHEP) study?,"Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group OBJECTIVE.--To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. DESIGN.--Multicenter, randomized, double-blind, placebo-controlled. SETTING.--Community-based ambulatory population in tertiary care centers. PARTICIPANTS.--4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. INTERVENTIONS.--Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. MAIN OUTCOME MEASURES.--Primary.--Nonfatal and fatal (total) stroke. Secondary.--Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. RESULTS.--Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. CONCLUSION.--In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000."
-What were the two antibiotic regimens compared in this clinical trial for treating children with ruptured appendicitis?,"A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis. This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis. Ninety-seven children were randomized. Forty-seven were assigned to the AGC regimen and 50 received CC. Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS). There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization. Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint. We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy."
-What are the limitations of physical examination techniques in diagnosing splenomegaly according to the context?,"The clinical diagnosis of splenomegaly. Assessing for the presence of splenomegaly is an important component of the physical examination. Although several methods of palpation and percussion of the spleen have been described, until recently they have not been validated by noninvasive imaging techniques such as ultrasonography, radionuclide scanning, and computed tomography that offer objective means to assess splenomegaly. We review the literature comparing various physical examination techniques with noninvasive imaging modalities and conclude that palpation and percussion of the spleen are complementary but frequently insensitive and that further studies are needed to evaluate the efficacy of specific diagnostic methods."
-What are the various surgical procedures recommended for treating cubital tunnel syndrome?,"The failed ulnar nerve transposition. Etiology and treatment. Various procedures have been recommended for the treatment of cubital tunnel syndrome. Simple decompression in situ, medial epicondylectomy, subcutaneous transposition, intramuscular transposition, and submuscular transposition all have their advocates. The results of the surgical treatment for cubital tunnel syndrome are related to the severity of the compressive neuropathy at the time of diagnosis and to the adequate decompression of the nerve at all sites of potential compression at the time of surgical treatment. Fourteen patients who had previously undergone surgical treatment for cubital tunnel syndrome were evaluated because of persistent pain, paresthesia, numbness, and motor weakness. All patients had documented persistent compression of the ulnar nerve on clinical and electromyographic evaluation. The indication for repeat surgical exploration in all patients was unremitting pain despite nonoperative treatment. All patients had been treated by neurolysis and submuscular transposition of the ulnar nerve as described by Learmonth. The causes of continued pain after initial surgery included retention of the medial intermuscular septum, dense perineural fibrosis of the nerve after intramuscular and subcutaneous transposition, adhesions of the nerve to the medial epicondylectomy site, and recurrent subluxation of the nerve over the medial epicondyle after subcutaneous transposition. Revision surgery was found to be highly successful for relief of pain and paresthesias; however, the recovery of motor function and return of sensibility were variable and unpredictable."
-How does verapamil help protect against renal injury at the cellular level?,"Role of calcium channel blockers in protection against experimental renal injury. The available evidence indicates that the first generation calcium channel blocker verapamil has a protective effect against both acute and chronic renal failure. At the cell membrane, verapamil helps minimize the effects of excess calcium influx after ischemic injury, evidenced by reduced uptake of 45Ca, thus lessening tubular injury from both calcium-activated phospholipases and mitochondrial calcium overload. In experimental chronic renal failure, the long-term administration of verapamil protects against renal dysfunction and damage, independent of any effect on systemic mean arterial pressure. Protective effects of verapamil are delineated in several models, supporting the presented hypothesis of the pathogenesis of renal failure."
-What was the clinical significance of microsporidia detection in HIV-1-infected patients with chronic diarrhoea?,"Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals To assess the importance of microsporidiosis of the small intestine in the pathogenesis of chronic diarrhoea in HIV-1-infected individuals, duodenal biopsy samples from the following three patient groups were prospectively evaluated for bacterial, viral, and parasitic pathogens by standard methods, and for microsporidia by light microscopy: 55 consecutive HIV-1-antibody-positive subjects with unexplained diarrhoea of at least 3 weeks duration (group A); 38 HIV-1-seropositive subjects without diarrhoea (group B) who consecutively underwent upper gastrointestinal endoscopy for various reasons; and 7 patients without known risk factors for HIV infection with chronic unexplained diarrhoea (group C). In groups A and B most subjects had had previous AIDS-defining opportunistic infections and the median peripheral blood CD4 lymphocyte count was less than 0.1 x 10(9)/l. Microsporidia were detected as the single pathogen in 15 of the group A compared with 1 (in whom diarrhoea subsequently developed) of the group B patients (p = 0.001) and none of the group C patients. With the exception of 4 of the group A patients, no other intestinal pathogens were identified in any of the patients. The median peripheral blood CD4 count was significantly lower in patients with detectable microsporidia than in those without microsporidiosis (0.03 x 10(9)/l vs 0.06 x 10(9)/l; p = 0.03); in all patients with microsporidiosis, the CD4 count was equal to or less than 0.1 x 10(9)/l. 13 patients with microsporidiosis were treated with metronidazole, in 10 of whom treatment led to a substantial improvement or disappearance of diarrhoea within days of starting therapy, but did not result in eradication of the parasite in the 5 patients who underwent repeat biopsy. The findings suggest that small-intestinal microsporidiosis is an important cause of chronic unexplained diarrhoea in HIV-1-infected individuals with pronounced cellular immune deficiency. This infection should therefore be added to the list of AIDS-defining opportunistic infections."
-What are the key differences in vascular reactivity between norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure?,"Differences in vascular reactivity in models of ischemic acute renal failure. To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded."
-What is the significance of S100-positive sustentacular cells in determining the malignancy of pheochromocytomas?,"S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. The absence or presence of S100-positive sustentacular cells has been previously shown to be correlated with benign and malignant pheochromocytomas and paragangliomas. We evaluated a total of 17 malignant and recurrent or locally aggressive adrenal pheochromocytomas for their quantity of sustentacular cells. An absence of sustentacular cells was demonstrated in the majority of malignant cases, while the locally aggressive or recurrent group usually contained an abundance of these cells. However, in one malignant case a constant moderate number of sustentacular cells in the primary site and in two sequential metastases was found. We conclude that the absence of sustentacular cells in pheochromocytomas may indicate a lesion with a greater potential for metastasis and that sustentacular cells, when they are present in a malignant pheochromocytoma, are an integral part of the tumor."
-What is the proposed solution for facilitating Nd-YAG laser hyaloidotomy in eyes prone to developing malignant glaucoma after surgery?,"Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation. Three cases of malignant glaucoma following extracapsular cataract extraction with 7 mm one-piece posterior chamber intraocular lens implantation are presented. Nd-YAG laser hyaloidotomy was successfully performed in all eyes, but was difficult and required several sessions in two eyes. In the third eye, which had a sector iridectomy, laser hyaloidotomy applied over the edge of the lens optic through the iridectomy resulted in brisk deepening of the anterior chamber and reduction of intraocular pressure. We propose that the one-piece 7 mm optic posterior chamber intraocular lens may constitute an obstacle to successful hyaloidotomy, mainly owing to its large size, as it may block aqueous percolation from the vitreous into the anterior chamber. Eyes prone to develop malignant glaucoma after surgery should have a sector or large peripheral iridectomy to facilitate postoperative Nd-YAG laser hyaloidotomy if required."
-What were the main indications for emergency pulmonary resection in the patients described in this context?,"Emergency pulmonary resection for pneumonia. High morbidity and mortality. Emergency pulmonary resection was performed because of complicated pneumonia in eight patients (5 pneumonectomies, 2 lobectomies, 1 bilobectomy) over a 2-year period. The patients' age range was 5 months to 43 years. The indications were rapid aggravation of respiratory insufficiency in children with staphylococcal pneumonia and enlarging pneumatoceles, and massive hemoptysis in patients with chronic destructive pneumonia. Two patients died after pneumonectomy, one from contralateral aspiration and one from cardiogenic shock. Postoperative complications occurred in four cases--bronchopleural fistula and pyopneumothorax in three and thoracic empyema with massive chest-wall infection in one. Only two patients had an uneventful postoperative course. Complications of pulmonary necrosis in pneumonia may dictate urgent pulmonary resection, often pneumonectomy. Surgery will be life-saving in most cases, but high morbidity is to be expected."
-What are the key risk factors for myocardial rupture after acute myocardial infarction?,"Myocardial rupture. Your patient's survival may depend on you. Myocardial rupture is the second leading cause of in-hospital death from acute myocardial infarction. It is most likely to occur in the elderly, women, and patients with transmural infarction and no previous history of angina. A high index of suspicion is critical to the diagnosis. Myocardial rupture should be suspected when recurrent chest pain or hemodynamic instability develops after myocardial infarction. Rapid intervention and appropriate infarct-limiting therapy may reduce the mortality rate of this catastrophic complication."
-What are the key contributing factors for developing an abdominal wall Actinomyces abscess associated with an intrauterine device?,"Abdominal wall Actinomyces abscess associated with an intrauterine device. A case report. An abdominal wall Actinomyces abscess occurred in a woman with an intrauterine device. Contributing factors were local trauma, spread from surrounding colonized body sites and symbiotic growth of other anaerobes. The diagnosis was based on the histologic finding of the sulfur granule. Special studies may be needed to distinguish this condition from other, similar ones (Nocardia, botryomycosis)."
-How does radionuclide ventriculography help in assessing prognosis after acute myocardial infarction?,"Radionuclide assessment of ventricular function and risk stratification after myocardial infarction. Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction."
-What uncommon complication occurred in a 38-year-old woman 7 days after lumbar myelography with iohexol?,"Intracerebral hemorrhage after lumbar myelography with iohexol: report of a case and review of the literature. Intracranial hemorrhage is an uncommon complication of dural puncture. In most instances, hematomas are subdural; they may be unilateral or bilateral. Rarely are intraparenchymal cerebral hemorrhages related to dural puncture. This report describes a delayed occurrence of bilateral intraparenchymal hemorrhages in a 38-year-old woman 7 days after lumbar myelography with iohexol. A review of the literature is presented."
-How does activity level modify the relationship between serum cholesterol level and coronary heart disease risk in older persons?,"Is the serum cholesterol-coronary heart disease relationship modified by activity level in older persons? Although coronary heart disease remains a leading cause of death and disability in old age, the relationship of serum cholesterol level to risk of coronary heart disease in old age is controversial. Data for 2,388 white persons aged 65-74 who participated in the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study (NHEFS) were examined to determine the relationship of serum cholesterol level to coronary heart disease incidence and whether activity level would modify this relationship. While there was no overall relationship between serum cholesterol level and coronary heart disease risk in either men or women, the relationship between serum cholesterol level and coronary heart disease differed within activity groups. For persons who were more active, serum cholesterol level was associated with a graded increase in risk of coronary heart disease, from 1.3 (95% CI 0.7, 2.3) in those with serum cholesterol level of 4.7-5.1 to 1.7 in those with serum cholesterol level of 6.2 mmol/L or more (95% CI 1.0, 2.7), when compared with those with serum cholesterol level below 4.7. For the least active persons, all levels of cholesterol were associated with a significant inverse relative risk, including cholesterol of 6.2 mmol/L or more (Relative risk = 0.4 (95% CI 0.2, 0.7]. These data suggest that factors such as activity level may modify the serum cholesterol-coronary heart disease association in old age. The serum cholesterol-coronary heart disease association in more active older persons resembles that seen in younger populations, whereas the association in less active persons is that of serum cholesterol level and risk of cancer or death. The modification of the serum cholesterol-coronary heart disease association by activity level may have implications for appropriate clinical management as well as appropriate design of research studies of this association."
-What evidence suggests an increase in GABA-ergic neurotransmission in patients with hepatic encephalopathy due to fulminant hepatic failure?,"Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure BACKGROUND. Increased gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathogenesis of hepatic encephalopathy. The mechanism by which GABA-ergic activity is increased in hepatic failure is unclear, but recent studies in animals with encephalopathy due to fulminant hepatic failure suggest that GABA-ergic neurotransmission may be increased by the presence of elevated concentrations of benzodiazepine agonists such as diazepam and N-desmethyldiazepam. METHODS AND RESULTS. Samples of frontal cortex were obtained at autopsy from 11 patients with hepatic encephalopathy who died of acetaminophen-induced fulminant hepatic failure and 8 patients who died of cardiovascular disease or trauma. None of the 19 patients had received benzodiazepines while hospitalized. Chromatographic analyses of extracts of these samples revealed 4 to 19 peaks representing substances that inhibited the binding of a radiolabeled imidazobenzodiazepine ([3H]flumazenil) to its receptors. Several of these peaks had retention times corresponding to those of known 1,4-benzodiazepines. Ultraviolet- and mass-spectroscopic analysis confirmed that two of these peaks represented diazepam and N-desmethyldiazepam. The patients who died of fulminant hepatic failure could be divided into two groups: six who had had significantly elevated brain concentrations (2-fold to 10-fold higher than normal) of substances inhibiting the binding of [3H]flumazenil and five who had normal concentrations. CONCLUSIONS. Brain concentrations of substances inhibiting the binding of [3H]flumazenil to its receptors are increased in some patients with hepatic encephalopathy due to fulminant hepatic failure. The origin of these substances is unknown, but these findings provide a rational basis for trials of benzodiazepine-receptor antagonists in the management of this disorder."
-What method did the researchers use to detect hepatitis B virus DNA in liver tissue samples?,"Detection of hepatitis B virus DNA in paraffin-embedded liver tissues in chronic hepatitis B or non-A, non-B, hepatitis using the polymerase chain reaction. We developed a polymerase chain reaction assay for the direct detection of hepatitis B virus in paraffin-embedded liver tissue and applied this assay to determine whether hepatitis B virus DNA exists in livers with chronic hepatitis non-A, non-B. Fifty five liver biopsy samples were studied: 11 from patients with HBeAg-positive chronic hepatitis (paraffin-embedded) and 44 from patients with chronic hepatitis non-A, non-B (21 paraffin-embedded; 25 fresh frozen). Thirty three (75%) of the non-A, non-B cases were positive for hepatitis C virus antibodies. Approximately 1 to 10 ng of DNA was extracted from the paraffin-embedded tissue and amplified using oligonucleotide (23-mer) primers specific for the S gene (positions 261 to 692). The beta-globin gene was used as an internal control for sensitivity because this is a single copy gene and allows for relative quantification. In each of the chronic hepatitis B livers, the expected 432-base-pair amplification product for hepatitis B virus DNA and beta-globin gene product were both detected. On the other hand, in the 21 paraffin-embedded chronic hepatitis non-A, non-B livers, no hepatitis B virus DNA was detected, although beta-globin gene was observed in all. Furthermore, in all 25 frozen non-A, non-B livers, beta-globin gene was observed, but no hepatitis B virus band was seen. The limit of detection of hepatitis B virus DNA by this method was estimated to be one genomic copy of hepatitis B virus DNA per cell."
-What is the potential advantage of the step-down method of FSH administration for ovulation induction in women with polycystic ovarian syndrome (PCOS)?,Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome. The step-down method can be an alternative method of ovulation induction in women with PCOS. This protocol can induce ovulation with a smaller dose of FSH and with lower incidence of excessive ovarian enlargement in comparison with the traditional fixed-dose administration method.
-What were the key findings of the 12-week trial of fluoxetine in patients with borderline or schizotypal personality disorders?,"Fluoxetine in the treatment of borderline and schizotypal personality disorders. Twenty-two patients meeting the criteria for borderline or schizotypal personality disorder or both participated in a prospective, nonblind 12-week trial of fluoxetine. There were significant reductions in self-injury and in scores on the Hopkins Symptom Checklist regardless of diagnosis. The results suggest that controlled trials of fluoxetine and investigations of the serotonergic system in these disorders would be useful."
-What is the proposed term for the special variant of dermatofibroma described in the case report?,"Atypical polypoid dermatofibroma: report of two cases. Two cases of a hitherto undescribed special variant of dermatofibroma are reported. A man and a woman, aged 57 and 52 years, respectively, had slowly growing cutaneous tumors on the lower extremities. The tumors were exophytic and polypoid, 10 and 6 cm in maximal diameters, respectively; they were covered by rough nonulcerated skin and were joined by a short pedicle to an indurated base. Histologic examination showed some features of an otherwise conventional dermatofibroma, whereas the polypoid component was hypercellular and showed striking atypia and scattered mitotic figures. After 32 and 28 months' follow-up, the lesions did not recur after surgical excision. We suggest the term atypical polypoid dermatofibroma to summarize the special clinicopathologic features of these tumors."
-What was the average hospital stay for patients with pelvic fractures in this study?,"Pelvic fracture from major blunt trauma. Outcome is determined by associated injuries. Pelvic hemorrhage has been implicated as the cause of death in 50% of patients who die following pelvic fractures. To establish correlates of morbidity and mortality from pelvic fractures due to blunt trauma, we reviewed 236 patients treated during 4 years. The average age of the 144 men and 92 women was 31.5 years, the average Injury Severity Score was 21.3, the average blood requirement was 5 units, and the average hospital stay was 16.8 days. One hundred fifty-two patients (64.4%) were injured in motor vehicle accidents, 33 (14%) had motor vehicle-pedestrian accidents, 16 (6.8%) had crush injuries, 12 (5.1%) each had either motorcycle accidents or falls, and 11 (4.6%) had miscellaneous accidents. Eighteen patients (7.6%) died, with seven (38.9%) deaths due to hemorrhage. Only one death was caused by pelvic hemorrhage. Other deaths were due to hemorrhage from other sites (6), head injury (5), sepsis or multiple-organ failure (4), pulmonary injury (1), and pulmonary embolus (1). None of the septic deaths was related to a pelvic hematoma. Multivariate multiple regression analysis showed that the severity of injury was correlated with indices of severity of pelvic fractures such as fracture site (p less than 0.0001), fracture displacement (p less than 0.005), pelvic stability (p less than 0.0001), and vector of injury (p less than 0.01). However death could not be predicted on the basis of these indices of severity (p greater than 0.28). Of the nine patients who underwent pelvic arteriography, three required embolization of actively bleeding pelvic vessels, but seven had intra-abdominal hemorrhage that required laparotomy, and eight developed a coagulopathy. Massive bleeding from pelvic fractures was uncommon, and the major threat of hemorrhage was from nonpelvic sites. Furthermore, although injury severity was correlated with the severity of the pelvic fracture, hospital outcome was determined by associated injuries and not by the pelvic fracture."
-What is the estimated yearly risk of Giardia infection for water systems using polluted waters compared to pristine waters?,"Risk assessment and control of waterborne giardiasis. BACKGROUND: Waterborne giardiasis has been increasing in the United States with 95 outbreaks reported over the last 25 years. The Safe Drinking Water Act has mandated control of this pathogen. METHODS: A risk assessment model was developed to estimate risk of infection after exposure to treated waters containing varying levels of Giardia cysts. The model was defined by a dose-response curve developed from human feeding studies for Giardia and assumed 2L of water consumption per day. Data on concentrations and distribution of the organism in source waters were used to assess exposure after varying reductions achieved through treatment. RESULTS: In surveys reporting prevalence and levels of Giardia cyst contamination, average levels of cysts in surface waters ranged from 0.33 to 104/100L; from pristine watersheds (protected from all human activity) 0.6 to 5/100L. Yearly risks were 4.8 x 10(-3) for systems using polluted waters and 1.3 x 10(-4) for pristine waters with a 10(-3) treatment reduction. CONCLUSION: Public Health officials will need to work with the water industry to ensure a risk of less than 1/10,000 for source waters with 0.7 to 70 cysts per 100 liters through treatment achieving reduction of 10(-3) to 10(-5), respectively, of Giardia cysts."
-What rare medical condition is described in this case report involving the cauda equina?,Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis.
-What unique mitochondrial DNA characteristics were found in the muscle biopsy specimens of the two children with combined Kearns-Sayre and MELAS syndrome features?,"Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression."
-What were the key psychiatric disorders found to be more prevalent in men with chronic low back pain compared to the control group?,"Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study. This study used structured diagnostic interviews and DSM-III criteria to assess lifetime prevalence and pre-morbid risk of psychiatric disorder in a sample of men with long-standing chronic back pain (CLPB) attending a primary care clinic. A control group of age and demographically matched men without history of back pain was also studied. Compared to controls, men with CLBP had significantly higher lifetime rates of major depression (32% vs. 16%), alcohol use disorder (64.9% vs. 38.8%), and a major anxiety disorder (30.9% vs. 14.3%). Almost all CLBP men ever experiencing a mood disorder reported recurrent, not single, episodes. The 6 month point prevalence of major depression, but not other disorders, was also significantly elevated for men with CLBP. In CLBP, the first episode of major depression generally (58.1%) followed pain onset. While the initial major depressive episode usually commenced within the first 2 years of established pain, late onset mood disorder was also common. By comparison in most cases (81%) onset of alcohol use disorders considerably preceded pain. When an age-matching procedure was used to gauge relative vulnerability to psychiatric illness in patients and controls, CLBP patients had significantly higher pre-pain rates of alcohol use disorder but not depression. After age of pain onset, CLBP subjects had over 9 times the risk of developing major depression, but had similar rates of developing alcoholism. We conclude that (1) alcohol use disorders rather than depression may increase risk of developing CLBP, and (2) risk of new onset and recurrent major depression remains high for men throughout their pain career. This suggests that psychological adaptation to long-standing pain may be less successful than previously thought, especially with regard to recurrent mood disorder."
-What are the two conflicting views regarding the nature of the transmissible agent in spongiform encephalopathies like scrapie?,"A 'unified theory' of prion propagation. There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleic acid. On the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the PrPc gene, it has been suggested that a nucleic acid must be a component of the agent. Can the two views be reconciled?."
-How do the regulatory elements within the 475-base-pair fragment of the sevenless gene contribute to its specific expression pattern during Drosophila eye development?,"Analysis of the enhancer element that controls expression of sevenless in the developing Drosophila eye. The sevenless gene encodes a protein-tyrosine kinase receptor expressed in a complex pattern during the development of the Drosophila melanogaster eye. We have previously shown that this pattern is regulated transcriptionally by an enhancer located in the body of the sevenless gene. Here we extend our analysis of the sevenless enhancer, defining a 475-base-pair fragment that contains elements necessary for the correct qualitative and quantitative expression of the sevenless gene. Within this fragment are sequence elements conserved in the sevenless gene of a distantly related Drosophila species and protected from DNase I digestion by nuclear extracts isolated from adult heads and imaginal discs. Partial deletions of the 475-base-pair fragment result in preferential loss of expression in different subsets of cells. These results suggest that the normal pattern of expression is generated by the combined action of separate cell-specific regulatory elements."
-What were the two major patterns of severe Helicobacter pylori infection identified in the CT scans?,"Helicobacter pylori gastritis mimicking gastric carcinoma at CT evaluation. The abdominal computed tomographic (CT) scans from 61 patients with biopsy-proved Helicobacter (formerly Campylobacter) pylori gastritis were retrospectively reviewed. The CT scans were interpreted on the basis of the original report of the findings at CT examination and without knowledge of the results of biopsy. Of 19 patients (31%) with gastric abnormalities at CT, 14 (74%) had inflammatory changes initially reported as suspicious for gastric malignancy; malignancy was entertained as the primary diagnosis in four of those patients. In five of the 19 abnormal cases (26%), the diagnosis with CT was gastritis. The two major patterns of severe H pylori infection identified were (a) circumferential antral wall thickening and (b) thickening of the posterior gastric wall along the greater curvature, with or without evidence of ulceration. Thickening averaged 1.5-2.0 cm in cases suspicious for malignancy. The majority of abnormalities involved the gastric antrum (68%). No cases demonstrated significant adenopathy, obliteration of fat planes, or invasion of adjacent organs."
-How do micrometastases of gastric cancer impact patient survival rates after node dissection?,"Non-ominous micrometastases of gastric cancer. So-called R2 or wider meticulous node dissection was performed in 1368 patients with resected gastric cancer invading beyond the submucosa but without distant metastases. Survival rates were similar in subsets of patients with or without microscopic node metastases and macroscopically normal lymph nodes. The extent of node metastases has previously been shown to be one of the two most important prognostic factors in gastric cancer without distant metastases, and its lack of impact in these patient groups was not explained by the imbalance of other prognostic factors. The findings indicate that micrometastases of gastric cancer are curable by a wide node dissection made in the absence of palpable abnormality. They also offer the possibility that an extensive node dissection may yield good stage-specific survival rates, in part because of upstaging of patients. The findings should influence the recording of node metastases for evaluation of stage-specific treatment results and for research purposes."
-What was the main finding regarding cardiovascular mortality in diabetic patients treated with diuretics for hypertension?,"Excess mortality associated with diuretic therapy in diabetes mellitus OBJECTIVE. To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN. Cohort analytic study with a median follow-up of 4.5 years. SETTING. Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS.--There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS.--Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS.--In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population."
-What are the key differences between radiation and pagetic osteogenic sarcomas compared to classical osteogenic sarcoma?,"Radiation and pagetic osteogenic sarcomas. Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition."
-What was the response rate and overall survival of patients with refractory lymphomas and cutaneous T-cell lymphoma treated with pentostatin in this Phase II trial?,"Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease. Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers."
-What were the main causes of bilateral blindness in the Central African Republic according to the study conducted between 1985 and 1989?,"Causes of blindness and visual handicap in the Central African Republic. The causes of bilateral blindness (best visual acuity less than 3/60) in 1371 people in the Central African Republic seen between 1985 and 1989 who attended eye clinics in 10 out of the 16 prefectures across the country are given. The main causes of bilateral blindness were cataract (51%), glaucoma (12.7%), and onchocerciasis (8.1%). In 710 patients with unilateral blindness the main causes were cataract (38%), glaucoma (10%), iritis (7.5%), and trauma (6.3%). Bilateral blindness in children was rarely seen. The causes of visual impairment (vision between 6/18 and 3/60) in 424 patients were cataract, including aphakia (38%), maculopathy (14%), and onchocerciasis (7%)."
-How does sucralfate enhance gastroduodenal protection and mucosal defense mechanisms?,"Mechanisms of gastroduodenal protection by sucralfate. Over the past 5-10 years, a number of studies have shown that topical sucralfate enhances a number of gastric and duodenal mechanisms, e.g., the ""mucus-bicarbonate barrier,"" mucosal hydrophobicity, mucosal blood flow, cell viability, and local production of prostaglandins, as well as endogenous mediators of tissue injury and repair. It seems likely that the complex actions of sucralfate are in part related to direct interaction between the drug or its components (aluminum, sucrose, and sulfate) and gastric mucosal tissues, and in part related to effects of the drug on the various mucosal mediators of tissue injury and repair. Local actions may play a role in accelerating healing of ulcer-damaged mucosa, but this does not explain the protective actions of sucralfate on normal mucosa. Thus sucralfate appears to enhance the protective function of the ""mucus-bicarbonate"" barrier by actions on both components. This may depend in part on an interaction with the unstirred layer overlying gastric epithelium. Sucralfate has also been shown to increase the hydrophobicity of mucus gel. There is little doubt that sucralfate increases local production and release of protective prostaglandins (PGs), but the precise role played by these agents in mediating mucosal protection and in chronic ulcer healing remains uncertain. Currently, the mechanism of action of sucralfate on vascular integrity remains unknown and the role of PGs in this protective function is unclear. There is little evidence that epidermal growth factor plays any role in mediating mucosal protection by sucralfate, but it may be important in its ulcer-healing action. Sucralfate has been shown to be truly ""cytoprotective"" in that it protects isolated epithelial cells from damage by noxious agents. In animals treated with sucralfate, the surface epithelial cells were disrupted, but necrotic lesions in the deep proliferative zone were virtually absent. It seems likely that investigations of the actions of sucralfate and its components will move ever closer to defining the target cells, the intracellular events, and the mediators that bring about its protective and ulcer-healing activity."
-What is the correlation between histological grade and bromodeoxyuridine (BUdR) labeling index in astrocytomas?,"Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases. The histological grade and the bromodeoxyuridine (BUdR) labeling index of 60 astrocytomas of ""ordinary"" cell types (fibrillary, protoplasmic, gemistocytic, and anaplastic astrocytomas and glioblastomas) were compared to determine whether the grading system reflects the proliferative potential of the tumors. The tumor grade was based on the presence or absence of four criteria (nuclear abnormalities, mitosis, necrosis, and vascular endothelial proliferation): Grade 1, no criterion, Grade 2, one criterion, Grade 3, two criteria; and Grade 4, three or four criteria. The BUdR labeling index, or percentage of S-phase cells, was calculated in paraffin-embedded tumor sections after in situ labeling by intraoperative intravenous infusion of BUdR, 200 mg/sq m. Exponential regression analyses showed a positive correlation between the histological grade and labeling index (r = 0.88, p less than 0.001) that was stronger than the correlations between log labeling index and age (r = 0.55, p less than 0.001) and between grade and age (r = 0.55, p less than 0.001). These results indicate that the histological grading system reflects the proliferative potential of ""ordinary"" astrocytomas."
-What are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease?,"Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the ""symptom index."" Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain."
-What percentage of infectious agents were identified in the study of acute infectious erythemas in children?,"Acute infectious erythemas in children: a clinico-microbiological study. One-hundred children with an acute illness comprising fever and widespread erythematous rash were prospectively studied to determine whether clinical presentations are helpful in defining the causative agent and to identify the most appropriate microbiological specimens. An infectious agent was identified in 65 children; 72% were viruses, 20% were bacteria, 5% were Mycoplasma pneumoniae and in 3% both viruses and bacteria were detected. The most common infectious agents were picornaviruses, an atypical presentation of measles and Group A beta-haemolytic Streptococcus. Different patterns of rash occurred with each of these infections. The clinical presentation of a child with an acute febrile illness and rash was unhelpful in defining the causative agent. Routine management should include a throat swab for bacterial investigation and in selected cases a blood sample for IgM viral titres."
-What was the relationship between serum cholesterol concentration and mortality from coronary heart disease in the Shanghai population studied?,"Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. OBJECTIVE--To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE--Death from coronary heart disease and other causes. RESULTS--The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION--Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a ""low"" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death."
-What was the primary aim of the study on renovascular hypertension?,"The value of tests predicting renovascular hypertension in patients with renal artery stenosis treated by angioplasty. The aim of this study was to evaluate tests predicting renovascular hypertension. This was done by relating the results of renal vein renin tests, the captopril test, and renal scintigraphic tests to the blood pressure outcome 12 months after relief of renal artery stenosis by percutaneous transluminal renal angioplasty in 31 patients. Cure was seen in eight (26%). Improved blood pressure was obtained in 12 patients (39%), and in 11 patients (35%), the result for blood pressure was a failure. The accuracies of the two mathematical models used to analyze the renal vein renin assays were 44% and 60%. The captopril test showed a sensitivity of 36% and an accuracy of 43%. Renal captopril technetium Tc 99m-labeled pentetic acid scintigraphy gave a sensitivity of 60%. Stepwise logistic regression analysis of clinical variables in relation to blood pressure response revealed age as the only factor significantly related to blood pressure outcome. We conclude that the tests used are unfit for helping select patients for percutaneous transluminal renal angioplasty and that age may have an important influence on outcome."
-What are the two surgical approaches used for treating congenital atresia of the external auditory canal in this study?,"Surgical approaches to congenital atresia of the external auditory canal. During the past 4 years, 22 patients with congenital atresia of the external auditory canal underwent 24 initial operations by either an anterior or transmastoid approach. No attempt at randomization was made, but the two groups were similar in number and pathology (in 14 cases approach was anterior and in 10 cases approach was transmastoid). Followup ranged from 6 months to 4 years. Hearing results were similar in the two groups (71% with air-bone gap less than 30 dB). There were no instances of facial nerve injury or sensorineural hearing loss. Facial nerve monitoring was used. Complications of stenosis and drainage were more common with the transmastoid approach. In both groups, hearing results were accomplished with the patients' intact ossicles or prosthetic reconstructions. Meticulous soft-tissue technique, with split-thickness grafts covering all exposed bone, is the key to preventing stenosis. For the three cases of patients with thick, acellular atresia plates, a different approach was developed. Maintaining proper orientation during the medial dissection is more difficult in these cases. By opening the antrum primarily and identifying the lateral canal, ossicles, and facial nerve, an ear canal can then be created anteriorly with these landmarks in view. An intact canal wall-like procedure is carried out. Although hearing results are similar, the anterior approach, because of fewer postoperative complications, is now our procedure of choice. Proper orientation and soft-tissue technique are the keys to successful correction of the congenitally atretic ear canal."
-How does brief hypoxia affect the afterdischarge mechanism in conscious humans?,"Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans. After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the ""afterdischarge."" Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing."
-What potential surgical complication occurred during the left radical nephrectomy for renal cell carcinoma?,"Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma. The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions."
-Can moderately mentally retarded adults improve their cardiovascular fitness through a minimally supervised exercise program?,"Effects of a minimally supervised exercise program for mentally retarded adults. Previous exercise studies that attempted to improve the cardiovascular fitness (CVF) of mentally retarded (MR) adults were flawed with methodological shortcomings that prevented conclusive results. At issue in these training studies were fitness test validity and reliability, exactness of duration and intensity of training, and an inordinate amount of supervision. Therefore, we sought to determine whether moderately MR adults (seven males, five females; IQ = 61 +/- 3, age = 25 +/- 3 yr) could improve their CVF through a minimally supervised 16-wk training program. Each subject repeated exercise tests twice on two different modes of exercise, the treadmill (TM) and Schwinn Air-Dyne ergometer (SAE), before training to ensure validity and reliability of initial CVF levels. Intensity and frequency of exercise were closely monitored. An observer was present during the training bouts, but, following initial instructions, no additional encouragement or instructions were given. Although the training program significantly increased peak VO2 (29.2 +/- 8 to 33.5 +/- 9 ml.kg-1.min-1) and peak ventilation (73 +/- 26 to 81 +/- 231.min-1) when assessed on the TM, significant changes in these same parameters were not seen when assessed on the SAE. The importance of these results was discussed."
-What was the overall 30-day postoperative cardiac mortality rate for patients aged 80 years and older undergoing cardiac surgery during the study period?,"Cardiac surgery in the octogenarian: perioperative outcome and clinical follow-up The perioperative and follow-up results of cardiac operations employing extracorporeal circulation and cold cardioplegic arrest were examined in 191 consecutive patients greater than or equal to 80 years of age having surgery over a 5 year period (1982 to 1986). Most patients had severe preoperative symptoms with functional class III (39.8%) or IV (57.1%) limitation. The overall 30 day postoperative cardiac mortality rate was 15.7%. The total in-hospital mortality rate was 18.8%; the mean postoperative hospital stay was 16.4 +/- 13.3 days. The perioperative mortality rate for elective operations was as follows: coronary artery bypass (5.6%), aortic valve replacement (9.6%), aortic valve replacement with coronary bypass (17.9%) and mitral valve surgery with or without coronary bypass (21.4%). Urgent operations were performed in 39 patients (20.4%) with a total perioperative mortality rate of 35.9%; urgent coronary artery bypass was performed in 26 patients (67%) with an in-hospital mortality rate of 23.1%. Clinical evidence of left ventricular failure, functional class IV symptoms, left ventricular ejection fraction less than 50%, mitral valve repair or replacement for severe mitral regurgitation and urgent operation were associated with an increased perioperative mortality rate. Follow-up study in all 155 patients surviving postoperative hospitalization at 22.6 +/- 14.8 months showed significant improvement in symptom status in all surgical subgroups. There were 18 follow-up deaths (11.6%); 10 were noncardiac. The actuarial survival rate of the entire study group was significantly better than that in age- and gender-matched control subjects (p = 0.037)."
-What did the study reveal about the relationship between ethnic identity and pain perception?,"Interethnic differences in pain perception. While several investigators have reported relationships between ethnic background and expression of pain, such relationships are in fact highly problematical. Few studies of pain and ethnicity have used quantitative measures of pain combined with multivariate methods of data analysis. Most have focussed on populations which, unlike many in the United States today, are characterized by highly distinct ethnic groups. The study reported here interviewed 536 persons recently treated for forms of cancer known to cause significant pain. Pain was assessed using standard, well validated instruments, including Graphic Rating Scales anchored in several alternative time-frames and the McGill Pain Questionnaire. The study took place in an area with a low proportion of recent immigrants and only small concentrations of distinct ethnic minorities. No statistically significant relationships were observed between ethnic identity and measures of pain sensation. However, pain described in affective terms according to the McGill Pain Questionnaire did vary among ethnicities. This observation suggests that cultures associated with specific ethnic identities still condition individual expression of pain despite the high degree of assimilation that has occurred among ethnic groups in the United States."
-"What is the role of platelet activating factor (PAF) in shock, sepsis, and multiple organ failure?","The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure. PAF has been implicated as a mediator of shock, sepsis and MOF. The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage. These effects are prevented by PAF antagonists. PAF induces many of the characteristic changes of MOF, including functional impairment in the lung, kidney, gastrointestinal tract and heart. PAF antagonists will inhibit these adverse effects. PAF antagonists are now being manufactured by a number of pharmaceutical companies studying the beneficial effects of PAF antagonists in human disease. Data from these studies promise valuable information with significant clinical relevance to the practicing surgeon."
-What were the effects of tocopherol and tocotrienol on rat mammary tumors induced by DMBA and NMU?,"A comparison of tocopherol and tocotrienol for the chemoprevention of chemically induced rat mammary tumors. Two forms of vitamin E, tocopherol and tocotrienol, were tested for chemopreventive activity in two chemically induced rat mammary-tumor models. When mammary tumors were induced by 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg), only the tocotrienol group had a statistically significant increase in tumor latency. There was no effect of either compound on tumor multiplicity. When tumors were induced by N-nitrosomethylurea (NMU, 30 mg/kg), neither analogue of vitamin E modified latency, whereas tocotrienol increased tumor multiplicity. In summary, neither vitamin analog had a major impact on mammary-tumor development after tumor induction with either DMBA or NMU."
-How do calcium-channel blockers like verapamil and diltiazem affect ventricular function differently in control hearts versus failing hearts?,"Increased negative inotropic effect of calcium-channel blockers in hypertrophied and failing rabbit heart. The effects on ventricular function of calcium channel blockers and isoproterenol were studied in isovolumically beating perfused control rabbit hearts and in hearts subjected to a double pressure plus volume overload studied at the early phase of heart failure. In control hearts, isoproterenol produced an increase of systolic ventricular function and relaxation that was maximal at 10(-7) M. In failing hearts, inotropic state increase in response to isoproterenol was significantly smaller (P less than .01) with no observed lusitropic effect. In control hearts, verapamil and diltiazem produced dose-dependent decreases of ventricular function which were larger with verapamil than with diltiazem (median drug concentration50 of developed pressure was, respectively, 1163 +/- 131 nM and 4524 +/- 451 nM, P less than .001). In failing hearts, contractility decrease was larger than in control hearts (median drug concentration50 of developed pressure was 604 +/- 69 nM and 2691 +/- 580 nM with verapamil and diltiazem, respectively). In contrast, Ro 40-5967, a new calcium-channel blocker, did not produce reductions of inotropic state with concentrations up to 10(-5) M. All three calcium-channel blockers produced a 2-fold increase of coronary flow at 10(-6) M. We conclude that the deleterious effect of verapamil and diltiazem in heart failure is due, at least in part, to a direct depressant effect of these drugs on contractility, which is larger than in control hearts. Additionally, the in vivo sympathetic compensation is probably reduced, as indicated by the decreased ventricular responsiveness to isoproterenol."
-What were the actuarial survival rates for children who underwent heart transplantation according to the international survey?,"Heart transplantation in children: an international survey. A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor."
-What is sclerotherapy and how is it used in the treatment of large varicose veins?,"Practical phlebology. Sclerotherapy of large veins. A practical, step-by-step guide for the sclerotherapy of large varicose veins is offered. First, an orientation regarding the place of sclerotherapy and surgery in the total treatment of varicose veins is given, with a practical clinical classification of varicose veins. This is followed by a detailed discussion of patient education before sclerotherapy, material to be used with recommended concentrations, injection technique, compression after sclerotherapy, instructions to the patient after injection, and procedures at subsequent visits."
-What did the nuclear magnetic resonance spectroscopy reveal about brain pH in patients after cardiac resuscitation?,"Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation. We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining."
-What is the significance of this case report regarding intraocular hemangiopericytoma?,"Supraciliary hemangiopericytoma. A 10-year-old black girl complaining of pain and decreased vision in the left eye was found to have a smoothly elevated ciliochoroidal mass involving the superonasal quadrant of the left eye. The mass appeared circumscribed and uniformly dense by computed tomography. The tumor was hyperintense to vitreous and cerebral white matter on T1-weighted magnetic resonance imaging but was hypointense to vitreous and hyperintense to white matter on T2-weighted magnetic resonance imaging. Results of gross examination of the enucleated eye showed a sharply circumscribed, tan, intraocular mass arising equatorially. Results of histopathologic examination showed a well-vascularized spindle cell proliferation with a sinusoidal pattern characteristic of hemangiopericytoma. This is the third reported case of intraocular hemangiopericytoma and the first in a pediatric patient."
-What is the proposed modification to the definition of early gastric cancer according to the study?,"Problems in the definition and treatment of early gastric cancer. Radical operation with extensive dissection of lymph nodes (R1, 48 patients; R2, 196 patients; R3, one patient) was performed in 245 out of 247 patients with early gastric cancer. The 5-year survival rate was only 73.2 per cent in the 34 patients with lymph node metastases (31.8 per cent). Analysis of factors influencing recurrence revealed that not only lymph node metastases but also the depth of cancer invasion could affect prognosis in early gastric cancer. This study suggests that radical operation with complete dissection of the first and second group of lymph nodes (R2 resection) is a safe and appropriate treatment even for early gastric cancer. We propose that the definition of early gastric cancer be modified to 'carcinoma with invasion confined to the mucosa or submucosa and without evidence of lymph node metastases'."
-What is the purpose of using the Cavitron ultrasonic surgical aspirator in resecting residual mediastinal germ cell masses?,"Resection of residual mediastinal germ cell masses with the Cavitron ultrasonic surgical aspirator. Residual mediastinal masses after chemotherapy for germ cell tumors should be resected. Complete excision of bulky residual masses may sometimes be difficult because of problems with exposure in the region of the great vessels and important nerves. Two cases are presented in which the Cavitron ultrasonic surgical aspirator (Valleylab Inc., Surgical Systems Division, Stamford, Conn.) facilitated excision of large masses after intensive chemotherapy. We found that the collapsed pseudocapsule remaining after aspiration of tumor mass allowed early improved exposure and safer dissection from neighboring vessels and neural structures. Complete excisions were accomplished and no viable tumor was found, so that the patients were spared the immediate need for further therapy. Both had uneventful recoveries."
-What relationship did the study find between platelet membrane fluidity and stroke risk factors in Alzheimer's disease patients?,"Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease. We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease."
-What were the key findings of the study on total knee arthroplasty using the posterior stabilized condylar prosthesis?,"Results of total knee arthroplasty using the posterior stabilized condylar prosthesis. A report of 137 consecutive cases. One hundred thirty-seven consecutive posterior stabilized total knee arthroplasties (TKAs) were reviewed. Average age of the patient was 61.1 years and length of postoperative follow-up period was 29.2 months. Patients were evaluated using the Hospital for Special Surgery (HSS) knee rating scores. Average preoperative scores improved from 52 to 92, postoperatively. Ninety-eight percent of patients had no pain or mild occasional pain postoperatively compared with 99% of patients experiencing severe to disabling pain preoperatively. Complications included one myocardial infarction, two deep venous thrombosis, one urinary tract infection, one patellar dislocation, and four wound problems. There were two incidences of seroma, one hematoma, and one deep infection requiring revision after joint debridement and systemic antibiotics. Also noted was one incidence of ligamentous laxity and one patella fracture."
-How does precordial ST segment depression impact the prognosis of patients with inferior myocardial infarction?,"Precordial ST segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. The impact of associated precordial ST segment depression in inferior myocardial infarction on angiographic and clinical outcomes after thrombolytic therapy and selective coronary angioplasty was studied in 583 patients with acute myocardial infarction. Anterior infarction (Group I), inferior infarction with precordial ST segment depression (Group II) and inferior infarction without precordial ST segment depression (Group III) were present in 289, 135 and 159 patients, respectively. Precordial ST segment depression was more frequent in circumflex than right coronary infarct-related arteries (44 [71%] of 62 versus 91 [40%] of 230; p = 0.000). Although acute patency rates were not statistically different, there was a trend toward different patency rates at day 7 (Group I 88%, Group II 84%, Group III 80%; p = 0.089) partly because of insignificantly higher reocclusion rates in inferior infarction without precordial ST segment depression (Group I 11%, Group II 10%, Group III 18%, p = 0.104). Infarct zone regional wall motion (standard deviations/chord) in inferior infarction was lower with precordial ST segment depression, both acutely (Group I -2.8 +/- 0.9, Group II -2.5 +/- 1.2, Group III 2.0 +/- 1.1; p = 0.000) and at day 7 (Group I -2.2 +/- 1.1, Group II -2.3 +/- 1.1, Group III -1.9 +/- 1.3; p = 0.011). Precordial ST segment depression was associated with a lower ejection fraction in inferior infarction both acutely (Group I 47 +/- 11%, Group II 53 +/- 11%, Group III 58 +/- 9%; p = 0.000) and at day 7 (Group I 49 +/- 12%, Group II 53 +/- 10%, Group III 58 +/- 8%; p = 0.000). Complication rates tended to be higher in inferior infarction when precordial ST segment depression was present. Mortality rates for Groups I, II and III were 8%, 6% and 5%, respectively. These results suggest that precordial ST segment depression in inferior infarction predicts a worse ventriculographic and clinical outcome despite reperfusion therapy."
-What was the primary finding of the study regarding the combination of verapamil and recombinant tissue plasminogen activator in preventing postoperative adhesions?,"Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model. Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route."
-What are the key muscle-related complications observed in patients with sickle cell anemia?,"Myonecrosis and myofibrosis as complications of sickle cell anemia. Painful crises in sickle cell anemia are associated with infarction and subsequent fibrosis of many different organs. Myonecrosis secondary to muscle infarction during a crisis and subsequent fibrosis are often not recognized as complications of sickle cell anemia. We describe four patients, all of whom had recurrent episodes of symmetric proximal muscle pain and swelling as prominent features of their crises. Muscle biopsies showed acute myonecrosis with a minimal inflammatory reaction as well as myofibrosis with abundant collagen deposition. Chronic sequelae consisted of muscle induration, atrophy, and contractures."
-How does chronic ethanol feeding affect the composition of high-density lipoprotein (HDL) subfractions in rats?,"Effect of chronic ethanol feeding on high density lipoprotein subfractions in rats. We have reported previously that chronic alcohol consumption in the rat produced elevated total serum high density lipoprotein (HDL) fraction, but HDL particles of the alcohol-fed rat were deficient in apolipoprotein (apo) E. In that report, serum HDL particles were prepared by successive ultracentrifugation method and there were concerns that the apo E deficiency in HDL particles was artificially produced by centrifugal forces. In the present report, apo Al affinity column chromatography was used instead of successive ultracentrifugation and it likewise yielded HDL particles from alcohol-fed rats that exhibited lower apo E: apo Al ratio than HDL from control rats (0.185 +/- 0.016 vs. 0.303 +/- 0.017, respectively). When the total serum lipoprotein fraction (d less than 1.21) was analyzed by high performance liquid chromatography (HPLC), both HDL and VLDL peaks were higher in alcohol-fed rats than controls. The size of apo E deficient HDL particles from alcohol-fed rats determined by HPLC did not differ from that of normal HDL particles. When HDL (1.063 less than d less than 1.21) was subfractionated into HDL2 (1.063 less than d less than 1.125) and HDL3 (1.125 less than d less than 1.21), only HDL2 of alcohol-fed rats showed lowered apo E: apo Al ratio when compared with same HDL subfraction of control animals. Therefore, the molecular structure of only HDL2 (but not HDL3) was affected by alcohol-feeding. Another HDL subpopulation which is enriched with apo E, i.e. HDL1 (1.054 less than d less than 1.063), was also prepared."
-How does echocardiography help in managing patients with chronic ischemic heart disease?,"Use of echocardiography for patient management in chronic ischemic heart disease. Myocardial ischemia causes regional myocardial contractile and relaxation abnormalities. The extent of ischemia is determined by the distribution and severity of coronary artery stenoses. In coronary heart disease, two powerful predictors of prognosis are the coronary anatomy and ventricular function. Management in coronary heart disease is directed by accurate diagnosis and individualized objectives. Echocardiography at rest and exercise, combined with Doppler and color flow imaging, are properly applied to the differential diagnosis of common clinical syndromes in ischemic heart disease, the identification of the proximal coronary arteries, and the effects of ischemia and prior infarction. Subsequent use of coronary arteriography partially depends on the philosophy regarding the applicability of coronary surgery or angioplasty in an individual patient. Prediction of multivessel, left main, or proximal left anterior descending coronary artery disease by extensive wall motion abnormalities or an abnormal left ventricular ejection fraction may direct the clinician to coronary arteriography to select among coronary surgery, angioplasty, or medical management."
-What were the key findings of the study comparing MOPP and MOPP/CABS treatment for advanced-stage Hodgkin's disease?,"Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP. One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival."
-What is the significance of HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension (IPH)?,"HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension. Immunohistochemical characteristics and relation to portal phlebosclerosis. We recently reported that HLA-DR antigen was expressed on the microvasculature of portal tracts more frequently in idiopathic portal hypertension (IPH) than in normal livers or in other hepatic diseases, and that this HLA-DR expression may be involved in the development of the portal venopathy characteristic of IPH. The present study was performed to evaluate the relationship between the HLA-DR expression and portal tract lesions, as well as to investigate the immunohistochemical characteristics of the HLA-DR-positive microvasculature using liver wedge biopsy specimens obtained from 32 patients with IPH. According to the degree of phlebosclerosis of the portal veins, the portal tracts were divided into three groups: mild, moderate, and severe. The microvasculature in portal tracts was positive for HLA-DR in 21 (66%) of the 32 specimens and in 133 (44%) of 302 portal tracts. In the 21 specimens, there was no significant difference in the prevalence of HLA-DR-positive microvasculature among the three groups: it occurred in 57 (66%) of 86 portal tracts in the mild group, 53 (61%) of 87 portal tracts in the moderate group, and 23 (49%) of 47 portal tracts in the severe group. The HLA-DR-positive microvasculature was positive for type IV collagen and receptors of Ulex europaeus lectin I, suggesting that HLA-DR-positive microvessels are blood vessels. These findings suggest that HLA-DR antigen is already expressed on portal microvessels in the incipient stage of IPH, and that HLA-DR expression persists during the progression of portal phlebosclerosis. The HLA-DR expression may be an initiating factor leading to immunologic assault on portal microvessels in IPH."
-What methods were used to prevent thromboembolic complications in urological surgery in this study?,"A prospective comparison of thromboembolic stockings, external sequential pneumatic compression stockings and heparin sodium/dihydroergotamine mesylate for the prevention of thromboembolic complications in urological surgery. Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66% of the patients undergoing a major urological operation. Thromboembolic stockings, external sequential pneumatic compression stockings and anticoagulant agents, such as heparin sodium plus dihydroergotamine mesylate, have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli. A total of 74 evaluable patients undergoing a major urological operation was randomized to receive either thromboembolic stockings, external sequential pneumatic compression stockings, or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli. 111Indium-labeled platelet scans, performed preoperatively and on days 1, 3 and 6 postoperatively, were used to diagnose deep venous thrombosis and pulmonary emboli. Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease. Deep venous thrombosis was detected in 5 of 25 patients (20%) with thromboembolic stockings, 3 of 24 (12.5%) with external sequential pneumatic compression stockings and 2 of 25 (8%) with heparin plus dihydroergotamine. There was no difference in blood loss or complications among the groups. Although statistical significance among the treatment groups was not reached in this study, the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine, and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli."
-What distinguishes patients with obstructive sleep apnea (OSA) from heavy snorers in terms of upper airway morphology?,"Why don't all heavy snorers have obstructive sleep apnea? Patients with obstructive sleep apnea (OSA) and heavy snorers without apnea both show intrathoracic suction pressures during sleep that exceed their static upper airway closing pressures. Complete airway occlusion, however, occurs only in the former patient group. We hypothesized that the kinetic properties of the airflow would be different in these two types of patients because of differences in upper airway morphology. The pharyngeal computed tomography (CT) was used to measure the cross-sectional areas of the upper airways in 15 patients with OSA, 25 nonapneic heavy snorers, and 14 control subjects while they were awake. Nocturnal breathing was monitored with the static charge-sensitive bed (SCSB). The patients with OSA had a narrower airspace at the velopharyngeal (VP) level than the controls (p less than 0.01); the nonapneic snorers did not differ from the other groups. At the tongue base (TB) and the hyoid bone (HB) levels there was no difference between the OSA and the control groups, but the nonapneic snorers had narrower airways at both of these levels compared with control subjects (p less than 0.01) and at the hyoid bone level compared with the OSA group (p less than 0.05). The VP/HB ratio was the parameter that best distinguished the patients with OSA from the nonapneic snorers (lower in the OSA group, p less than 0.001). We suggest that airway collapse during sleep is favored by a narrow velopharynx associated with large hypopharynx. Some heavy snorers may not have an oropharyngeal collapse because the peak inspiratory suction pressure could already be damped down at the level of the relatively narrow hypopharyngeal airways."
-What rare complication did the patient develop after internal jugular vein catheterization?,"Internal mammary artery subclavian vein fistula following internal jugular vein catheterization. A case report and review of the literature. We have recently treated a patient with an arteriovenous fistula that developed after a right internal jugular vein catheterization. The patient was found to have a pulsatile hematoma and a bruit five days after removal of a temporary pacemaker catheter. Digital subtraction arteriography documented a fistula between the right internal mammary artery and subclavian vein. The fistula was surgically repaired via the cervical route. To our knowledge, an arteriovenous fistula between the internal mammary artery and subclavian vein has not been previously described as a complication of a percutaneous internal jugular vein catheterization."
-What was the aim of the experiments in this animal model study of gluten-induced enteropathy?,"Animal model of gluten induced enteropathy in mice. The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy."
-What potential complications can arise from intralesional corticosteroid therapy for periocular capillary hemangiomas?,"Adrenal suppression and growth retardation after injection of periocular capillary hemangioma with corticosteroids. Adrenal suppression and/or growth retardation were noted in two patients after injection of periocular capillary hemangiomas with corticosteroids. Parents should be warned of these two potential complications of intralesional corticosteroid therapy. Baseline and posttreatment adrenal function should be monitored. If iatrogenic adrenal suppression occurs, supplemental systemic corticosteroids may be necessary in situations involving systemic stress such as infection or surgery."
-What is idiopathic myointimal hyperplasia of mesenteric veins and what are its key clinical characteristics?,"Idiopathic myointimal hyperplasia of mesenteric veins. Nonthrombotic occlusion or stenosis of the mesenteric veins is a rare cause of intestinal ischemia that usually occurs in association with systemic vasculitis. The current report includes four male patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins and their intramural branches; neither vasculitis nor arterial involvement were present. Three of the four patients were less than or equal to 38 years of age; the fourth was 67. All four patients were previously healthy and had no history of drug use of any kind. Clinical findings included abdominal pain, diarrhea, bloody stools, and colonic strictures discovered by barium enema. The intima of the mesenteric and intestinal mural veins was focally thickened by a marked increase in cells and matrix between the endothelium and internal elastic lamina, whereas the vessel walls external to the thickened intima appeared normal. Histochemistry and immunoreactivity with antibodies to muscle-specific actins (HHF-35) disclosed that the intimal thickening was caused by proliferation of smooth muscle cells in a proteoglycan matrix. All patients recovered completely after segmental resection of the ischemic portion of the colon and had no recurrence of intestinal symptoms on follow-up of up to 7 years. These unusual venous lesions do not appear to have been previously described; their etiology and pathogenesis remain unknown."
-What were the long-term outcomes of menstrual cycles and fertility for patients with different types of secondary amenorrhea after a 10-year follow-up?,"Ten-year follow-up of patients with secondary amenorrhea and normal prolactin. A group of 46 patients with secondary amenorrhea without galactorrhea or hyperprolactinemia were studied retrospectively after being clinically categorized into four groups with the use of progesterone-induced uterine bleeding and measurement of serum gonadotropins and prolactin levels. The ability to have regular spontaneous menstrual cycles and to conceive was assessed after a follow-up period of 10 years. Patients who had been classified as having hypothalamic pituitary ""failure"" (hypoestrogenic amenorrhea) with low levels of circulating estradiol had a greater rate of recovery of spontaneous ovulation and menses when compared with patients who had been classified as having only hypothalamic pituitary dysfunction (euestrogenic amenorrhea). The patients with diagnosis of hyperandrogenic chronic anovulation or polycystic ovary syndrome generally required clomiphene citrate for induction of ovulation and almost all the patients with premature ovarian failure (hypergonadotropic amenorrhea) remained estrogen-deficient and unable to ovulate. Hyperprolactinemia or an identifiable pituitary adenoma has not developed in any of the patients to date."
-What motor abnormalities were observed in the second patient that could potentially promote bacterial overgrowth in the Roux limb?,"Could recurrent cholangitis after Roux-en-Y hepaticojejunostomy be explained by motor intestinal anomalies? A manometric study. The aim of this study was to describe the motor patterns found in two patients with recurrent cholangitis episodes after Roux-en-Y hepaticojejunostomy. In one patient, cholangitis was due to a stenosis of the anastomosis between the limb and the left intrahepatic bile duct, while motility of the limb, duodenum, and distal jejunum was normal. In the second patient, no anatomical explanation was found for cholangitis attacks. However, although the duodenal motor activity was normal, the motility of the limb and of the jejunum below the jejunojejunal anastomosis was grossly abnormal: permanent minute rhythm, phase IIIs absent or rare and slowly propagated, all motor abnormalities that could promote bacterial overgrowth in the limb. This stresses the interest in performing motor studies of the Roux-limb when cholangitis remains unexplained after Roux-en-Y hepaticojejunostomy."
-What did the study reveal about eosinophil infiltration in orbital pseudotumor compared to control specimens?,"Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis."
-What is the primary purpose of using superselective embolization in treating arteriovenous fistulas in renal transplant patients?,"Arteriovenous fistulas complicating biopsy of renal allografts: treatment of bleeding with superselective embolization. The use of superselective embolization was assessed as a treatment for bleeding from postbiopsy arteriovenous fistulas (AVFs) in renal transplants. AVFs commonly occur after biopsy procedures in renal transplants, but severe bleeding is rare. Transcatheter embolization can be used to control bleeding, but unless it is sufficiently selective, the procedure results in loss of significant amounts of renal parenchyma. During a 4-year period, embolization procedures were attempted in seven patients 30-65 years old. All had AVFs shown on arteriography. Five patients underwent embolization; occlusion occurred only in the branch supplying the AVF. In one patient with three large AVFs, two were found to have occluded the day after embolization was attempted. In another, an AVF occluded when superselective catheter position was achieved but before embolization. Catheter manipulation in these cases may have precipitated occlusion. In five cases, coaxial embolization techniques were used. Embolization materials consisted of coils in three cases: 0.038 in. (0.97 mm) in one case, 0.025 in. (0.64 mm) in one case, 0.018 in. (0.46 mm) in one case; 0.038 in. (0.97 mm) coils and gelatin foam particles in one case; and localized contrast extravasation in one case. Serum creatinine level was measured before and after embolization in all patients, and radionuclide studies were undertaken in three cases. In all patients, bleeding was effectively controlled. None of the patients showed an increase in serum creatinine level after embolization, and in four, significant improvement was seen. Nuclear medicine studies showed no loss of renal function and a dramatic improvement in one patient. No complications due to the procedure were seen. Our experience suggests that superselective embolization with coaxial catheter techniques is an effective method of treating bleeding from postbiopsy AVFs in renal transplants with minimal loss of renal parenchyma."
-How does preexisting cerebral ischemia affect the sympathetic nervous system's response to increased intracranial pressure?,"Effect of preexisting brain ischemia on sympathetic nerve response to intracranial hypertension. The performance of the sympathetic nervous system during sustained moderate cerebral ischemia (CI) was examined in the present study. For this purpose, a Cushing response was elicited repeatedly during incomplete global CI in anesthetized artificially ventilated cats after vagotomy and baroreceptor denervation. In control animals without CI, sympathetic activity in response to brief elevation of intracranial pressure (ICP) showed a well-repeatable two-phase reaction. During CI there was a progressive deterioration of background sympathetic nerve discharge (SND) over a period of 30 min. SND response to repeated elevation of ICP was initially similar to control response but later with progression of CI was seriously changed. 1) Instead of the usual hyperactivation, sympathetic nerve activity was depressed during intracranial hypertension. 2) The characteristic desynchronized activity either appeared later during the reperfusion period or remained absent. The progressive loss of SND response to raised ICP in developed CI was compared with the changes seen in experiments in which repeated ICP elevations were superimposed on asphyxia. These findings suggest that the sympathetic component of the Cushing reaction strongly depends on the actual state of brain stem autonomic circuits and may be seriously altered in pathological situations involving ischemic brain injury."
-How does the intracellular free magnesium concentration differ between normal brain tissue and brain tumor tissue?,"Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T. We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain."
-What are the potential otolaryngologic symptoms associated with gastroesophageal reflux (GER)?,"Otolaryngologic manifestations of gastroesophageal reflux. The exact incidence of gastroesophageal reflux (GER) is unknown, although it is estimated that at least 25% of patients with GER have head and neck symptoms alone. These symptoms may consist of one or more of the following: excess salivation, hoarseness, ""post-nasal drip,"" voice change, persistent coughing, food sticking in the throat, globus hystericus, otalgia, throat clearing, neck pain, sore throats, the sensation of a lump in the throat, choking spells, and bronchospasm. Carcinoma of the larynx and upper aerodigestive tract may be a consequence of chronic reflux. GER, especially when the classic symptoms of reflux are absent, is frequently overlooked as a cause of these problems. This article reviews the symptoms and pathophysiology of these conditions. The diagnostic and therapeutic modalities available to us in managing these patients are also discussed."
-What are the current limitations of using blood flow velocimetry in obstetric practice?,"The current status of maternal and fetal blood flow velocimetry. Significant progress has been achieved in regard to normative data for uteroplacental and fetal blood flow velocity and the factors which may affect these observations. Associations have been demonstrated between abnormal indices of maternal and fetal blood flow velocity and pregnancy-induced hypertension, fetal growth retardation, fetal blood gas measures, and intrapartum clinical fetal distress. However, in general, the predictive power is modest and no evidence has yet been provided to indicate that these measures can be used as a screening test in the general obstetric population. Continuing research is highly desirable. At the present time, the use of Doppler assessment of blood flow in pregnancy should be limited to the investigational setting."
-What is the relationship between drusen of the optic disc and central retinal vein occlusion in this case study?,"Central retinal vein occlusion associated with drusen of the optic disc. A 43-year-old man had gradual visual changes OD. Funduscopic examination revealed central retinal vein occlusion OD. Complete ocular examination revealed bilateral drusen of the optic disc, confirmed by b-scan ultrasonography. Complete systemic evaluation showed no other etiology for the central retinal vein occlusion. Over a ten-year follow-up, in the absence of systemic disease or other local ocular anomalies, we concluded that central retinal vein occlusion can arise from external compression secondary to drusen of the optic disc."
-What are the key differences observed in the clinical outcomes of the two girls with congenital sideroblastic anaemia?,"Congenital sideroblastic anaemia in two girls. Transfusion dependent congenital sideroblastic anaemia occurred in infancy in two unrelated girls. One girl developed early organ failure which was not prevented by standard chelation treatment. The combination of modest iron burden and putative intrinsic mitochondrial dysfunction could have accounted for the clinical picture. The other girl remained well, receiving regular transfusion and standard chelation treatment. She had normal liver function and no other evidence of organ damage. The syndrome is unlikely to be due to extreme lyonisation in carriers of the usual X-linked condition. The contrasting clinical patterns seen in these two patients suggest that transfusion dependent congenital sideroblastic anaemia may comprise a heterogeneous group of disorders. It is suggested that such children be carefully monitored for evidence of increasing iron overload so that organ damage can be prevented."
-What novel cell line and experimental model did the researchers establish for studying human pancreatic carcinoid tumors?,"Novel therapy for the treatment of human carcinoid. Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS."
-What changes in magnetic resonance imaging can help diagnose spinal cord infarcts at different stages?,"Magnetic resonance imaging of human spinal cord infarction. Magnetic resonance images obtained in two cases of spinal cord infarction are described: one with hemorrhagic thoracic cord infarct, the other with ischemic cervical cord infarct with sequential magnetic resonance imagings. An enlarged cord with strand-shape or longitudinal hypointensity on both T1- and T2-weighted images was noticed in the hemorrhagic infarct; hypointensity on the T2-weighted image was thought to be due to hemosiderin, which shortens T2 relaxation. In the ischemic infarct, a small, round area of hypointensity on T1-weighted images, and of hyperintensity on T2-weighted images, noted 9 hours postictus (""early infarct"") changed on the 22nd day to a cephalocaudal strandlike hypointensity on T1-weighted image, which was enhanced by Gd-DTPA. The hypointensity suggested ""pencil-like softening"" in ""medium"" age infarct. On postictal day 49, it showed an extensive homogeneous hypointensity involving several segments of the cord on T1-weighted images and hyperintensity on T2-weighted images with negative Gd-DTPA enhancement suggesting ""late transverse infarct."" We considered that these changes are of value in diagnosing spinal cord infarcts on magnetic resonance imagings."
-What is the incidence of portal thrombosis after splenectomy in patients with idiopathic portal hypertension (IPH) compared to patients with cirrhosis of the liver?,"High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension. Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough."
-What was the overall occurrence rate of gastroduodenal mucosal damage in this study of critically ill patients receiving total parenteral nutrition?,"Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients."
-What is the effectiveness of intraperitoneal thrombolytic agents like urokinase or streptokinase in treating relapsing or persistent peritonitis in CAPD patients?,"Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis. Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis."
-"How do the expression levels of c-jun, jun-B, and c-fos RNA transcripts differ between primary melanocytes and metastatic melanoma cell strains?","Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas. Analysis of the regulation of c-jun, jun-B, and c-fos RNA transcript expression was performed in human primary melanocytes and metastatic melanoma cell strains. The medium requirements for human melanocyte in vitro growth are phorbol esters, agents that elevate intracellular cAMP levels, hormones, and growth factors. Cellular jun, jun-B, and c-fos gene expression are known to be affected by growth promoting agents. In primary melanocytes, the expression of c-jun, jun-B, and c-fos RNA transcripts was dependent on the growth-promoting agents present in the medium. Uniformly high c-jun, jun-B, and c-fos RNA transcript levels were observed in melanocytes cultivated in complete medium. Higher levels of c-jun RNA transcripts and low levels of c-fos RNA transcripts were observed in melanocytes cultivated in plain medium. In contrast, a range of c-jun, jun-B, and c-fos RNA transcript levels was detected in metastatic melanoma cell strains cultivated in medium with or without serum. In general, an increase in jun-B and c-fos RNA transcript expression and a decrease in c-jun RNA transcript expression was observed in metastatic melanomas compared to neonatal melanocytes. These data suggest a potential role for c-jun, jun-B, and c-fos genes in the transformation of melanocytes to malignant melanoma."
-What was the primary objective of the study on pain characterization in cancer patients?,"Pain characterization in cancer patients and the analgetic response to epidural morphine. In 48 patients with pain related to malignancy, a pain characterization was performed during oral opioid therapy. After an optimal epidural morphine regimen had been established, the alteration in pain relief was evaluated by means of a visual analogue scale. The CSF and plasma morphine concentrations at minimum steady state were then analysed in 28 patients and related to the degree of pain relief. The efficacy of the spinal treatment ranked in the following order: somatic greater than visceral greater than radiating = 0, but the difference was only significant between the somatic and radiating pain groups. There was a tendency for continuous pain to be better relieved than intermittent pain. No correlations were found between the CSF or plasma morphine concentrations and the degree of pain relief, suggesting that not all pain impulses are modulated in a dose-dependent manner by morphine at the spinal level. Pain characterization may be instrumental in providing an optimal spinal opioid analgesia in malignancy. Moreover, there is a need for better defined diagnostic criteria for clinical pain characterization."
-How can small DNA alterations or abnormalities be detected in genetic diseases using restriction endonuclease techniques?,"Diagnosis of genetic disease by primer-specified restriction map modification, with application to cystic fibrosis and retinitis pigmentosa Detection of small alterations or abnormalities in genomic DNA (eg, point mutations or small deletions) has become increasingly important in the diagnosis of genetic disease and polymorphism. When a mutation or polymorphism creates a new restriction endonuclease site, it can easily be identified by polymerase chain reaction (PCR) amplification of the DNA region of interest, followed by digestion with the restriction endonuclease. However, useful restriction sites are the exception, and a variety of specialised techniques have been developed to identify subtle DNA abnormalities. We have shown that where a DNA mutation does not create a useful novel restriction site, such a site can be introduced by PCR and specially chosen primers. The approach is simple and inexpensive and should be broadly applicable in the diagnosis of genetic polymorphism and mutation. The technique is illustrated here by the three base-pair deletion responsible for most cases of cystic fibrosis and by detection of the point mutation in the rhodopsin gene that has been associated with some cases of autosomal dominant retinitis pigmentosa."
-What is the significance of the mitral valvuloplasty performed 5 years after the repair of a sinus venosus atrial septal defect?,"Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty."
-What quantitative nucleolar features were found to be most useful in distinguishing between follicular adenoma and follicular carcinoma of the thyroid?,"Value of quantitative nucleolar features in the preoperative cytological diagnosis of follicular neoplasias of the thyroid. Nucleolar prevalence, size, and outline were investigated on cytological material from cold thyroid nodules obtained by fine needle aspiration. The percentage of nucleolated nuclei in follicular adenoma (32 cases) was less than in follicular carcinoma (26 cases). In adenoma most nuclei contained one nucleolus, and nuclei with two or more nucleoli were less common than in carcinoma where most cases showed the highest nucleolar diameter values. There was some overlap between adenomas and carcinomas, however, when the mean of the 10 largest values of the major nucleolar diameter was considered. In follicular carcinoma the percentage of marginated nucleoli--that is, those touching the nuclear membrane--was, in general, greater than 20%; in adenoma the values were equal to or lower than 16%. The overlap index showed that the percentages of marginated nucleoli and nucleolated nuclei are the two best discriminatory features between adenoma and carcinoma."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-How does the masseter muscle respond to respiratory stimuli like hypercapnia and inspiratory loading?,"Respiratory-related recruitment of the masseter: response to hypercapnia and loading. To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway."
-What are the key characteristics of acute pandysautonomic neuropathy according to the given context?,"Acute pandysautonomic neuropathy. Acute pandysautonomic neuropathy is characterized by severe postganglionic sympathetic and parasympathetic dysfunction, with relative or complete sparing of motor and sensory function. Of four reported cases with sural nerve biopsies, two were normal and two abnormal, revealing loss of small myelinated and unmyelinated fibers. We present a patient with pandysautonomic neuropathy and elevated CSF protein whose sural nerve biopsy showed active axonal degeneration."
-What are the most prominent clinical signs of aseptic meningitis syndrome observed in cardiac transplant patients?,"Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction."
-What criteria were used to determine when patients could be weaned from mechanical ventilation and extubated after transsternal thymectomy for myasthenia gravis?,"Extubation after transsternal thymectomy for myasthenia gravis: a prospective analysis. Recommendations concerning postoperative extubation after thymectomy for myasthenia gravis are presently based upon retrospective chart reviews. We present the results of a prospective investigation of time to extubation after thymectomy for 14 patients over a 12-month period based upon a protocol that included preoperative immunologic therapy, combined epidural and general anesthesia, postoperative epidural narcotic analgesia, and a standardized approach to discontinuation of ventilatory support. After a neurologist took measures to optimize preoperative neuromuscular function, all 14 patients received agents to produce lumbar epidural anesthesia and light general anesthesia. Muscle relaxants were avoided in all but one patient. Postoperative analgesia was initially maintained with epidural hydromorphone, then therapy was switched to patient-controlled intravenous morphine sulfate. Criteria for weaning from mechanical ventilation, first measured at the end of anesthesia, were partial pressure of oxygen (arterial) greater than or equal to 90 mm Hg (fraction of inspired oxygen = 0.40), partial pressure of carbon dioxide (arterial) less than or equal to 50 mm Hg, pH greater than or equal to 7.30, and respiratory rate less than or equal to 30 breaths/min. If these criteria were not met, ventilatory support was continued postoperatively with intermittent mandatory ventilation, and the patient was weaned gradually from this support. Criteria for extubation included meeting the criteria for weaning, vital capacity greater than or equal to 10 mL/kg, and inspiratory pressure better than -30 cm H2O. Criteria for reintubation included tachypnea (respiratory rate greater than 40 breaths/min), respiratory acidosis not due to narcotics, or vital capacity less than or equal to 8 mL/kg. The mean time to extubation was 9 hours (range, 0.75 to 25 hours). Mean preoperative vital capacity was 2.59 +/- 0.64 L (range, 1.90 to 4.20), which decreased approximately 50% to 1.19 +/- 0.39 L (range, 0.70 to 2.0) at the time of extubation. No patient required reintubation. Half of the patients required postoperative anticholinesterase therapy based upon serial neurologic examinations; there were no instances of cholinergic crisis. Thirteen patients returned to the ward on the first postoperative day, and one on the second day. Thirteen patients preferred epidural analgesia to patient-controlled analgesia. The time to extubation and average length of stay in an intensive care setting were markedly reduced compared to those reported in previous retrospective studies. We conclude that a multidisciplinary approach that optimizes neuromuscular function and decreases poststernotomy pulmonary insult will shorten the time to extubation and decrease the length of stay in the intensive care or recovery room after thymectomy."
-What was the laser technique used for treating ovarian endometriomas in this study?,"The use of potassium-titanyl-phosphate laser for laparoscopic removal of ovarian endometrioma. From January 1989 through January 1990, 31 patients thought to have ovarian endometrioma at ultrasonography were treated by operative laparoscopy and potassium-titanyl-phosphate laser. The endometriomas ranged from 2 to 9.2 cm in diameter by preoperative transvaginal ultrasonography. The operative procedure used was a three-puncture technique with a 600 micron fiber attached to a potassium-titanyl-phosphate laser. The power setting was 10 W with a continuous pulse. In all cases endometriomas were opened, drained, and irrigated, and the potassium-titanyl-phosphate laser was used to vaporize or remove the entire cyst lining. The ovarian edges were inverted with the laser at the end of the procedure. With one exception, there was no recurrence of endometrioma at 1, 3, and 6 months after the procedure, on the basis of transvaginal ultrasonography or laparoscopy. In one case, 4 months after the initial laparoscopic procedure, exploratory laparotomy was performed for resection of a large, recurrent endometrioma. The use of the potassium-titanyl-phosphate laser allows the laparoscopic surgeon an aggressive approach to ovarian endometriomas that in the past necessitated exploratory laparotomy."
-What percentage of patients experienced vasovagal reactions during breast-imaging procedures in this study?,"Localization and needle aspiration of breast lesions: complications in 370 cases. A prospective study of the immediate complications of 370 consecutive breast-imaging procedures (203 wire localizations and 167 radiographically or sonographically guided fine-needle aspirations) is reported. Vasovagal reactions occurred in 27 (7%) of 370 cases, ranging in severity from syncope (four of 370, 1%) to mild light-headedness. These vasovagal reactions were independent of procedure type or use of local anesthesia, but were more common in younger patients. Other complications included prolonged (5 min or longer) bleeding (three of 370, 1%) and extreme pain (two of 370, 1%). One patient was found to have malignant hypertension. We conclude that wire localizations and imaging-guided aspirations are generally well tolerated procedures. However, vasovagal reactions are frequent enough to warrant close observation of patients. Radiologists and breast-imaging personnel should be able to recognize and treat vasovagal reactions."
-What imaging technique was crucial in identifying the pontine glioma in this patient with hemifacial spasm?,"Occult pontine glioma in a patient with hemifacial spasm. Hemifacial spasm due to an intracranial mass lesion is rare. We describe a 29-year-old man with hemifacial spasm successfully treated with botulinum A toxin injections for 2 years. The development of acquired diplopia secondary to acquired sixth cranial nerve palsy prompted investigation. Computed tomography done at the time of original diagnosis and on three other occasions (concentrating on the brain stem and cerebellopontine angle) failed to demonstrate an intracranial mass lesion. Magnetic resonance imaging (MRI) showed a large mass lesion in the pons presumed to be a glioma. Patients with hemifacial spasm who have atypical features, especially those with associated neurologic findings, should be screened for tumours. Our case illustrates the superiority of MRI in demonstrating pontine gliomas causing hemifacial spasm."
-How do monoclonal antibodies help in visualizing myocardial necrosis in dogs and humans?,"Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains. The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis."
-What was the success rate of treating primary vesicoureteric reflux using subureteric injection of Polytef paste in this study?,"Primary vesicoureteric reflux: treatment with subureteric injection of Polytef paste. A series of 34 children with 40 primary refluxing ureters were treated endoscopically with a subureteric injection of polytetrafluoroethylene paste (Polytef). The amount injected ranged between 0.1 and 0.8 ml (mean 0.3). A single injection cured the reflux in 26 ureters (65%) and the grade of reflux improved in a further 9 ureters. Seven ureters required a second injection and reflux was cured in 6 of these. The overall cure rate was therefore 80% after the second injection. There was one complication due to self-limiting ureteric obstruction following injection. The procedure is quick, easy to perform and effective. We have some reservations about the long-term efficiency and safety of subureteric Polytef injection in children."
-What serum biomarkers were studied in patients with metastatic renal cell carcinoma and what were their key findings?,"Serum biomarkers in metastatic renal cell carcinoma. To identify possible clinically valuable markers of metastatic renal cell carcinoma, we measured the serum concentrations of several commercially available biomarkers in 117 patients with this disease. The alpha-fetoprotein level was measured in 75 patients and was elevated in 8 (11%); elevation did not correlate with the presence of liver metastasis. Beta subunit of human chorionic gonadotropin levels increased in 8 of 83 patients tested (10%). C-terminal parathyroid hormone levels were measured in 79 patients and were elevated in 15 (19%); their serum creatinine level was normal. Thirteen of this group had normal serum calcium levels, whereas 7 patients with hypercalcemia and no clinically evident bone metastasis had normal parathyroid hormone levels. In only 2 of 72 patients, serum lactate dehydrogenase and its isoenzyme 1 were elevated. Only 1 of 85 patients had mildly elevated serum carcinoembryonic antigen, in contrast to 3 of 7 patients with metastatic transitional cell carcinoma of the renal pelvis who had moderately elevated carcinoembryonic antigen. Elevations in alpha-fetoprotein, human chorionic gonadotropin, and parathyroid hormone correlated with the course of the disease in 13 patients for whom follow-up measurements were available; measurement of these markers, however, is only useful in a small proportion of patients with metastatic renal cell carcinoma."
-What was the purpose of the study comparing Trisdine bladder instillations and O'Neil catheters in patients with acute spinal cord trauma?,"Bladder instillations of trisdine compared with catheter introducer for reduction of bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma. An open, prospective, randomised trial was conducted to compare the incidence of significant bacteriuria following 2 methods of intermittent urethral catheterisation in patients with acute spinal cord trauma. Twenty-two patients were catheterised with a Nelaton catheter and 50 ml of Trisdine were instilled into the bladder and left there immediately prior to withdrawal of the catheter. Fifteen patients were catheterised with a Nelaton catheter with a special introducer to improve asepsis (O'Neil catheter). The mean incidence of significant bacteriuria in males and females who received Trisdine bladder instillations was 0.58 and 0.48% per catheterisation respectively; in males and females catheterised with the O'Neil catheter it was 1.16 and 2.93% per catheterisation respectively. The instillation of Trisdine into the bladder after each passage of a catheter resulted in a significantly lower incidence of bacteriuria compared with that which resulted from the use of the O'Neil catheter. The former method is therefore to be preferred for aseptic intermittent urethral catheterisation in patients with acute spinal cord trauma."
-What percentage of patients survived long-term after receiving the Bio-Medicus ventricular assist device during cardiac surgery?,"Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients."
-What method did the researchers use to estimate the pressure difference between arms and legs in patients with suspected recoarctation of the aorta?,"Estimation of Doppler gradients at rest and during exercise in patients with recoarctation of the aorta. In patients with suspected recoarctation of the aorta the estimation of the pressure difference between the arms and legs is an important part of the examination. Because this difference is often augmented when the circulation is stressed by exercise, exercise tests are a useful part of the evaluation. Doppler echocardiography was used to estimate this pressure difference in 16 adult patients in whom simultaneous pressure and Doppler recordings were made both at rest and during exercise. There was a close correlation between the invasive peak instantaneous gradient and the Doppler gradient both at rest and during exercise. There was only a moderate correlation between the invasive peak to peak gradient and the Doppler gradient at rest and during exercise. Doppler echocardiography is recommended as an easy and accurate method of estimating the peak instantaneous gradient both at rest and during exercise in patients with suspected recoarctation."
-"How does abdominal surgery affect protein, RNA, and nucleotide synthesis in lymphocytes?","Stimulation of protein, RNA, and nucleotide synthesis in lymphocytes after abdominal surgery is not affected by postoperative amino acid supply. The effects of abdominal surgery on protein, RNA, and de novo purine nucleotide synthesis in lymphocytes, and modification of these changes by postoperative amino acid supply, were investigated in 24 patients undergoing cholecystectomy (n = 12) or removal of gastric cancer (n = 12). Mono-nuclear cells were isolated from the peripheral venous blood and incubated with radioactive tracers in vitro. Protein and RNA synthesis, as measured using [14C] glycine and [3H]uridine, respectively, increased postoperatively. Nucleotide synthesis determined by the incorporation of radioactivity from [14C] glycine into nucleotides increased simultaneously. The concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP) estimated by the incorporation of [14C]adenine into nucleotides also increased. These changes were greater and of longer duration in patients with cancer operation than in those with cholecystectomy. In neither case were they affected by the amount of amino acid intake, or increases in energy intake. These results suggest that abdominal surgery stimulates protein and ribonucleic acid (RNA) synthesis in lymphocytes. Increased RNA synthesis may be ensured by increased synthesis of nucleotides, and increased PRPP concentrations appear to regulate the rate of nucleotide synthesis. The responses are apparently dependent upon the severity of surgery, but unrelated to the amount of amino acid supplied postoperatively."
-Does intravenous aminophylline reduce the risk of relapse in patients with decompensated chronic obstructive pulmonary disease (COPD)?,"Aminophylline in the outpatient management of decompensated chronic obstructive pulmonary disease. The objective of this study was to determine if IV aminophylline reduces the risk of relapse after treatment of decompensated COPD in an ED. Forty-six visits in which IV aminophylline was given (T visits) were compared with an equal number of visits in which it was withheld (N visits) with respect to pretreatment serum theophylline level, number of treatments with nebulized bronchodilators and use of parenteral beta-adrenergic drugs, IV corticosteroids and prednisone. The difference in 48-h relapse rates for T and N visits was examined by McNemar's test. No differences were found between T and N visits with respect to vital signs, pretreatment FEV1, arterial blood gas values, hematocrit level or blood leukocyte count. The 48-h relapse rate for T visits (22.2 percent) was significantly higher than for N visits (6.7 percent; p = 0.035). Aminophylline does not appear to be beneficial for outpatients with decompensated COPD and may be harmful."
-How does the administration of estradiol and progesterone affect luteinizing hormone (LH) pulse frequency in women with polycystic ovarian disease?,"Reduction of gonadotropin-releasing hormone pulse frequency is associated with subsequent selective follicle-stimulating hormone secretion in women with polycystic ovarian disease. Polycystic ovarian disease (PCO) is characterized by hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. Mean plasma FSH concentrations are low, while LH is elevated in a majority of patients. LH pulsatile secretion has been shown to occur at rapid follicular phase frequencies (approximately one pulse per h) in PCO, suggesting persistent rapid frequency GnRH secretion in this disorder. Anovulatory women with PCO were given estradiol (E2; Estraderm skin patches) and progesterone (P; vaginal suppositories) to produce midluteal concentrations for 21 days. The aim was to determine if E2 and P would slow LH (GnRH) pulse frequency and if this would result in augmented FSH secretion and follicular development after withdrawal of E2 and P. Plasma LH was measured every 10 min for 8 h before, during (days 10 and 20), and 7 days after withdrawal of E2 and P (day 28). On each of these study days FSH was measured hourly, and E2 and P were measured every 2 h. After sampling, GnRH (25 and 250 ng/kg, iv) was given to assess pituitary responsiveness. Follicular development was monitored by vaginal ultrasound through day 34 of the study. Basal LH frequency was 8.5 +/- 0.5 pulses/8 h (mean +/- SEM). During E2 and P, LH pulse frequency fell to 3.3 +/- 1.0 (10 days) and 2.3 +/- 0.8 (20 days), 39% and 27% of the basal value, respectively, and subsequently increased to 5.6 +/- 0.7 (66% of basal) 7 days after withdrawal of E2 and P. LH pulse amplitude (basal, 7.2 +/- 1.5 IU/L) was not reduced until day 20, but remained suppressed (3.9 +/- 1.1 IU/L) on day 28. As a result, mean LH (basal, 21.0 +/- 3.5 IU/L) fell progressively during E2 and P, to 3.8 +/- 1.2 IU/L on day 20, and remained low (39% of basal) 7 days after steroid withdrawal. Mean plasma FSH (basal, 7.1 +/- 0.9 IU/L) also fell during steroid administration, but in contrast to LH, had risen to 93% of the basal value by 7 days after E2 and P. LH release in response to exogenous GnRH revealed marked initial responses which did not decrease until day 20, but remained suppressed (8% of basal) after withdrawal of E2 and P. FSH responses were also suppressed on day 20, but had increased to 75% of the basal value by day 28. Initiation of follicular development occurred in all patients, and the lead follicle measured 12.3 +/- 0.8 mm 13 days post-E2 and P. Ovulation occurred in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What is circumspinal decompression and how does it address thoracic myelopathy caused by ossification of the posterior longitudinal ligament and ligamentum flavum?,"Circumspinal decompression for thoracic myelopathy due to combined ossification of the posterior longitudinal ligament and ligamentum flavum. Ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the ligamentum flavum (OLF) in the thoracic spine can result in serious myelopathy, leading to circumferential compression of the spinal cord in advanced stages of the disease. The authors performed circumspinal decompression (circumferential decompression of the spinal cord) on these patients. This operation consists of two steps: posterior and lateral decompression of the spinal cord by removal of the OLF (first step) and anterior removal of the OPLL for anterior decompression (second step), followed by interbody fusion. In the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura to easily and safely remove the OPLL anteriorly at the second step. In the second step, the surgical approach varies according to the affected level; costotransversectomy in the upper thoracic spine and standard thoracotomy in the middle or lower thoracic spine. According to the authors, circumspinal decompression is not an easy procedure, but from their results in 10 patients, they identify it as a radical and promising surgical procedure."
-What percentage of patients with pulmonary embolism experienced dyspnea or tachypnea?,"Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. The history, physical examination, chest radiograph, electrocardiogram and blood gases were evaluated in patients with suspected acute pulmonary embolism (PE) and no history or evidence of pre-existing cardiac or pulmonary disease. The investigation focused upon patients with no previous cardiac or pulmonary disease in order to evaluate the clinical characteristics that were due only to PE. Acute PE was present in 117 patients and PE was excluded in 248 patients. Among the patients with PE, dyspnea or tachypnea (greater than or equal to 20/min) was present in 105 of 117 (90 percent). Dyspnea, hemoptysis, or pleuritic pain was present in 107 of 117 (91 percent). The partial pressure of oxygen in arterial blood on room air was less than 80 mm Hg in 65 of 88 (74 percent). The alveolar-arterial oxygen gradient was greater than 20 mm Hg in 76 of 88 (86 percent). The chest radiograph was abnormal in 98 of 117 (84 percent). Atelectasis and/or pulmonary parenchymal abnormalities were most common, 79 of 117 (68 percent). Nonspecific ST segment or T wave change was the most common electrocardiographic abnormality, in 44 of 89 (49 percent). Dyspnea, tachypnea, or signs of deep venous thrombosis was present in 107 of 117 (91 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain or atelectasis or a parenchymal abnormality on the chest radiograph was present in 115 of 117 (98 percent). In conclusion, among the patients with pulmonary embolism that were identified, only a small percentage did not have these important manifestations or combinations of manifestations. Clinical evaluation, though nonspecific, is of considerable value in the selection of patients in whom there is a need for further diagnostic studies."
-What are the key challenges in managing osteogenic sarcoma in children and adolescents?,"Management of osteogenic sarcoma in children and adolescents. The management of osteogenic sarcoma in children has made a fantastic step on the survival rate, but there still remains unexpected late metastatic recurrence even in initially good responders to chemotherapy and lower survival rate in the bad responder group. Therefore, the research on etiology and on the understanding and rating of oncologic power of the tumoral cells as well as other kinds of treatment (vaccine, immunotherapy, and other types of chemotherapy) must be increased. The initial function after replacement is good and is often excellent but increasing deterioration is noticed during each follow-up evaluation. A considerable effort is still to be done for bone and joint replacement. Biocompatible material with mechanical strength and resistance to wear will be used for a long time because of the young age of the patients. There must be better use and understanding of the allograft revascularization, as well as a better biologic connection between the bone host and replacement device. This will probably be used in the future with less cement and more of a modular system. The final prognosis will remain for a long time in the perfect cooperation between the various members of the teams (oncologist, surgeon, imager, pathologist, and research team) who treat the patients."
-What was the total morbidity rate for complications in the study of long-term seizure monitoring using subdural strip electrodes?,"The morbidity of long-term seizure monitoring using subdural strip electrodes. The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%."
-What were the significant predictors of event-free survival after balloon aortic valvuloplasty?,"Predictors of event-free survival after balloon aortic valvuloplasty. BACKGROUND. Balloon aortic valvuloplasty was developed as an alternative to aortic-valve replacement in selected elderly patients with aortic stenosis. The use of this procedure is limited, however, by a high incidence of restenosis. METHODS. Between December 1985 and April 1989, valvuloplasty was performed in 205 patients. We evaluated 40 demographic and hemodynamic variables as univariate predictors of event-free survival by Cox regression analysis and identified independent predictors of event-free survival by stepwise multivariate analysis. RESULTS. Early hemodynamic results indicated a decrease in the peak transaortic-valve pressure gradient from 67 +/- 28 to 33 +/- 15 mm Hg after valvuloplasty and an increase in aortic-valve area from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2 (P less than 0.001 for both comparisons). The rate of event-free survival (defined as survival without recurrent symptoms, repeated valvuloplasty, or aortic-valve replacement) was 18 percent over the mean (+/- SD) follow-up period of 24 +/- 12 months (range, 1 to 47). Significant predictors of event-free survival included the left ventricular ejection fraction and the left ventricular and aortic systolic pressure before valvuloplasty, and the percent reduction in the aortic-valve pressure gradient; the pulmonary-capillary wedge pressure was inversely associated with event-free survival. Although the predicted event-free survival rate for the entire patient group was 50 percent at one year (95 percent confidence interval, 43 to 57 percent) and 25 percent at two years (95 percent confidence interval, 19 to 31 percent), the probability of event-free survival at one year varied between 23 and 65 percent when patients were stratified according to three independent predictors: the aortic systolic pressure, the pulmonary-capillary wedge pressure, and the percent reduction in the peak aortic-valve gradient. CONCLUSIONS. The most important predictors of event-free survival after balloon aortic valvuloplasty were related to base-line left ventricular performance. The best long-term results after valvuloplasty were observed among patients who would also have been expected to have excellent long-term results after aortic-valve replacement."
-"What medical condition did the pregnant young woman experience, and how was it treated?","Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. We describe a pregnant young woman with branch retinal arteriolar occlusions, encephalopathy, and hearing loss in whom we demonstrated a patent foramen ovale. She improved while receiving anticoagulants and no immunosuppressive therapy. The microangiopathic syndrome of retinopathy, encephalopathy, and deafness may be due to a disturbance of coagulation and/or microembolism."
-What are the key characteristics of eosinophilic pustular folliculitis?,"Eosinophilic pustular folliculitis. Eosinophilic pustular folliculitis is characterized by the spontaneous development of recurrent, sterile papules, pustules, and plaques on the face, trunk, arms, and occasionally the palms and soles. Although the large majority of the reported cases have occurred in Eastern Asians, most patients in the United States have been infants or men seropositive for human immunodeficiency virus. We describe a North American woman with eosinophilic pustular folliculitis who was neither seropositive for human immunodeficiency virus nor of Asiatic descent."
-What medical condition did the 44-year-old male present with in the emergency department?,"Delirium and lactic acidosis caused by ethanol and niacin coingestion. A 44-year-old male presented to the emergency department with altered mental status. He was receiving niacin therapy for hypercholesterolemia, and 16 hours earlier had ingested a large quantity of wine. Past medical history was otherwise unremarkable; physical examination revealed paranoid ideation and asterixis. Laboratory evaluation was significant for metabolic acidosis with a calculated anion gap of 39. Liver enzymes were elevated, and lactic acid level was 9.5 mmol/L (normal: 0.5 to 2.2 mmol/L). White blood cell count was 23,100, but all cultures were negative, and all other diagnostic studies, including bilirubin, prothrombin time, and ammonia were normal. The patient recovered rapidly with hydration and administration of thiamine and magnesium. After psychiatric evaluation, a diagnosis of toxic delirium due to niacin and ethanol coingestion was made. This is the first case reporting toxic delirium and lactic acidosis due to niacin and ethanol coingestion. This occurred in the absence of significant hepatic impairment. Possible mechanisms for the observed derangements are discussed."
-What factors determine the severity and management of bacterial skin and soft tissue infections?,"Treatment of bacterial skin and soft tissue infections. Bacterial skin infections occur commonly and range in severity from mild to life threatening. The severity of skin infections, and their management and prognosis, can depend on the mechanism of infection, the skin structures involved and the infecting organism or organisms. Primary skin infections result from invasion of microorganisms through tiny breaks in the epidermis or from the spread of microorganisms through the bloodstream. Secondary infections arise from pre-existing trauma, burns or surgical wounds; infections involving the soft tissues underlying the skin are also discussed. These also frequently occur in areas of trauma, operation or ischemia. The cause, bacteriologic factors and management of skin infections were studied, with special attention to pyodermas, infections of the foot in diabetic patients and necrotizing soft tissue infections. Choice of appropriate antibiotic agents depends in large part on the infecting organism and patterns of antibiotic susceptibility. In necrotizing soft tissue infections, survival or limb salvage may depend on prompt surgical intervention. In these instances and in some of advanced primary skin infections in which bacteremia is involved, parenteral antibiotics are required. The available options are discussed and a report on the data with the combination agent ticarcillin disodium and clavulanate potassium is presented."
-What was the technical success rate of placing self-expandable stents in treating iliac artery obstruction or stenosis?,"Iliac artery stenosis or obstruction after unsuccessful balloon angioplasty: treatment with a self-expandable stent. Obstruction or stenosis of the iliac artery was treated by placement of a self-expandable stent in 91 patients. A total of 100 lesions was treated. All patients had had poor results of balloon angioplasty including residual stenosis, iliac occlusion, and dissection. The stent used in all cases was a self-expandable stainless steel endoprosthesis mounted on a 7- or 9-French catheter and covered by an invaginated tubular rolling membrane. The diameter of the expanded stent varied from 7 to 12 mm. A total of 129 stents was placed. Technical success was 97%. Thromboses occurred immediately after placement in two patients and within the first month in six; these were mainly due to residual obstruction. Eighty-two (93%) of 88 patients with a follow-up longer than 3 months had no recurrent symptoms. Restenosis caused by intimal hyperplasia inside the stent occurred in 10 patients; these required repeated intervention in only four cases. In the remaining six patients, no further complications occurred. Our results show that self-expanding endoprostheses are of value for improving the results of inadequate percutaneous transluminal angioplasty."
-How does ulinastatin affect polymorphonuclear leukocyte elastase levels and pulmonary vascular resistance after esophageal cancer surgery?,"Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations. To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment."
-How does platelet angiotensin II binding differ between normotensive and hypertensive pregnant women?,"Platelet angiotensin II binding sites in normotensive and hypertensive women. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy."
-What challenges do cytologists face when interpreting gastrointestinal cytology specimens?,"Gastrointestinal cytology. Since the development of the fiberoptic endoscope, laboratories have received cytologic specimens obtained from all segments of the gastrointestinal tract in increasing numbers to identify infectious agents and neoplasms. Adenocarcinomas generally are easily diagnosed and distinguished from reparative atypia, but their precursor lesions, dysplasia and adenomas, provide greater interpretive challenges. The same is true for such entities as malignant lymphomas. Most mesenchymal tumors remain outside the diagnostic capabilities of most cytologists."
-How do the expression patterns of alpha smooth muscle actin and desmin in perisinusoidal cells change between normal adult liver tissue and pathological liver conditions?,"Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs."
-What percentage of women in the Charleston tricounty area reported having a mammogram within the past year?,"Breast cancer screening in a biracial community: the Charleston tricounty experience. Breast cancer remains a major cause of death among women in South Carolina. Mammography, breast self-examination, and clinical breast examination are effective methods for early detection and subsequent mortality reduction. The Tricounty Breast Cancer Screening Survey assessed knowledge of these methods and recommendations among 503 women in the Charleston area. While 57% of all respondents reported performing breast self-examination at least once per month, 13% of blacks and 6% of whites reported that they do not know how to perform the procedure. Clinical breast examinations within the past year were reported by 69%, yet 11% of blacks and 4% of whites reported that they had never had the examination. More than one third (40%) of all 503 women reported ever having had a mammogram, and 22% reported having had one within the past year. However, 18% of the blacks and 5% of whites reported never having heard of the procedure. The major barriers to mammography appear to be the belief that women do not need regular mammograms and the lack of recommendations by their physicians. Survey results support the need for educating women about what the procedures are, the importance of using them regularly, and the means to comply with them."
-What was the primary objective of the study examining skin test reactivity in patients with lung and breast cancer?,"Skin test reactivity in patients suffering from lung and breast cancer. Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer."
-How does isradipine potentially protect against thromboembolic diseases in patients with mild hypertension?,"Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism. Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity."
-How do mothers adjust their babies' clothing and bedding in response to different temperatures and seasons?,"How mothers keep their babies warm. Details of room temperature, clothing, and bedding used by night and by day and in winter and in summer were recorded for 649 babies aged 8 to 26 weeks. Room temperature at night was significantly related to outside temperature and duration of heating. Total insulation was significantly related to outside temperature and to minimum room temperature, but there was wide variation in insulation at the same room temperature. High levels of insulation for a given room temperature were found particularly at night and in winter, and were associated with the use of thick or doubled duvets and with swaddling. At least half the babies threw off some or all of their bedding at night, and at least a quarter sweated. Younger mothers and mothers in the lower social groups put more bedclothes over their babies, and the latter also kept their rooms warmer. Many mothers kept their babies warmer during infections."
-What percentage of patients with a closed mastoid cavity were satisfied with their hearing aid?,"Use of hearing aids by patients with closed mastoid cavity. Twenty-five patients who had undergone a closed-cavity tympanomastoidectomy in our Unit and wore a hearing aid in the operated ear were reviewed, and information was recorded on the use of the aid, and the patients' impression about it. The information obtained was analysed and compared with similar data from 39 hearing aid users of similar age with no history of ear surgery. Eighty per cent of the patients with a closed mastoid cavity were satisfied with the aid, and no significant difference was found between the two groups regarding the impression about the aid (chi square 3.06, p = 0.08), or the problems with it, which, in most of the cases, were related to several changes of mould (chi square 2.19, p = 0.13). The various recorded parameters are discussed, and it is concluded that the patients with a closed mastoid cavity can tolerate a hearing aid in the operated ear at least as well as the control subjects with no ear surgery."
-What is the frequency of T-cell receptor delta gene recombination observed in acute lymphoblastic leukemias (ALL)?,"T-cell receptor delta gene recombination in common acute lymphoblastic leukemia: preferential usage of V delta 2 and frequent involvement of the J alpha cluster. A high frequency (greater than 80%) of acute lymphoblastic leukemias (ALL) exhibit a recombination of the T-cell receptor (TCR) delta chain locus. Interestingly, distinct TCR delta elements are preferentially used in immunologic subtypes. In a recent series of 201 children with common ALL (cALL) we observed a TCR delta rearrangement in 162 patients, 57% of the latter showing a hybridization pattern in Southern blots suggestive of a V delta 2 to D delta 3 recombination. To verify this interpretation and to elucidate in more detail the diversity of this common type of TCR delta recombination we amplified and sequenced the junctional region of nine cALL patients and cell line REH-6 by polymerase chain reaction (PCR). A V delta 2 D delta 3 recombination was confirmed in all cases; convincing evidence for the participation of D delta 1 or D delta 2 elements was not obtained. Eight of nine patients and REH-6 showed complete 5' D delta 3 boundaries within V delta 2 D delta 3 segments, a limitation of junctional diversity also detected in 50% of peripheral blood cell clones derived from two healthy probands. Notably, sequence identity at the V delta 2 D delta 3 junction was demonstrated for a cALL and one of the control clones. Another group of 35 of 162 cALL patients was characterized by V delta 2 rearrangements and biallelic deletion of J delta and C delta sequences. Using a J alpha consensus primer, PCR-directed sequence analysis demonstrated V delta 2 D delta 3 J alpha recombinations in all four cases analyzed by this approach. The J alpha segments of these patients differed, but were identical or homologous to published J alpha elements. Our data suggest a recombination pathway of the TCR delta/alpha locus leading to chimeric TCR alpha molecules, containing V delta and, remarkably, also D delta sequences."
-What were the antiproliferative effects of cytokines on squamous cell carcinoma of the head and neck cell lines in this study?,"Antiproliferative effects of cytokines on squamous cell carcinoma. A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly."
-What are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease?,"Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the ""symptom index."" Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain."
-What were the response rates and median survival times for patients in the chemotherapy arm (arm A) and the best supportive care arm (arm B) in this randomized trial of advanced non-small-cell lung cancer?,"A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer. From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy."
-How do tocotrienols affect liver cell damage and enzyme activities in rats treated with 2-acetylaminofluorene (AAF)?,"Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats. The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis."
-How does thrombolysis affect the incidence of late potentials in patients within 10 days of acute myocardial infarction?,"Effect of thrombolysis on the evolution of late potentials within 10 days of infarction. Patients with late potentials in the signal averaged electrocardiogram are more at risk of lethal arrhythmias in the period after acute myocardial infarction. To test the effects of thrombolysis on the incidence and evolution of late potentials, 158 consecutive patients were prospectively studied during the first 10 days after acute myocardial infarction. The study population consisted of two groups: 93 control patients treated conservatively and 65 patients treated with intravenous thrombolysis. Recordings of signal averaged electrocardiogram were obtained within two days and 7-10 days after infarction. The incidence of late potentials in the first two days after infarction was not significantly different in the thrombolytic and control groups (14% v 11.8%). By 7-10 days the incidence of late potentials among patients who underwent thrombolysis remained unchanged (14%); however, it increased significantly in the control group (11.8% to 22.5%). Thus thrombolysis seems to reduce the evolution of late potentials within 10 days of infarction. Because the risk of fatal arrhythmias is higher in patients with late potentials this study may partly explain the reduced mortality after thrombolysis."
-What is the rare condition described in this case report involving a patient with Sjogren's disease and a choroid plexus mass?,"Inflammatory pseudotumor of the choroid plexus in Sjogren's disease. We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjogren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass."
-What potential risks were associated with the colic medication mixture given to the eight infants in the study?,"Colic medication and apparent life-threatening events. Eight infants with histories of apnea and cyanosis were referred to the Southwest SIDS Research Institute for evaluation of apparent life threatening events (ALTE). All of the infants had been treated for colic with a 1:1 concentration of dimenhydrinate (Dramamine) and phenobarbital, hyoscyamine sulfate, atropine sulfate and scopolamine hydrobromide (Donnatal). The medication was pre-mixed by local pharmacists. A comprehensive work-up failed to reveal a cause for the ALTE in any infant. The Dramamine/Donnatal mixture was withdrawn and polygraphic evaluation was conducted. Cardiorespiratory abnormalities were identified in all eight infants and significant gastroesophageal reflux (GER) was documented in four. The possibility that colic medication contributes to cardiorespiratory instability and GER in vulnerable infants requires serious consideration and further evaluation."
-How did acetazolamide therapy impact the visual acuity and macular edema in this pseudophakic patient?,"A direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy. We report the case of a patient with pseudophakic cystoid macular edema whose visual acuity improved promptly with oral administration of 500 mg of acetazolamide extended-release capsules BID for two weeks. However, vision worsened again within two weeks of discontinuation of the treatment. On resumption of acetazolamide therapy for three weeks, and its slow withdrawal during the following three weeks, the macular edema eventually resolved, and vision returned to normal. Our observation provides a direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy and shows the importance of tapering the doses of this regimen."
-"What was the prevalence of headache with migrainous features among low-tension glaucoma, primary open-angle glaucoma, and normal subjects in this Japanese study?","Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese. We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients."
-How does high-resolution ultrasound help in evaluating cervical esophageal motility in patients with progressive systemic sclerosis?,"Cervical esophageal motility: evaluation with US in progressive systemic sclerosis. High-resolution ultrasound (US) showed that initial peristalsis propelled ingested soda smoothly and rapidly in 20 volunteers without symptoms who met both manometric and radionuclide esophageal scintigraphic (RES) criteria for normal motility. Twenty-eight patients with progressive systemic sclerosis were classified according to results of RES as follows: group 1, normal esophageal motility (three patients [11%]); group 2, hypomotility of the esophagus, excluding the cervical esophagus (18 patients [64%]); and group 3, hypomotility of the cervical esophagus (seven patients [25%]). In the seven patients of group 3, US demonstrated that an incomplete peristalsis sequence or a feeble peristalsis propelled the soda in a slow and/or to-and-fro motion with low velocities. In the other 21 patients (75%), the soda passed through the esophagus smoothly and rapidly. Retention of soda in the cervical esophagus was not limited to patients with hypomotility of the cervical esophagus. It is concluded that US is useful in evaluation of cervical esophageal motility."
-How does tumor-bearing affect albumin synthesis and degradation in mice compared to non-tumor-bearing animals?,"Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition. Hepatic albumin synthesis, serum albumin turnover, and hepatic albumin messenger RNA (mRNA) content were evaluated in mice bearing a transplantable low differentiated tumor (MCG 101). Results obtained on tumor-bearing mice were compared with results obtained from non-tumor-bearing animals that were either freely fed, food restricted so that their body composition was similar to tumor-bearing animals (pair-weighed), fed a protein-free diet for 5 days, or fasted for 48 hours. Tumor-bearing animals became hypoalbuminemic (33 +/- 5 vs. 44 +/- 3 g/L in freely fed mice), which could be explained by both depressed albumin synthesis (1.95% +/- 0.20% vs. 2.67% +/- 0.27%/h in freely fed mice) and increased albumin degradation. Pair-weighed and protein-calorie malnourished controls had reductions in albumin synthesis (1.81% +/- 0.18% and 1.67% +/- 0.17%/h, respectively) similar to tumor-bearing animals, and the starved controls had the lowest synthetic rates (1.07% +/- 0.10%/h). Albumin degradation was increased only in tumor-bearing animals. Hepatic albumin mRNA in undernourished animals was less (tumor bearing, 32% +/- 5%; pair weighed, 47% +/- 4%; 48 hours fasted, 18% +/- 2%; and protein-calorie malnourished, 26% +/- 3%) than 50% of the mRNA content in the livers of freely fed control mice. Messenger RNA-directed synthesis of albumin in vitro was also depressed to a variable degree in tumor-bearing and malnourished non-tumor-bearing controls. The hypoalbuminemia in tumor-bearing animals could not be prevented by daily injections of a prostaglandin synthesis inhibitor (indomethacin, 1 microgram/g body wt), but the hepatic acute phase protein serum amyloid P decreased from 157 +/- 12 to 103 +/- 9 micrograms/mL in indomethacin-treated tumor-bearing mice (P less than 0.01). It is concluded that increased albumin degradation seen in tumor-bearing animals cannot be explained by associated malnutrition, whereas tumor-associated malnutrition can explain to a large extent the depressed albumin synthesis. Decreased albumin synthesis in tumor-bearing animals correlated in part with a decreased quantity of liver albumin mRNA. The results of the current study are consistent with either a reduced transcription of the albumin gene or a change in albumin mRNA processing and stability communicated by anorexia and malnutrition."
-What is Cogan's syndrome and what are its potential neurological complications?,"Cogan's syndrome complicated by lacunar brain infarcts. Cogan's syndrome, nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction, is an uncommon disease of young adults, probably a manifestation of vasculitis. A 32 year old woman with this syndrome developed a thalamic syndrome with amnesia and dysphasia due to lacunar infarcts."
-"How does autologous bone marrow (ABM) infusion impact neutrophil count recovery in patients receiving high-dose cyclophosphamide, etoposide, and cisplatin?","Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin. Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients."
-What were the main findings of the endoscopic and histological examination in people with and without dyspepsia in this Norwegian population-based study?,"Prevalences of endoscopic and histological findings in subjects with and without dyspepsia OBJECTIVE--To examine the association between dyspeptic symptoms and endoscopic and histological diagnoses. DESIGN--Cross sectional study of people with dyspepsia and controls matched for age and sex identified by questionnaire survey of all inhabitants aged 20 to 69. Endoscopy and histological examination was performed with the examiner blind to whether or not the patient had dyspepsia. SETTING--Population based survey in Sorreisa, Norway. SUBJECTS--All people with dyspepsia and age and sex matched people without dyspepsia were offered endoscopy. A total of 309 people with dyspepsia and 310 without dyspepsia underwent endoscopy, giving 273 matched pairs. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses made according to internationally accepted standards. RESULTS--In all, 1802 of 2027 (88.9%) people returned the questionnaire. Of the 163 subjects who refused endoscopy, 114 were controls. Of five endoscopic and four histological diagnoses only peptic ulcer disease, endoscopic duodenitis, and active chronic gastritis were diagnosed significantly more often in people with dyspepsia. In all, 30% to 50% of the diagnoses of mucosal inflammation and peptic ulcer disease were made among subjects without dyspepsia, and only 10% of both those with and those without dyspepsia had normal endoscopic findings. CONCLUSIONS--The diagnostic findings, with possible exceptions of peptic ulcer disease and endoscopic duodenitis, showed no association of clinical value with dyspeptic symptoms. The small number of ""normal"" endoscopic findings in both those with and those without dyspepsia challenge well accepted endoscopic and histological diagnostic criteria with relation to the upper gastrointestinal tract."
-How are atrial natriuretic factor mRNA levels correlated with plasma concentrations and heart pressures in patients with heart failure?,"Transcription, storage and release of atrial natriuretic factor in the failing human heart. 1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure- and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atrial are related to left ventricular filling pressures in the failing human heart."
-What makes this case of Hodgkin's disease unique in the context of HIV-seropositive patients?,"Intracerebral Hodgkin's disease in a human immunodeficiency virus-seropositive patient. Intracerebral involvement of Hodgkin's disease (HD) is rarely described, with only 42 cases in the literature. Since the outbreak of the acquired immune deficiency syndrome (AIDS) epidemic, there has been an increasing number of human immunodeficiency virus (HIV)-infected (HIV+) persons who have diffuse non-Hodgkin's lymphoma and, more recently, atypical aggressive HD. The authors report the case of a patient with a history of intravenous drug abuse (IVDA) and Stage IVB HD who, after a drug-induced clinical remission, had intracerebral mixed-cellularity HD. This appears to be the first report of intracerebral HD in a person who is HIV+."
-How do enterocytes from patients with inflammatory bowel disease (IBD) differ from normal enterocytes in their interaction with T cells?,"Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment."
-What is the relationship between leukoaraiosis and ventricular size in patients with ischemic stroke?,"Leukoaraiosis and ventricular enlargement in patients with ischemic stroke. We studied the relationship between ventricular size and nonspecific periventricular lucency on computed tomograms (leukoaraiosis) in 192 patients with ischemic stroke. Leukoaraiosis did not occur in 21 patients less than 50 years of age; ventricular size could not be measured in an additional 29. Leukoaraiosis was graded from 0 to 4 on a semiquantitative scale; bicaudate, frontal horn, and posterior horn indices were used as measures of ventricular size. Patients with leukoaraiosis were older (difference between means 7 years, t = 5.3, df = 140, p less than 0.0001) and had larger bicaudate indices (difference between means 0.023, t = 3.54, df = 140, p = 0.0007) than patients without leukoaraiosis. Multiple regression analysis demonstrated that the effects of age and leukoaraiosis were independent. No effect of lesion type (cortical or lacunar infarct, or both) on bicaudate index could be demonstrated. Larger values for the bicaudate index were associated with a predominantly anterior location of leukoaraiosis. The frontal horn and occipital horn indices increased with age, but we could not find an effect of leukoaraiosis on these indices."
-What was the primary objective of the Canadian Atrial Fibrillation Anticoagulation (CAFA) Study?,"Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other ""positive"" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17)."
-What is the importance of anticoagulation therapy after stent implantation in venous bypass grafts?,"The importance of adequate anticoagulation to prevent early thrombosis after stenting of stenosed venous bypass grafts. Stent implantation in native coronary arteries may be complicated by acute thrombosis, despite the use of stringent anticoagulation. Thrombotic occlusion of stented venous grafts may occur less frequently, possibly because of the larger caliber of these grafts. We report our experience with 46 stents (Wallstent, Medinvent, Lausanne, Switzerland) implanted in 35 lesions of 24 consecutive patients (mean age 64 years, range 43 to 75). Two overlapping stents were implanted in seven patients, and three overlapping stents were positioned in two. After implantation, activated partial thromboplastin time was maintained at two to three times the control level by intravenous administration of heparin (160 to 550 mg daily) until thrombotest values were reduced 5% to 10% by acenocoumarol. Impending thrombotic occlusion was recognized in two suboptimally anticoagulated patients: patient A after implantation of four stents and patient B after anticoagulation therapy was discontinued because of acute upper gastrointestinal bleeding. Coronary artery bypass grafting was performed successfully in both patients. A third patient had a myocardial infarction on day 7 after stent implantation, in spite of adequate anticoagulation and optimal medical drug therapy. It is concluded that stringent anticoagulation therapy appears mandatory to maintain graft patency after stent implantation."
-How does the consumption of fish and sea mammals relate to blood pressure during pregnancy among Inuit women in the Keewatin region?,"Blood pressure during pregnancy in Canadian Inuit: community differences related to diet. OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted."
-Can early anti-pseudomonas chemotherapy prevent chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis patients?,"Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy."
-What is the relationship between the severity of primary biliary cirrhosis and pulmonary function in non-smoking patients?,"Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked. We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjogren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity."
-What are the major barriers that impede access to health care for millions of residents in the United States?,"Access to health care. One neurologist's perspective. Millions of residents of the United States have difficulty obtaining health care. Barriers impeding access to care include poverty, physical unavailability of health care services, absence of health insurance, and physicians unwilling to care for uninsured patients. Many patients do not successfully use health services because of educational, cultural, and language barriers. A major access barrier is lack of health insurance. Over 30 million people in the United States have none, the so-called medically indigent. Among them are over 3 million people with neurologic disorders. They have additional barriers to overcome because often they cannot work, cannot drive, have difficulty using public transportation, and have major cognitive and communication impairments. Medical and governmental bodies are debating solutions to the health care access crisis. Physicians should actively participate in this national debate. Neurologists should address the special needs of patients with neurological disorders."
-How did enflurane anesthesia affect the inducibility of ventricular tachycardia in patients undergoing cardiac ablation?,"Effects of enflurane on inducibility of ventricular tachycardia. The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventricular tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age +/- standard deviation 55 +/- 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with high-energy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before (""baseline study I"") and the second at the beginning of the ablation procedure (""baseline study II"") while the patient was awake and nonsedated. The third programmed stimulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide (""enflurane study""). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesia, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia."
-What was the mean age of patients diagnosed with endometrial adenocarcinoma in this Norwegian study?,"Endometrial adenocarcinoma in Norway. A study of a total population. Fifteen hundred sixty-six patients with adenocarcinoma of the endometrioid type (AC) were studied. These accounted for 78.9% of all 1985 patients with confirmed endometrial carcinoma diagnosed in Norway in the period 1970 through 1978. Four hundred and sixty-nine patients (29.9%) had well-differentiated tumors, 677 (43.2%) were moderately and 420 (26.8%) poorly differentiated. Eighty-one percent of the patients had surgicopathologic Stage I disease, 11% Stage II, 6% Stage III, and 2% Stage IV. Mean age at diagnosis was 62.1 years (range, 36 to 91). The crude 5-year and 10-year survival rates for all patients were 74.1% and 62.2%, respectively. Five-year crude survival was 86.8% for Grade 1 and 58.3% for Grade 3 tumors. The 5-year crude survival for patients with intramucosal tumors was 88.7% as opposed to 46.9% for patients with tumors infiltrating to the serosa. Sixty-six percent of the patients with vessel invasion survived for 5 years in contrast to 88.6% for patients without vessel invasion. Histologic grade, myometrial infiltration, vessel invasion, and lymphocyte reaction surrounding the tumor were strongly interrelated. Multivariate analysis showed that the age of the patient at the time of diagnosis was the most important single prognostic factor. Disregarding age, survival in operated patients was more dependent on the depth of myometrial invasion than on grade and stage of disease."
-What are the key characteristics of pain perception and coping strategies in patients with noncardiac chest pain (NCCP)?,"Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain."
-What problem can occur following craniofacial procedures involving periosteum stripping over the zygomatic maxillary complex?,"Periosteal suspension of the lower eyelid and cheek following subciliary exposure of facial fractures. Following craniofacial procedures that involve stripping of the periosteum and soft tissue over the zygomatic maxillary complex, descent of soft tissue with a decrease in anterior projection over the malar area and increase in fullness in the nasolabial fold have been seen to be a problem by these authors. Simple repositioning of the soft tissues to their normal anatomic position may be used to alleviate this problem."
-What is the primary advantage of using an uncemented porous-coated anatomic (PCA) hip system in total hip arthroplasty?,"Noncemented porous-coated anatomic total hip arthroplasty. In 1984, as an alternate to the acrylic fixation of the components of total hip arthroplasty, the use of an uncemented porous-coated anatomic (PCA) hip system with a beaded porous coating to achieve biologic fixation was initiated. Since then, 44 patients with cementless acetabular components and 35 patients with cementless femoral components have been followed for a minimum of 24 months and an average of 37 months. Harris hip scores averaged 90.5 at most recent follow-up intervals. No reoperations were necessary for failures of fixation or change in position of the acetabular component. Ominous roentgenographic signs such as progressive bead shedding, progressive radiolucencies, or progressive component migration have not occurred. Two femoral component revisions have been necessary: one for intractable pain and one for pain and roentgenographic loosening. Although thigh pain has been prevalent (20%), all patients have been accommodated and have retained stable hip scores. Progressive radiolucencies and progressive implant subsidence have been rare occurrences. The authors continue to use the cementless acetabular component in all cases of total hip arthroplasty in which initial stability can be obtained. It is their preference to cement the femoral component in patients over 65 or when initial stability cannot be achieved."
-What are interferons and how do they modulate the immune response?,"Immunologic effects of interferon. Interferons can be defined as a family of induced proteins sharing the capacity to exert pleiotropic effects on cell functions and to render cells resistant to virus infection. They are activating genes coding for a number of enzymes, most of which have not yet been characterized, and also by enhancing the synthesis of cell surface components. This enables interferons to modulate the immune response at different levels. This article will focus on the effects of interferon on antigen presentation, regulation of the immune response, activation of macrophage functions, and on its role in the pathogenesis of some diseases."
-What percentage of patients with neurosarcoidosis experienced seizures as the first manifestation of the disease?,"Clinical implications of seizures in neurosarcoidosis. Seizures are a recognized manifestation of neurosarcoidosis, but their clinical relevance is not well established. We reviewed the characteristics, clinical correlations, and prognosis of seizures in 79 patients with neurosarcoidosis. Thirteen (15%) of the 79 patients had seizures, and in eight patients (10%) a seizure was the first manifestation of neurosarcoidosis. These seizures were generalized tonic-clonic seizures in 12 patients (92%) and partial seizures in four patients (31%). The patients with neurosarcoidosis with seizures were more likely to have a progressive or relapsing clinical course and intracranial mass lesions (four patients [31%]), encephalopathy or vasculopathy (eight patients [62%]), or hydrocephalus (five patients [38%]). These central nervous system disorders, rather than the seizures per se, were responsible for most of the serious morbidity and the two deaths (15%) among our patients with seizures. Indeed seizure control was good in 11 (85%) of 13 patients treated with combinations of steroids and antiepileptic medications. Seizures are an important sign in neurosarcoidosis because they are associated with more severe and progressive or relapsing forms of central nervous system sarcoidosis and may be an early manifestation of such disorders."
-What were the MR imaging findings for hepatocellular carcinoma lesions before and after percutaneous ethanol injection (PEI)?,"Small hepatocellular carcinoma treated with percutaneous ethanol injection: MR imaging findings. Fifty-seven magnetic resonance (MR) imaging examinations were obtained at 0.5 T in 19 patients before and after percutaneous ethanol injection (PEI) for 23 hepatocellular carcinoma (HCC) lesions less than 3.5 cm in diameter. Seventeen patients also underwent MR imaging 6 months after completion of therapy. In 11 patients, computed tomography was performed before and after treatment. After PEI, fine-needle biopsy specimens were obtained in all cases. Before treatment, HCC lesions had low signal intensity on T1-weighted images in 13 cases, had the same signal intensity as normal liver parenchyma in six, and had high signal intensity in four; all 23 tumors had high signal intensity on T2-weighted images. After treatment and at 6-month follow-up, all 21 lesions that contained no malignant cells at fine-needle biopsy had high signal intensity on T1-weighted images and had low signal intensity on T2-weighted images. The remaining two HCC lesions in which tumor necrosis was not achieved with PEI displayed a different MR pattern, since the residual neoplastic tissue showed no change in signal intensity on either T1- or T2-weighted images. The authors conclude that MR imaging may be useful for evaluating the effectiveness of PEI in achieving tumor regression."
-"How does nicotine affect gastric mucosal damage, and what protective measures were found to reduce its harmful effects?","Nicotine induced gastric injury. A quantitative macroscopic and microscopic analysis of the protective effects of sucralfate and feeding. Nicotine, while an important component of cigarettes, does not cause gross gastric mucosal damage, although its microscopic effect remains unknown. We have evaluated the histology and the microvascular permeability of (a) the effect of nicotine alone or in combination with ethanol on the gastric mucosa of rats and (b) the effect of feeding and sucralfate on the mucosa of rats treated with nicotine and ethanol. Mucosal injury was assessed histologically by the depth of injury and microvascular permeability by the leakage of fluorescein isothiocyanate-labelled albumin. Our results show that nicotine induced microscopic mucosal damage and accentuated the damage induced by alcohol. The damaging effects on mucosa of nicotine and ethanol, alone or in combination, were reduced by pretreatment with sucralfate. Similarly, feeding reduced the degree of mucosal injury. Nicotine and ethanol increased leakage of albumin into the interstitium and the leakage was reduced after sucralfate pretreatment. This study substantiates the adverse effect of smoking on mucosal damage. Vascular factors are probably involved in the pathogenesis."
-How do fibroblasts from kidneys with interstitial fibrosis (FKIF cells) differ from normal kidney fibroblasts (NKF cells) in terms of growth and collagen synthesis?,"Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. Fibroblast cultures from normal human kidneys (NKF cells) and kidneys affected with interstitial fibrosis (FKIF cells) were analyzed for in vitro growth, differentiation dynamics, and collagen synthesis. FKIF cells are characterized by hyperproliferative growth, resulting in a prolonged mitotic lifespan, by an altered differentiation pattern, and by the expression of the FKIF cell-specific protein ""fibrosin"" (molecular weight 53 kd, isoelectric point [pi] 6.1). Furthermore, FKIF cells synthesize four to five times more total collagen per cell as compared with NKF cells, and the relative amounts of the collagen types produced (type I, III, and V) are significantly different from controls. Thus, the in vitro cell system of FKIF cells may help to elucidate the underlying mechanisms triggering the induction and progression of renal interstitial fibrosis in vivo."
-What is iniencephaly and how was the infant in this case report treated?,"Deformity correction and long-term survival in an infant with iniencephaly. Case report. The authors describe the case of a male infant who was diagnosed prenatally as having iniencephaly. Since birth, the child has grown, thrived, and undergone two successful operations to correct his cervical deformity. This case demonstrates that the iniencephaly defect is not uniformly fatal and that neurosurgical intervention may offer significant improvement in the cervical deformity."
-What did the statistical analysis reveal about the timing of chest pain onset in patients with myocardial infarction?,Circadian variation in the frequency of onset of chest pain in acute myocardial infarction. The time of onset of chest pain was studied prospectively in 1154 consecutive patients admitted to a coronary care unit with myocardial infarction during a five year period. Statistical analysis confirmed a previous finding in a retrospective study of a bimodal frequency distribution with peaks in the time of onset of chest pain between 2330 and 0030 hours and between 0630 and 0830 hours.
-How do angiotensin converting enzyme inhibitors like perindopril affect vascular resistance in spontaneously hypertensive rats (SHR)?,"Angiotensin converting enzyme inhibitors, regional vascular hemodynamics, and the development and prevention of experimental genetic hypertension. During the development of hypertension in young spontaneously hypertensive rats (SHR) vascular resistance is increased, particularly in the renal circulation, and, to a lesser extent, in the splanchnic bed. Treatment with angiotensin converting enzyme inhibitors in young SHR reverses the renovascular abnormalities more effectively than simple vasodilators, suggesting that the resistance changes may depend on angiotensin II. Perindopril treatment during the development of hypertension causes a reduction in blood pressure as a result of a fall in total peripheral resistance, which persists long after treatment is stopped. These long-term effects can be prevented by replacing angiotensin during perindopril treatment. Not all organs share the long-term resistance changes following perindopril treatment, which are most marked in the renal, splanchnic, and cerebral circulations. The heterogeneous patterns of regional vascular resistance during the development and after prevention of hypertension with angiotensin converting enzyme inhibitors in SHR suggest that local factors, for example, angiotensin II related to the tissue renin-angiotensin system or local adrenergic activity, may be important in the genesis of high blood pressure in this genetic model."
-How do oral glycopyrrolate and oral atropine compare in preventing cardiovascular depression during halothane anesthesia induction in infants?,"Is premedication with oral glycopyrrolate as effective as oral atropine in attenuating cardiovascular depression in infants receiving halothane for induction of anesthesia? The authors conducted a double-blind study to compare premedication with oral glycopyrrolate and oral atropine in prevention of bradycardia and hypotension during induction of anesthesia with halothane-N2O in 90 outpatient infants and children aged 1-18 mo who were randomized into three groups to receive either an oral placebo, oral atropine (0.02 mg/kg), or oral glycopyrrolate (0.05 mg/kg) approximately 1 h before induction of anesthesia. Heart rate and mean arterial pressure were measured before drug administration, just before induction of anesthesia, and every minute until surgical stimulation occurred. Glycopyrrolate, at the dose used, was significantly less effective than atropine in attenuating bradycardia during induction; neither glycopyrrolate nor atropine altered the incidence or degree of hypotension. Antisialagogic activity and side effects were comparable, except for significantly more flushing with atropine."
-What unusual hemorrhagic manifestations did the 19-year-old man with sickle cell anemia develop during a painful crisis?,"Case report: epidural and bilateral retroorbital hematomas complicating sickle cell anemia. Early in the course of a painful crisis, a 19-year-old man with known sickle cell anemia (SCA) developed a clinical picture that resembled either early cavernous sinus thrombosis or retroorbital and bifrontal microinfarcts. A brain computer tomography scan demonstrated bilateral retroorbital hemorrhages along with a left frontal epidural hematoma. In the absence of trauma, thrombocytopenia, or any other detectable hemostatic defect, this type of hemorrhagic manifestation in the setting of SCA has not, to our knowledge, been previously reported in the literature."
-What are the key differences between vigorous and classic achalasia according to the study?,"Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. Compared with classic achalasia, vigorous achalasia has been defined as achalasia with relatively high esophageal contraction amplitudes, often with minimal esophageal dilation and prominent tertiary contractions on radiographs, and with the presence of chest pain. However, no study using current manometric techniques has compared manometric, radiographic, and clinical findings in vigorous and classic achalasia or questioned the usefulness of making this distinction. Fifty-four cases involving patients with achalasia whose radiographic and manometric studies were performed within 6 months of each other were available for review. Patients with vigorous achalasia (n = 17), defined by amplitude greater than or equal to 37 mm Hg, and patients with classic achalasia (n = 37), defined as amplitude less than 37 mm Hg, had substantial overlap in radiographic parameters of esophageal dilation, tortuosity, and tertiary contractions. Manometric properties of repetitive waves and lower esophageal sphincter pressure and clinical aspects of chest pain, dysphagia, heartburn, and satisfactory responses to pneumatic dilation were similar in both forms of achalasia. A separate analysis of patients with mean contraction amplitude greater than 60 mm Hg revealed similar findings. It is concluded that use of amplitude as a criterion for classifying achalasia is arbitrary and of dubious value."
-What was the prevalence of obesity among American Indian adults according to the 1987 National Medical Expenditure Survey?,"Prevalence of obesity in American Indians and Alaska Natives. Obesity is an important risk factor for cardiovascular diseases and non-insulin-dependent diabetes, which are chronic diseases that afflict American Indians and Alaska Natives today. Because American Indians are not represented in most national health and nutrition surveys, there is a paucity of data on actual prevalence of obesity in American Indians. We estimated prevalence of overweight and obesity for American Indian adults, school-age children, and preschool children from existing data. The prevalence of obesity in adults was estimated from self-reported weights and heights obtained from a special survey of American Indians performed as part of the 1987 National Medical Expenditure Survey. Prevalence of obesity in American Indians was 13.7% for men and 16.5% for women, which was higher than the US rates of 9.1% and 8.2%, respectively. Obesity rates in American Indian adolescents and preschool children were higher than the respective rates for US all-races combined."
-How does dipyridamole echocardiography test (DET) help in detecting jeopardized myocardium after thrombolytic therapy?,"Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy. BACKGROUND. We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS. Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS. DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention."
-What percentage of postmenopausal women experienced persistent side effects from tamoxifen treatment in this study?,"Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance."
-What were the significant risk factors related to an obstructing tumor in Japanese patients with colorectal cancer?,"Prognostic factors in Japanese patients with colorectal cancer: the significance of large bowel obstruction--univariate and multivariate analyses. In order to define prognostic factors in colorectal carcinoma, univariate and multivariate analyses were carried out on data from 113 Japanese patients treated in a typical general hospital in Japan. In the univariate analysis, a poor prognosis was seen in those with poorly differentiated adenocarcinoma, in tumors that perforated the visceral peritoneum or that invaded directly other organs or structures (T4), in metastasis to the nodes along the main vascular pedicle (N3), in lymphatic permeation, in blood vessel invasion, in peritoneal dissemination, in Dukes C stage, and in those with lesions presenting with large bowel obstruction. Of these, only lymph node metastasis and peritoneal dissemination had an independent prognostic significance when a multivariate Cox analysis was performed. The significant risk factors related to an obstructing tumor were determined by multivariate logistic regression analysis. The significant variables were patient's age, nodal involvement and peritoneal dissemination. Since lymph node metastasis and peritoneal dissemination proved significant in both multivariate analyses, we propose that the presence of large bowel obstruction is not an independent prognostic factor in patients with colorectal carcinoma. In poor-risk patients who have an obstructing tumor, a staged operation should be attempted for definitive curative surgery."
-How do the clinical manifestations of loiasis differ between endemic and non-endemic populations?,"Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis."
-What percentage of elderly patients in the primary care setting reported having at least weekly heartburn?,"Prevalence of gastroesophageal reflux in elderly patients in a primary care setting. Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER--none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed."
-What percentage of laboratory and nursing training programs made the hepatitis B vaccine available to their students?,"Availability and use of hepatitis B vaccine in laboratory and nursing schools in the United States. Hepatitis B is a well-documented occupational hazard for health care workers, including both laboratory and nursing personnel. Since the development of effective hepatitis B vaccines, the Immunization Practices Advisory Committee (ACIP) has recommended that health care workers receive the vaccine. In this study, 78 laboratory training programs and 83 nursing training programs were surveyed regarding availability and usage of hepatitis B vaccine. The hepatitis B vaccine was made available to students in 81 percent of the laboratory programs and 23 percent of the nursing programs. In those programs making the vaccine available, only 59 percent of the laboratory programs and 5 percent of the nursing programs reported a high (greater than 75 percent) use by students. Concern about cost and payment for the vaccine was the most common reason (80 percent) noted by laboratory schools that did not have hepatitis B vaccination programs for students. Of the nursing schools that did not have vaccine programs, 58 percent had not yet considered a program. At laboratory schools with vaccination programs, who paid for the vaccine (hospital or school versus student) was among the most important determinants for vaccine usage by students. These findings point out that some laboratory schools and many nursing schools have not applied the ACIP recommendations to their own programs. Educational efforts and creative payment plans for the vaccine are needed to increase the availability and use of hepatitis B vaccine among laboratory and nursing students."
-What was the purpose of using polymerase chain reaction in this study of multiple sclerosis patients?,"Analysis of retroviral sequences in the spinal form of multiple sclerosis. The polymerase chain reaction was used, in a blind study, to look for retroviral sequences in DNA extracted from the peripheral blood mononuclear cells of 11 patients with the spinal form of multiple sclerosis (MS). Control subjects consisted of 7 patients with other neurological diseases and 5 healthy blood donors. Three sets of oligonucleotides were used. They could detect all known human oncoretroviruses, lentiviruses, or spumaretroviruses. The primers recognized conserved sequences in the long terminal repeats of the proviral DNA. Control experiments showed that the primers crossreacted within the human immunodeficiency virus or human T-cell lymphotropic virus group and that they provided the expected level of sensitivity. Therefore the assay could have detected not only known human retroviruses but also new related members. In spite of this, no retroviral sequences were detected in either the MS or the control specimen."
-What was the main objective of the clinical trial involving the E5 murine monoclonal IgM antibody?,"A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated."
-How does complete Freund's adjuvant (CFA) treatment affect diabetes onset and insulitis in NOD mice?,"Prevention of insulitis and diabetes onset by treatment with complete Freund's adjuvant in NOD mice. In studies of immune cell defects in autoimmune diabetes mellitus, we observed that complete Freund's adjuvant (CFA) prevented the onset of diabetes when injected into 8- to 10-wk-old prediabetic nonobese diabetic (NOD) mice. The prevalence of the onset of diabetes in the CFA-injected versus uninjected NOD mice was 2 of 81 (2.5%) vs. 231 of 379 (61%) among females and 2 of 44 (4.5%) vs. 83 of 336 (25%) among males, respectively. The incidence of histologically identifiable insulitis was significantly reduced in CFA-treated prediabetic female NOD mice (18%) compared with the incidence in female age-matched controls (70%). Splenocytes or Mac-(1+)-enriched splenocytes from CFA-treated NOD mice, when cotransferred with splenocytes from diabetic mice, reduced the incidence of diabetes provoked by diabetic splenocytes in vivo. In the spleen, CFA injection induced sustained increases in cell proliferation and an associated major increase in the numbers of an immature cell type that expressed the Mac-1 surface antigen. In CFA-treated NOD mice, lymphocytes derived from the spleen failed to respond in vitro to stimulation by the mitogen concanavalin A or by anti-CD3. When cocultured, Mac-1+ cells, enriched from the splenocytes of CFA-treated mice, suppressed concanavalin A- or anti-CD3-induced proliferation of T lymphocytes derived from either the spleen or thymus of untreated NOD mice. Therefore, treatment with CFA prevents the development of diabetes, and concomitantly, insulitis while stimulating the generation of splenic suppressor cells that are capable of suppressing diabetogenic T-lymphocyte function in vivo and in vitro."
-What was the purpose of the study comparing intermittent intravenous injections and patient-controlled analgesia for sickle cell crisis pain in the emergency department?,"Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department. BACKGROUND.--The purpose of this study is a prospective assessment of morphine sulfate administration by intermittent intravenous (IV) injections (Int-IV) vs patient-controlled analgesia (PCA) in patients in the emergency department (ED) with sickle cell crisis pain. METHODS.--Patients were at bed rest and received intravenous hydration. Linear analog scale for pain intensity and verbal pain scale, level of alertness, and vital signs were assessed prior to therapy, every 60 minutes thereafter, and at the time of discharge from the ED. Patients were randomized to Int-IV or PCA. During phase 1, patients in the Int-IV group received morphine sulfate 4 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 2 mg bolus then 1.0 mg with a 6-minute lockout. During phase 2, patients in the Int-IV group received morphine sulfate 8 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 5 mg bolus then 2.7 mg with a 10-minute lockout. Data were analyzed by unpaired t test, general linear modeling, Mann-Whitney U test, and chi 2 test. RESULTS.--During phase 1, 10 patients (28.3 +/- 7.3 years) received Int-IV and 10 patients (33.9 +/- 12.5 years) received PCA. Treatment groups did not differ significantly regarding duration of pain, amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, level of alertness, or vital signs except for a significantly lower final respiratory rate with Int-IV. In phase 2, 12 patients (28.4 +/- 5.6 years) received Int-IV and 13 patients (26.8 +/- 8.1 years) received PCA. The PCA groups had a significantly shorter elapsed time between onset of pain and treatment (7.3 +/- 6.5 hours) when compared with the Int-IV group (18 +/- 16.9 hours). Treatment groups did not differ significantly with respect to total amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, vital signs, or level of alertness. The PCA group had a significant reduction in length of stay in the ED during phase 2 when compared with phase 1. The ED discharge rate and the incidence of side effects did not differ significantly between groups. CONCLUSION.--At both the low- and high-dose regimens, PCA is equally safe and effective and may be used in place of Int-IV administration of morphine in the ED treatment of sickle cell crisis pain."
-What was the main finding of the study regarding alcohol consumption and supraventricular tachyarrhythmias?,"Alcohol consumption of patients with supraventricular tachyarrhythmias other than atrial fibrillation. We studied the recent alcohol consumption and other possible precipitating factors in 99 consecutive patients (53 men and 46 women) all under 65 years of age with sustained re-entry and automatic supraventricular tachyarrhythmias and compared them with those of two groups of controls. One control group was derived from the Emergency Room patients and matched for age and sex; the other group (44 men, 22 women, mean age 48.7 years) was randomly selected from the general out-of-hospital population. There were 50 patients with supraventricular tachycardia, 30 with atrial flutter, and 19 with paroxysmal atrial tachycardia. Coronary heart disease (14% of patients), hypertension (10%), and dilated cardiomyopathy (6%) were the most prevalent cardiovascular diseases associated with the arrhythmias. The self-reported alcohol consumption of patients with arrhythmias during the week preceding the arrhythmia did not differ significantly from that of hospital or population controls, although significantly more patients than controls had liver enzyme levels above normal; neither were there any significant differences between the groups regarding prevalence for alcoholism as judged by the CAGE questionnaire. The results were essentially similar when patients with supraventricular tachycardia and those with intra-atrial tachyarrhythmias (flutter and paroxysmal tachycardia) were separately compared with the controls. We conclude that alcohol consumption, although a risk factor for atrial fibrillation, is not associated with the induction of other supraventricular tachyarrhythmias in patients of working age."
-What are the potential health risks associated with prolonged inhalation of mineral spirits?,"Mineral spirits inhalation associated with hemolysis, pulmonary edema, and ventricular fibrillation. A previously healthy 42-year-old woman developed severe dyspnea, chest discomfort, and malaise several hours after prolonged exposure to concentrated vapors from mineral spirits. On the way to the hospital, she sustained a cardiopulmonary arrest; on arrival several minutes later, she was found to be in ventricular fibrillation and was resuscitated. Her hospital course included slowly resolving cardiac abnormalities, amnesia, noncardiogenic pulmonary edema, abrupt hemolytic anemia, sustained rhabdomyolysis, and other metabolic abnormalities. It is highly probable that this syndrome represented acute and near-lethal toxicity caused by the inhalational exposure to the petroleum distillate known as mineral spirits. It is important that physicians be aware of this syndrome in order to recognize it on presentation and to warn patients of the risk of such toxic exposure."
-What was the outcome of ciprofloxacin treatment for patients with refractory chronic bacterial prostatitis caused by Escherichia coli?,Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months. A total of 16 men suffering from refractory chronic bacterial prostatitis caused by Escherichia coli was treated with ciprofloxacin for 4 weeks. After a median followup of 30 months (range 21 to 36 months) 10 of the 16 patients were considered cured as judged by bacteriological results and clinical symptoms. In 2 men a second ciprofloxacin regimen obviously showed success also. In 2 patients ciprofloxacin therapy failed and in 2 therapy had to be discontinued due to side effects of the central nervous system.
-What are the four categories of hypertension in pregnancy?,"Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years? High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive."
-What are the key characteristics of desmoplastic small cell tumors based on microscopic and immunohistochemical findings?,"Desmoplastic small cell tumors of the peritoneum coexpressing mesenchymal and epithelial markers. Desmoplastic small cell tumors arising diffusely within the abdomen and lacking an apparent organ of origin are rare. Most previously reported cases occurred in children, but young adult patients also have been described. Light microscopic examination shows the tumors to be composed of nests of small cells surrounded by an abundant desmoplastic stroma. Immunohistochemical findings reveal multidirectional differentiation with coexpression of cytokeratin, milk fat globule, neuron-specific enolase, Leu-7, desmin, and vimentin. Electron microscopic examination demonstrates paranuclear condensations of intermediate filaments. The authors describe two patients who died of their disease, despite aggressive chemotherapy and surgical intervention."
-What were the mortality rates for ischaemic heart disease and cerebrovascular disease among different ethnic groups in England and Wales during the 1970s and 1980s?,"Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade."
-What was the average peak effect of botulinum toxin treatment for tremors in this study?,"Botulinum toxin treatment of tremors. We report the results of an open trial of botulinum toxin (Botox) in the treatment of 51 patients with disabling tremors, classified as dystonic (14), essential (12), combination of dystonic and essential (22), parkinsonian (1), peripherally induced (1), and midbrain (1). The average age of the patients was 55.8 years, and duration of symptoms was 13.9 years. During a total of 160 treatment visits, an average of 242 +/- 75 units of Botox was injected per visit in cervical muscles of 42 patients with head tremor and 95 +/- 38 in forearm muscles of 10 patients with hand tremor; one patient was injected in both. The average peak effect for all patients was rated as 3.0 (0 to 4 scale). Thirty-five (67%) patients improved (peak effect greater than or equal to 1). The average latency from injection to response was 6.8 days, and the average duration of maximum improvement was 10.5 weeks. Local complications, lasting an average of 20.6 days, were noted in 17 (40%) patients injected for head tremor, consisting chiefly of dysphagia in 12 (29%), transient neck weakness in four (10%), and local pain in two (5%). Six (60%) patients with hand tremor had transient focal weakness. EMG recordings showed decreased amplitude of EMG bursts after Botox treatment. The results of this pilot study indicate that Botox injections can be used to control tremor in patients in whom other forms of therapy have failed."
-What complications did the patients with chickenpox pneumonia experience in this case report?,"Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation."
-How does tumor cell DNA content (ploidy) relate to recurrence rates in colorectal cancer patients?,"A prospective evaluation of the effect of tumor cell DNA content on recurrence in colorectal cancer. Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy."
-What are the key challenges emergency physicians face when treating patients with headaches?,"Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache."
-What genetic modifications cause the nonsecretory alpha-chain disease plasma cells to produce only membrane-form alpha-chain?,"Gene deletions force nonsecretory alpha-chain disease plasma cells to produce membrane-form alpha-chain only. We studied a case of nonsecretory alpha-chain disease. The proliferating plasma cells contained a short transcript coding for a truncated membrane-form alpha 1-chain. The productive alpha-gene bore several noncontiguous deletions affecting the VHDJH and CH1 regions. Two deletions were accompanied with peculiar insertions containing duplications. The first insertion contained an acceptor splice site and was present in part in the mature transcript, thus coding for an abnormal aminoterminal peptide. Another deletion located 3' to CH3 eliminated the polyadenylation site of secreted-form alpha-mRNA. As a result, only membrane-form alpha mRNA was present in the tumoral plasma cells, thus explaining the nonsecretory phenotype of the disease. Comparison of cDNA and genomic sequences showed that the previously undescribed human alpha membrane region is encoded by a single exon, beginning with two alternate acceptor splice sites, and comprises either 65 or 71 amino acids."
-What is the purpose of the anterior sternal retraction technique in reoperative median sternotomy?,Anterior sternal retraction for reoperative median sternotomy. The incidence of reoperative median sternotomy for repeat cardiac surgery is increasing. Reoperative median sternotomy is associated with a higher morbidity and mortality than first-time cardiac surgery. A portion of this morbidity and mortality may be due to direct injury to the heart and great vessels in the process of reopening the sternum. We report a new technique utilizing anterior sternal retraction that allows division of adhesions between the undersurface of the sternum and the heart and great vessels under direct vision. This technique enables the surgeon to minimize the risk of serious injury to these underlying structures during reoperative cardiac surgery.
-How does physical overdistension of the ventricular wall affect the production of atrial natriuretic peptide (ANP) in cardiomyocytes?,"Physical overdistension converts ventricular cardiomyocytes to acquire endocrine property and regulate ventricular atrial natriuretic peptide production. Atrial natriuretic peptide (ANP) is present in adult atria but at very low concentrations in normal adult mammalian ventricles. In the atria, the production of ANP is regulated by physical distension of the atrial wall. The same phenomenon was investigated in the ventricles of rats and men. Cardiac tissues from human ventricular aneurysm (n = 5), spontaneously hypertensive rats (n = 30), and rats that had overloaded left ventricles induced by surgery (n = 84) were studied with the methods of light microscopic immunocytochemistry, electron microscopic immunogold staining, and RNA-RNA tissue in situ hybridization. It was found that the levels of ANP gene expression, ANP immunoreactivity, and ANP-containing specific granules in the overburdened ventricles were elevated and their degrees of fluctuation were directly proportional to the force of physical distension applied to the ventricular cardiomyocytes. In rats, ANP mRNA and ANP immunoreactivity returned to the control level seven days after the ventricular overload was surgically released. The changes of ANP and its mRNA in the ventricles were related more closely to the changes of intraventricular pressure than to cardiocytic hypertrophy. In addition, ANP immunoreactivity was demonstrated in Purkinje cells and periarteriolar cardiomyocytes in the ventricles of normotensive rats. In conclusion, physical overstretch of the ventricle wall is likely to be the triggering factor affecting ventricular cardiomyocytes to acquire endocrine property, and also to regulate the production of ventricular ANP, thereby contributing to the control of the blood volume and the blood pressure."
-What were the key functional outcomes observed in children with sickle-cell disease who had experienced strokes?,"Functional outcomes of children with sickle-cell disease affected by stroke. The nature and degree of functional recovery after stroke in children with sickle-cell disease (SCD) has not been extensively investigated. The purpose of this study was to evaluate retrospectively the functional status of 14 SCD children who had had strokes and to compare them with age-matched and gender-matched SCD children who had not had strokes. By doing so, we would be able to quantify the eventual physical and cognitive functional outcomes of survivors of stroke secondary to SCD and assess the impact of stroke on these patients. These children (five boys and nine girls) with SCD and stroke(s) were 11.6 +/- 4.3 years of age (range five to 18 years). They experienced one to three strokes at a mean age of 6.1 +/- 5.2 years (range one to 17 years). A series of tests were administered to these subjects to evaluate physical and psychosocial functions. These tests were performed at least one year after the latest stroke. This study showed that all of the SCD-stroke children were physically independent. Only a few had impairments of hand functions and mild difficulties in self-care activities. However, most of these children demonstrated intellectual deficits ranging from borderline to moderate mental retardation, reduced language functions ranging from low normal to retarded range, and problems in adjustment. Intelligence quotient of the children with SCD-stroke(s) was significantly lower than those of age-matched and gender-matched nonstroke SCD children, suggesting that stroke caused an adverse effect on the cognitive functioning of these children. The results indicate that in the SCD-stroke children psychosocial deficits outweighed physical disabilities."
-What percentage of appendicitis cases were perforated during the 5-year review at the Guthrie Medical Center?,"Acute appendicitis. A 5-year review. A startling 31 per cent rate of perforated appendicitis in 1984 prompted a 5-year review at the Guthrie Medical Center. An increase over previous rates of 13 per cent and 0 per cent in 1964 and 1944 was confirmed in this study. Perforation accompanied 44 of 240 cases of appendicitis (18.3%); diagnostic accuracy in 295 cases undergoing operation was 81.4 per cent. Groups at risk for perforation were patients in the first decade of life (34.3% with perforations) and those over 50 years of age (48% perforated). Perforation rates were generally inversely related to accuracy. Accuracy was poorest in women in the second to fourth decade or those in the mid-portion of the menstrual cycle. When the appendix was not perforated, complications occurred in 8.7 per cent of patients while 29.5 per cent with a perforation had a complication. The mean hospital stay was prolonged by 2.5 days if the appendix was perforated. An increased awareness of the risk by both the public and physicians is essential to reduce the number of perforations."
-What method did the study suggest for determining the optimal time to remove a nephrostomy tube?,Intrarenal pressure following pyeloplasty or percutaneous surgery. In a study of 37 patients it was shown that recording the intrapelvic pressure is a safe and reliable means of judging the best time to remove a nephrostomy tube. No post-operative complications were encountered and the procedure has the added advantage of avoiding the use of X-rays.
-What is oncocytic metaplasia of the pharynx and how was it typically discovered in the reviewed cases?,"Oncocytic metaplasia of the pharynx. Oncocytic metaplasia of the pharynx has been infrequently described, with only two previous cases in the literature. With the advent of panendoscopy during the last decade, however, a better understanding of this histopathologic diagnosis is desirable. Thirty-three cases are reviewed, with thirty occurring in the nasopharynx. This was most commonly discovered as an unrelated finding during endoscopic evaluation of a head and neck mass or malignancy in twenty-two patients, either histologically after random biopsy or after biopsy of small but visible lesions. An additional eight cases manifested otitis media or eustachian tube dysfunction. The histology, terminology, and benign clinical nature of these lesions are discussed."
-How did the researchers use a cholera toxin transgene to study the effects of cAMP on pituitary growth hormone-producing cells?,"Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering."
-What was the outcome of the balloon dilatation attempts on fetuses with critical aortic stenosis?,"Balloon dilatation of the aortic valve in the fetus: a report of two cases. Because they had irreversible damage to the left ventricular myocardium none of 12 patients with critical aortic stenosis diagnosed prenatally survived after postnatal treatment. This experience prompted three attempts at intrauterine balloon dilatation of the aortic valve in two fetuses with this condition. On each attempt the balloon catheter was successfully delivered to the left ventricle. In the first fetus the aortic valve was not crossed and the fetus died the next day. In the second fetus the balloon was correctly positioned across the aortic valve and inflated in the valve ring. After delivery, a further balloon angioplasty was performed; this relieved the stenosis but the patient died five weeks later from persisting left ventricular dysfunction related to endocardial fibroelastosis. Balloon angioplasty is feasible in fetal life but the prognosis depends on the ability of the relief of stenosis to limit, prevent, or allow regression of left ventricular damage before delivery."
-What is the new method described for dealing with late-presenting spontaneous esophageal ruptures?,"New method for dealing with late-presenting spontaneous esophageal ruptures. A new technique is described for dealing with late-presenting spontaneous esophageal ruptures. This method requires only a short period of general anesthesia to drain the periesophageal abscess by a drainage tube inserted into the abscess cavity from the esophagus with the aid of a gastroscope and fluoroscopy. Gastric fluids are diverted from the esophageal rupture with a gastrostomy, and a jejunostomy is used for enteral feeding. The esophagus is retained, and closure of the fistula with resumption of normal swallowing is documented with serial sinograms."
-What anaesthetic technique was used for a parturient with severe mitral stenosis and pulmonary hypertension during an urgent Caesarean section?,"Alfentanil for urgent caesarean section in a patient with severe mitral stenosis and pulmonary hypertension. We present the case of a parturient with severe mitral stenosis and pulmonary hypertension who received general anaesthesia using alfentanil for urgent Caesarean section. Alfentanil promoted haemodynamic stability and allowed immediate postoperative extubation. Epidural morphine provided postoperative analgesia. This combination permitted early ambulation and prevention of thromboembolism. A disadvantage of this technique, neonatal respiratory depression, was promptly reversed with a single dose of naloxone. The anaesthetic management of mitral stenosis in pregnancy is discussed and the neonatal pharmacokinetics of maternally administered alfentanil are presented."
-What is the specific genetic mutation identified in the patient with adenosine deaminase deficiency (ADA-SCID)?,"Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). We have identified a previously unrecognized missense mutation in a patient with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The mutation is a G646-to-A transition at a CG dinucleotide and predicts a glycine-to-arginine substitution at codon 216. Computer analysis of secondary structure predicts a major alteration with loss of a beta-pleated sheet in a highly conserved region of the protein. The basepair substitution also generates a new site for the restriction enzyme BstXI in exon 7 of the genomic DNA. Digestion of genomic DNA from the patient and from his parents revealed that he was homozygous for the mutation and that his mother and father were carriers. This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase. Analysis of DNA from 21 additional patients with ADA-SCID and from 19 unrelated normals revealed that, while none of the normal individuals showed the abnormal restriction fragment, two of the 21 patients studied were heterozygous for the G646-to-A mutation."
-What are the key factors for survival in cases of spontaneous abdominal arteriovenous fistulae?,"Spontaneous abdominal arteriovenous fistulae: report of eight cases and review of the literature. The spontaneous rupture of an abdominal aneurysm into an adjacent major vein results in a profound and rapidly worsening haemodynamic disturbance. Survival depends on prompt diagnosis and closure of the fistula at operation. Eight cases are reported and modes of presentation, diagnostic criteria and management principles are reviewed in a detailed analysis of 148 cases in the English literature."
-How does the acidity of nebulized salbutamol solution affect oxygen levels in wheezy infants?,"Hypoxaemia after nebulised salbutamol in wheezy infants: the importance of aerosol acidity. The effect of nebulised iso-osmolar, preservative free, but acidic salbutamol solution was studied in 34 acutely wheezing infants aged 1-17 months. Transcutaneous oxygen pressure (TcPO2) and oxygen saturation (SO2) fell significantly during the first five minutes after nebulisation with further deterioration at 15-20 minutes. Ten of these infants were followed up for another two hours and showed slight improvement. Even after the second hour TcPO2 had not reached baseline values. Three months later the response to salbutamol and a placebo of equal acidity (pH 3.9) was studied in 11 infants from the same group, now free of symptoms. Lung function tests were included and showed no significant changes in specific conductance and volume corrected maximum expiratory flows (Vmax at functional residual capacity/thoracic gas volume). However, hypoxaemia occurred after the acidic placebo with a significant drop of TcPO2 (mean 0.9 kPa); SO2 decreased similarly but this did not reach significance. After salbutamol there was a further significant deterioration of mean TcPO2 (1.4 kPa) and of SO2. These results show that beside a possible pharmacological effect of salbutamol the acidity of the aerosol also induces hypoxaemia in infants."
-How does the study validate the technique for quantifying myocardial blood flow using oxygen-15-labeled carbon dioxide and positron emission tomography?,"Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. BACKGROUND. Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. METHODS AND RESULTS. The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001). CONCLUSIONS. PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients."
-What was the average cost of averting death or severe disability through neurosurgical intervention in this study?,"Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community."
-What morphological abnormalities were observed in the sural nerves of patients with inherited tendency to pressure palsy (ITPP)?,"Uncompacted inner myelin lamellae in inherited tendency to pressure palsy. Nerves in patients with inherited tendency to pressure palsy (ITPP) are susceptible to degrees of traction or compression which in nonaffected persons do not induce neuropathic symptoms or deficits, conduction block of fibers, or electromyographic changes characteristic of the disorder. Two observations suggest a widespread asymptomatic abnormality of nerves: 1) low conduction velocity of clinically unaffected nerves, and 2) focal thickenings (tomacula) on teased myelinated fibers of clinically unaffected sural nerves. Sural nerves from five patients and five healthy subjects were assessed for morphologic abnormality in ITPP that might account for the susceptibility of nerves to compression. Teased nerve fibers showed a higher frequency of segmental demyelination or remyelination, or both (p less than 0.003). The mean frequency of fibers showing focal myelin thickenings was 57 +/- 10% in ITPP and 0% in controls. In electron micrographs, regions of uncompacted myelin lamellae, usually affecting the innermost lamellae and extending for a variable distance averaging 9 +/- 4 microns were seen in 11 +/- 4% of fibers in ITPP. None were found in the control nerves. The finding of uncompacted myelin lamellae may suggest an abnormality of myelin composition or of interaction of Schwann cells and axons accounting for the increased susceptibility to pressure palsy, tomaculous formation, or demyelination. From electron microscopic evaluation of serial skip sections we infer that myelin of tomaculae is in continuity with internodal myelin and is reduplicated (full-thickness or cleaved layers are longitudinally or circumferentially folded-back on themselves)."
-What are the key characteristics of mouse mannose-binding proteins A and C based on their molecular characterization?,"Molecular characterization of the mouse mannose-binding proteins. The mannose-binding protein A but not C is an acute phase reactant. Mannose-binding proteins play a role in first line host defense against a variety of pathogens. We report the molecular cloning of two mouse mannose-binding proteins designated A and C based on their close identity with their rat homologues. The deduced amino acid sequence of the mouse mannose-binding proteins, as with rat and the human forms, have an NH2 terminus that is rich in cysteine that stabilizes a collagen alpha helix followed by a carboxyl- terminal carbohydrate binding domain. We further show that the mouse mannose-binding protein A mRNA, as with the human, is induced like the acute phase reactant serum amyloid P protein, yet the expression of mouse mannose-binding protein C mRNA is not regulated above its low baseline level. The expression of both mannose-binding proteins A and C mRNA is restricted to the liver under basal and stress conditions."
-What is the purpose of the clinical trial involving Cronassial in patients with Chagas' disease?,"Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo."
-What is the clinical significance of nonvisualization in HIDA scans after endoscopic retrograde sphincterotomy in patients with and without cholelithiasis?,"Biliary patency imaging after endoscopic retrograde sphincterotomy with gallbladder in situ. Clinical impact of nonvisualization. We prospectively performed nuclear biliary patency imaging (HIDA scanning) in 62 patients who had undergone endoscopic retrograde sphincterotomy for management of pancreaticobiliary disease with their gallbladders in situ. Elective cholecystectomy was not recommended because of advanced age, comorbidity, or absence of gallstones. All patients had patent cystic ducts at endoscopic retrograde cholangiopancreatography balloon cholangiography. Eighteen (29.1%) of 62 patients had nonvisualizing HIDA scans, and in 44 (70.9%) of 62 visualization was normal or delayed. Six cholecystectomies were required for colic (n = 1), acute cholecystitis (n = 4), and acute cholecystocholedochal fistula with cholangitis (n = 1). Among the patients with cholelithiasis and nonvisualization (n = 13), five (38.5%) required surgery, whereas only one (4.8%) of 21 patients with cholelithiasis and visualization required surgery. Nonvisualizing HIDA scans are frequent (30%) after endoscopic retrograde sphincterotomy and have no clinical relevance in patients without cholelithiasis but predict the need for cholecystectomy within 16 months in 38.5% of patients with cholelithiasis."
-How did damage to the fornix affect memory function in the two patients after colloid cyst removal?,"Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans."
-What was the outcome of autologous bone marrow transplantation (ABMT) for patients with neuroblastoma in this study?,"High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method."
-What innovative approach was used to place a stent in a patient with malignant biliary obstruction complicated by ascites?,"Malignant biliary obstruction complicated by ascites: transjugular insertion of an expandable metallic endoprosthesis. Although the transjugular approach has long been used to provide safe access to the liver, it has not been used for placement of stents in biliary obstruction. The recent development of an expandable metallic endoprosthesis now makes this method more feasible. The case of a patient with malignant biliary obstruction complicated by ascites is presented herein. Palliation was achieved with an expandable biliary endoprosthesis placed by the transjugular-hepatic vein approach."
-How do spousal caregivers and adult children differ in their caregiving responsibilities and support received for brain-impaired adults?,"Time spent caregiving and help received by spouses and adult children of brain-impaired adults. Caregivers for brain-impaired adults differ in living arrangements, amount of time spent giving care, and assistance received from family and friends and from paid help depending on their kin relationship and employment status. Spousal caregivers devote large amounts of time to caregiving, and husbands spend no less time than wives. Most caregivers receive little assistance from other family members and friends, but husbands receive more than others. Employed spouses receive more paid help than those without jobs, but employment does not affect the amount of paid help received by adult daughters."
-How can surgical interventions help manage epilepsy in patients with brain tumors?,Epilepsy and brain tumors: implications for treatment. Primary intraparenchymal tumors of the brain are important etiologic factors in partial or focal epilepsy. Indolent low-grade gliomas may be associated with a long-standing seizure disorder refractory to medical treatment. Surgical resection of the neoplasm and the epileptogenic area may render patients seizure-free. Removal of the tumor alone may also be associated with an excellent survival rate and surgical outcome. Conventional neurosurgical procedures are restricted in patients with tumors that are deep-seated lesions or involve functional cerebral cortex. Computer-assisted stereotactic surgical procedures have been developed for biopsy and resection of intra-axial brain-mass lesions. Stereotactic tumor resection may allow pathological determination of intracranial lesions and produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.
-What is labyrinthitis ossificans and how does it potentially impact cochlear implantation?,"Labyrinthitis ossificans: histopathologic consideration for cochlear implantation. Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased."
-What health risks can welding pose to workers according to the given context?,Fume fever and reactive airways dysfunction syndrome in a welder. I have reported a case of fume fever and concurrent reactive airways dysfunction syndrome (RADS) after welding. The RADS should be added to the list of potential hazards associated with welding.
-What are the key immunohistochemical findings in carcinosarcomas of the uterus and ovary?,"Carcinoma (malignant mixed mullerian [mesodermal] tumor) of the uterus and ovary. Correlation of clinical, pathologic, and immunohistochemical features in 29 cases. We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed mullerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases."
-How does Borrelia burgdorferi stimulate glioma cells to secrete interleukin-6 in the context of neuroborreliosis?,"Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6. Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors."
-What percentage of eyes maintained visual acuity at 20/60 or better after cataract extraction following brachytherapy for choroidal malignant melanoma?,"Cataract extraction after brachytherapy for malignant melanoma of the choroid. Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid."
-What unique finding was observed in the cardiac examination of a 29-year-old man and his 4-year-old son?,"Familial aneurysms of the interventricular septum. Congenital aneurysms of the interventricular septum were found in a 29 year old man and his four year old son. Both were symptom free. In both, M mode and cross sectional echocardiography showed an aneurysm in the mid-muscular trabecular portion of the ventricular septum with considerable paradoxical motion of the aneurysmal segment. Otherwise the chamber dimensions, intracardiac structures, and cardiac function were normal for age. Congenital aneurysm of the interventricular septum is rare and these familial cases may be unique."
-What was the mean increase in graft diameter observed in the ultrasound measurements compared to the manufacturer's recorded box size?,"Clinical significance of aortic graft dilation. To determine if there is a relationship between aortic graft dilation and graft complications, 443 serial ultrasound studies performed on 106 patients were analyzed. Of 443 studies, 243 were done retrospectively on 59 patients from 3 to 144 months (mean, 38 months) after graft implantation. Forty-seven additional patients were studied prospectively, with direct measurement of external graft diameter after aortic clamp release. Subsequent ultrasound examinations at 3, 6, 9, and 12 months and then annually (n = 200) were routinely performed. Mean follow-up was 12 months (range, 3 to 48). Knitted double velour Dacron prostheses were used in all cases reported in this study. This cohort was culled from our ongoing graft surveillance program, which includes grafts of other materials and manufacturers. Comparison of the manufacturer's recorded box size with follow-up ultrasound measurements in all cases demonstrated a mean increase in graft diameter of 3.7 mm (23%). Little dilation occurred after 1 year. In 47 patients with direct graft diameter measurements taken after declamping, an immediate mean increase of 1.7 mm (11%) was noted. Dilation was not related to surgical indication (aneurysm vs occlusive disease) or hypertension. Analysis of the 10% segment of the series with the greatest dilation (mean, 39%) did not demonstrate a predilection for graft complications. No significant dilation was noted in the single cases encountered of femoral and iliac anastomotic aneurysms and perigraft seroma. Although dilation of knitted Dacron grafts is to be anticipated, no association between graft dilation and graft complications was found in this series."
-How can quantitative motor performance tests help in early detection of Parkinson's disease?,"Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are ""at risk for"" Parkinson's disease and other related disorders."
-What were the independent prognostic factors identified in the multivariate analysis of primary sclerosing cholangitis patients?,"Natural history and prognostic variables in primary sclerosing cholangitis. The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation."
-What were the two major psychological insights about orthognathic surgery patients that emerged from this research?,"Psychological aspects of orthognathic surgery: how people respond to facial change. This study was undertaken to explore the motivations and problems shared by adult orthognathic surgical patients over the age of 25. Objective findings included demographic information and reasons for seeking surgery. The majority of 65 respondents cited functional problems as their primary reason for seeking treatment. Eighty-nine percent were pleased with esthetic changes, and 83% responded that the functional problem had been corrected. For most, the greatest discomfort related to the surgery was the postoperative intensive care unit. Two of the most common side effects of the surgery were the loss of sensation in the lips and chin area and a short period of depression. Women had depression more often than men but were more enthusiastic about the final results of the procedure. Two major areas of interest to surgeons emerged from the research. First, although women have functional problems, the majority seem to have a desire for cosmetic improvement. Having a functional problem seemed to provide the psychological permission necessary to spend the time and money for a cosmetic change. The second point focused on the need for good communication between surgeon and patient. The patients who were more positive toward the procedure and more satisfied with the results were those who were better informed and who thought they had a good system of communication with the orthodontist, surgeon, and their respective staffs."
-How does partial ischaemia affect free-radical damage compared to total ischaemia in rabbit skin flaps?,"Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals. 1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-"How does the volume of low-grade, latent prostate cancer tissue relate to the incidence of high-grade clinical cancer?","Low-grade, latent prostate cancer volume: predictor of clinical cancer incidence? We hypothesize that each cell in low-grade (Gleason grade 1-3) prostate cancer tissue is at risk of transformation into a cell which produces a high-grade (Gleason grade 4-5) clinical cancer after a short period of growth. As a consequence, the volume of low-grade, latent cancer tissue in the prostate glands of men at any age determines their incidence rate for high-grade, clinical cancer a few years later. Autopsy and incidence data for both white men and black men support this conclusion, with a tumor growth period of about 7 years. The transformation rate is similar for black men and for white men, about 0.024 high-grade cancers per year per cm3 of low-grade, latent cancer volume. Our hypothesis explains the infrequent occurrence of clinical cancer despite the high prevalence of latent cancer, the steep rise of clinical cancer incidence with age despite the slow rise of latent cancer prevalence with age, and the disparities in clinical cancer incidence among some populations despite their similar latent cancer prevalence. This hypothesis suggests that low-grade cancer volume is a critical determinant of clinical cancer risk."
-"What were the electrophysiologic effects of UK-68,798 in a canine model of sudden coronary death?","The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent. The electrophysiologic and antifibrillatory properties of UK-68,798 were studied in vivo in a conscious canine model of sudden coronary death. Electrophysiologic testing was performed on conscious male mongrel dogs (14.5-21.5 kg) 3 to 5 days after surgical induction of an anterior myocardial infarction by occlusion (2 h)-reperfusion of the left anterior descending coronary artery. Compared to saline-treated control animals, UK-68,798 at a dose of 0.9 mg/kg i.v. did not (P = .083) suppress the induction of ventricular tachycardia by programmed electrical stimulation. Six of 12 UK-68,798-treated dogs remained inducible, whereas 10 of 12 vehicle-treated dogs responded to electrical induction of arrhythmia. When compared to predrug inducibility, UK-68,798 significantly (P = .007) reduced the incidence of programmed electrical stimulation-induced ventricular tachycardia. In five of the six dogs inducible after UK-68,798 administration, the cycle length of the induced ventricular tachycardia was prolonged (P = .007) compared to the predrug cycle length. Heart rate, PR interval and QRS duration were not affected by UK-68,798 administration. The rate-corrected QT interval was prolonged (P less than .05) by UK-68,798. The ventricular effective refractory period was increased by UK-68,798 (158 +/- 7 msec, predrug vs. 185 +/- 7 msec, postdrug). Subsequent to programmed electrical stimulation, a 150 microA anodal current was applied to the luminal surface of the left circumflex coronary artery to induce transient episodes of posterolateral ischemia in response to electrolytic injury of the vessel wall."
-What is the significance of the leucocyte alkaline phosphatase (LAP) score in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS)?,"Use of leucocyte alkaline phosphatase (LAP) score in differentiating malignant from benign paraproteinaemias. The leucocyte alkaline phosphatase (LAP) score of peripheral blood neutrophils was examined in 20 patients with multiple myeloma and compared with the score in 18 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean (95% confidence limit) LAP score in those with multiple myeloma was 186 (169-218) compared with 92 (64-120) in the MGUS group. In the multiple myeloma group all but one patient had a high LAP score, irrespective of disease. No cause for raised LAP, such as infection, was present in any of the patients with multiple myeloma. In the MGUS group six patients had a raised LAP score; in two of them another cause for such a rise was present (autoimmune haemolytic anaemia and primary thrombocythaemia). In neither group did the LAP score correlate with duration of the disease, bone marrow plasma cell count, paraprotein concentration, haemoglobin, total white cell or neutrophil count. It is concluded that a normal LAP count in patients with paraproteinaemia suggests a benign condition, but a raised count does not indicate a malignant condition."
-How do ATP-dependent K+ channels modulate pulmonary vascular responses during severe hypoxia in ferret lungs?,"ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 less than or equal to 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs [( glucose] less than 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14 +/- 0.4 mM had the same effect. As a result, initial vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCl, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events."
-What is the cost-effectiveness of periodic colonoscopic surveillance after the removal of an adenomatous colon polyp?,"Colonoscopic surveillance after polypectomy: considerations of cost effectiveness. OBJECTIVE: To assess the cost effectiveness of the current recommendation that persons who have had an adenomatous colon polyp removed have periodic colonoscopic surveillance at fixed and regular intervals. DESIGN: Cost-effectiveness analysis using data from the medical literature in a simulation model to estimate the costs of and the risk for perforation associated with periodic colonoscopic surveillance for a 50-year-old man followed for 30 years. MAIN RESULTS: A program of colonoscopy every 3 years would incur cumulatively a 1.4% risk for colon perforation, a 0.11% risk for perforation-related death, and direct physician costs of $2071 for colonoscopy (discounted at 5%). If a 50-year-old man's cumulative remaining risk for death from cancer is 2.5% after the removal of a single small adenoma and if effectiveness of colonoscopic surveillance every 3 years is 100%, then one death from cancer could be prevented by doing 283 colonoscopies, incurring 0.6 perforations, 0.04 perforation-related deaths, and direct physician costs of $82,000. If surveillance were 50% effective and the cumulative remaining risk for death from cancer were 1.25%--a plausible scenario--1131 colonoscopies would be required to prevent one death from cancer, incurring 2.3 perforations, 0.17 perforation-related deaths, and physician costs of $331,000. CONCLUSIONS: The cost effectiveness of colonoscopic surveillance is very sensitive to estimates of the cumulative remaining risk for death from cancer after polypectomy as well as to surveillance efficacy. For persons whose remaining risk for death from cancer may be low, such as persons with a single small adenoma, recommendations for colonoscopic surveillance at fixed and regular intervals may be excessively costly."
-What was the purpose of asking donors questions about gastrointestinal symptoms during blood donation screening?,"Screening blood donors for gastrointestinal illness: a strategy to eliminate carriers of Yersinia enterocolitica. Recent reports of fatal transfusion-associated Yersinia enterocolitica sepsis prompted a study of the feasibility of adding a question to the routine donor health history as a method of reducing this risk. In three American Red Cross blood centers, 11,323 donors were asked one of two questions about gastrointestinal symptoms during their health history screenings. Affirmative responses were obtained from 0.6 or 4.0 percent of the donors, depending on how the question was asked. In one center, more than 6 percent of donors gave affirmative answers. The efficacy of asking a relatively simple question about gastrointestinal symptoms as a way of preventing Y. enterocolitica should be evaluated further, because relatively large numbers of donors may respond affirmatively. Other methods of reducing the risk of transfusion-associated Y. enterocolitica infection should be pursued."
-What were the key findings of the study comparing chorionic villus sampling and amniocentesis as prenatal genetic diagnostic procedures?,"Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis. Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital."
-How can an immunocytochemical (ICC) panel help improve the diagnostic accuracy of cytologic examination in serous effusions?,"Immunocytochemical panel for the identification of malignant cells in serous effusions. The cytologic diagnosis of malignancy in serous effusions can be challenging. An immunocytochemical (ICC) panel using commercially available antibodies (to carcinoembryonic antigen [CEA], epithelial membrane antigen [EMA], B72.3, Leu-M1, cytokeratin [CK], leukocyte common antigen [LCA], S-100 protein, and vimentin) was applied to cell blocks fixed in methyl Carnoy's solution that were from 55 consecutive pleural, peritoneal, and pericardial fluid specimens. The results were correlated with data from clinical records and routine cytologic studies. Final cytologic diagnoses included 26 of adenocarcinoma and 1 of mesothelioma. The remaining 28 cases were considered to be benign (reactive) proliferations. EMA, CEA, B72.3, and Leu-M1 were present in 96%, 77%, 58%, and 42% of adenocarcinomas, respectively. These determinants were absent in the mesothelioma and the reactive effusions, although anti-CEA yielded strong background staining of inflammatory cells. The CK markers identified malignant cells in 93% of cases, but consistently stained mesothelial cells as well. Antivimentin strongly labeled mesothelial cells in all cases, with weak to absent staining of malignant cells. In 3 of 26 carcinoma cases (12%), the ICC panel identified malignant cells that were not recognized initially on routine cytologic examination. In 1 of 26 cases (4%), the panel was falsely negative. Use of this approach can improve the diagnostic accuracy of cytologic examination of serous fluids. The ICC panel is especially helpful when atypical mesothelial proliferation is present, or in cases that are clinically suspect for malignancy, but cytologically negative because there are only a few malignant cells, or those that are cytologically bland."
-What was the cause of the patient's failure to regain consciousness after a total hip replacement surgery?,"Failure to awaken after general anaesthesia secondary to paradoxical venous embolus. A patient is presented who failed to regain consciousness after an apparently uneventful nine-hour revision of a total hip replacement. There were no clinically important haemodynamic changes during the operation, and oxygen saturation, capnography and acid base balance were normal throughout. Postop CT of the head showed a large left MCA infarct with midline shift. At autopsy, the patient was found to have a previously unsuspected patent foramen ovale, and a venous embolus in the left internal carotid artery, which probably had originated from the periprostatic venous plexus with a large infarct in the distribution of the left anterior and middle cerebral arteries. The authors conclude that massive paradoxical venous emboli can occur during surgery with minimal haemodynamic changes."
-How did the healing rates of gastric ulcers compare between enprostil and ranitidine in this clinical study?,"Gastric ulcer healing: a comparison of enprostil versus ranitidine. Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers."
-How does the Fos-Jun protein complex potentially suppress osteocalcin gene transcription during osteoblast proliferation?,"Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the proliferation period of osteoblast phenotype development. We present evidence that AP-1 (HeLa cell-activating protein 1) sites residing within two promoter elements of the osteocalcin gene bind the Fos-Jun protein complex: the osteocalcin box (OC box; nucleotides -99 to -76), which contains a CCAAT motif as a central element and influences tissue-specific basal levels of osteocalcin gene transcription, and the vitamin D-responsive element (VDRE; nucleotides -462 to -440), which mediates enhancement of osteocalcin gene transcription. Gel electrophoretic mobility-shift analysis demonstrated high AP-1 binding activity in proliferating osteoblasts and dramatic changes in this activity after the down-regulation of proliferation and the initiation of extracellular-matrix mineralization in primary cultures of normal diploid osteoblasts. Methylation interference analysis established at single nucleotide resolution that purified recombinant Fos and Jun proteins bind in a sequence-specific manner to the AP-1 sites within the VDRE and OC box. Similarly, an AP-1 motif within a putative VDRE of the alkaline phosphatase gene, which is also expressed after the completion of proliferation, binds the Fos-Jun complex. These results support a model in which coordinate occupancy of the AP-1 sites in the VDRE and OC box in proliferating osteoblasts may suppress both basal level and vitamin D-enhanced osteocalcin gene transcription as well as transcription of other genes associated with osteoblast differentiation--a phenomenon we describe as phenotype suppression. This model is further supported by binding of the Fos-Jun complex at an AP-1 site in the type alpha I collagen promoter that is contiguous with, but not overlapping, the VDRE. Such a sequence organization in the collagen VDRE motif is compatible with vitamin D modulation of collagen but not with osteocalcin and alkaline phosphatase expression in proliferating osteoblasts."
-What potential therapeutic effect of pentoxifylline was observed in patients being treated for claudication of the lower extremities?,Pentoxifylline in the treatment of vascular impotence--case reports. Vascular impotence is a common medical problem for which available therapies are limited. Three impotent patients observed in the authors' practice who were receiving pentoxifylline for treatment of claudication of the lower extremities spontaneously reported improved sexual function. A controlled trial of pentoxifylline for vascular impotence may be warranted.
-How can gonadotropin-releasing hormone analogs help improve ovulation and pregnancy rates in patients with polycystic ovary syndrome?,"Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs. Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog."
-What are the common pathologic features shared by ANCA-associated vasculitides?,"Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. Antineutrophil cytoplasmic autoantibodies (ANCA) are a useful diagnostic serologic marker for the most common forms of necrotizing vasculitis, provide a means of categorizing vasculitides so that diagnostically useful shared pathologic and clinical characteristics can be recognized, and offer insight into the pathogenesis of previously idiopathic diseases. ANCA-associated vasculitides can be categorized into a number of distinctive clinicopathologic categories, eg, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary renal syndrome, microscopic polyarteritis nodosa, leukocytoclastic angiitis, and necrotizing and crescentic glomerulonephritis. At least the latter four syndromes can also be caused by other ANCA-negative immunopathogenic mechanisms, eg, immune complex deposition. Therefore, thorough diagnostic classification requires both an assessment of clinicopathologic category, as well as an assessment of immunopathologic category. Although different ANCA-associated vasculitic syndromes have distinctive clinical and pathologic features, all ANCA-associated vasculitides share a number of common pathologic features, ie, focal distribution, necrosis, and neutrophil infiltration. ANCA assays have very good sensitivity and specificity for ANCA-associated diseases, but the prevalence of these diseases in the patient population being analyzed must be taken into consideration when determining the predictive value of a test result. As with all serologic tests, ANCA results must be integrated with other clinical and pathologic data in order to reach the most accurate diagnostic conclusion."
-How does chronic xerostomia affect esophageal acid exposure and potential injury?,"Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency."
-What immunohistochemical markers were used to distinguish sarcomatoid liver carcinomas from true sarcomas?,"An immunohistochemical study of sarcomatoid liver carcinomas. Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver."
-What were the main causes of death in patients who underwent emergency surgery for colorectal cancer?,"Outcome after emergency surgery for cancer of the large intestine. The data for 77 patients with colorectal cancer who underwent emergency surgery for acute intestinal obstruction (57 patients) or perforation (20 patients) within 24 h of admission were evaluated. The patients were older and had more advanced disease than patients undergoing elective surgery for colorectal cancer. Emergency surgery for carcinoma of the right colon consisted of primary resection in 95 per cent of cases and was followed by a 28 per cent mortality rate. Perforated tumours of the left colon and rectum were managed by primary resection in 82 per cent of cases with a 22 per cent mortality rate. In contrast, obstructing tumours of the left colon and rectum were treated by primary resection in 38 per cent of cases with a 6 per cent mortality rate, and by primary decompression in 62 per cent of cases with a 25 per cent mortality rate. The overall postoperative mortality rate was 23 per cent and increased with advanced tumour disease, perforation and peritonitis. Cardiac decompensation and intraabdominal sepsis were the major causes of death. Although the long-term survival rate following emergency surgery was worse than after elective surgery, improvements in outcome should be achieved by better management of the initial emergency situation."
-What are the key characteristics of pain perception and coping strategies in patients with noncardiac chest pain (NCCP)?,"Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain."
-What are the key diagnostic features of superficial thrombophlebitis?,"Acute venous thrombosis. Therapeutic choices for superficial and deep veins. Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence."
-What were the key findings of the decision-analysis study on prophylactic intravenous immune globulin in chronic lymphocytic leukemia patients?,"Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia [see comment] BACKGROUND. A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS. We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality-adjusted life expectancy. RESULTS. Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS. Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective."
-What was the key finding regarding pain perception during gastric distension in patients with chronic idiopathic dyspepsia?,"Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research."
-What percentage of lower respiratory tract infections in Thai children were associated with viral infections and Chlamydia trachomatis during the study period?,"A study of nonbacterial agents of acute lower respiratory tract infection in Thai children. From January 1986 to December 1987, 596 children less than 5 years of age with lower respiratory tract infection (LRI)--manifested as laryngitis, croup, bronchitis, bronchiolitis, and pneumonia--were studied for evidence of infection with respiratory tract viruses Mycoplasma pneumoniae, and Chlamydia trachomatis. Of the 596 children in the study, 315 were ambulatory and 281 were hospitalized. Virologic studies included isolation and rapid diagnosis of virus from specimens of nasopharyngeal aspirate (NPA) and serologic studies of blood samples. Cultures of NPA for C. trachomatis were performed for children less than 6 months of age who had pneumonia. Of the LRI cases, 45% were associated with viral infections of the respiratory tract and 12.1% were associated with C. trachomatis. Respiratory syncytial virus (RSV) accounted for 45.2% of infections with viral agents and was associated with acute bronchitis, acute bronchiolitis, and pneumonia. Parainfluenza type 3 virus was the most common virus found in conjunction with laryngitis and croup. The incidence of infections due to RSV peaked in July and August, while that of infections due to parainfluenza viruses peaked in February and March; influenza viruses and adenoviruses were isolated throughout the year."
-What are the key considerations for physicians when managing febrile seizures and counseling parents?,Febrile seizure. Caring for patients--and their parents. Management of febrile seizure involves diagnosis and treatment of the underlying cause and assessment of risk factors for recurrence. What should physicians tell anxious parents about this frightening occurrence? Is prophylaxis with anticonvulsant agents appropriate? The authors address these questions and discuss the changing approach to management of febrile seizure.
-What was the miss-rate of large colorectal polyps found in this prospective blinded trial of tandem colonoscopy?,Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps. We prospectively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring tandem colonoscopy. Sixty-three lesions greater than or equal to 1 cm in size were discovered and none were missed. Confidence intervals of 95% are a miss-rate of 0 to 4.6%. We conclude that less than 5% of large colorectal polyps are missed during the index colonoscopic examination in a well-prepared colon.
-What was the outcome of the six-year-old boy with symptomatic cerebral swelling complicating diabetic ketoacidosis?,"Symptomatic cerebral swelling complicating diabetic ketoacidosis documented by intraventricular pressure monitoring: survival without neurologic sequela. A six-year-old boy developed symptomatic cerebral swelling four hours after the initiation of treatment for newly diagnosed diabetes mellitus complicated by ketoacidosis. Ventriculostomy documented intracranial pressure over a two-day period. Increased intracranial pressure unresponsive to controlled hyperventilation and sedation was treated by administering a diuretic and by drainage via a ventriculostomy. Intracranial pressure monitoring was a useful adjunct in management of this rare, but often lethal, complication of diabetes mellitus. One year later, both school performance and the results of a neurologic examination were normal."
-What were the independent predictors of heart failure identified in the study using multivariant stepwise logistic regression analysis?,"Predicting left heart failure after a myocardial infarction: a preliminary study of the value of echocardiographic measures of left ventricular filling and wall motion. Heart failure occurs from both systolic and diastolic dysfunction. To determine whether simple Doppler echocardiographic measures of left ventricular filling could improve upon the ability of systolic function to predict heart failure after infarction, patients with acute myocardial infarction were studied within the first 36 hours by Doppler and two-dimensional echocardiography. Forty-eight patients who did not have heart failure before the Doppler echocardiographic study and who did not have myocardial revascularization, moderate or severe mitral regurgitation, or other complications during recovery were monitored for 6 months or to the onset of heart failure (n = 10). The univariate predictors of heart failure were age (p less than 0.05), anterior infarction (p less than 0.05), early diastolic peak filling velocity (p = 0.05), filling velocity with atrial systole (p less than 0.05), the ratio of these velocities (p less than 0.001), the percentage of filling with atrial systole (p less than 0.001), and the wall motion score index (p less than 0.001). However, the only independent predictors of heart failure by use of multivariant stepwise logistic regression analysis were the wall motion score index (p less than 0.05) and either the ratio of early and late peak filling velocities (p less than 0.001) or the percentage of filling with atrial systole (p less than 0.001). The combined use of a measure of systolic function and measures of the relative contribution of atrial systole to ventricular filling were useful predictors in identifying patients likely to develop subsequent heart failure after myocardial infarction."
-What were the key clinical patterns observed in paediatric urolithiasis across different stone types in this retrospective study?,"Clinical patterns of paediatric urolithiasis. A series of 270 paediatric stone patients was studied retrospectively according to the clinical pattern of urolithiasis (age and sex, stone location, stone analysis, recurrence rate) and aetiology of stone disease (infection, anatomical, metabolic or idiopathic). Infection stones occurred earliest and more commonly in males and were usually upper tract struvite calculi related to Proteus infection. Anatomical stones were most commonly associated with pelviureteric junction (PUJ) obstruction and had a high recurrence rate, despite surgical correction of obstruction. Idiopathic stones most resembled those found in adult urolithiasis by virtue of occurring latest, being sited in the ureter more often and being more frequently composed of calcium oxalate. Metabolic stones were most frequently calcium phosphate or cystine and virtually all were renal. They comprised the smallest group but had the highest recurrence rate."
-How did the response to desflurane differ between normal and malignant hyperthermia-susceptible swine in the study?,"Desflurane is a trigger of malignant hyperthermia in susceptible swine. Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility."
-How does dipyridamole improve the specificity of thallium-201 single-photon emission computed tomography in detecting coronary artery disease in patients with left bundle branch block?,"Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole. Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB."
-"How are depression, chronic fatigue, and chronic pain interconnected in terms of their psychological and neurobiological factors?","Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery."
-What prognostic factors were found to be associated with a higher recurrence rate in papillary carcinoma of the thyroid in this retrospective study?,"Prognostic factors in papillary carcinoma of the thyroid. In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hurthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men."
-How does local thrombin synthesis contribute to platelet recruitment and thrombus stabilization in heparinized blood?,"Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization."
-How does the p53 gene mutation correlate with the progression of chronic myelocytic leukemia (CML) in this patient's case study?,Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
-What is the relationship between silent myocardial ischemia and autonomic dysfunction in diabetic patients?,"Detection of silent myocardial ischemia in diabetes mellitus. The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as greater than or equal to 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as greater than or equal to 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia."
-What was the purpose of the study comparing the use of dexapolyspectran drops in one ear versus the control ear after tympanostomy tube insertion?,"Use of prophylactic otic drops after tympanostomy tube insertion. In a 1-year prospective study, 60 patients with chronic serous otitis media underwent bilateral tympanocentesis with tube insertion. The right ear was treated with dexapolyspectran (a solution consisting of polymyxin B sulfate, neomycin sulfate, sulfonamide, and hydrocortisone) intraoperatively and for 72 hours afterward, and the left ear served as the control. All patients were followed up at weekly intervals for the first month. Five (8.3%) out of 60 experimental ears had purulent otorrhea within the first 14 days after surgery, compared with eight (13.3%) out of 60 control ears. Statistical analysis showed no difference between the two groups."
-What was the treatment approach for the patient with pancreatic islet cell carcinoma and how long did the remission last?,"Pancreatic islet cell carcinoma with hypercalcemia: complete remission 5 years after surgical excision and chemotherapy. A 45-yr-old man who presented with hypercalcemia was found to have an abdominal mass that was a pancreatic islet cell carcinoma. Although clinical features were suggestive of primary hyperparathyroidism, his parathyroid hormone level was not elevated. The patient underwent a radical resection of the pancreatic neoplasm which was situated in the tail of the gland. After surgery, the serum calcium fell within the normal range, suggesting that the tumor was responsible for production of a parathyroid hormone-like substance. Because of malignant histologic features of the lesion, a chemotherapeutic regimen including 5-fluorouracil and streptozotocin was indicated. Five years later, the tumor has remained in total remission."
-What specific mitochondrial DNA mutation was found to be associated with myoclonus epilepsy and ragged-red fibers (MERRF) in this study?,"Rapid detection of the A----G(8344) mutation of mtDNA in Italian families with myoclonus epilepsy and ragged-red fibers (MERRF). We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy (Shoffner et al. 1990). We confirmed this association in five of seven Italian MERRF pedigrees. The mutation was specific for the MERRF trait, because it was never found in mtDNA of non-MERRF individuals, including 14 normal and 110 diseased controls. Our study corroborates the idea that the A----G(8344) mutation is the most frequent and widespread genetic cause of MERRF."
-What is the relationship between arachidonic acid metabolism and brain edema in different types of brain pathologies?,"""Ex vivo"" release of eicosanoid from human brain tissue: its relevance in the development of brain edema. The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The ""ex vivo"" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05)."
-How does pentoxifylline affect intestinal microvascular blood flow during resuscitation from hemorrhagic shock?,"Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock. We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow."
-What was the primary aim of the study investigating the antihypertensive effects of ketanserin?,"The acute and chronic antihypertensive effects of ketanserin cannot be explained by blockade of vascular serotonin, type 2, receptors or alpha 1-adrenergic receptors. The mechanism underlying the antihypertensive effect of acute and chronic administration of ketanserin was investigated in eight hypertensive patients. Intrabrachial artery infusions of serotonin and the selective alpha 1-adrenergic receptor agonist methoxamine were given before and 1 hour after a single oral dose of 20 mg ketanserin and after 4 weeks of treatment with 20 to 40 mg twice daily. Blood pressure was reduced by ketanserin both after the initial dose (p less than 0.01) and after 4 weeks of treatment (p less than 0.01). During placebo, serotonin, 1 ng/kg/min, increased forearm blood flow by 51% +/- 9% (p less than 0.01), whereas the highest dose induced a decrease in flow (-33% +/- 6%; p less than 0.01). Methoxamine elicited a vasoconstriction (p less than 0.001). These effects of serotonin and methoxamine were not influenced by either the initial dose of ketanserin or after 4 weeks of treatment. It is concluded that serotonin cannot be considered a general endogenous pressor agent in these patients. The antihypertensive effects of ketanserin cannot be attributed to either vascular alpha 1-receptor or serotonin, type 2, receptor blockade."
-What was the survival rate of patients with paracetamol overdose who underwent liver transplantation in this study?,"Liver transplantation after paracetamol overdose. OBJECTIVE--To evaluate the role of liver transplantation after paracetamol overdose. DESIGN--Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING--Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES--Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS--30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION--Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol."
-What medical condition did the 31-year-old alcoholic woman suffer from and how was it treated?,The perils of Pauline: visual loss in a tippler [clinical conference] A 31-year-old alcoholic woman who smoked had subacute visual loss. She was treated for tobacco-alcohol amblyopia with subsequent improvement in vision.
-Does delaying antibiotic therapy by 48 hours affect the recurrence rate of group A beta-hemolytic streptococcal (GABHS) pharyngitis?,"Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate."
-What are the endocrine and reproductive effects observed in patients after total body irradiation for haematological malignancy?,"Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. The endocrine and reproductive sequelae of total body irradiation for haematological malignancy have been studied in 21 patients (11 male) who were treated with 10 Gy in five fractions or 12 or 13.2 Gy in six fractions over 3 days. Eighteen patients (eight male) aged 16-49 years underwent dynamic tests of the hypothalamic-pituitary axis with insulin hypoglycaemia, thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone stimulation and basal measurement of prolactin, sex steroids and thyroid hormones. Growth hormone responses (mean peak 64 +/- 36 mU/l, range 21-146 mU/l) and cortisol responses (mean peak 831 +/- 122 nmol/l, range 626-1105 nmol/l) were all within the normal range. Two patients had minimally elevated serum prolactin levels (445 and 588 mU/l, normal less than 350 mU/l). Serum thyroxine levels (57-133 nmol/l) were normal but six patients had elevated basal thyrotrophin (TSH) levels (6-9 mU/l) and seven had an exaggerated TSH response to thyrotrophin releasing hormone, indicating radiation-induced damage to the thyroid. Amenorrhea developed within 3 months of irradiation in all females and oestradiol levels were low, at 37-108 pmol/l (mean 58 +/- 22 pmol/l). Severe oligospermia or azoospermia was noted in men tested 5-70 months after irradiation and testicular volume was below the normal adult range in five of seven men assessed. Serum testosterone levels (12.4-35 nmol/l) were normal. Gonadotrophin-releasing hormone-stimulated gonadotrophin levels were elevated in all patients. However, two men have fathered two children each; one has refused semen analysis, but the other has a sperm count of 7 x 10(6)/ml (60 per cent motile, 20 per cent abnormal forms) 70 months after irradiation. When given by the above fractionated regimens, the endocrine sequelae of total body irradiation are limited to gonadal failure requiring oestrogen replacement in women and severe impairment of fertility in men. Subclinical thyroid dysfunction has been seen in 39 per cent of patients there is no evidence of direct damage to the hypothalamic pituitary axis."
-What is the key treatment approach for the patient with steroid-responsive tubular aggregate myopathy described in this case report?,"Steroid-responsive tubular aggregate myopathy. We report a man with an acute myalgia/cramp syndrome and tubular aggregates on his muscle biopsy. He was placed on prednisone and was found to be exquisitely sensitive to the drug, with changes of only 5 mg precipitating recurrence of symptoms. He was eventually tapered off all steroids, without symptoms, and repeat biopsy showed no tubular aggregates. We recommend similar patients be given a trial of high-dose steroids."
-What did the study find about the relationship between racial differences and the incidence of hypertensive end-stage renal disease (HT-ESRD)?,"Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease? Prospectively collected data on the incidence of treated hypertensive end-stage renal disease (HT-ESRD) were analyzed to investigate whether the higher rate of HT-ESRD in blacks compared with whites is due to differences in putative ESRD risk factors. The overall age-adjusted relative risks of HT-ESRD for black compared with white residents in the Maryland Regional ESRD Registry (Network 31) Catchment Area were 7.4 (95% confidence interval, 5.9 to 9.4) and 9.9 (95% confidence interval, 7.4 to 13.1) for men and women, respectively. In a population level analysis, race-specific HT-ESRD incidence rates in the black and white populations of 13 regions in Network 31 were related to the prevalence of putative ESRD risk factors in those populations. The latter were estimated from the 1981-1982 Maryland Statewide Household Hypertension Survey. Black populations had a 5.6-fold (95% confidence interval, 3.9 to 8.1) higher unadjusted incidence of HT-ESRD than white populations. The HT-ESRD incidence in a population was also directly related to that population's prevalence of hypertension, severe hypertension, and diabetes mellitus and inversely related to measures of socioeconomic status and mean age at diagnosis of hypertension. When adjusted simultaneously for age, prevalence of hypertension, severe hypertension, diabetes, and level of education, the risk of HT-ESRD was still 4.5 (95% confidence interval, 3.2 to 6.2) times higher for black compared with white populations. Our findings failed to support the hypothesis that race-related differences in the prevalence, severity, or age at onset of hypertension, in the prevalence of diabetes or in socioeconomic status, explain the well-recognized black-white differences in the HT-ESRD incidence."
-What oral lesions were found to be more prevalent in HIV-infected homosexual and bisexual men compared to HIV-negative subjects?,"The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts. To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status."
-How does streptokinase treatment affect chest pain duration in patients with acute myocardial infarction?,"The effect of streptokinase on chest pain in acute myocardial infarction. Treatment with intravenous streptokinase is known to restore blood flow to the ischaemic myocardium in patients with acute myocardial infarction. However, little is known about its effect on chest pain. In a retrospective cohort study, 76 patients treated with streptokinase were compared to 76 patients not treated with streptokinase. All patients had acute myocardial infarction and less than 6 h of cardiac symptoms. Patients treated with streptokinase had a significantly lower need for nicomorphine (median 20 mg) than patients not treated with streptokinase (median 41 mg). Correspondingly, the median duration (3.5 h) of pain was reduced significantly in patients treated with streptokinase compared to patients not treated (24 h). We conclude that intravenous streptokinase given in the acute phase of myocardial infarction is effective in reducing the duration of cardiac chest pain."
-What was the disease-free survival rate for patients with Stage I and II Hodgkin's disease treated with subtotal nodal irradiation in this study?,"Cure of early-stage Hodgkin's disease with subtotal nodal irradiation. Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure."
-How does prolonged hemorrhagic shock affect the regeneration of plasma coagulant masses in rabbits?,"Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit. BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration."
-What specific genetic abnormalities have been identified as potentially important in the progression from normal to malignant colonic mucosa?,"Genetics of colon cancer. Strikingly rapid advances in the identification of genetic events that are important in colonic carcinogenesis have been made in the past several years. Specific inherited (adenomatous polyposis coli gene) and acquired (ras gene point mutations; c-myc gene amplification; allelic deletion at specific sites on chromosomes 5, 17, and 18) genetic abnormalities appear to be capable of mediating steps in the progression from normal to malignant colonic mucosa. Understanding these genetic factors and how they influence cellular function will have a profound effect on medical practice. High-risk populations will be (and are being) identified by genetic markers, thus allowing prevention and screening to be more precisely targeted to the population at risk; intervention strategies will be designed on the basis of the known cellular defects of neoplastic colonic mucosa; and new molecular preventive and therapeutic approaches can be developed."
-What rare intrathoracic complications can occur in acute pancreatitis according to the given context?,Rare intrathoracic complications in acute pancreatitis. Ascites and pleural effusions may complicate pancreatitis but pericarditis with pericardial effusion and tamponade is rare and necrosis of mediastinal fat has not been described before. All these complications occurred in the case reported here.
-How does the expression of TNF receptors on neoplastic B-CLL cells change when cultured in vitro compared to their state in vivo?,"Receptors for tumor necrosis factor on neoplastic B cells from chronic lymphocytic leukemia are expressed in vitro but not in vivo. Recombinant tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces proliferation of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms involved in regulating TNF responsiveness, we have examined TNF receptor expression on neoplastic B-CLL cells. We have demonstrated that freshly isolated neoplastic B cells from patients with CLL did not express TNF receptors. After 1 day of incubation in culture medium, TNF receptors were detectable in the range of 540 to 1,500/cell. Kinetic experiments revealed that receptor expression was half-maximal after 3 hours of culturing and required de novo protein synthesis. The Scatchard plots of TNF-alpha binding indicated a single set of high-affinity TNF receptors with a dissociation constant of 70 pmol/L. TNF receptor expression in vitro was found in all examined cases. All cytokines tested, with the exception of IL-2, did not influence the expression of TNF receptors. The TNF receptor expression is enhanced in B-CLL cells cultured in the presence of interleukin-2 when compared with the receptor expression of cells cultured in medium alone. Our data suggest that neoplastic B-CLL cells in patients with stable disease do not express TNF receptors in vivo and that an unknown mechanism suppressing TNF receptor expression in vivo may play a role in growth regulation of neoplastic B cells."
-What were the initial surgical techniques used for patients before balloon angioplasty in this study?,"Balloon angioplasty for recurrent coarctation of aorta. Immediate and long-term results BACKGROUND. As angioplasty techniques have been refined and larger low-profile balloons developed, a nonsurgical approach to recoarctation has become available. Several reports have documented both the efficacy and safety of this procedure. However, there are little data available on the long-term follow-up of these patients. This report details the initial results and long-term evaluation of both the relief of obstruction and the presence of hypertension after balloon angioplasty for recurrent coarctation. METHODS AND RESULTS. Balloon angioplasty for recurrent coarctation of the aorta was performed 29 times in 26 patients at a median age of 4 years and 9 months (range, 4 months to 29 years), with eight patients less than 1 year old. Initial surgical techniques were end-to-end anastomosis in 11 patients, subclavian flap aortoplasty in 11 patients, and patch aortoplasty in four patients. Angioplasty was performed at a median interval of 2 years and 7 months (range, 4 months to 23 years) after surgery. Mean peak systolic pressure difference across the coarctation decreased from 40.0 +/- 16.8 to 10.3 +/- 9.5 mm Hg (p less than 0.05) after the initial angioplasty, and mean diameter of the aortic lumen at the coarctation site increased from 5.8 +/- 3.5 to 9.0 +/- 4.3 mm (p less than 0.05). There was no mortality, and only one patient developed an aneurysm (4%). Three patients underwent repeat angioplasty for a pressure difference of more than 20 mm Hg. Long-term follow-up is available on 24 of 26 patients with a mean follow-up of 42 +/- 24 months (range, 12-88 months). Mean peak systolic pressure difference across the area of coarctation decreased from 40.3 +/- 17.4 before angioplasty to 8.5 +/- 8.3 mm Hg after final angioplasty (p less than 0.05) and 7.5 +/- 7.5 mm Hg at follow-up. Mean peak systolic blood pressure in the upper extremities decreased from 133.1 +/- 14.9 before angioplasty to 111.1 +/- 14.1 mm Hg at long-term follow-up (p less than 0.05). CONCLUSIONS. Balloon angioplasty should be considered the treatment of choice for relief of recurrent aortic coarctation."
-What is the relationship between syringomyelia and congenital intraspinal lipoma in this case study?,Syringomyelia secondary to congenital intraspinal lipoma. Preoperative evaluation using serial magnetic resonance imaging was performed on an infant with lumbosacral lipoma. Syrinx formation arising just above the lipoma was observed in conjunction with rapid growth of the lipoma. Definite shrinkage of syringomyelia was obtained after radical excision of the lipoma. The syrinx formation was possibly caused by compression from the extramedullary lipoma.
-How does persistent measles virus infection affect endothelin 1 signaling in C6 rat glioma cells?,"Loss of the endothelin signal pathway in C6 rat glioma cells persistently infected with measles virus. Endothelin 1 causes a strong Ca2+ signal in C6 rat glioma cells as measured by fura-2 fluorescence. This endothelin 1-induced Ca2+ signal was not observed when the cells were persistently infected with a measles virus strain of subacute sclerosing panencephalitis (SSPE, strain Lec). Binding of 125I-labeled endothelin 1 to the C6/SSPE cells was less than 5% of the binding to the C6 control cells, suggesting that the impairment in signal transduction was due to a loss of binding sites for endothelin 1. Treatment of the C6/SSPE cells with measles antiserum resulted in the loss of expression of viral proteins located in the membrane as well as inside the cells (antigenic modulation), but it restored neither the endothelin 1-induced Ca2+ rise nor the 125I-endothelin 1 binding. Cocultivation of uninfected C6 cells with C6/SSPE cells (9:1 ratio) resulting in contact-mediated transmission of measles virus showed that the 125I-endothelin 1 binding activity was gradually lost as a consequence of persistent virus infection."
-What is the incidence of stroke during pregnancy according to the study conducted at Parkland Memorial Hospital?,"Cerebrovascular accidents complicating pregnancy and the puerperium. The decreasing incidence of direct causes of maternal death over the past half century has led to a heightened awareness of nonobstetric factors responsible for maternal mortality. For example, cerebrovascular accidents are an important nonobstetric cause of maternal morbidity and mortality. During the 6.5-year period from 1984 to mid-1990, we encountered 15 women in whom pregnancy or the puerperium was complicated by an acute cerebrovascular accident. Six of these women had hemorrhagic strokes and nine had ischemic strokes. During this same time, approximately 90,000 women were delivered at Parkland Memorial Hospital, and thus the incidence of stroke was about one in 6000 pregnancies. Chronic hypertension or preeclampsia was causative in three cases of hemorrhagic stroke. It is important that 20% of the women died as a result of stroke, and of the 12 survivors, 40% have residual neurologic deficits. An aggressive work-up to define the etiology of stroke is necessary in order to implement cause-specific management, with subsequent reduction in morbidity and mortality."
-What were the key differences in clinical outcomes between patients who underwent mitral valve replacement with and without preservation of the posterior leaflet?,"Clinical results of mitral valve replacement with and without preservation of the posterior mitral valve leaflet and subvalvular apparatus. In this study we attempted to investigate the importance of posterior leaflet preservation during mitral valve replacement (MVR). One hundred and forty randomly selected patients with isolated mitral insufficiency were studied, half of whom had MVR with preservation of the posterior leaflet (Group I), whereas in the other half conventional MVR was performed, without preservation of the posterior leaflet (Group II). Within these two groups there were no in hospital deaths, but 5 patients in Group II were admitted to the hospital with congestive heart failure and 3 of them died after approximately 6 months. Long term mortality rate was 4.2% in Group II. Ejection fraction (EF) decreased postoperatively from 56% to 50% in Group I (p less than 0.05), and from 59% to 49% in Group II (p less than 0.05). Fifteen patients in each group and aged below 30 with sinus rhythm and in the first functional capacity according to the New York Heart Association classification (NYHA) were subjected to exercise study, 18 months after the operation. After exercise EF increased from 47% to 64% in Group I and decreased from 51% to 47% in Group II. These findings suggested that MVR with the preservation of the chordae tendineae can be done with a low morbidity and mortality rate in the early and late postoperative period."
-How does platelet-activating factor (PAF) contribute to complement activation and tissue injury in mice?,"Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice. We previously showed that TNF and endotoxin (LPS) synergize to activate the complement system and produce shock and bowel injury in normal mice. However, C5-deficient mice were protected from these adverse effects. In this study, we show that in mice, platelet-activating factor (PAF) antagonist prevents TNF- and LPS-induced complement activation, bowel injury, and death, indicating that PAF mediates the actions of TNF and LPS. We then examined the role of the complement system in PAF-induced shock and tissue injury. We found that 1) PAF (3 micrograms/kg) induces shock, hemoconcentration, bowel necrosis, and death in normal mice, whereas C5-deficient mice are protected from these effects. (Protection was abrogated when the dose of PAF was raised to 5 micrograms/kg.) Furthermore, when C5-deficient mice were reconstituted with normal serum, they also developed shock, bowel injury, and death in response to PAF. Thus, C5 is required for PAF to induce injury. 2) PAF activates the complement system in vivo, but not in vitro. The mechanism of complement activation by PAF is unclear. Inasmuch as PAF stimulates neutrophils to release protease that may activate the complement system, we examined the effect of neutrophil depletion on PAF-induced injury and complement activation. We found that neutrophil depletion fails to prevent PAF-induced complement activation, although PAF-induced lethality is much reduced. We conclude that PAF causes complement activation, and acts in synergy with active complement fragments to produce shock and tissue injury. Neutrophils probably do not play the pivotal role in PAF-induced complement activation."
-What was the purpose of the study on the Graseby patient-controlled analgesia system?,Evaluation of the Graseby PCAS. A clinical and laboratory study. The Graseby patient-controlled analgesia system was evaluated in the laboratory and in clinical use. The problems encountered with eight examples used to treat 510 patients are reported. Laboratory performance revealed the unit to be accurate at infusion volumes of 1 and 2 ml.
-What is the purpose of the review by the Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee?,"Occupational and industrial toxin exposures and the gastrointestinal tract. Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee. The subcommittee on Gastrointestinal Toxicology of the Patient Care Committee of the American College of Gastroenterology has reviewed potential effects of exposures to occupational and industrial hazards on the gastrointestinal tract, liver and pancreas. This review is presented to 1) share clinical data concerning gastrointestinal toxicology, 2) emphasize the paucity of available information to the practicing clinician, and 3) stimulate basic research interest in this field."
-What is the recommended initial antibiotic combination for treating necrotizing fasciitis according to the review?,Necrotizing fasciitis. Ten cases of necrotizing fasciitis are reviewed. Three patients died but only two of these deaths were due to uncontrolled septicaemia. All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice. Prompt and aggressive surgical debridement remains the cornerstone of management.
-What was the total possible loss of calcium during the preparation of paraffin blocks and slide preparation in the study of breast specimen microcalcifications?,"Breast specimen microcalcifications: radiographic validation and pathologic-radiologic correlation. A prospective analysis of specimens from location and biopsy of mammographically suspect microcalcifications in 108 patients was carried out to determine if microcalcifications were lost during histopathologic processing and the clinical relevance of such loss. Nine hundred sixty-eight paraffin blocks were prepared from 425 gross tissue slices containing calcifications identified at radiography of the specimens. Calcium was apparently lost both during preparation of the blocks (13.6%) and after slide preparation (12.6%), for a total possible loss of 26.2%. All specimens demonstrated calcification histologically. One pathology report was amended because of information obtained after recuts, but all cancers were detected on original slides whether or not calcifications were identified initially. The results indicate that, by following the suggestions offered to ensure adequate histopathologic sampling of calcification seen at mammography, most if not all of the calcification present can be detected on the original slide."
-What is the significance of the zinc finger protein gene cluster deletion in the mouse embryonic lethal mutation tw18?,A cluster of related zinc finger protein genes is deleted in the mouse embryonic lethal mutation tw18. We report that a number of related zinc finger protein genes are closely linked on mouse chromosome 17. At least four of these genes are transcribed in the 8.5-day postcoitum embryo and are deleted in the t complex early acting embryonic lethal mutation tw18. We have evidence that additional finger protein genes are located in this region. These findings demonstrate that related finger protein genes can be clustered in the murine genome and identify genes that may be considered as candidates for the tw18 mutation.
-How does regional cerebral blood flow differ between aphasic stroke patients and control subjects during a functional naming test?,"Remote cortical dysfunction in aphasic stroke patients. We studied the effect of deep-seated left hemispheric lesions on cortical blood flow in 18 right-handed aphasic stroke patients. Regional cerebral blood flow was measured at rest and during the performance of a functional naming test using the two-dimensional xenon-133 inhalation method. Compared with 10 controls, at rest the patients showed regional cortical hypoperfusion in the left frontoparietal region. In the controls, activation patterns from the rest to the test condition involved mainly the left hemisphere areas. In the patients, a lack of blood flow change was observed in several areas that were usually hypoperfused at rest. However, in patients with slight verbal expression disorders there were obvious blood flow increases in other brain regions in both hemispheres. Such cortical functional reorganization and the presence of a remote cortical dysfunction could play a role in the pathophysiology of language disorders."
-How did the researchers study the chemosensory responses of the carotid body in this in vitro preparation?,"In vitro perfused-superfused cat carotid body for physiological and pharmacological studies. An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible."
-What was the efficacy of different oral doses of ondansetron in preventing nausea and emesis in breast cancer patients receiving cyclophosphamide-doxorubicin chemotherapy?,"Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy. We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related."
-What challenges can arise when differentiating between germ cell tumors and central nervous system sarcoidosis?,"Germ cell tumors masquerading as central nervous system sarcoidosis. The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis."
-What did the researchers discover about circulating ICAM-1 isoforms in the study of healthy young volunteers?,"Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Intercellular adhesion molecule-1 (ICAM-1, CD54) is an important early marker of immune activation and response. Evidence on its role has come from immunohistological staining of tissues, since no free circulating ICAM-1 has been detected. By means of monoclonal antibodies against ICAM-1 and a sensitive chemiluminescence technique, free circulating ICAM-1 was detected in serum from sixteen healthy young volunteers. The concentrations varied among the subjects. Non-denaturing gel separation methods showed that ICAM-1 circulates in at least three isoforms, the proportions of which also varied. These findings have important implications for the investigation, diagnosis, and therapeutic monitoring of various inflammatory, neoplastic, and immune disorders."
-What makes pancreatic cancer a particularly challenging disease to treat?,"Biology of pancreatic cancer. Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer."
-How do the bile acid compositions differ between intrahepatic and extrahepatic brown pigment stones?,"Microanalysis of bile acid composition in intrahepatic calculi and its etiological significance. Brown pigment stones in the intrahepatic bile ducts were compared with those found in the extrahepatic bile ducts with special reference to the bile acids modified by bacterial intervention, that is, unconjugated, glucuronidated, secondary, and ketonic bile acid fractions. The former showed significantly lower amounts of total bile acids (P less than 0.01) and lower proportions of unconjugated bile acid fraction (P less than 0.01), secondary bile acid fraction (P less than 0.05), and ketonic bile acid fraction (P less than 0.05) to total bile acids than the latter. The discriminant analysis using these bile acid parameters led to complete separation between intrahepatic and extrahepatic stones in the case of brown pigment stones. In contrast, cholesterol stones in the intrahepatic bile ducts showed the bile acid composition close to those found in the extrahepatic ducts and gallbladder. The above data show that the bacterial infection plays a less important role in the formation and ensuing growth of most intrahepatic brown pigment stones than in extrahepatic stones, and that factors other than or in addition to bacterial infection are involved."
-What were the independent predictors of respiratory failure in patients undergoing thoracoabdominal aortic aneurysm repair?,"A prospective study of respiratory failure after high-risk surgery on the thoracoabdominal aorta. From June 1960 to September 1990, 1414 patients underwent repair of thoracoabdominal aortic aneurysms, of whom 112 (8%) had pulmonary complications requiring respiratory support with tracheostomy; subsequently 45 (40%) died in the hospital. We determined by stepwise logistic regression analysis, in a prospective study of high-risk type I and II thoracoabdominal aortic aneurysms repairs, the independent predictors of respiratory failure, defined as respiratory ventilation exceeding 48 hours after operation. In 98 patients studied, 38 (39%) were women, 60 (61%) were men, 54 (55%) had type II thoracoabdominal aortic aneurysms, 34 (35%) had aortic dissection, 19 (19%) were nonsmokers, 40 (41%) exsmokers, and 39 (40%) active smokers. Before operation, 55 (56%) had chronic pulmonary disease with respiratory failure developing in 58% (p = 0.0005 versus no chronic pulmonary disease, 10/43, 23%), and of the 26 patients in the lower quarter of forced expiratory volume (1 sec) (FEV1 less than or equal to 1.45 L) respiratory failure developed in 61% (p = 0.035). In-hospital survival was 98% and 83% (p = 0.008), respectively, and cumulative survival at 6 months by Kaplan-Meier analysis was 96% and 80% (p = 0.004, log-rank test), respectively, for patients without respiratory failure (N = 56/98, 57%) and with respiratory failure (N = 42/98, 43%). On univariate analysis, the following were associated with respiratory failure (p less than 0.05): FEV1, FEV1% predicted, FVC, FEF25, FEF25% predicted, FEF25-75, FEF25-75% predicted, PaCO2 Pao2, symptoms, smoking history, chronic pulmonary disease, cryoprecipitate volume, postoperative neuromuscular deficit, cardiac complications, reoperation for bleeding, renal complication, stress ulceration, postoperative creatinine level, postoperative dialysis, and postoperative encephalopathy. The independent predictors of respiratory failure were (p less than 0.05): chronic pulmonary disease, smoking history, cardiac and renal complications. In patients with chronic pulmonary disease, the only independent predictor was FEF25 (p = 0.030). These observations may be of value in selecting patients for elective operation."
-How did electrical muscle stimulation affect periodic leg movements in sleep for the patients in the study?,"Nonpharmacologic treatment of periodic leg movements in sleep. The effects of a 30-minute stimulation of the dorsiflexors of the feet and toes before bedtime were investigated in eight patients with periodic leg movements in sleep (PLMS). None were taking medications at the time of the investigation. All subjects were treated with the EMS-250 Neuromuscular Stimulator, which has a maximum output per channel of 1.5mA and a frequency of 47Hz. Stimuli were delivered via a pulse train (on for 1.5sec and off for 1.8sec). A single all-night polysomnogram after this stimulation showed that all patients responded to stimulation, with reduction of leg movements from an average pretreatment PLMS index of 44.6 per hour to a posttreatment PLMS index of 14 per hour (p less than .01). Nocturnal leg movements were primarily reduced during the non-REM sleep. Multiple indices of sleep continuity did not change significantly, although there was a trend toward better sleep consolidation."
-What is the relationship between absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery and the development of necrotising enterocolitis?,"Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis. Absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery were identified in 25 high risk pregnancies. In six pregnancies the fetus was abnormal and all but one of these ended in perinatal death. Of the 19 morphologically normal fetuses, three died in utero and there were four neonatal or infant deaths. The mortality rate was 48% for all pregnancies and 37% for those with morphologically normal fetuses. There was a highly significant increased risk for the development of necrotising enterocolitis in these morphologically normal fetuses with AREDF (53%) compared with controls (6%) who did have umbilical artery end diastolic flow velocities in fetal life. There were no significant differences between the matched pairs for parameters of neonatal outcome chosen to reflect neonatal morbidity. These findings demonstrate the close association between AREDF and necrotising enterocolitis that appears to be independent of other variables such as degree of growth retardation, prematurity, and perinatal asphyxia."
-How do interpersonal conflicts differ in their impact on chronic pain for patients with arthritis versus those with myofascial disorders?,"The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology. This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed."
-What makes the dislocation of an osseointegrated screw a rare event?,Total avulsion of an osseointegrated screw. The close union achieved between pure grade titanium and healthy bone makes dislocation a rare event. We report the case of the total avulsion of an apparently well-integrated implant from a healthy mastoid bone.
-What was the key finding regarding chromosome 14 inheritance in the patient with a Robertsonian translocation?,"Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. A 9-year-old mentally retarded girl with multiple congenital anomalies was found to carry a balanced 13/14 Robertsonian translocation [45,XX,t(13q14q)] which was also present in her father. Her mother carried a balanced reciprocal translocation between chromosomes 1 and 14 [46,XX,t(1;14) (q32;q32)]. Both of her parents were phenotypically normal. Molecular studies were carried out to determine the parental origin of chromosomes 1, 13, and 14 in the patient. Using probes for D14S13 and D14S22, we could show that the patient inherited both chromosomes 14 from her father and none from her mother. Similar studies using probes for chromosomes 1 (D1S76) and 13 (D13S37) loci showed the presence of both maternal and paternal alleles in the patient. Our findings indicate that paternal uniparental heterodisomy for chromosome 14 most likely accounts for the phenotypic abnormalities observed in our patient. It is suggested that uniparental disomy may be the basis for abnormal development in at least some phenotypically abnormal familial balanced-translocation carriers."
-What factors were found to be most strongly correlated with sleep problems in the South Australian community health survey?,"Sleep difficulties, pain and other correlates. A multiple regression analysis was used with variables relevant to sleeping problems from a large community health survey in South Australia. The variables that were found to be most strongly correlated with sleep problems were, in order of importance, pain, anxiety, age, somatic health and annual household income, all of which accounted for 22% of the variance. Weight problems, depression and sex of the respondent were not so important in this analysis. Arthritis, which often increases with age, appeared to be most strongly associated with pain, explaining in part why sleeping problems increase with age. Anxiety, pain and poor somatic health were most strongly associated with lying awake at night or sleeping badly, and anxiety and pain were most strongly correlated with taking longer to get to sleep. Poor somatic health and anxiety were most strongly associated with waking early, and age and pain were the most important variables in taking tablets to aid sleep."
-What are the key findings of the study regarding patient-controlled analgesia in children?,Long-term patient-controlled analgesia in children. Three children who received patient-controlled analgesia for periods of up to 41 days are described. In each case patient-controlled analgesia allowed pain control to be achieved in difficult situations. No patient developed tolerance or clinical signs of dependence. This use of long-term patient-controlled analgesia warrants further evaluation.
-What are the key findings of the study regarding infectious disease transmission in outpatient healthcare settings?,"Transmission of infectious diseases in outpatient health care settings. Increased provision of health care in outpatient settings and concerns about occupational transmission of infections have focused attention on the risk of transmission of infectious diseases in ambulatory health care settings. In contrast to inpatient nosocomial infections, infections transmitted in outpatient settings are neither systematically monitored nor likely to be detected by routine qi surveillance. To better define the spectrum of such events, we reviewed the literature to identify cases and clusters of infections associated with outpatient health care. In this review, we identified and epidemiologically characterized 53 such reports that occurred from 1961 through 1990. Transmission occurred in general medical offices, clinics, and emergency departments (23); ophthalmologists' offices and clinics (11); dental offices (13); and alternative-care settings (six). Our findings suggest that inpatient infection-control practices should be extended to outpatient health care settings by assigning specific responsibility for infection control and by adapting surveillance methods and prevention measures."
-How do Staphylococcus epidermidis and Escherichia coli compare in their ability to induce inflammatory responses and physiological changes in rabbits?,"Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli. Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism."
-"What complication occurred in the patient who underwent endoscopic variceal sclerotherapy, and how was it discovered?","Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence. Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy."
-What were the three major inclusion criteria for patients in this deep vein thrombosis prevention study?,"Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of Logiparin and standard heparin. H.B.P.M. Research Group. A total of 1290 patients were enrolled in a randomized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin, Logiparin, in the prevention of deep vein thrombosis (DVT) in general surgery. Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT. Patients were randomized to receive unfractionated heparin (UH) 5000 units b.d., Logiparin 2500 units daily or Logiparin 3500 units daily. Each treatment was given subcutaneously 2 h before surgery and continued for 7-10 days. Daily 125I-labelled fibrinogen uptake tests (FUTs) were performed from day 2 to day 7 to detect DVT, and phleboangiography was used to confirm the diagnosis. The wound was examined on a daily basis to check for haematoma formation, and all patients were followed up for 1 month after operation. All three treatment arms were well matched for age, sex, weight, diagnosis and type of operation performed. The three major inclusion criteria in the trial were malignancy, age over 60 years and a history of varicose veins. Positive FUTs (UH = 4.2 per cent, Logiparin 2500 units daily = 7.9 per cent, Logiparin 3500 units daily = 3.7 per cent) and positive angiograms (UH = 3.0 per cent, Logiparin 2500 units daily = 5.6 per cent, Logiparin 3500 units daily = 2.3 per cent) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups. The rates of major complications (severe haemorrhage, death, pulmonary embolism, reintervention) were similar in the three groups."
-What treatment was found to be effective for a 28-year-old woman with pulmonary endometriosis after surgical procedures and other treatments failed?,"Treatment of pulmonary endometriosis with a long-acting GnRH agonist. We report the case of a patient who was successfully treated with a long-acting GnRH agonist for pulmonary endometriosis. This 28-year-old woman had symptomatic pleural endometriosis, documented by biopsies, as well as symptomatic pelvic endometriosis. Two surgical procedures, consisting of excision of pleural endometriotic tissue and partial pleurectomies, failed to relieve her chest symptoms. Little relief was achieved with pseudopregnancy treatment. Satisfactory symptomatic improvement was obtained with danazol, but this medication had to be discontinued because of severe side effects. Trial of a GnRH agonist, leuprolide acetate, achieved complete remission of her chest symptoms; in addition, the patient became pregnant immediately after cessation of therapy. Gonadotropin-releasing hormone agonist therapy may be an important therapeutic alternative for women with pulmonary endometriosis who cannot tolerate danazol treatment and in whom surgical therapy fails to relieve the chest symptoms."
-What was the patient and graft survival rate in this study of primary liver transplants using FK 506?,"One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults. An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration."
-How did the hepatic perfusion index (HPI) change before and after mesenteric revascularization in this patient with mesenteric angina?,"Hepatic perfusion index (HPI) in mesenteric angina and following successful revascularization. This is a case report of a 45 year old man who had previously undergone a small bowel resection for acute mesenteric ischaemia. He subsequently suffered from mesenteric angina due to stenosis of the origin of the superior mesenteric artery and intermittent claudication due to aorto-iliac atheroma. The patient underwent a successful aorto-bifemoral Y graft and small bowel revascularization with a saphenous vein graft between the Y graft and the accessible proximal portion of the superior mesenteric artery. Before vascular reconstruction, the hepatic perfusion indices (HPI) in both the fasted and fed states were elevated; after mesenteric revascularization the HPI values were substantially lowered. The hepatic perfusion index may, by demonstrating functional abnormality, be useful in the diagnosis of mesenteric ischaemia and also in the assessment of treatment. Further evaluation of HPI in patients with suspected mesenteric ischaemia is therefore required."
-What are the key cardiac complications associated with Kawasaki disease?,"Diagnosis and management of Kawasaki disease. Kawasaki disease is an acute vasculitis characterized by mucosal inflammation, rash, cervical adenopathy, indurative edema of the hands and feet, and late membranous desquamation of the fingertips. Early cardiac effects include myocarditis (occasionally with congestive heart failure), pericardial inflammation, and, rarely, valve involvement. Coronary artery aneurysms are a long-term concern because coronary thrombosis with myocardial infarction can be a late manifestation. The origin of Kawasaki disease is unknown, but an infectious agent is most likely. Management consists of aspirin for control of fever and inflammatory manifestations and intravenous gamma globulin for the prevention of coronary aneurysm formation. Careful late follow-up is required, especially for patients with persistent coronary abnormalities. Giant aneurysms (greater than 8 mm) are more likely to progress to coronary obstructive disease, and coronary bypass grafts have been required for some patients. Late coronary artery manifestations in patients with mild early coronary dilatation have not been described. However, since long-term epidemiologic studies have not yet been performed, it is prudent to consider childhood Kawasaki disease to be a potential risk factor for coronary disease, especially in atherosclerosis-prone Western societies."
-What was the localization and pattern of HPV 16 E4 protein expression observed in cervical biopsy tissues?,"Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation."
-How did actigraphic monitoring help in understanding the potential risks of discontinuing lithium treatment in bipolar patients?,"Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles. In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation."
-What blood conservation techniques were used in this study of 500 consecutive coronary artery bypass operations?,"Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations. With use of a nonpharmacological, simple, and inexpensive program for blood conservation, 500 consecutive patients underwent elective coronary artery bypass grafting without need of homologous red cell transfusions in 493 (98.6%). At least one internal mammary artery was grafted in all but 1 patient, with supplemental saphenous vein grafts. Intraoperatively, autologous heparinized blood was removed before bypass and retransfused at the conclusion of extracorporeal circulation. The volume remaining in the oxygenator and tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after operation. The mean postoperative mediastinal blood loss was 643 +/- 354 mL, whereas 624 +/- 296 mL was autotransfused. Thirteen patients (2.6%) needed reexploration for bleeding, of whom 7 (7/500, 1.4%) received homologous blood. No other patients required red cell transfusions. In addition, 9 patients were given a mean of 2.6 units of fresh frozen plasma because of suspected coagulopathy. No platelets were transfused, and no cryoprecipitate therapy was undertaken. Thus, in total, 484 patients (96.8%) were not exposed to any homologous blood products during the hospital stay. At discharge, the mean hemoglobin concentration was 121 +/- 14 g/L (12.1 +/- 1.4 g/dL) and the hematocrit, 0.36 +/- 0.04. Postoperative complications were few. There was one in-hospital death (0.2%)."
-What was the outcome of the study on patients with gastro-oesophageal reflux disease without oesophagitis?,"Natural history of gastro-oesophageal reflux disease without oesophagitis. This retrospective study was undertaken to characterise the clinical course and reflux pattern of patients with gastro-oesophageal reflux without evidence of oesophagitis. We investigated 33 patients (12 women, 21 men; mean age 36 years) with typical symptoms, a negative oesophagoscopy, and a 24 hour oesophageal pH-metry indicative of pathological gastro-oesophageal reflux. All patients received antacids or prokinetic drugs or both for three to six months. Nineteen of 33 patients still had symptoms at the end of treatment, of whom five had developed erosive changes of the oesophageal mucosa. The other 14 discontinued treatment and remained asymptomatic during a six month follow up period. Comparison of the pretreatment pH-metry data of the 19 symptomatic patients and the 14 asymptomatic patients showed no differences in the pattern of gastro-oesophageal reflux in the two groups. We conclude that in a substantial proportion of patients with pathological reflux without oesophagitis symptoms may persist and mucosal lesions may develop during conventional treatment without any apparent change in the reflux. Patients who developed endoscopic oesophagitis did not have a more severe pretreatment pattern of gastro-oesophageal reflux when compared with those who did not develop oesophageal mucosal damage."
-How does copper loading affect the recovery of heart function after ischemia and reperfusion in an isolated rat heart model?,"Copper loading of hearts increases postischemic reperfusion injury. We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal."
-What were the key findings regarding gastric cancer incidence and mortality in Scotland between 1978 and 1987?,"Gastric cancer in Scotland: changing epidemiology, unchanging workload. OBJECTIVE--To determine the changes in incidence of and mortality from gastric cancer in Scotland between 1978 and 1987 and in the operative workload in Lothian between 1979 and 1988. DESIGN--Analysis of national incidence statistics for gastric cancer derived from the Scottish national cancer registry, deaths from gastric cancer recorded by the registrar general for Scotland, and Lothian surgical audit data. SETTING--Scotland and Lothian Health Board area. PATIENTS--Patients in Scotland with gastric cancer during 1978 to 1987 inclusive; patients in Scotland with gastric cancer recorded on their death certificate as cause of death during 1978 to 1987; patients who had an operation in Lothian for gastric cancer during 1979 to 1988. MAIN OUTCOME MEASURES--Changes in incidence of and mortality from gastric cancer in Scotland from 1978 to 1987 and in the number of operations performed for gastric cancer in Lothian from 1979 to 1988. RESULTS--Mortality from gastric cancer in Scotland fell by about 25% over the 10 years. The incidence and standardised incidence of gastric cancer showed a marginal decline of about 9%. The differences in trends between incidence and mortality were significant (p less than 0.05). CONCLUSIONS--This study shows that the surgical workload associated with gastric cancer is not declining. This is because the incidence has remained almost static, which may be due to the relative increase in the numbers of older people in the population, who are at greater risk of developing gastric cancer. Gastric cancer should not be regarded as a disease in decline. Incidence and workload should determine resources allocated to this disease rather than mortality statistics."
-What is the definition of a mucin-hypersecreting tumor of the pancreas according to the study?,"Mucin-hypersecreting tumor of the pancreas with mucin extrusion through an enlarged papilla. Patient records, imaging films, macroscopic and microscopic features, and clinical follow-up data of seven Japanese patients with a mucin-hypersecreting tumor of the pancreas were reviewed. The mucin-hypersecreting tumor was defined as an enlarged major or minor papilla with a dilated orifice and visible mucin oozing on endoscopy. The series consisted of six men and one woman ranging from 47 to 79 yr old. The excretion of mucin through a patulous orifice of the enlarged ampulla of Vater was seen in six patients and of the enlarged minor papilla in the other patient with pancreas divisum. The main pancreatic duct was dilated in all patients. Amorphous mucin was seen in the dilated duct of five patients, and papillary nodules were present in two patients. Computed tomography and/or ultrasonography showed dilatation of the main pancreatic duct with multilocular cysts in six patients and with a solid tumor in the other patient. The tumor was located diffusely in the main pancreatic duct in one patient, whereas it was confined to branches in the head (four patients), body (one patient), or tail (one patient) of the pancreas in the six other patients. Histopathologic diagnosis was a cyst lined by hyperplastic mucus-secreting epithelium in one patient, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in two. Five patients underwent resection and have survived for 1-46 months after the operation. The authors would like to emphasize this endoscopic syndrome because about half of mucin-hypersecreting tumors are malignant with a favorable prognosis."
-What was the correlation between immunological reactions and the time course of cerebral vasospasm in the primate model?,"The correlation between immunological reaction in the arterial wall and the time course of the development of cerebral vasospasm in a primate model. To investigate the role of immunological reactions in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH), the authors studied the correlation between immune/inflammatory reactions in the arterial wall and the time course of vasospasm in primates. Twenty monkeys were divided into four groups of 5 animals each: 1) a control group of sham-operated animals, 2) animals subjected to angiography 3 days after the induction of SAH (3-day SAH), 3) animals subjected to angiography 7 days after SAH (1-week SAH), and 4) animals subjected to angiography 7 and 14 days after SAH (2-week SAH). To induce SAH, the main cerebral arteries on the right were dissected free of the arachnoid, and an autologous blood clot was placed around the arteries. To evaluate vasospasm, all animals underwent a baseline angiogram before SAH; angiography was repeated at different intervals in each group, as outlined above. Histopathological changes and the deposition of the immunoglobulin IgG in the arterial wall were evaluated immunohistochemically in each group. The cerebral arteries on the side of the clot showed evidence of mild vasospasm (-24.6% reduction) on the angiogram performed on Day 3, severe vasospasm (-51.7%) on Day 7, and mild vasospasm (-12.8%) on Day 14. The infiltration of inflammatory cells was most marked in the spastic arterial wall in the 1-week SAH group. In the 2-week SAH group, severe myonecrosis and intimal disruption were observed, even in the vessels that showed only mild vasospasm, and the inflammatory reactions had almost abated."
-How does the length of the waiting list impact the survival benefit of cardiac transplantation for outpatients?,"Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. Many patients are accepted for cardiac transplantation during a period of clinical instability associated with a high risk of death, even though most can be discharged home to await transplantation. As the waiting lists lengthen, priority is awarded solely on the basis of the waiting time of outpatients, who now usually undergo transplantation after they have already survived a major period of jeopardy. To determine the impact of the current waiting times and priority system on the previously expected benefit offered by transplantation, 1-year actuarial survival without transplantation was recalculated after each month without transplantation for 214 potential candidates with an ejection fraction of 0.17 +/- 0.05 discharged on tailored medical therapy after evaluation. These data were compared with the 1-year survival data of 88 outpatients who underwent transplantation. Actuarial survival after 1 year was 67% on tailored therapy compared with 88% after transplantation (p = 0.009). Death without transplantation was sudden in 43 of 51 patients, resulting from hemodynamic decompensation in 8. For outpatients already surviving 6 months without transplantation, actuarial survival over the next 12 months was 83% without transplantation. Thus, the expected improvement in survival after transplantation would be only 5% over the subsequent year for patients waiting 6 months, which is the waiting time for many outpatients. Such patients should be reevaluated to determine whether transplantation remains indicated during the next year."
-How many cases of occipital meningoceles in patients with Dandy-Walker syndrome have been reported in this study?,"Occipital meningoceles in patients with the Dandy-Walker syndrome. Occipital cephaloceles in the Dandy-Walker syndrome are not rare. To date, 28 cases have been reported. We report on 8 cases of associated occipital meningocele, totalling 16% of all patients with the Dandy-Walker syndrome in our series. In all patients, communication existed between the posterior fossa cyst and the occipital meningocele. In 2 patients, the occipital meningocele disappeared after cerebrospinal fluid shunting and never required surgical repair. It appears that the cranial defect had ossified and resulted in self-closure. Poor intellectual development in persons with the Dandy-Walker syndrome is associated with the presence of other central nervous system and systemic abnormalities and not with occipital meningoceles alone."
-How do intermediate biomarkers help in understanding the predisposition to gastrointestinal cancer?,"Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: introduction and perspective. In this article, abnormalities in the proliferation and differentiation of gastrointestinal cells are described in diseases that increase predisposition to gastrointestinal cancer. Recent findings related to the effects of calcium on gastrointestinal cell proliferation, differentiation, and tumor occurrence in rodent models and in human subjects are summarized."
-What is the primary cause of malnutrition in patients with malignant disease?,"Nutritional support of patients with cancer of the gastrointestinal tract. Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established."
-What percentage of subjects reported symptom relief after using a neutral-angle wrist splint for carpal tunnel syndrome?,"Carpal tunnel syndrome: objective measures and splint use. One hundred five adults with carpal tunnel syndrome (CTS) were studied to assess the efficacy of a neutral-angle wrist splint, and to identify criteria for splint referral. Ten observations before and after treatment were analyzed with descriptive and inferential statistics. After splint use, 67% of the subjects reported symptom relief. T-test comparison of sensory latency of values before and after treatment indicated improvement for the total group. Chi-square and t-tests failed to reveal significant differences between relief and no-relief groups for gender, affected hand, presence of concomitant conditions, duration of symptoms before treatment, age, length of time between pretreatment and posttreatment nerve conduction testing, initial nerve latency of motor and sensory fibers, or the difference between pretreatment and posttreatment sensory latencies. A significant difference was found for motor latency; the relief group improved and the no-relief group deteriorated. Data suggest that splinting is most effective if applied within three months of symptom onset. Those with damage to the wrist structures or median nerve were least responsive to splinting."
-What was the typical duration of antibiotic treatment for patients with Whipple's disease in this study?,"Short-term antibiotic treatment in Whipple's disease. We report the results of short-term antibiotic treatment in 19 patients with Whipple's disease (WD). The diagnosis was based on clinical features and on a characteristic small bowel biopsy. Patients received treatment for a mean of 7.9 weeks (range 4-20). Fourteen were treated with de-methyl-chlortetracycline (600 mg/day), and 1 also received chloramphenicol (1 g/day); 1 was treated with ampicillin (2 g/day), and 4 were treated with amoxicillin (1.5 g/day). In all patients, the clinical response was rapid and excellent, body weight increased significantly, diarrhea subsided, and fecal fat values returned to normal. Intestinal biopsies obtained after treatment was completed showed significant improvement based on a decrease in the number of macrophages staining positive with periodic acid-Schiff (PAS), normalization of villous structure, and decreased dilatation of lymphatic channels; free bacilli were absent, as shown both by light and electron microscopy. Seventeen patients have been followed for a mean of 99.4 months (range 6-300). Two died 30 and 72 months after diagnosis of Whipple's disease, 1 of laryngeal carcinoma and the other of colonic carcinoma. Fifteen patients are in excellent health. Three patients treated with tetracycline have had clinical and/or histologic relapses. In our experience, short-course antibiotic treatment with tetracycline or ampicillin and derivatives can be effective in WD, with few relapses and excellent outcome. No neurologic symptoms, either initially or during follow-up were observed."
-What was the overall prevalence rate of dementia among individuals aged 85 years and older in the Leiden community survey?,"Prevalence of dementia in the 'oldest old' of a Dutch community. OBJECTIVE: To estimate the prevalence rate of dementia in subjects 85 years of age and over. DESIGN: A two-phase design with the Mini-Mental State Examination (MMSE) in the screening phase and the Geriatric Mental State Schedule (GMS) in the diagnostic phase. SETTING: Community survey including subjects in residential care. SUBJECTS: All (n = 1,259) inhabitants of Leiden, The Netherlands, aged 85 years and over on December 1, 1986. First phase participation rate was 71% (17% dropout due to death); second phase participation rate was 82%. MAIN OUTCOME MEASURE: DSM-III diagnosis of dementia without further specification of the etiology of the dementia. RESULTS: An overall prevalence rate of 23% (95% C.I.: 19%-26%) was found. This included 12% mild dementia, 7% moderate and 4% severe dementia. The prevalence rate was higher among women (24%) than among men (18%). It increased with age from 19% (95% C.I.: 16%-22%) in the group of 85-89 years to 32% (95% C.I.: 26%-39%) in the group of 90-94 years to 41% (95% C.I.: 25%-58%) in the 95+ group. CONCLUSION: A fifth of the 85+ and a third of the 90+ population suffer from dementia with an indication that half of the 95+ population is affected. With the expected steep rise in the number of the oldest old, dementia will stay a major health problem in the near future."
-What was the purpose of the study on mastoid cavities and how was the symptom score determined?,"Mastoid misery: quantifying the distress in a radical cavity. Seventy-eight mastoid cavities were studied in 39 patients who required revision surgery for troublesome symptoms. A retrospective questionnaire was used to assign a symptom score to each patient in his pre and post-operative condition. The 5 leading symptoms of pain, wax, discharge, smell and giddiness were reviewed. A score of 15 points represented the worst case and zero the best. The average improvement after surgery was 4.7 points. Hearing was not considered in this study."
-What was the average lifetime benefit of chemotherapy for 45-year-old and 60-year-old women with node-negative breast cancer according to the decision-analysis model?,"Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. A decision-analysis model. BACKGROUND. In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. METHODS. Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. RESULTS. For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of $18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups. CONCLUSIONS. Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients' risk preferences."
-What percentage of patients with civilian craniocerebral gunshot wounds survived with a good outcome?,"Civilian craniocerebral gunshot wounds. Experience with 120 patients who incurred a gunshot wound to the head with dural penetration is presented. All of the patients were managed by a standard resuscitation protocol and assigned a clinical grade based on their level of consciousness both at the time of presentation and at 2 to 4 months after injury. Fifty patients (42%) underwent surgery. Twenty-eight patients (23%) had a good recovery, 19 (16%) were moderately disabled, 6 (5%) were severely disabled, and 67 (56%) died. All patients who were alert and awake with a normal or near normal neurological examination at the time of admission survived with a good outcome. All but 4 patients who were comatose at the time of admission died. Nine patients, however, who were not comatose at the time of admission died from potentially preventable causes. In 3 of these patients, a more aggressive diagnostic approach (including cerebral angiography) may have altered their ultimate outcome. An expeditious approach to the trauma victim with a comprehensive management scheme after injury may have altered the course in the remainder of these patients."
-What were the key findings of the study on total androgen ablation using Zoladex plus flutamide compared to orchiectomy in prostate cancer patients?,"Total androgen ablation: European experience. The EORTC GU Group. Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups."
-What percentage of nursing home residents in the study had a nutrient-modified diet prescription?,"Use of modified diets in nursing homes. Randomly chosen medical charts of 212 elderly subjects in 11 nursing homes were reviewed to determine which characteristics of the subjects were most closely associated with their diet prescriptions. The chart reviews indicated that 104 (49.0%) of the 212 subjects had some type of nutrient-modified diet prescription. Eight patients who were tube fed were not included in subsequent analyses. Sodium restriction was the most common modification (60 [29.4%] of the remaining 204 patients) and calorie-controlled diets were also common (52 [25.5%] of the patients). Of the 55 patients with hypertension, 31 (56.4%) had no sodium restriction. Only 10% of all low-sodium diets limited sodium to 2 g per day. Of the 38 patients with diabetes, 7 (18.4%) had no prescription for calorie control, and there was no indication that increased dietary fiber was encouraged for diabetic patients. Only one of the 121 subjects with a diagnosis of coronary heart disease or atherosclerosis had a prescription for a cholesterol-lowering diet. Characteristics of the subjects not specifically related to diet or diagnosis, such as age, sex, duration of stay, and level of care, had no significant relationship to diet prescription. These findings suggest that the practitioners in our sample were not convinced of the efficacy of modified diets to control disease for most nursing home residents."
-What improvements in lung function were observed in patients who underwent thoracoscopic carbon dioxide laser treatment for bullous emphysema?,"Thoracoscopic carbon dioxide laser treatment of bullous emphysema. A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation."
-What is the relationship between methotrexate cumulative dose and the progression of liver disease in patients with rheumatoid arthritis or psoriatic arthritis?,"Methotrexate and histologic hepatic abnormalities: a meta-analysis. STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS: A total of 636 patients from 15 studies. RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity."
-What is the recommended strategy to manage nitrate tolerance in patients?,"A practical guide to nitrate use. Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension."
-What types of tumors were most commonly associated with radial nerve paralysis in this review?,"Radial nerve paralysis and tumor. This paper presents ten cases of radial nerve paralysis because of tumor and reviews 38 previously reported cases. The tumor distribution was 35 lipomas, four neurofibromas, four ganglions, three neuromas, one fibroma, and one neurilemoma. Malignant tumors are not discussed in this review. Electromyography is of value if diagnostic problems occur. Postoperative results are normally good."
-What was unusual about the ECG findings in this patient with fulminant hepatic failure?,"Massive ST-segment elevation without myocardial injury in a patient with fulminant hepatic failure and cerebral edema. A 49-year-old woman presented in fulminant hepatic failure. The ECG showed dramatic ST-segment elevation, suggesting diffuse myocardial injury. However, echocardiography, creatine phosphokinase enzyme determinations, and examination of the heart at autopsy (six days later) failed to demonstrate any physiologic, anatomic, or histologic evidence of abnormality. The appearance of ST-segment elevation in this setting should not prompt treatment for cardiac disease or limit the candidacy for liver transplantation of such critically ill patients."
-What is the proposed pathophysiological reason for the rarity of peripheral neuropathy in sickle cell disease?,Mononeuropathy in sickle cell anemia: anatomical and pathophysiological basis for its rarity. Peripheral neuropathy is a rare complication of sickle cell disease. We report a young black woman with sickle cell anemia who developed a proximal median mononeuropathy in the setting of sickle cell crisis. The clinical and electrodiagnostic features are consistent with an ischemic mechanism from the sickling process. The pathophysiological basis for the rarity of this complication may be related to the rich anastomotic microvasculature of peripheral nerve and the unique large size of the capillaries of this vascular network.
-What was the success rate of scleral buckling surgery for rhegmatogenous retinal detachments in patients with severe myopia during the study period?,"Scleral buckling for rhegmatogenous retinal detachment associated with severe myopia. From Jan. 1, 1980, to Dec. 31, 1989, we performed scleral buckling surgery on 48 eyes of 46 patients for rhegmatogenous retinal detachments associated with severe myopia (greater than 5.00 diopters). Forty eyes of 38 patients were observed for at least six months, and the mean follow-up period was 46 months. Intraoperative complications occurred in four of 48 eyes (8%) and included retinal incarceration (two eyes), choroidal hemorrhage (one eye), and choroidal detachment (one eye). Three of the 40 eyes (7.5%) followed up for more than six months developed a recurrent retinal detachment and underwent a revision of the scleral buckle. At the last follow-up examination, the retinas of all 40 eyes were totally reattached. Final visual acuity of 20/40 or better was attained in 26 of 40 eyes (65%). Because of the low rate of intraoperative complications and the high rate of success, scleral buckling is recommended for most patients with rhegmatogenous retinal detachments associated with severe myopia."
-What are the five breast cancer screening strategies compared in the cost-effectiveness analysis in Japan?,"Cost-effectiveness analysis of mass screening for breast cancer in Japan. The official Japanese recommendation for breast cancer screening is physical examination by a physician, in contrast to US recommendations of mammography. In this analysis of breast cancer screening, the authors used Japanese data in a cost-effectiveness model to compare the following five strategies: (1) no screening (N); (2) physical examination alone (PE); (3) mammography (MG); (4) PE followed by MG if PE findings were abnormal (PE----MG); and (5) PE combined with MG for all screened women (PE + MG). None of these programs would save medical expenditures. The total discounted net costs per patient (in US dollars) were as follows: N, +54; PE, +412; MG, +517; PE----MG, +340; and PE + MG, +731. The number of years of life saved per cohort of 100,000 asymptomatic Japanese women would range from 708 (PE----MG) to 3724 (PG + MG). The additional cost of each strategy (compared with N) per additional year of life would be +49,700 for PE, +40,400 for PE----MG, +14,300 for MG, and +18,000 for PE + MG. The least costly screening option (PE----MG) does not have the lowest cost per additional year of life saved (MG does). MG would be preferable to the current Japanese recommendation of PE alone."
-What was the key finding regarding c-erbB-2 gene product expression in lobular breast neoplasia?,"C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Lobular carcinoma in situ (LCIS) has uncertain malignant potential; biologic markers that will identify patients at risk for a poor clinical outcome have been sought actively. Amplification of the c-erbB-2 protooncogene has been correlated with poor prognosis in invasive mammary carcinoma, and immunohistochemical evaluation for expression of the oncogene protein has been correlated with gene amplification. The authors retrospectively evaluated 62 cases of lobular neoplasia for expression of the c-erbB-2 gene product on formalin-fixed, deparaffinized sections, using two monoclonal anti-erbB-2 (p185) antibodies (c-neu Ab3 and m-erb) and one polyclonal anti-erbB-2 antibody (pAb 1) by the avidin-biotin-peroxidase method. All 62 cases were negative with the pAb 1 antibody; one of 62 cases was weakly positive with the c-neu Ab3 in a membranous pattern. Expression of c-erbB-2 gene product was identified on adjacent invasive ductal carcinoma in one case and in adjacent ductal carcinoma in situ in another. None of 15 cases if infiltrating lobular carcinoma was positive with either of the two anti-c-erbB-2 antibodies. Strong positivity was found on benign epithelium in one case, demonstrating epitheliosis. In summary, evidence of expression of the c-erbB-2 gene product was found in one of 57 cases of LCIS and none of 15 cases of invasive lobular carcinoma. This suggests that, in contrast to reported data concerning intraductal and invasive ductal carcinoma, c-erbB-2 oncogene amplification and/or overexpression does not play a significant role in the progression of lobular breast neoplasia."
-What percentage of head and neck squamous cell carcinoma patients had elevated carcinoembryonic antigen (CEA) levels in this study?,"Carcinoembryonic antigen and head and neck cancer. Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated (greater than or equal to 2.5 ng/ml). Only 13% of the patients had clearly elevated CEA levels (greater than 5 ng/ml). CEA levels were significantly higher in patients with advanced, e.g. stage IV, disease but a correlation between serum CEA concentration and prognosis was not found. Patients who smoked had significantly higher serum CEA levels than non-smoking patients. In the serial determinations slight CEA elevations could be found in only 50% of patients with tumour recurrence. Combined with the data from the literature we conclude that serum CEA determination is not useful in predicting the outcome in patients with a head and neck squamous carcinoma."
-What diagnostic imaging technique was used to identify the spinal cord herniation and intradural spinal arachnoid cyst?,"Spinal cord herniation associated with an intradural spinal arachnoid cyst diagnosed by magnetic resonance imaging. Two rare cases of spinal cord herniation associated with intradural spinal arachnoid cyst are reported. A preoperative magnetic resonance imaging scan demonstrated the presence of spinal cord herniation, identified as a protrusion continuous with the spinal cord. Surgery upon the intradural spinal arachnoid cyst improved progressive neurological dysfunction. The authors postulate that spinal cord herniation occurred for the following reason: The pressure of the intradural arachnoid cyst on the dorsal aspect of the spinal cord caused thinning of the dura, leading to a tear and, thus, the development of an extradural arachnoid cyst. Along with the enlargement of intradural arachnoid cyst, the spinal cord herniated through the tear in the dura into the extradural arachnoid cyst."
-How did the researchers use pulsed Doppler technique to evaluate blood flow velocity in the pulmonary artery of dogs with acute pulmonary hypertension?,"Intraluminal pulsed Doppler evaluation of the pulmonary artery velocity time curve in a canine model of acute pulmonary hypertension. The velocity pattern of the blood flow in the pulmonary artery was investigated in an animal model of acute pulmonary hypertension. Nine anesthetized, open-chest dogs were embolized with polystyrene microspheres, and the velocity pattern of the blood flow in the pulmonary artery was studied with use of an invasive pulsed Doppler technique. Phasic intraluminal velocity was recorded with use of a miniature piezoelectric crystal activated by 20-MHz Doppler pulses and mounted on the tip of a needle probe introduced into the pulmonary artery. The recorded Doppler quadrature signals were processed by spectral analysis. Significant increases occurred in mean, systolic, and diastolic pulmonary arterial pressures (p less than 0.0002), in pulmonary vascular resistance (p less than 0.005), and in negative velocity time (duration in milliseconds that the mean velocity was directed toward the pulmonic valve) (p less than 0.002). Significant decreases occurred in right ventricular ejection time (p less than 0.006) and in positive velocity time (duration in milliseconds that the mean velocity was directed away from the pulmonic valve) (p less than 0.005). A significant shortening in the time to peak velocity (acceleration time) was found (p less than 0.005). Second-order regression analyses demonstrated an inverse correlation between the ratio of positive velocity time to negative velocity time and the mean pulmonary artery pressure in all animals (r = 0.71). These findings should be compared with the velocity patterns of the blood flow in the pulmonary artery obtained under pulmonary hypertensive conditions due to various causes to facilitate interpretation and understanding of clinical investigations."
-How does the energy state of pig lungs change under different levels of oxygen and cyanide exposure?,"Energy state and vasomotor tone in hypoxic pig lungs. To evaluate the role of energy state in pulmonary vascular responses to hypoxia, we exposed isolated pig lungs to decreases in inspired PO2 or increases in perfusate NaCN concentration. Lung energy state was assessed by 31P nuclear magnetic resonance spectroscopy or measurement of adenine nucleotides by high-pressure liquid chromatography in freeze-clamped biopsies. In ventilated lungs, inspired PO2 of 200 (normoxia), 50 (hypoxia), and 0 Torr (anoxia) did not change adenine nucleotides but resulted in steady-state pulmonary arterial pressure (Ppa) values of 15.5 +/- 1.4, 30.3 +/- 1.8, and 17.2 +/- 1.9 mmHg, respectively, indicating vasoconstriction during hypoxia and reversal of vasoconstriction during anoxia. In degassed lungs, similar changes in Ppa were observed; however, energy state deteriorated during anoxia. An increase in perfusate NaCN concentration from 0 to 0.1 mM progressively increased Ppa and did not alter adenine nucleotides, whereas 1 mM reversed this vasoconstriction and caused deterioration of energy state. These results suggest that 1) pulmonary vasoconstrictor responses to hypoxia or cyanide occurred independently of whole lung energy state, 2) the inability of the pulmonary vasculature to sustain hypoxic vasoconstriction during anoxia might be associated with decreased energy state in some lung compartment, and 3) atelectasis was detrimental to whole lung energy state."
-Does aerobic exercise training provide significantly better physical performance improvements compared to light exercise for patients recovering from acute myocardial infarction?,"Effect of early programmes of high and low intensity exercise on physical performance after transmural acute myocardial infarction. Does a programme of light exercise training after acute myocardial infarction produce the same improvement in treadmill performance as aerobic exercise training? Three hundred and eight men from a consecutive series of 479 men with transmural (Q wave) acute myocardial infarction, admitted to a single coronary care unit, were randomly allocated to eight weeks of group aerobic exercise training or group light exercise. Groups were well matched for all characteristics other than site of infarction, which did not significantly affect results. Mean (SD) physical working capacity (metabolic equivalents) determined by treadmill testing at the start of the study (in the third week after infarction) was 6.8 (2.2) v 6.7 (2.5) METs, at the end (in the eleventh week after infarction) 10.8 (2.3) v 9.9 (2.4) METs, and at 12 month review 10.8 (2.4) v 10.7 (1.9) METs for the exercise training group and the light exercise group respectively. The difference of 0.9 METs at the end of the study was the only significant difference between groups. There were no significant intergroup differences at any stage in resting and maximal heart rate, resting and maximal systolic blood pressure, or rate-pressure product. Apart from a small temporarily greater physical working capacity, the physical benefits of aerobic exercise training were equally well achieved by group light exercise."
-What were the key findings regarding nocturnal body temperature in women with premenstrual syndrome (PMS) and late luteal phase dysphoric disorder (LLPDD)?,"High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder. OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects."
-What specific HLA-DQ alleles were found to be associated with insulin-dependent diabetes mellitus (IDDM) susceptibility in Japanese and white populations?,"Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites. Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups."
-What was the success rate of tumor destruction in patients with colorectal villous adenomas using endoscopic resection and Nd:YAG laser photocoagulation?,"Endoscopic treatment by snare electrocoagulation prior to Nd:YAG laser photocoagulation in 85 voluminous colorectal villous adenomas. The association of endoscopic resection with Nd:YAG laser photocoagulation was used to treat benign colorectal villous adenomas. Eight-five patients were included: 49 with surgical contraindications, 35 for whom surgical resection appeared to be too hazardous, and 1 who refused surgery. Forty-five tumors had an axial extension between 1 and 3 cm, and 40 tumors had an axial extension of at least 4 cm. Diathermic snare resection was performed to remove large tumoral fragments prior to laser photocoagulation of the residual flat lesions. Treatments were repeated every 15 days until total tumor destruction was achieved. A carcinoma was detected in biopsy specimens obtained during endoscopic treatment of five patients. Two patients were lost to follow-up. Treatment results could be analyzed in 78 patients. Successful treatment was achieved in 67 patients. Tumor destruction was complete in 77 percent of patients who had lesions of at least 4 cm diameter and in 93 percent of patients with smaller lesions. The axial extension of the tumor was the main factor affecting the results of treatment. No major complications occurred. During the average 103-week follow-up period, 21 percent of the patients with total tumor destruction had a recurrence. The risk of recurrence was correlated with the number of initial treatment sessions and previous surgery treatment. It would appear that the treatment with endoscopic resection prior to Nd:YAG laser photocoagulation is a safe and effective method in the destruction of colorectal villous adenomas."
-How do the fixed-reference and floating-reference systems differ in their assessment of wall motion abnormalities in patients with myocardial infarction?,"Reference systems in echocardiographic quantitative wall motion analysis with registration of respiration. Registration of respiration allows analysis at the end-expiratory phase and may thus favor the use of the fixed-reference system versus the floating-reference system in echocardiographic quantitative wall motion analysis. Analysis is performed on two-dimensional echocardiograms of 44 normal subjects, 38 patients with anterior myocardial infarction, and 17 patients with posterior myocardial infarction. Two different models for wall motion analysis are applied, each using the fixed-reference system and the floating-reference system, respectively. In patients with anterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the anterior, septal, and apical walls, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. In patients with posterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the posterior wall, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. These findings indicate that the fixed-reference system is superior to the floating-reference system in quantification of wall motion of end-expiratory two-dimensional echocardiograms."
-"In the study comparing diamorphine and morphine, what was the overall finding regarding the speed of onset of analgesic effect?","Comparison of speed of onset of analgesic effect of diamorphine and morphine. In a random, double-blind crossover trial using an ischaemic limb pain model we have assessed the speed of onset of analgesia after an i.v. bolus of equipotent doses of diamorphine and morphine in 12 healthy male volunteers. Pain and its subsequent relief were assessed by means of a visual analogue scale. Two of the subjects found diamorphine acted quicker than morphine, one found no difference and nine found that morphine was quicker than diamorphine. The mean time to diamorphine effect was 53% greater than for morphine (P less than 0.005, Wilcoxon rank sum test). These findings suggest that, for rapid relief of pain, morphine is more suitable than diamorphine."
-What unique neurological condition was observed in the 30-year-old woman that suggested a potential loss of nerve growth factor (NGF) trophic action?,"New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides. A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF."
-How does left ventricular hypertrophy (LVH) relate to cardiovascular disease risk in patients with hypertension?,"Left ventricular hypertrophy in hypertension. Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography, and with this technique it has been shown that evidence of LVH is an important independent risk factor for cardiovascular disease. The major cause of death in patients with hypertension and LVH is coronary artery disease. Therefore an understanding of the interrelationships between these two disorders is fundamental, and it is now clear that the hypertrophied ventricle is vulnerable to myocardial ischemia. Appreciation of the mechanisms of sudden death has also increased, although the exact situation in patients with LVH remains to be clarified. Regression of LVH is known to occur with the use of several different antihypertensive drugs. Recent studies indicate that the calcium blocking agent nicardipine, in addition to beta-blocking drugs and angiotensin-converting enzyme inhibitors, brings about LVH regression without any deterioration of left ventricular function. However, further studies are needed to assess the long-term benefits of this regression."
-What medical condition did the 27-year-old man with osteogenesis imperfecta develop after sustaining a femoral fracture?,Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.
-What treatment method was used to achieve tumor regression in patients with gastrointestinal leiomyosarcoma liver metastases?,Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.
-What is the Damus-Kaye-Stansel operation and what type of heart conditions is it used to treat?,"The Damus-Fontan procedure. The Damus-Kaye-Stansel operation is a useful technique for the treatment of complex cyanotic congenital heart disease when there is obstruction between the systemic ventricle and the aorta. Modifications of the technique include transection of the aorta and the pulmonary artery, anastomosis of the contiguous aortic and pulmonary walls, and connection of the distal aorta to the perimeter of the new bivalved proximal great artery. In addition, the bidirectional cavopulmonary shunt technique can be used with or without the Fontan procedure. Six patients underwent a Damus-Fontan operation, and all survived. Two patients underwent the Damus-cavopulmonary shunt (hemi-Fontan) procedure, and 1 survived. The postoperative status of the 7 survivors is good to excellent. Follow-up ranges from 2 months to 7 1/2 years."
-What is the proposed mechanism of anastomotic obstruction after stapled enteroanastomosis in this medical case report?,Anastomotic obstruction after stapled enteroanastomosis. We have recently treated two cases of anastomotic obstruction after side-to-side stapled enteroanastomosis. Complete obstruction of a stapled small-bowel anastomosis has not been reported to our knowledge. The mechanism of the obstruction appears to be the healing together of the cut edges of viable bowel beyond the inverted stapled lines. An alternative method of constructing the functional end-to-end enteroanastomosis that is offered is intended to prevent the occurrence of postoperative anastomotic obstruction.
-What percentage of children at the Children's Hospital in Bangkok were found to have bloody diarrhea?,"Epidemiologic aspects of shigellosis and other causes of dysentery in Thailand. Nearly 20% of children seen in the outpatient department of Children's Hospital in Bangkok, Thailand, for diarrheal disease had bloody diarrhea. Shigella species and enteroinvasive Escherichia coli--isolated from 13% and 2% of children with diarrhea, respectively--were the most frequent causes of bloody diarrhea. Campylobacter species and nontyphoidal Salmonella species were also isolated frequently but were much less often associated with bloody diarrhea. Shigella species were rarely isolated from patients who did not have diarrhea, while Campylobacter and Salmonella species were isolated frequently from well children. None of the species isolated always caused bloody diarrhea. Studies on infection with Campylobacter suggest that natural immunity may prevent bloody diarrhea and in fact may eventually prevent all disease due to this organism. Studies of endemic Shigella flexneri and epidemic Shigella dysenteriae 1 in Thailand have shown that immunity may also explain an age-related decrease in rates of S. flexneri infection but not in rates of S. dysenteriae 1 isolation."
-How does hypertension impact stroke risk in the black population?,"Cerebrovascular disease in hypertensive blacks. There is convincing evidence that all grades of persistent diastolic hypertension, especially in blacks, should be treated in order to prevent stroke and other cardiovascular complications. Studies are now in progress to gather additional information concerning isolated systolic hypertension, especially in the aged. Inasmuch as at least one half or more of stroke deaths in blacks develop as the result of hypertension, lowering blood pressure offers the perfect opportunity to reduce considerably the frequency of this devastating illness. The recent dramatic fall in U.S. stroke mortality, greatest in the black female, is a commendable achievement, but the flattening of the declining mortality curve over the past several years should be a cause for alarm and intensive investigation."
-What are gastrointestinal lipomas and how are they typically identified during radiologic examination?,"Gastrointestinal lipomas: a radiologic and pathologic review. Lipomas of the gastrointestinal tract are an infrequent finding on radiologic examination; however, they occur often enough to warrant consideration in the differential diagnosis of mass lesions of the gut. In many instances, their morphologic characteristics allow the specific diagnosis of a lipoma. In this report, we review gastrointestinal lipomas with an emphasis on their radiologic and pathologic correlation."
-How did the researchers classify patients with orthostatic disorders based on their blood pressure and heart rate responses when standing?,"Spectrum of orthostatic disorders: classification based on an analysis of the short-term circulatory response upon standing. 1. In 31 consecutively referred patients (20 females, 11 males) with overt or suspected orthostatic disorders, the changes in blood pressure and heart rate that occur in the first 2 min of standing were analysed. 2. Blood pressure was measured continuously by Finapres. The blood pressure and heart rate responses after 1-2 min of standing (early steady-state response) were used to classify the patients as follows: group I (n = 17, age 42 +/- 17 years), normal early steady-state blood pressure and heart rate responses; group II (n = 5, age 40 +/- 14 years), combination of normal early steady-state blood pressure and postural tachycardia; group III (n = 9, age 51 +/- 14 years), hypotensive orthostatic response with (4/9) or without (5/9) postural tachycardia. We examined whether additional information could be obtained by beat-to-beat analysis of the initial circulatory response (first 30 s). It was quantified by identifying the blood pressure trough and overshoot and the maximum heart rate and relative bradycardia. 3. The initial drop in systolic and diastolic blood pressures did not differ between the three groups. A recovery of blood pressure with a systolic and/or diastolic blood pressure overshoot was present in all group I and II patients, but was absent in all except two patients in group III. The initial maximum heart rate increase did not differ between the three groups. The relative bradycardia was less in groups II and III than in group I. 4. We conclude that analysis of the beat-to-beat blood pressure changes in the first 30 s after the onset of standing provides almost all the information that is necessary to determine abnormalities in orthostatic circulatory control."
-How does atrial appendectomy affect the secretion of atrial natriuretic polypeptide in dogs with high-output heart failure?,"Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide? The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure."
-What type of adverse skin reaction did the patient experience when taking medications containing pseudoephedrine and norephedrine hydrochloride?,"Systemic contact dermatitis from pseudoephedrine. A patient with rhinitis developed systemic contact dermatitis when starting oral treatment with Rhinalair, containing pseudoephedrine hydrochloride. A few months later, another oral treatment Rinutan, containing norephedrine hydrochloride, provoked a more severe generalized eczema. Patch test reactions were strongly positive to ephedrine and pseudoephedrine, slightly positive to phenylephrine and negative to epinephrine. Norephedrine was not tested."
-What were the two antibiotic combinations compared in this study for prophylaxis of infection following colorectal surgery?,"Colorectal surgery: short-term prophylaxis with clindamycin plus aztreonam or gentamicin. A randomized study was conducted to compare the effectiveness of aztreonam plus clindamycin with that of gentamicin plus clindamycin for prophylaxis of infection following colorectal surgery. A total of 138 patients undergoing elective colorectal surgery were randomized to treatment with clindamycin (600 mg) plus either aztreonam (1 g) or gentamicin (80 mg) 30 minutes before and 8 and 16 hours after surgery. The study included 122 patients (88.4%) with colorectal carcinoma. Samples from the abdominal cavity and from the subcutaneous tissues were taken for bacteriologic study. All samples from the abdominal cavity yielded microorganisms; both aerobic and anaerobic bacteria were isolated. Wound infections occurred in eight patients (12.1%) in the aztreonam group and in 12 patients (16.7%) in the gentamicin group. Escherichia coli, Bacteroides species, enterococci, and staphylococci were isolated most frequently from wounds and were often isolated from bacteriologic samples from the abdominal cavity of the same patients. The incidence of septic complications reflected the extent of nutritional and immunologic impairment. No significant differences were found between groups in the rate of urinary tract or lower respiratory tract infections. Aztreonam/clindamycin appears to be a valid alternative to gentamicin/clindamycin for the prophylaxis of infections following colorectal surgery."
-What percentage of patients with CHARGE Association had upper airway abnormalities beyond choanal atresia and cleft lip and palate?,"Incidence and management of airway problems in the CHARGE Association. The airway problems associated with anaesthesia in patients with the CHARGE Association have been underreported. We undertook a retrospective review of 50 cases, of which anaesthetic records were available for 37 patients. Apart from choanal atresia and cleft lip and palate, 56% of patients has some other upper airway abnormality. There appeared to be greater difficulty in tracheal intubation with increase in age in four patients. The incidence and management of airway abnormalities are discussed."
-What potential complications can arise from overfeeding critically ill patients according to the context?,"Report of a hidden case of overfeeding. Nutritional support is essential to the care of the critically ill patient, but complications of overfeeding can occur. Precise metabolic measurement by indirect calorimetry can detect problems of nutrition and allow adjustment in caloric intake. This case study illustrates the complications of carbon dioxide retention and inability to wean from mechanical ventilation with subsequent prevention of further complications."
-Why was trimethoprim-sulfamethoxazole (TMP-SMX) ineffective in treating experimental enterococcal endocarditis in the rat model?,"Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis. To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection."
-What significant finding was made regarding the p53 gene in a patient with an intracranial ependymoma?,"Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited."
-What was the relationship between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram in patients with acute myocardial infarction?,"Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction. This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery."
-How does insulin resistance affect inhibin levels in women with polycystic ovary syndrome (PCOS) compared to control subjects?,"Serum inhibin levels in polycystic ovary syndrome: effect of insulin resistance and insulin secretion. Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women."
-What were the findings of the study regarding the presence of human papillomavirus (HPV) DNA in cervical adenocarcinoma?,"Absence of human papilloma virus in cervical adenocarcinoma determined by in situ hybridisation. A few studies using DNA technology have suggested that human papillomavirus (HPV) may be an aetiological factor for adenocarcinoma of the uterine cervix. Twenty one cases of cervical adenocarcinoma were studied by in situ hybridisation using biotinylated DNA probes for HPV types 6, 11, 16 and 18 and a streptavidin, biotinylated alkaline phosphatase detection system. Intranuclear HPV DNA was detected in none of the adenocarcinomas, while positive controls gave a clear intranuclear signal. Adjacent areas of normal, koilocytic, and dysplastic squamous epithelium also gave positive results. It may be that squamous epithelium contaminates adenocarcinomas reported as positive by Southern blotting. Our results showing absence of detectable HPV DNA within adenocarcinomas suggest that HPV infection may not have a major role in the aetiology of adenocarcinoma of the uterine cervix."
-How does combined treatment with pulsatile LH-RH and hMG affect follicular development in patients with polycystic ovaries?,"Treatment with pulsatile luteinizing hormone-releasing hormone modulates folliculogenesis in response to ovarian stimulation with exogenous gonadotropins in patients with polycystic ovaries. Combined treatment with pulsatile LH-RH and hMG, given to eight patients who had anovulation associated with PCO and resistant to CC, significantly reduced the number of large follicles induced by hMG alone. A direct effect of pulsatile LH-RH on the ovary is postulated. This combined treatment eased the problems of multifollicular development, thereby increasing efficiency and reducing complications in patients with PCO stimulated by gonadotropins."
-What were the initial findings of the clinical study on granisetron for treating migraine headaches?,"First clinical study of the selective 5-HT3 antagonist, granisetron (BRL 43694), in the acute treatment of migraine headache. Granisetron (BRL 43694), a selective 5-HT3 receptor antagonist, was assessed as acute therapy for the first time in migraine patients. In an open pilot study 7 migraine attacks were treated in 6 patients. All but 1 patient experienced marked and rapid relief from the headache, and nausea and vomiting were rapidly resolved in the 6 cases where these symptoms accompanied the attack. No side effects were recorded. Development of granisetron for migraine was suspended during the study for extraneous reasons."
-"What are the differences in the expression of Tn, sialosyl Tn, and T antigens across normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma?","Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis."
-How does QTc prolongation relate to the risk of sudden death in patients with and without cardiac dysfunction?,"QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. BACKGROUND. QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. METHODS AND RESULTS. In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. CONCLUSIONS. These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death."
-"What were the key findings regarding adverse events in children who completed treatment for acute lymphoblastic leukemia across studies VIII, IX, and X?","Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X. We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure."
-What is the purpose of the educational device described in the context related to Mohs micrographic surgery?,An educational device for Mohs micrographic surgery. A three-dimensional model of basal cell carcinoma. Mohs micrographic surgery for skin cancer (fresh-tissue technique) involves the processing of tissue in a complex fashion. The advantages of this method relate to the asymmetric three-dimensional growth of basal cell carcinoma (BCC). A device is described here based on published knowledge about the growth of BCC. The model demonstrates the precise way in which Mohs surgery varies from other surgical approaches to yield higher cure rates in specific circumstances. This device may be helpful in educating residents and medical students about Mohs surgery and in preparing patients for this procedure.
-What was the incidence of ischemic injury to the spinal cord or lumbosacral plexus following abdominal aorta operations during the study period?,"Ischemic injury to the spinal cord or lumbosacral plexus after aorto-iliac reconstruction. Between January 1, 1980, and June 30, 1989, 9 patients (6 males and 3 females) developed ischemic injury to the spinal cord or lumbosacral plexus following 3,320 operations on the abdominal aorta (0.3%). The incidence of this complication was 0.1% (2 of 1,901) after elective and 1.4% (3 of 210) after emergency abdominal aortic aneurysm repair, and 0.3% (4 of 1,209) after repair for occlusive disease. Three of the latter had prior clinical evidence of distal embolization. Eight grafts were bifurcated (aorto-iliac:four, aorto-femoral: three, aorto-ilio-femoral:one). One patient underwent extra-anatomic revascularization. Only two patients had supraceliac aortic cross-clamping and one patient underwent exclusion of both internal iliac arteries. Four patients had hypotension. Early mortality was 22% (two of nine). Severe perioperative complications, mostly due to associated visceral and somatic ischemia and sepsis, were present in seven of the nine patients. The extent and type of the neurologic injury correlated with long-term outcome. Patients with ischemic injury of the lumbosacral roots or plexus had better recovery. Attention to the pelvic circulation and the collateral blood supply is important. Use of gentle technique to prevent embolization, avoidance of hypotension and prolonged supraceliac cross-clamping, revascularization of at least one internal iliac artery, and the use of heparin may decrease but not eliminate paraplegia. Once this unexpected complication occurs, careful neurologic evaluation should be done to localize the lesion and aid prognosis."
-What is the significance of Agrobacterium radiobacter peritonitis in the two patients on chronic peritoneal dialysis?,"Agrobacterium radiobacter peritonitis in two patients maintained on chronic peritoneal dialysis. We report two patients with end-stage renal disease maintained on chronic peritoneal dialysis who developed peritonitis in which the infecting organism was Agrobacterium radiobacter, normally a rare pathogen in humans. Both patients initially responded to antibiotics, but later relapsed and required catheter removal. Neither had been exposed to soil or plant material. A radiobacter is yet another of a growing list of unusual organisms that infect the peritoneal cavity of peritoneal dialysis patients."
-How does calcium potentially help in reducing the risk of colon cancer according to the given context?,"Modulating effects of calcium in animal models of colon carcinogenesis and short-term studies in subjects at increased risk for colon cancer. A substantive amount of evidence from animal models supports the hypothesis that dietary fat is an etiological factor in colon cancer. Although various theories account for possible mechanisms, it is clear that under the influence of a basic colonic pH, fatty acids and bile acids may become highly surfactant in the colon, causing cell loss and compensatory hyperproliferation. Calcium likely reduces lipid damage in the colon by complexing with fat to form mineral-fat complexes or soaps. It has been shown in an increasing number of animal experiments that calcium has the ability to inhibit colon cancer. In limited studies in man, the colonic hyperproliferation associated with increased risk for colon cancer has been reversed for short periods by administration of supplemental dietary calcium. Taken together the available evidence suggests that increases in the daily intake of calcium in the diet may provide a means of colorectal-cancer control."
-What is the recommended treatment approach for symptomatic cavernous malformations of the brain stem?,"Cavernous malformations of the brain stem. Once they become symptomatic, cavernous malformations of the brain stem appear to cause progressive morbidity from repetitive hemorrhage, and can even be fatal. Twenty-four patients with long-tract and/or cranial nerve findings from their cavernous malformations of the brain stem were seen for initial evaluation or surgical consultation and thereafter received either surgical or continued conservative treatment. The decision to operate was based on the proximity of the cavernous malformation to the pial surface of the brain stem, the patient's neurological status, and the number of symptomatic episodes. Sixteen patients were treated by definitive surgery directed at excision of their malformation. In four patients, associated venous malformations influenced the surgical approach and their recognition avoided the risk of inappropriate excision of the venous malformation. Although some of the 16 patients had transient, immediate, postoperative worsening of their neurological deficits, the outcome of all except one was the same or improved. Only one patient developed recurrent symptoms: a new deficit 2 1/2 years after surgery required reoperation after regrowth of the cavernous malformation. She has been neurologically stable since the second surgery. One patient died 6 months postoperatively from a shunt infection and sepsis. The eight conservatively treated patients are followed with annual magnetic resonance imaging studies. One has a dramatic associated venous malformation. Seven patients have either minor intermittent or no symptoms, and the eighth died from a hemorrhage 1 year after his initial presentation. Based on these results, surgical extirpation of symptomatic cavernous malformations of the brain stem appears to be the treatment of choice when a patient is symptomatic, the lesion is located superficially, and an operative approach can spare eloquent tissue. When cavernous malformations of the brain stem are completely excised, cure appears permanent."
-What chromosomal translocation was observed in the meningioma cells of patient MN32?,"A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene. Cytogenetic analysis of meningioma cells from one particular patient (MN32) displayed the stem-line karyo-type 45, XY, -1, 4p+, 22q-, 22q+, which thus had rearrangements of both chromosomes 22. The 22q+ marker appeared as a dicentric: 22 pter----q11::1p11----qter. The reciprocal product of this translocation has presumably been lost because it lacked a centromere. The 22q- chromosome also appeared to have lost sequences distal to band q11. We assumed that this marker could have been the result of a reciprocal translocation between chromosomes 4 and 22. To investigate the 4p+ and 22q- chromosomes in more detail, human-hamster somatic cell hybrids were constructed that segregated the 22q- and 4p+ chromosomes. Southern blot analysis with DNA from these hybrids showed that sequences from 22q were indeed translocated to 4p+ and that reciprocally sequences from 4p were translocated to 22q-, demonstrating a balanced t(4;22)(p16;q11). On the basis of these results we presume that in this tumor a tumor-suppressor gene is deleted in the case of the 22q+ marker and that the t(4;22) disrupts the second allele of this gene. The latter translocation was mapped between D22S1 and D22S15, a distance of 1 cM on the linkage map of this chromosome. The area in which we have located the translocation is within the region where the gene predisposing to neurofibromatosis 2 has been mapped."
-How does the activity of calcium-independent plasmalogen-selective phospholipase A2 change during myocardial ischemia?,"The rapid and reversible activation of a calcium-independent plasmalogen-selective phospholipase A2 during myocardial ischemia. Recent studies have demonstrated the existence of two members of a novel family of calcium-independent plasmalogen-selective phospholipases A2 in mammalian myocardium (Wolf, R. A., and R. W. Gross. 1985. J. Biol. Chem. 260:7295-7303; and Hazen, S. L., D. A. Ford, and R. W. Gross. 1991. J. Biol. Chem. 266:5629-5633). To examine the potential role of these calcium-independent phospholipases A2 in mediating membrane dysfunction during early myocardial ischemia, the temporal course of alterations in phospholipase A2 activity during global ischemia in Langendorf perfused rabbit hearts was quantified and compared with traditionally accepted markers of myocytic ischemic injury and anaerobic metabolism. We now report that membrane-associated calcium-independent plasmalogen-selective phospholipase A2 activity increased over 400% during 2 min of global ischemia (P less than 0.01), was near maximally activated (greater than 10-fold) after only 5 min of ischemia, and remained activated throughout the entire ischemic interval examined (2-60 min). Activation of membrane-associated plasmalogen-selective phospholipase A2 after 5 min of myocardial ischemia was rapidly reversible during reperfusion of ischemic tissue. Both the activation of phospholipase A2 and its reversibility during reperfusion were temporally correlated to alterations in myocytic anaerobic metabolism. Furthermore, activation of membrane-associated phospholipase A2 was essentially complete before electron microscopic evidence of cellular damage. Collectively, these results identify dynamic alterations in calcium-independent plasmalogen-selective phospholipase A2 activity during myocardial ischemia which precede irreversible cellular injury and demonstrate that activation of plasmalogen-selective phospholipase A2 is amongst the earliest biochemical alterations in ischemic myocardium."
-What was the purpose of the study on thallium-201 scintigraphy and how reproducible were the quantitative measurements?,"Reproducibility of quantitative planar thallium-201 scintigraphy: quantitative criteria for reversibility of myocardial perfusion defects. Fifty-two paired stress/delayed planar 201TI studies (27 exercise studies, 25 dipyridamole studies) were processed twice by seven technologists to assess inter- and intraobserver variability. The reproducibility was inversely related to the size of 201TI perfusion abnormalities. Intraobserver variability was not different between exercise and dipyridamole studies for lesions of similar size. Based upon intraobserver variability, objective quantitative criteria for reversibility of perfusion abnormalities were defined. These objective criteria were tested prospectively in a separate group of 35 201TI studies and compared with the subjective interpretation of quantitative circumferential profiles. Overall, exact agreement existed in 78% of images (kappa statistic k = 0.66). We conclude that quantification of planar 201TI scans is highly reproducible, with acceptable inter- and intraobserver variability. Objective criteria for lesion reversibility correlated well with analysis by experienced observers."
-What are the main components of delay in treatment for acute myocardial infarction?,"Delays in the treatment of acute myocardial infarction: an overview. Delays in treatment of acute myocardial infarction prevent a substantial portion of patients from receiving maximal benefit from reperfusion therapy. Median delay between onset of symptoms and arrival at the hospital is 2 to 4 hours. Average time between arrival at the hospital and initiation of thrombolytic therapy is 84 minutes. Approximately 50% of patients hospitalized for suspected acute myocardial infarction do not use the emergency medical service system. Delay before treatment can be divided into several components: patient delay, emergency medical service delay, and hospital delay. Factors contributing to delay in each component and possible approaches to decreasing these delays are discussed. The effects of treatment delay on prognosis and future care-seeking behavior of patients hospitalized with suspected acute myocardial infarction are also discussed."
-"How does Na,K-ATPase activity change in different nephron segments in rats with moderate heart failure compared to the control group?","Na,K-ATPase in isolated nephron segments in rats with experimental heart failure. To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control)."
-What were the key findings regarding the prognosis of Hodgkin's disease in patients aged 60 to 79 years compared to patients aged 40 to 59 years?,"The prognosis of Hodgkin's disease in older adults. This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates."
-"How do the concentrations of somatostatin, gastrin-releasing peptide (GRP), and gastrin differ in the stomachs of rats with streptozotocin-induced diabetes and insulinoma compared to control rats?","Somatostatin, gastrin-releasing peptide and gastrin in the stomach of rats with streptozotocin-induced diabetes and insulinoma. Somatostatin, gastrin-releasing peptide (GRP) and gastrin were measured in the stomach of rats with streptozotocin-induced diabetes, insulinoma-bearing rats and their respective controls. Rats injected with streptozotocin exhibited hyperphagia, insulinopenia and severe hyperglycemia. Stomach weights, and the concentrations and total amounts of GRP and gastrin in the stomach, were similar to nondiabetic control rats. The concentration of somatostatin in the stomach of diabetic rats was 25% greater, but the total stomach content of somatostatin was similar to that of control rats. Insulinoma-bearing rats exhibited hyperphagia, hyperinsulinemia and hypoglycemia. Concentrations of GRP and gastrin in the stomach were 72% and 19% lower, respectively, than in control rats. Despite 45% greater stomach weight, the total stomach content of GRP was 61% lower. Stomach concentrations of somatostatin, and total stomach contents of somatostatin and gastrin, were similar in insulinoma-bearing and control rats. The results demonstrate abnormalities in the stomach concentrations of regulatory peptides in rats with diabetes and insulinoma. These abnormalities are not attributable to changes in food intake alone, suggesting specific effects of these metabolic diseases on gastric regulatory peptides and gastric function."
-"What rare condition was observed in the 4-year-old girl with sinusitis, and how was it diagnosed and treated?","Periorbital hematoma secondary to sinusitis in a child. Periorbital abscess secondary to sinusitis is a well-recognized entity in children. However, subperiosteal hematoma is extremely rare and has been reported in only four adult patients. This article presents the case of a 4-year-old girl with sinusitis, proptosis, and decreased visual acuity. Surgical exploration of the orbit revealed the presence of a large organizing subperiosteal hematoma that was drained. The presence of a periorbital hematoma should be suspected in patients with acute onset of proptosis and findings of a periorbital mass and sinusitis on computed tomographic scan."
-How does dopamine release in the nucleus tractus solitarii change during severe hypoxia in rabbits?,"Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits. A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures."
-What is gliomatosis peritonei and what unique transformation was observed in this case report?,"Gliomatosis peritonei with malignant transformation: a case report and review of the literature. Gliomatosis peritonei is the implantation of glial tissue within the peritoneal cavity associated with ovarian teratomas. Previous reports have emphasized improved outcomes when these implants are found to be mature, even if the ovarian component is immature. A 16-year-old female with grade 3 immature teratoma was found on two subsequent laparotomies to have extensive peritoneal implantation of mature glial tissue. More than 5 years after the original surgery she was found to have a malignant abdominal glial neoplasm. This case illustrates a rare finding of malignant transformation of previously mature gliomatosis peritonei."
-How does glucagon affect the serum total bile acid levels in patients with different stages of liver cirrhosis?,"Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis. Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver."
-How can PCR analysis of BCR-abl fusion transcripts help in detecting potential relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia patients after bone marrow transplantation?,"Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph-) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL."
-What was the hospital mortality rate for patients undergoing coronary bypass reoperation with bilateral internal mammary artery grafts compared to those receiving primary revascularization?,"Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups."
-What was the purpose of the Rheumatoid Arthritis Azathioprine Registry (RAAR) established in 1982?,"Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. The Rheumatoid Arthritis Azathioprine Registry (RAAR) was established in 1982 to examine the safety of azathioprine (AZA) and other disease modifying agents (DMARD) in the treatment of RA. In yearly followup over the past 7 years, 20 malignant conditions have been reported in 530 DMARD treated adult patients with RA. Incidence density ratios (IDR) and standardized morbidity ratios (SMR) were calculated to assess cancer risk. For all cancers the SMR was 1.52 (95% CI 0.90-2.60). For men the SMR was 1.71 (95% CI 0.84-3.52); for women the SMR was 1.52 (95% CI 0.89-2.60). Adjusted for age, the IDR was highest in the 70-79-year-old study population (3.41). The age and sex adjusted SMR for lymphoproliferative disorders and myeloma was 8.05 (95% CI 3.30-20.81). The SMR for lung cancer (n = 6) was also increased (3.37; 95% CI 1.58-7.34). Compared with the general population, patients with RA requiring DMARD therapy may be at increased risk of malignancy, particularly lymphoproliferative disorders. The RAAR is an important prospective technique which will ultimately permit assessment of neoplasia risk by type and duration of DMARD therapy."
-What advantages does adenosine have over dipyridamole as a pharmacologic stress agent in positron emission tomography (PET) imaging?,"Adenosine in myocardial perfusion imaging using positron emission tomography. Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction."
-What are the precipitating factors for colovesical fistula in the described diabetic patient?,Colovesical fistula secondary to vesical gangrene in a diabetic patient. We present a case of colovesical fistula secondary to vesical gangrene. Precipitating factors were diabetes and vesical distension caused by the obstruction of an indwelling catheter. This complication is an exceptional outcome in gangrenous cystitis and it requires emergency surgical treatment.
-How did the atrial natriuretic factor analog A68828 affect glomerular filtration rate (GFR) in a postischemic acute renal failure model?,"Beneficial effect of the atrial natriuretic factor analog A68828 in postischemic acute renal failure. Short-term administration of atrial peptides has been reported to improve renal function in several animal models of acute renal failure. We designed experiments that determined the effect of a 13-amino acid analog of atrial natriuretic factor (ANF), A68828, on renal function in the postischemic model of acute renal failure. Experiments were conducted using euvolemic, male Sprague-Dawley rats (200-250 g) under Inactin anesthesia. Acute renal failure was induced by complete occlusion of both renal arteries for 30 min. After release of the clamp, vehicle (0.1% bovine serum albumin in saline), A68828 (3, 10 or 30 micrograms/kg/min), dopamine (10 micrograms/kg/min), A68828 (10 micrograms/kg/min) plus dopamine (10 micrograms/kg/min) or ANF (1-28) (0.5 micrograms/kg/min) were infused i.v. for a 2-h period. A68828 at 10 micrograms/kg/min produced a significant increase in glomerular filtration rate (GFR) compared with vehicle controls (0.39 +/- 0.08 vs. 0.19 +/- 0.04 ml/min/100 g; P less than .05) despite a lower arterial pressure (87 +/- 5 vs. 101 +/- 5 mm Hg; P less than .05). A subpressor dose of dopamine had no effect on GFR during the postischemic period (0.25 +/- 0.11 ml/min/100 g). Dopamine in combination with A68828 prevented the decrease in arterial pressure seen with A68828 alone but did not potentiate the beneficial effects on GFR (0.28 +/- 0.05 ml/min/100 g). ANF (1-28) at 0.5 micrograms/kg/min increased GFR to levels nearly identical to those induced by A68828 (0.40 +/- 0.04 ml/min/100 g). These results indicate that infusion of a reduced-size analog of ANF improves renal function in the immediate postischemic period. Furthermore, prevention of the hypotensive effects of the analog with dopamine provides no additional beneficial effect."
-What is clear cell cribriform hyperplasia (CCCH) of the prostate and what were the key findings of this study?,"Clear cell cribriform hyperplasia of the prostate. Immunohistochemical and DNA flow cytometric study. Clear cell cribriform hyperplasia (CCCH) of the prostate is an unusual form of benign prostatic hyperplasia characterized by a nodular proliferation of clear cells with small, uniform nuclei. The authors studied 15 cases of CCCH by immunohistochemistry and 13 of them by DNA flow cytometry to establish the immunohistochemical and DNA profile of this lesion. Patients ranged in age from 58 to 88 years (mean, 68 years). Follow-up of a mean of 22 months showed all patients alive with no evidence of malignant prostatic disease. All 13 CCCHs showed diploid DNA content; in contrast, among 4 papillary/cribriform carcinomas of the prostate used for comparison, 3 were aneuploid and 1 was diploid. A basal cell layer was demonstrated in all 15 CCCHs by the use of the 34 beta E12 anti-high-molecular-weight keratin antibody (EAB-903) that reacts with the basal cells but not with the acinar cells of the prostate. A continuous basal cell layer was not evident in the carcinomas. The blandness of the epithelium, the well-defined nodular configuration, the presence of a basal cell layer demonstrable by immunocytochemistry, and the lack of aneuploidy as determined by DNA flow cytometry together lend support to the concept that CCCH is a benign lesion."
-What is cramp-fasciculation syndrome and how was it treated in the reported patients?,"Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder. We report nine patients with muscle aching, cramps, stiffness, exercise intolerance, and peripheral nerve hyperexcitability. Neurologic examination showed calf fasciculations in seven, quadriceps myokymia in two, and deltoid myokymia in one patient. Two patients had mild increase in serum creatine kinase. Muscle biopsy showed either no abnormality (three patients) or mild neurogenic changes (four patients). Fasciculations were the only abnormality on routine electrodiagnostic studies. Supramaximal stimulation of the median, ulnar, peroneal, and posterior tibial nerves at frequencies of 0.5, 1, 2, and 5 Hz produced showers of electrical potentials following the M response in at least one nerve. In three patients, the fasciculations and evoked electrical potentials were abolished by regional application of curare but not nerve block. Carbamazepine therapy caused moderate-to-marked reduction of symptoms and nerve hyperexcitability. We designate this hyperexcitable peripheral nerve disorder as the ""cramp-fasciculation syndrome.""."
-What diagnostic methods are recommended for identifying acid peptic disease in adolescents?,"Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment. Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life."
-How did the perceived beliefs of others and attitudes impact regimen compliance among myocardial infarction patients two years after the intervention?,"Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens."
-What was the incidence of allergic reactions in patients receiving long-term benzathine penicillin prophylaxis for rheumatic fever?,"Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group. 1790 patients from 11 countries were enrolled in a prospective international study to determine the incidence of allergic reactions to monthly intramuscular benzathine penicillin (penicillin G benzathine) injections to prevent recurrences of rheumatic fever. After 32,430 injections during 2736 patient years of observation, 57 of the 1790 patients (3.2%) had an allergic reaction. 4 had anaphylaxis, an incidence of 0.2% (1.2/10,000 injections), all in patients over 12 years of age, and 1 patient died, a fatality incidence of 0.05% (0.31/10,000 injections). These rates are similar to those described for patients without rheumatic fever who receive short-term treatment with parenteral penicillin. Rheumatic fever recurred in 8 of 1790 patients (0.45%) who received benzathine penicillin prophylaxis compared with 11 of 96 (11.5%) who did not comply with treatment. Life-threatening allergic reactions are rare in patients on long-term parenteral benzathine penicillin to prevent recurrences of rheumatic fever; the long-term benefits of such prophylaxis by far outweigh the risk of a serious allergic reaction."
-How does the degree of carotid arterial stenosis affect cerebral blood flow reactivity to hypercapnia?,"Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results. To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia."
-How does protein kinase C (PK-C) contribute to parathyroid hormone (PTH)-induced desensitization in UMR-106 osteosarcoma cells?,"Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells. We have investigated mechanisms of PTH-induced homologous desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced desensitization. Thus, PK-C seemed to play a major role in rPTH-induced desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced homologous desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells."
-How did the use of the Hemonetics cell saver apparatus impact blood transfusion requirements during coronary artery bypass graft surgery?,"The benefit of the Hemonetics cell saver apparatus during cardiac surgery. This retrospective chart review of 155 patients having coronary artery bypass graft surgery (CABG) over a two-month period determined whether the use of a cell saver apparatus (CSA) (1) reduced or increased the requirements for homologous blood; (2) increased the incidence of post-surgical bleeding; (3) was cost-effective. Two groups of patients were identified. Group 1 (n = 99) received both CSA processed red blood cells and homologous blood components. Requirement for homologous blood products was reduced in the first 24 hr after surgery (0.5 +/- 1.0 vs 1.3 +/- 1.8 units; P less than 0.05) when compared with Group 2 (n = 56) in whom only homologous blood products were utilized. More patients in Group 1 had no transfusion requirements (45 vs 8; P less than 0.05) and there was no increased risk of major haemorrhage. When the capital costs are included, utilization of the CSA was not cost-effective. We conclude that utilisation of a CSA was safe, with no increased risk of bleeding, reduced requirements for homologous blood transfusions, but added to the cost of the procedure."
-What percentage of patients in the study had syncope produced by orthostatic testing?,"Abnormal responses to orthostatic testing in children and adolescents with recurrent unexplained syncope. Syncope in the pediatric age group is a frequent event. Most often the cause is readily apparent--i.e., orthostatic hypotension or a vasovagal event. However, there are a large number of children with frequent recurrent unexplained syncope. Neither history, physical examination, nor standard testing reveals a cause. One hundred four consecutive patients were evaluated by orthostatic testing after standard methods found no cause for the recurrent syncope. Forty-seven (44%) of these 104 patients had syncope produced by orthostatic testing. Twenty-six of the 47 (55%) became syncopal within 5 minutes of testing initiation and 21 of the 47 (45%) after 5 to 11 minutes of testing. These patients had an average decrease of 81.5 mm Hg in blood pressure and a 25 beat/min decrease in heart rate. Of 12 control subjects, none lost consciousness with standing times as long as 14 minutes. Pacing was ineffective in preventing syncope, as two patients with a previously implanted normally functioning pacemaker had recurrent syncope clinically. Syncope was also induced by orthostatic testing, with the pacemaker showing a normal response with pacing as the patient became bradycardic. The syncopal event produced by orthostatic testing occurred with a downward blood pressure trend and a narrowing of the pulse pressure without a significant increase in heart rate. This was followed by a sudden drop in blood pressure and then by bradycardia. There is a group of children and adolescents with recurrent unexplained syncope due to abnormal orthostatic control mechanisms. Orthostatic testing appears helpful in identifying these patients."
-What were the two methods of epidural diamorphine administration compared in this study?,"Lumbar epidural diamorphine following thoracic surgery. A comparison of infusion and bolus administration. Twenty-two patients received a single dose of diamorphine 5 mg through a lumbar epidural catheter before thoracic surgery. The patients were transferred after surgery to a high dependency unit where they were allocated randomly to receive either an infusion of epidural diamorphine at a rate of 1 mg/hour (group 1) or bolus doses of epidural diamorphine 5 mg on demand (group 2). There was no statistically significant difference between the groups in visual analogue pain scores in the first 18 postoperative hours. Arterial carbon dioxide tension was elevated in both groups and was consistently higher in group 1 than in group 2, with a statistically significant intergroup difference 12 hours after operation. Respiratory rate was not a useful index of respiratory depression. The commonest nonrespiratory side effect was urinary retention, but the incidences of this and other minor side effects were similar in the two groups."
-How accurate is MR imaging with a body coil in estimating prostate tumor volumes?,"Carcinoma of the prostate: MR images obtained with body coils do not accurately reflect tumor volume. MR imaging with a body coil is unreliable in directly demonstrating tumor spread through the prostatic capsule. However, the likelihood of extracapsular spread of prostatic cancer rises with increasing tumor volume. The aim of our study was to assess the accuracy of MR with a body coil in diagnosing capsular penetration indirectly via an estimation of prostatic tumor volumes. Twenty-six patients with proved prostatic cancer that was clinically confined to the gland underwent MR imaging before radical prostatectomy and whole-mount pathologic sectioning of the specimen. Twenty of 31 lesions prospectively outlined on the MR images corresponded to cancers outlined on the pathology slides, and tumor volumes were calculated by using a voxel summation technique. On MR, tumor volume was underestimated in 11 of 20 cases and overestimated in nine of 20 cases. Only two of 20 size estimates based on MR findings were within 10% of actual tumor volume. Overlap in MR tumor volumes was significant between lesions with and without capsular penetration at microscopy. Factors contributing to inaccuracies in measurements of tumor volume on MR images included the variable histologic make-up of the tumors. Our results show that, although knowledge of the size of a prostatic lesion is important in predicting the behavior of the tumor, MR imaging with a body coil is not reliable for accurate estimation of tumor volume."
-What is Parathyroid Hypertensive Factor (PHF) and in what percentage of North American essential hypertensive patients is it found?,"Purification of parathyroid hypertensive factor from plasma of spontaneously hypertensive rats. Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor that may be related to elevation of blood pressure in 30-40% of North American essential hypertensive patients. PHF is also found in several animal models of hypertension, including spontaneously hypertensive rats, and deoxycorticosterone acetate salt hypertensive rats. Plasma collected from spontaneously hypertensive rats (SHR) was used in the present study for purification of PHF. Plasma was dialyzed at a molecular mass cutoff of 1 kDa, and then ultrafiltered at a molecular mass cutoff of 5 kDa. PHF activity, as determined by bioassay (characteristic delayed hypertensive response in normotensive rat) was retained in the fraction that was greater than 1 kDa and less than 5 kDa. Dialyzed and ultrafiltered SHR plasma was fractionated by molecular-exclusion chromatography, either with Bio-Gel P-6 liquid chromatography, or TSK 2000 SW HPLC. The biological activity was detected in a discrete region corresponding to a molecular mass of 2.5-3 kDa. When the molecular-exclusion fraction was subsequently fractionated by reverse-phase HPLC, biological activity was located in a single discrete peak, which did not occur in plasma from normotensive rats prepared in a similar manner. The biologically active fraction of PHF was inactivated by trypsin; this and its UV spectrum indicate the presence of a peptide structure."
-What is a nasal schwannoma and what is the recommended treatment approach?,Nasal schwannoma. A 36-year-old man with a nasal septal mass is presented. The diagnosis of a benign neoplasm arising from peripheral nerve Schwann cells was made by excisional biopsy. A benign nerve sheath tumor may be either a schwannoma or neurofibroma. Schwannomas may be distinguished from neurofibroma by clinical and histologic criteria. Malignant degeneration and intracranial extension may complicate the course of a nasal schwannoma. Complete excision is the preferred therapy.
-What signs of essential fatty acid deficiency were observed in infants receiving a medium-chain-triglyceride (MCT) infant formula?,"Essential fatty acid deficiency associated with the use of a medium-chain-triglyceride infant formula in pediatric hepatobiliary disease. Serum phospholipid fatty acid patterns were determined by gas chromatography in four infants with hepatobiliary disease receiving a formula with a high content of medium-chain-triglyceride (MCT) oil. All four infants demonstrated signs of essential fatty acid deficiency, characterized by decreased arachidonic acid and increased palmitoleic and oleic acids. All had substantial concentrations of the pathologic triene 5,8,11-eicosatrienoic acid. Three of four had decreased linoleic acid concentrations and abnormal ratios of triene to tetraene (5,8,11-eicosatrienoic acid: arachidonic acid), greater than 0.38. One patient may have experienced growth failure due to abnormal essential fatty acid status. Infants with the potential for fat malabsorption should only receive MCT-oil feedings with well above the generally recommended requirements for linoleic acid (3% of total caloric intake)."
-What is the main purpose of the postoperative infusional continuous regional analgesia (PICRA) technique described in the context?,"Postoperative infusional continuous regional analgesia. A technique for relief of postoperative pain following major extremity surgery. A new technique using postoperative infusional continuous regional analgesia (PICRA) for postoperative pain relief was investigated in 23 surgical patients treated by amputation (12 patients) or by limb-salvage resection operations (11 patients). Bupivacaine was delivered into peripheral nerve sheaths via catheters placed therein at the time of surgery. Only patients in whom the nerves were easily accessible were treated. Catheters were placed in the axillary sheath, the lumbosacral trunk, and the femoral nerve sheaths of patients treated with shoulder girdle and pelvic procedures (resections and amputations), and within the sciatic nerve sheath of those treated with lower extremity procedures. The anesthetic agent was delivered at controllable rates. Regional analgesia was obtained in the operative site with minimal motor or sensory decrease. To assess the efficacy of this technique, the results of this study group were compared with those of a matched group of 11 patients treated with similar surgical procedures but who received epidural morphine. Eleven of the 23 patients on PICRA required no supplemental narcotic agents. The mean level of the narcotic agents required by the remaining 13 PICRA patients was approximately one third of that required by the matched group of 11 patients receiving epidural morphine. Overall, the patients on PICRA had an 80% reduction of narcotic requirements when compared to the historical controls. The technique is reliable and can be performed by the surgeon, requiring about a ten-minute increase in operating time. It has potentially wide application in orthopedics in procedures in which the major nerves are easily accessible (e.g., pelvic fractures and revision hip surgery) and for patients with intractable pain of the extremities."
-What are the key findings of the immunoelectronmicroscopic study regarding the binding sites of jejunal antibodies (JAB) in patients with dermatitis herpetiformis?,"Extracellular binding sites of IgA anti-jejunal antibodies on normal small bowel detected by indirect immunoelectronmicroscopy. Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA."
-What are the key findings regarding amenorrhoea in women with non-alcoholic chronic liver disease?,"Amenorrhoea in women with non-alcoholic chronic liver disease. Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage."
-What is the purpose of computer-assisted superimposition of magnetic resonance and high-resolution SPECT images in this study?,"Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain. A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy."
-What are the typical 2-year survival rates for dementia patients in outpatient clinics and nursing homes?,"Survival of patients with dementia. The evidence on survival in dementia is summarized. There are no reliable data on survival after onset of dementia or after first contact with medical services. People with dementia in outpatient clinics and nursing homes have 2-year survival rates of 75% (range 60%-95%) and 50% (range 30%-65%), respectively. Differences in survival between patients with senile dementia of the Alzheimer's type (SDAT) and multi infarct dementia (MID) are small. Women in nursing homes have a better prognosis than men (2-year survival rates, 60% vs 40%). Dementia patients have a considerable excess mortality when compared to the vital statistics. There is no evidence for improvement of survival rates during recent decades. Recommendations for future studies are made."
-What percentage of patients in the study had lesions not ideal for balloon angioplasty?,"Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty BACKGROUND. Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates. METHODS AND RESULTS. In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively. CONCLUSIONS. In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients."
-What percentage of postmenopausal women with adnexal masses were found to have malignant tumors in this study?,"The postmenopausal adnexal mass: correlation between ultrasonic and pathologic findings. One hundred two postmenopausal women underwent ultrasonographic evaluation of adnexal masses before surgery. Twenty-nine (28%) had malignant tumors and 73 (72%) had benign tumors. Two of 33 patients with a ""simple cyst"" smaller than 5 cm in diameter by ultrasound had malignant ovarian tumors. Twenty-two of the 52 women (42%) with ""complex masses"" by ultrasound and five of the 17 (29%) with solid tumors had ovarian cancer. For predicting malignancy in ovarian tumors, abdominal ultrasonography had a positive predictive value of 39% and a negative predictive value of 94%. If a negative sonogram had been relied upon, 6% of malignant ovarian tumors in postmenopausal women might have been missed."
-What were the key findings of the study comparing enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure?,"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination."
-What treatment was used for Pneumocystis carinii pneumonia in heart transplant patients and how effective was it?,"Pneumocystis carinii pneumonia after heart transplantation. Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation."
-What novel technique was developed for detecting Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections?,"Detection of single copies of Epstein-Barr virus in paraffin wax sections by non-radioactive in situ hybridisation. A highly sensitive non-isotopic in situ hybridisation technique was developed for the localisation of Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections. The method uses a repeated sequence of the EBV genome as a probe, labelled with the novel reporter molecule, digoxigenin. The method can identify individual copies of EBV by detection of both EBV DNA and highly localised RNA transcripts. A combination of careful proteolytic digestion of tissue sections, high temperature denaturation of probe and target DNA, and sensitive immunocytochemical detection are used to attain single copy sensitivity. The technique is quicker and simpler to perform than some other methods used for the identification of EBV, and provides simultaneous morphological information which cannot be obtained by methods using tissue extracts. This method permits the investigation of the role of EBV in neoplastic conditions of lymphoid and epithelial cells, and may prove valuable in determining the sites of latent virus in healthy subjects."
-What imaging technique was used to locate the intrathoracic meningocele in the patient with neurofibromatosis?,"Intrathoracic meningocele associated with neurofibromatosis: case report. The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy."
-"What is cyclosporine, and how does it potentially cause hypertension in patients?",Mechanism of cyclosporine-induced hypertension. Cyclosporine is a common immunosuppressive agent used in solid organ and bone marrow transplants and the treatment of some immunological diseases. It has been established that treatment with cyclosporine can cause a patient to develop hypertension within a few weeks of treatment. This review will examine this effect and effective ways to treat it.
-"How do serum, salivary, and intestinal IgA anti-gliadin antibody levels differ in celiac disease patients compared to controls?","Mucosal and systemic IgA anti-gliadin antibody in celiac disease. Contrasting patterns of response in serum, saliva, and intestinal secretions. Serum IgA anti-gliadin antibody estimation is a recognized screening method for celiac disease. However, celiac disease is primarily a small intestinal mucosal disorder, and so we have examined the possibility that secreted, mucosal IgA anti-gliadin antibody might provide a more relevant measure of gluten sensitivity than that obtained from serum tests. Serum IgA anti-gliadin antibody and serum, salivary, and small intestinal aspirate IgA anti-gliadin antibody were measured by enzyme-linked immunosorbent assay. Serum IgA and IgG anti-gliadin antibody were markedly increased in untreated celiacs (N = 31) as compared to normals (N = 20) or disease controls (N = 39) (P less than 0.0001). Levels were lower in treated (N = 30) than untreated celiacs (P less than 0.001). In intestinal aspirates both untreated and treated patients had similar levels of IgA anti-gliadin antibody (P = 0.48), but both were significantly higher than in controls (P less than 0.01). Salivary IgA anti-gliadin antibody, by contrast, was not increased in celiac patients as compared to controls. Serum IgA anti-gliadin antibody was the most sensitive (84%) and specific (95%) test for detecting untreated celiac disease. It was also the most useful in patient follow-up where it provides an early objective indicator of adherence to a gluten-free diet. Mucosal IgA responses to gliadin in celiac disease appear to be compartmentalized, with different portions of the gastrointestinal tract functioning as separate immunological organs. Our results also demonstrate that serum and secretory IgA production are under independent control."
-How does intraaortic balloon pumping (IABP) affect reocclusion rates and left ventricular function in patients with acute myocardial infarction after successful percutaneous transluminal coronary angioplasty (PTCA)?,"Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction. To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 +/- 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p less than 0.05). An increase in ejection fraction in group II compared with group I was marginally significant (4.5 +/- 12.2% vs 9.2 +/- 13.0%, p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function."
-What were the five-year disease-free survival rates for different treatment stages of IIB osteosarcoma in this study?,"IIB osteosarcoma. Current management and survival statistics in the USSR. Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease-free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease-free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion."
-How did the jitter and blocking characteristics of motor end-plates differ between patients with myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) at different stimulation rates?,"Single motor end-plates in myasthenia gravis and LEMS at different firing rates. The jitter and frequency of blocking was studied at single motor end-plates in 10 patients with myasthenia gravis (MG) and in a patient with Lambert-Eaton myasthenic syndrome (LEMS), using single fiber EMG (SFEMG) with axonal microstimulation at rates varying from 0.5 Hz to 20 Hz. While some myasthenic motor end-plates showed lowest degrees of transmission disturbance at the lowest rates and most pronounced abnormality at the highest rates of stimulation, over one-half were most abnormal at intermediate rates and improved at higher rates. In 1 patient, all end-plates behaved in this way. On the other hand, all end-plates in the LEMS patient showed the expected improvement of the abnormal jitter and blocking on increasing the stimulation rate. It is argued that improvement of jitter and blocking at higher rates, unless dramatic, does not necessarily suggest a presynaptic abnormality."
-What was the main finding of the study comparing low and high doses of ethanolamine oleate in treating esophageal varices?,"Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant."
-"What were the key findings regarding proarrhythmia, cardiac arrest, and death in young patients receiving encainide and flecainide?","Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease."
-How does plasma glucose level affect infarct size in focal cerebral ischemia-reperfusion?,"Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious."
-How does hypoalbuminemia impact various physiological processes in the human body?,"The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted."
-How does blood pressure serve as a predictor of cardiovascular diseases according to the Framingham Study?,"Blood pressure as a risk factor for cardiovascular disease. The Framingham Study--30 years of follow-up Data from 30 years of follow-up of the original Framingham Study cohort of 5,070 men and women aged 30-62 years who were first examined during the period 1948-1952 and who were free of cardiovascular disease reveal that blood pressure is a strong and consistent predictor of the development of coronary heart disease, stroke, transient ischemic attack, and congestive heart failure. Other factors related to blood pressure like obesity, left ventricular hypertrophy as demonstrated on electrocardiograms, and heart enlargement as shown by x-ray radiography made several selective additional independent contributions to risk; heart enlargement by x-ray radiography was the best predictor of congestive heart failure."
-What challenges do physicians face in distinguishing between Crohn's colitis and amebic colitis?,"Crohn's colitis complicated by superimposed invasive amebic colitis. The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD."
-What was the proportion of melanomas diagnosed in patients under 30 years old during the study period?,"Malignant melanoma occurring in those aged under 30 in the west of Scotland 1979-1986: a study of incidence, clinical features, pathological features and survival. The study population consisted of the 95 patients who presented with cutaneous malignant melanoma in the west of Scotland between 1979 and 1986 and who were aged under 30 at the time of diagnosis. Over this 7-year period, 1299 melanomas were diagnosed in all age groups in this geographical area, increasing in incidence by 82% from 135 in 1979 to 246 in 1986. The proportion of melanomas diagnosed before the patients' thirtieth birthday remained constant at 6%. None were diagnosed in the under-15 age-group, and none developed on giant congenital naevi. Forty-two of the 95 melanomas (44%) in the under-30 group developed on a small naevus present either from birth or early childhood. These melanomas were thicker than those apparently developing on normal skin, but once controlled for tumour thickness and sex the presence of a pre-existing naevus did not affect 5-year survival. The overall 5-year survival was 76% with poorer survival associated with thicker tumours and male sex. This study suggests that small early onset naevi may have a higher potential for post-pubertal malignant change than has been previously recognized."
-What were the haemodynamic changes observed during the apnoea test for diagnosing brain death?,"Haemodynamic changes during the apnoea test for diagnosis of brain death. Haemodynamic responses to the apnoea test for the diagnosis of brain death were investigated in nine patients with severe head injury or cerebrovascular disease. To prove apnoea, the ventilator was disconnected for ten minutes and oxygen was insufflated to avoid hypoxaemia. No respiratory movement was seen in any patient. Ten minutes after disconnecting the ventilator, PaCO2 was increased to 78 +/- 3 mmHg and pH was reduced to 7.17 +/- 0.02. Adequate oxygenation was maintained in all patients. Cardiac output increased from 4.8 +/- 0.7 to 5.7 +/- 0.8 L.min-1 (P less than 0.05), and mean pulmonary artery pressure increased from 11 +/- 1 to 17 +/- 2 mmHg (P less than 0.01). However, mean arterial pressure, heart rate, pulmonary artery wedge pressure and right atrial pressure did not change. Plasma catecholamines were measured in three patients. Plasma norepinephrine concentrations increased in all three patients but the changes in plasma epinephrine were minimal. These circulatory responses to acute hypercapnia were less than those reported in awake volunteers and in patients during general anaesthesia. However, since plasma norepinephrine concentration increased during the test, some sympathoadrenal response, probably of spinal origin, was present, and may have prevented the direct depressant circulatory effects of acute hypercapnia. In conclusion, the apnoea test did not produce haemodynamic disturbances when respiratory acidosis was limited to a pH 7.17 +/- 0.02 and PaCO2 60-80 mmHg."
-How do energy-absorbing steering wheels compare to standard steering wheels in terms of facial injury severity?,"Traumatic facial injuries with steering wheel loading. This study was conducted to evaluate the biomechanics of facial fractures caused by steering wheel loading. Twelve intact fresh human cadaver heads were impacted onto standard or energy-absorbing steering wheels with a custom-designed and validated vertical-drop apparatus. Either zygoma was impacted once at a velocity of 2.0-6.9 m/s. The specimens were oriented to permit a direct comparison between pretest and posttest radiography, and two-dimensional and three-dimensional CT images. Bone mineral content was determined, and biomechanical forces, accelerations, and deformations were recorded. More severe fractures were associated with higher forces on the zygoma. With increasing velocities, fractures initiated at the zygomatic region propagated to other unilateral regions such as the mandible and orbit or to the contralateral side. Less facial trauma was observed with energy-absorbing steering wheels compared with standard wheels at similar impact velocities. Bone mineral content did not correlate well with specimen age or with fracture severity. Clinically significant fractures were identifiable on 3-D CT images. The flexibility of 3-D CT in evaluating the spatial extent of facial abnormalities in different orientations may have significant impact in planning surgical procedures."
-What was the relationship between nocturnal hypoxaemia and serum erythropoietin concentrations in patients with obstructive sleep apnoea?,Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
-What are the key components of the computer-assisted neurosurgical navigational system described in the context?,"A frameless, armless navigational system for computer-assisted neurosurgery. Technical note. A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures."
-How does diclofenac affect the healing of gastroduodenal mucosal lesions according to the study?,"Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions."
-What are the three main types of pharmacologic agents used in the treatment of congestive heart failure according to the context?,"Progressive congestive heart failure. Ways to approach office management. Treatment of congestive heart failure depends on the cause, precipitating factors, and symptoms of the disease in each patient. Dr Kahn outlines the use of the three main types of pharmacologic agents given for heart failure--diuretics, vasodilators, and digoxin. He describes a stepwise regimen, whereby agents are added as needed to improve symptoms and prolong life."
-What method was used to evaluate the main parameters of liver circulation in this study?,"Combined evaluation of total and functional liver plasma flows and intrahepatic shunting A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation."
-What is the primary treatment method described for superior vena cava thrombosis in this case report?,Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).
-What characterizes the subtype of global aphasia described in this study?,"The aphasic isolate. A clinical-CT scan study of a particularly severe subgroup of global aphasics. This paper outlines the clinical and CT scan features of a subtype of global aphasia, characterized by an extreme loss of communicative abilities, verbal as well as nonverbal. Three to four weeks after a left hemisphere stroke, 17 patients were completely unable to communicate with people addressing them. Though there were differences in their willingness to interact with the environment, they were characterized by complete loss of speech output and by inaccessibility to any kind of message, whether given verbally or through gestures. Patients who survived were reassessed 6 and 12 mos later and half of them were still found in a state of complete communicative isolation. The remainder had somewhat improved, but remained globally aphasic. The attempt to find a CT scan basis for this picture was disappointing. Only 35% of patients had a lesional pattern in agreement with the traditional view that ascribes global aphasia to the involvement of Broca's and Wernicke's areas. The location of lesion in the other cases spanned from anterior cortical damage, to posterior cortical damage, to deep nuclei damage and none of the lesions that have been proposed to account for subcortical global aphasia was consistently observed."
-What were the success and mortality rates for different clinical scenarios in PTCA for patients with unstable angina?,"Clinical factors affecting the immediate outcome of PTCA in patients with unstable angina and poor candidates for surgery. Percutaneous Transluminal Coronary Angioplasty (PTCA) has been successfully applied in unstable angina to carefully selected patients. In this study, PTCA was performed in 277 consecutive patients suffering from unstable angina and for whom bypass surgery was not a valid alternative because either of inoperable conditions or of emergency, or because surgery was not the best option. All patients were admitted first to the intensive care unit where an attempt was made to control unstable angina under conventional medical therapy using at least iv nitroderivative, heparin, and calcium blockers. After a standardized preparation PTCA was performed either as an emergency procedure in medically refractory unstable angina (107 cases) or as an elective procedure in controlled situations after a 7 to 10 days symptom-free period. Three hundred fifty-three coronary vessels were attempted. Results of this group are compared with those of a control group made of 670 consecutive stable patients recruited during the same period, and clinical characteristics are envisaged as potential predictive factors. Unstable angina is undoubtedly associated with a higher overall complication rate, but the immediate outcome is strongly affected by the clinical context. As an example, respective success and mortality rates are: 93% and 0% when a full revascularization is attempted; 91% and 0% in elective procedures in patients under 60; 87% and 1.2% in elective PTCA for multiple vessel disease; 80% and 6.5% in emergency PTCA; 80% and 11% in the overall triple vessel disease; 84% and 16% in patients with deeply altered ejection fraction; and 58% and 26% in triple vessel disease with 2 previously occluded coronary arteries."
-What are the hemodynamic effects of octreotide in patients with autonomic neuropathy?,"Hemodynamic effects of octreotide in patients with autonomic neuropathy. BACKGROUND. The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. METHODS AND RESULTS. Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. CONCLUSION. The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output."
-What is the difference between disease and illness according to the given context?,"Medical aspects of delayed convalescence. Disease and illness are not synonymous. In most instances, disease is demonstrable by anatomic, physiologic, biochemical, microbiologic, or immunologic abnormalities. Disease is a pathologic process. Not all persons with a disease are sick or ill. Symptoms of illness associated with a disease may be manifest or persist after the disease has disappeared. The absence of demonstrable disease, however, does not necessarily mean that symptoms of illness are unreal. Recovery from disease and recovery from illness are not always equated. Many factors, including personal characteristics and social circumstances, can be responsible for recovery from disease and illness. Chronic fatigue syndrome or symptoms of illness can persist in some patients but not in others after many different diseases."
-What are the six characteristic features that help identify psychogenic disorders of stance and gait?,"How to identify psychogenic disorders of stance and gait. A video study in 37 patients. Thirty-seven patients with psychogenic disorders of stance and gait were clinically evaluated, recorded on video, and analysed with regard to clinical phenomenology. Characteristic, suggestive and unspecific features were identified. Six characteristic features proved most valuable for diagnosis of psychogenesis, as they occurred alone or in combination in 97% of patients: (1) momentary fluctuations of stance and gait, often in response to suggestion; (2) excessive slowness or hesitation of locomotion incompatible with neurological disease; (3) ""psychogenic"" Romberg test with a build-up of sway amplitudes after a silent latency or with improvement by distraction; (4) uneconomic postures with wastage of muscular energy; (5) the ""walking on ice"" gait pattern, which is characterized by small cautious steps with fixed ankle joints; (6) sudden buckling of the knees, usually without falls. Seventy-three percent of patients had additional suggestive features. Classification into characteristic subtypes was not found useful because predominant features varied from patient to patient and occurred in various combinations. Factitious impairment of stance and gait was studied in 13 healthy drama students. Simulated gait dysfunction appeared less conspicuous and more difficult to diagnose than the clinical psychogenic disorders."
-What are the key management recommendations for orbital lymphangioma based on the analysis of thirty cases?,"An analysis of thirty cases of orbital lymphangioma. Pathophysiologic considerations and management recommendations. Thirty cases of orbital lymphangioma were reviewed. Clinical, imaging, and microscopic findings were integrated to develop a pathophysiologic construct and management guidelines. The basic lesion might be considered an abortive vascular system which arborizes among normal structures. Intrinsic hemorrhage expands portions of the small-caliber network into large blood cysts, prompting clinical recognition. While major hemorrhage led to early surgery in 12 cases, long pretreatment intervals could be analyzed in 17 others. Twelve patients had second hemorrhages of varied magnitude, from 2 weeks to 15 years after initial recognition; five patients did not in an average of 6.8 years. Some blood cysts contracted spontaneously. Among 23 operated cases, 12 patients had major new bleeds from 4 days to 12 years after initial surgery; 11 patients did not in an average of 4.2 years. Poor final visual acuity was associated with multiple surgeries. The authors advocate conservatism in surgical case selection and in operative dissection."
-What was the success rate of laser-assisted balloon angioplasty in this multicenter study?,"Percutaneous coronary excimer laser-assisted angioplasty: initial multicenter experience in 141 patients. Initial multicenter clinical experience with percutaneous coronary excimer laser-assisted angioplasty is described for 158 lesions in 141 patients. Using a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% improvement in luminal diameter) was achieved in 138 (87%) of 158 lesions, with a reduction to less than 50% stenosis noted in 77 lesions (49%). Overall, laser-assisted balloon angioplasty success (less than 50% residual stenosis without major complication) was observed in 129 (91%) of 141 patients. Procedural complications (abrupt closure 1.3%, side branch occlusion 1.9%, intimal dissection 6.3%, embolization 1.3%, filling defect 1.3%, perforation 1.9% and spasm 1.3% and major complications (non-Q wave myocardial infarction 4.8%, emergency coronary bypass surgery 3.5% and death 0%) were infrequent and predominantly related to subsequent balloon angioplasty. In the early follow-up period (range 1 to 10 months, mean 7), 111 (79%) of the 141 patients remain asymptomatic, whereas symptoms have recurred in 27 (19%) and 3 patients (2.1%) have died. Thus, percutaneous coronary excimer laser angioplasty appears to be a feasible and safe procedure. Assessment of the impact of this technology on the acute complications of and restenosis rates after angioplasty awaits further follow-up analysis."
-How does the frequency of Helicobacter pylori infection change with age according to the study?,"Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection."
-How did changes in carbon dioxide tension (PCO2) affect respiratory resistance in healthy and asthmatic subjects?,"Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented."
-What is a gliofibroma and why is it considered a rare type of tumor?,"Gliofibroma. Case report. The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature."
-What ultrasound findings can help sonologists suspect midgut malrotation complicated by volvulus in infants?,"Midgut volvulus in infants: diagnosis with US. Work in progress. The authors present findings from ultrasound (US) studies that can alert sonologists to the possibility of midgut malrotation complicated by volvulus in neonates and infants. A fluid-filled, distended duodenum seen at US examination in infants is a nonspecific sign of duodenal obstruction, as well as one of the signs of midgut malrotation. In addition, dilated, thick-walled bowel loops, mainly to the right of the spine, and peritoneal fluid were found at abdominal US examinations of three infants with midgut malrotation complicated by volvulus. In one infant with uncomplicated midgut malrotation, only signs of duodenal obstruction were present. The findings at US of duodenal obstruction associated with thickened bowel loops to the right of the spine and peritoneal fluid should lead the sonologist to suspect midgut malrotation complicated by volvulus, a potentially fatal condition, and an upper gastrointestinal series should then be performed to confirm the diagnosis."
-What was the impact of higher haloperidol doses compared to neuroleptic threshold (NT) doses on patients with schizophrenia in this study?,"Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects."
-What are the three different types of colonic contractions that achieve the basic motor functions of the colon?,"Physiology and pathophysiology of colonic motor activity (2). The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS)."
-How does food restriction affect the daily concentration pattern of plasma corticosterone in male Fischer 344 rats?,"Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes."
-How do calcium antagonists and agonists affect halothane-induced contracture in muscle bundles from patients susceptible to malignant hyperthermia?,"Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia. The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors."
-How does the effect of TNF-alpha on IFN-gamma-induced MHC class II expression vary depending on the cell's maturation and differentiation stage?,"Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. MHC class II induction by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. TNF-alpha has been found both to enhance and also to inhibit IFN-gamma-induced MHC class II expression. In the present studies, the effect of TNF-alpha on IFN-gamma induced MHC class II expression was tested in various cell lines. On the basis of the data, we propose that, depending on the stage of differentiation and maturation of the cells, TNF-alpha might synergize or antagonize the affects of IFN-gamma on the regulation of MHC class II expression. Thus, in immature cells such as HL-60 or THP-1, TNF-alpha enhances IFN-gamma-induced class II expression. However, when differentiation was induced in these cells by TPA or IFN-gamma, the additive effect of TNF-alpha on the IFN-gamma induced DR expression was eliminated. Furthermore, TNF-alpha down-regulates the IFN-gamma-induced class II expression in differentiated cells such as human skin fibroblasts or activated macrophages. In bone marrow cells induced to differentiate in vitro, TNF-alpha decreased the IFN-gamma-induced MHC class II expression in a maturation-dependent fashion. These results provide a rational explanation for the conflicting reports regarding the effect of TNF-alpha on IFN-gamma-induced class II expression. But more importantly they may be relevant to the biologic function of TNF-alpha. Thus, we show that TNF-alpha-treated mice have reduced level of Ia expression on peritoneal macrophages and in vivo treatment with TNF-alpha antagonizes the ability of IFN-gamma to induce class II expression on these macrophages."
-What were the key findings of the study comparing enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure?,"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination."
-What was the main purpose of comparing endoscopic injection sclerotherapy (EIS) with conservative treatment in patients with unresectable hepatocellular carcinoma and bleeding esophageal varices?,"Endoscopic injection sclerotherapy versus conservative treatment for patients with unresectable hepatocellular carcinoma and bleeding esophageal varices. We performed endoscopic injection sclerotherapy (EIS) in the treatment of 37 patients with bleeding esophageal varices due to unresectable hepatocellular carcinoma (HCC). The results were compared with those in another 33 HCC patients treated only conservatively, without EIS, during the same period. A majority of both groups died within 3 weeks after treatment. Comparing the two groups, there was no significant difference in fatal bleeding (66% vs 75%), but significantly fewer of the EIS patients died of the index hemorrhage (43% vs. 83%; p less than 0.01). Also, in the absence of portal vein thrombosis, EIS significantly reduced the risk of fatal bleeding (31% vs. 73%; p less than 0.25). The mean days of survival were 32 +/- 15 (range, 2 to 320) in the EIS group and 10 +/- 14 (range, 2 to 270) in the compared group (p less than 0.001). We conclude that EIS provides temporary control of acute esophageal variceal bleeding in patients with unresectable HCC. The major factors contributing to EIS failure are the lethal propensity of the underlying disease and portal vein thrombosis."
-What is the relationship between proteinuria and tubulointerstitial nephritis in experimental nephrosis in rats?,"A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis."
-What are the key categories of etiologic treatments for dizziness mentioned in the context?,"The dizzy patient: etiologic treatment. The basis for the vestibular complaint in dizzy patients should be viewed as having an etiology rather than a description of its clinical presentation. Effective treatment of vestibular disorders is based on the stabilization of the vestibular abnormality, to allow for central vestibular compensation. While not all of the etiologies for dizziness have been described, there are effective etiologic treatments available. These fit into categories of neurotransmitters, blood sugar and blood fat control, hormones, minerals, and treatments for autoimmune dizziness."
-How does the contractile response of aorta to alpha 1-adrenergic stimulation differ between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in a calcium-free medium?,"Contractile response of aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium is reduced in spontaneous hypertension. Vascular responses of aortic rings to alpha 1-adrenergic stimulation by phenylephrine (Phe) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied in Ca(2+)-containing medium and Ca(2+)-free medium plus 50 mumol/L EGTA. Although there was no difference in the sustained force development between SHR and WKY vessels in response to 100 mmol/L KCl or 10 mumol/L Phe in Ca(2+)-containing medium, the transient contractile response to 10 mumol/L Phe in Ca(2+)-free medium was substantially smaller in SHR compared to that in WKY. Subsequent addition of 2.5 mmol/L Ca2+ restored the sustained contractile response to a similar level in both SHR and WKY vessels. The transient contractile response to Phe in Ca(2+)-free medium containing EGTA, presumably due to the release of intracellular Ca2+, decreased progressively with preincubation time in Ca(2+)-free medium, indicating intracellular Ca2+ depletion. Such a temporal change of aortic response was more pronounced in SHR than in WKY. The subsequent response to Ca2+ repletion in the presence of Phe, on the other hand, increased progressively with Ca(2+)-depletion period and was higher in SHR than in WKY. The rate of relaxation after washout of Phe was slower in SHR aorta compared to WKY aorta. These results, together with our earlier findings, collectively suggest that the previous known deficiency in Ca2+ pumping mechanisms of vascular muscle microsomes leading to a reduced functional size of intracellular Ca2+ pool may account for the smaller contractile response of SHR aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium and the slower rate of relaxation."
-What did the twin study reveal about the genetic factors in epilepsy and febrile seizures?,"The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures."
-What unusual combination of neurological and vascular symptoms was observed in the patient with primary antiphospholipid antibody syndrome?,"Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome. We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome."
-What were the limitations of coronary flow reserve measurements in assessing the efficacy of coronary angioplasty within the first 24 hours?,"Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. To determine functional and anatomic changes in the first 24 hours after coronary angioplasty, we studied at random 15 patients (9 men, mean age 60 years) who underwent coronary angioplasty of 16 coronary arteries. Quantitative coronary angiography and coronary flow reserve measurements from digitized coronary angiograms were performed before, immediately after, and 24 hours after coronary angioplasty. Calculated were the minimal luminal diameter, obstruction area, and percentage diameter stenosis from two preferably orthogonal projections. Prior myocardial infarction in the myocardial region of interest was present in four patients. Seven patients had multivessel disease. Collateral vessels supplying the compromised flow region were observed in three patients. Six patients had refractory unstable angina pectoris. After coronary angioplasty, angiographically visible dissection was noted in six patients, whereas side branch occlusion was observed in one. Minimal luminal diameter before, immediately after, and 24 hours after was 0.93 +/- 0.18 mm, 1.53 +/- 28 mm, and 1.53 +/- 0.21 mm, respectively; obstruction area was 0.70 +/- 0.26 mm2, 1.92 +/- 0.69 mm2, and 1.87 +/- 0.51 mm2, respectively; diameter stenosis was 60.4 +/- 8.0%, 36.8 +/- 11.4%, and 37.6 +/- 5.3%, respectively. The coronary flow reserve (lower limit of normal with this technique 3.4) was essentially the same before and immediately after coronary angioplasty (1.26 +/- 0.59 vs 1.30 +/- 0.42, p = NS) with a slight improvement to 1.78 +/- 0.90 (p less than 0.05) 1 day later. Coronary artery dimensions correlated poorly with coronary blood flow reserve before and after angioplasty."
-What are the key clinical features of posterior cortical dementia as described in this case study?,"Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET."
-What was the overall 5-year actuarial disease-free survival rate after salvage surgery for patients with carcinoma of the buccal mucosa?,"Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05)."
-What is the significance of reactive astrogliosis in the subcortical white matter of amyotrophic lateral sclerosis (ALS) brains?,"Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown."
-What were the key findings of the serial echocardiographic study on HIV-infected individuals regarding cardiac abnormalities?,"Reversibility of cardiac abnormalities in human immunodeficiency virus (HIV)-infected individuals: a serial echocardiographic study. Seventy adults who tested positive for human immunodeficiency virus (HIV) were prospectively studied with serial echocardiography to better define the prevalence and progression of cardiac disease in such patients. Fifty outpatients (Group A), including 44 with acquired immunodeficiency syndrome (AIDS) and 6 with AIDS-related complex, and 20 additional patients (Group B) with asymptomatic HIV infection had baseline echocardiographic studies at a time when no patient had symptomatic heart disease. Follow-up studies were performed at 9 +/- 3 months in 52 patients (74%) and again at 15 +/- 3 months after baseline studies in 29 patients (41%). During the study, 22 patients (44%) in Group A and 1 patient (5%) in Group B died. Cardiac abnormalities were noted in 26 patients (52%) in Group A and 8 patients (40%) in Group B (p = NS) on initial or follow-up study. An abnormal left ventricular ejection fraction (less than 45%) or fractional shortening (less than 28%) was seen in seven patients in Group A; of these, three had normal left ventricular function on a later echocardiogram. One patient in Group B had persistent left ventricular dysfunction. All patients in Group A with left ventricular dysfunction on two serial studies died within 1 year after the initial echocardiogram. Ejection fraction did not change between baseline and two follow-up studies in either group (A: 52 +/- 9 vs. 56 +/- 9 vs. 55 +/- 5%, p = NS; B: 58 +/- 6 vs. 58 +/- 5 vs. 59 +/- 6%, p = NS). Right-sided cardiac enlargement resolved in 18 patients (44%), including 5 of 10 in Group A and 3 of 8 in Group B."
-How does a single gluten challenge affect intestinal permeability in patients with coeliac disease compared to healthy controls?,"Intestinal permeability after single dose gluten challenge in coeliac disease. The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood."
-What was the mortality rate associated with class IC antiarrhythmic drug overdose in this study?,"Clinical course and outcome in class IC antiarrhythmic overdose. 120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome."
-What were the key findings of the pilot study on sphincter-sparing management of rectal adenocarcinoma?,"A pilot study of sphincter-sparing management of adenocarcinoma of the rectum. After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy."
-How does transesophageal echocardiography compare to transthoracic echocardiography in detecting valvular vegetations in patients with suspected infectious endocarditis?,"Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography."
-How does native C5a (nC5a) differ from recombinant C5a (rC5a) in inducing histamine release from cutaneous mast cells in BALB/c mice?,"C5a, cutaneous mast cells, and inflammation: in vitro and in vivo studies in a murine model. To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin."
-How does elevated intravesical pressure affect blood perfusion in colocystoplasty according to the fluorometric study?,"Elevated intravesical pressure causes arterial hypoperfusion in canine colocystoplasty: a fluorometric assessment. Since 1988 there have been 15 reported cases of late, spontaneously ruptured intestinal cystoplasties at bowel sites remote from the anastomosis. Ischemic necrosis has been suggested as a possible etiology. We examined this hypothesis by quantifying the uptake of intravascular fluorescein in the augmented bowel of adult mongrel canines. There was a statistically significant decrease in fluorescein uptake at high intravesical pressures, which appeared to be most pronounced at the antimesenteric border. This laboratory study supports a recent clinical report of histological changes pathognomonic for chronic ischemia in the augmented bowel of patients with spontaneous rupture."
-What is the relationship between ventricular arrhythmias and the patency of the infarct-related coronary artery after thrombolytic therapy?,"Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy. In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen."
-What percentage of atypical hyperplasia cases showed a direct mammographic-histologic correlation in the study?,"Atypical hyperplasia of the breast: mammographic appearance and histologic correlation. The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found in 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographic-histologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a five- to tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly mammographic follow-up is suggested once AH is discovered."
-What was the main hypothesis tested in this randomized study of cesarean delivery?,"A randomized study of closure of the peritoneum at cesarean delivery. This study was conducted to test the hypothesis that nonclosure of the visceral and parietal peritoneum during low transverse cervical cesarean delivery is not associated with increased intraoperative or immediate postoperative complications. One hundred thirteen patients scheduled for low transverse cervical cesarean were randomized to either closure of both the visceral and parietal peritoneum with absorbable suture (N = 59) or no peritoneal closure (N = 54). Patients were cared for in the usual postoperative manner without reference to treatment group. There were no demographic differences between the groups and no differences in method(s) of anesthesia, operative indication(s), or use of peripartum epidural narcotics. The incidence of fever, endometritis, or wound infection was similar between groups. There were no differences in the number of patients requiring parenteral narcotic analgesia or in the number of doses per patient. The number of oral analgesic doses was significantly greater with closure than without (P = .014). The frequency with which postoperative ileus was diagnosed in each group was similar, and there was no difference regarding the day on which patients were advanced to liquid or select diets. Bowel stimulants were administered more frequently to the closure than to non-closure patients (P = .03). The average operating time was shorter for the open group than for the closure group (P less than .005). We conclude that non-closure of the visceral and parietal peritoneum at low transverse cervical cesarean delivery appears to have no adverse effect on immediate postoperative recovery, may decrease postoperative narcotic requirements, allows less complicated return of bowel function, and provides a simplified and shorter surgical procedure."
-What was the primary purpose of performing transcervical resection of the endometrium (TCRE) in this study?,"Experience with the first 250 endometrial resections for menorrhagia [published erratum appears in Lancet 1991 Jan 1;337(8753):1362] 234 patients with menorrhagia were treated hysteroscopically by transcervical resection of the endometrium (TCRE) instead of hysterectomy. 250 procedures were performed under general anaesthesia (63%) or under sedation plus local anaesthesia (38%). The endometrium was excised either totally (91%) or partially (9%) in all but one case, and 56 (22%) of the patients underwent simultaneous resection of submucous fibroids. Surgical time (range 10-100 min) varied with the gynaecologist's experience. 479 ml was the average volume of uterine irrigant absorbed by the patient. Blood loss was usually slight. Operative complications were uncommon, but 4 (2%) women sustained a uterine perforation (without serious sequelae), 7 (3%) absorbed more than 2 litres of fluid, and 1 required tamponade to control postoperative bleeding. Hospital stay was short and full recovery usual by 1-2 weeks. Menstrual symptoms improved in over 90% of the patients throughout the follow-up of up to 2 1/2 years; 27-42% of the women became amenorrhoeic at some time after total TCRE. Results were best in women greater than 35 years of age, but was not influenced by the presence of fibroids or pretreatment dysmenorrhoea. 10 (4%) women later underwent hysterectomy. Hysteroscopy 3 and 12 months after surgery revealed a small, fibrotic uterine cavity in the majority."
-How does the increased collagen content in hypertrophic cardiomyopathy affect heart function?,"Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in ""normal"" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease."
-What was the relationship between nocturnal hypoxaemia and serum erythropoietin concentrations in patients with obstructive sleep apnoea?,Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
-What suture technique and material were found to result in less stenosis when performing tracheal anastomosis in a growing animal model?,"Growth of tracheal anastomoses: advantage of absorbable interrupted sutures [published erratum appears in Ann Thorac Surg 1991 Jul;52(1):176] Growth of the trachea after complete transection and anastomosis was studied in four groups of 1-month-old New Zealand white rabbits. The trachea was transected at the fifth cartilaginous ring and then anastomosed with continuous 6-0 polypropylene (Prolene) (group 1), interrupted 6-0 polypropylene (group 2), continuous 6-0 polydioxanone (PDS) (group 3), or interrupted 6-0 PDS (group 4). The animals were followed up for 90 to 103 days (mean follow-up, 95 days). At the time the animals were killed, body weight had increased 125% (1.2 to 2.7 +/- 0.18 kg). Growth of the trachea was assessed at the time of death. Results from this study suggest that growth of a tracheal anastomosis is retarded in a growing animal model. The degree of resultant stenosis was significantly less when an absorbable suture material (PDS) and an interrupted suturing technique were used."
-What is the purpose of using impedance plethysmography in monitoring muscle perfusion after free tissue transfer?,"Impedance plethysmography: a new method for continuous muscle perfusion monitoring. Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion."
-What pathological features were observed in the small vessels of the nonelderly demented patients with sclerosing vasculopathy?,"Sclerosing vasculopathy of the central nervous system in nonelderly demented patients. Three nonelderly patients without hypertension whose clinical and radiologic features otherwise resembled Binswanger's subcortical arteriosclerotic encephalopathy underwent biopsy of the hyperintense periventricular lesions seen on magnetic resonance imaging. The pathologic findings of the periventricular lesions consisted of gliosis with mild rarefaction and edema of the white matter. All patients had a sclerosing vasculopathy of unknown cause, which involved numerous small vessels within the periventricular lesions. The vessels stained negatively for amyloid, amyloid precursors, desmin, vimentin, keratin, immunoglobulin, and complement. On electron microscopy, small arteries, arterioles, venules, and capillaries were characterized by swollen astrocytic foot processes surrounding the vessels; dense, perivascular collagen packing; crystalline arrays of filaments within basement membrane; giant lipid-laden lysosomes within perivascular cells; and narrowing of the vascular lumina. Similar changes were not seen in a control group of 19 patients. The pathologic features of the vessels in these cases are distinct from the vasculopathy associated with Binswanger's subcortical arteriosclerotic encephalopathy. We suggest that a spectrum of vasculopathies may be associated with dementia and periventricular hyperintense lesions on magnetic resonance imaging."
-What were the different management approaches used for treating pancreatic fluid collections in this study?,"Invasive treatment of pancreatic fluid collections with surgical and nonsurgical methods. Pancreatic fluid collections (PFC) can be drained surgically or nonsurgically with endoscopic or radiologic techniques. To define subgroups of patients with PFC who would benefit from the new modalities, we reviewed a period (1977 to 1990) during which both surgical and nonsurgical invasive techniques were available. Patients with phlegmon or necrosis at initial diagnosis were excluded. Sixty-five patients (35 male, 30 female) underwent 1 or more drainage procedures. A mean postprocedure follow-up of 10.2 months was available for 59 patients. Initial management was nonsurgical in 80% of patients. Procedures in patients with follow-up comprised invasive nonsurgical drainage (n = 25), invasive nonsurgical drainage plus surgery (n = 22), and surgery only (n = 12). Results for each group, respectively, were: morbidity, 20%, 20%, and 24%; mortality, 8%, 5%, and 0%; and successful drainage, 92%, 82%, and 83%. The choice of management appeared to be based on etiology and radiologic characteristics. Patients with nonalcohol- and nonbiliary-associated pancreatitis without a radiographically defined wall were more common in the invasive nonsurgical group and were successfully treated without surgery. Nonsurgical invasive techniques are efficacious in the treatment of PFC in this subgroup of patients."
-What was the primary objective of the seromuscular enterocystoplasty experiment in rats?,"Seromuscular enterocystoplasty in rats. Enterocystoplasty is commonly used in clinical practice. Many of its undesirable effects, that is infections, stones, mucus production, absorption of urinary components into the blood stream and risk of cancer, result from the intestinal mucosa lining the urinary tract. We report on the feasibility of creating an enterocytoplasty with a seromuscular colonic segment that acquires a transitional epithelial lining. Augmentation enterocystoplasty was performed in 51 male, 500 gm., Sprague-Dawley rats with a 1.82 cm.2 patch of left colon from which the mucosa had been stripped. The serosal surface was used as lining for the enterocystoplasty. The intestinal patch and the bladder capacity at known pressure were measured at operation and at sacrifice. The histology of the enterocystoplasty was studied in detail following sacrifice. Of the animals 40 survived without significant complications and were sacrificed at a mean postoperative time of 30 days (range 5 to 80 days). In the remaining 11 rats a bladder stone developed but it did not seem to affect the outcome of the experiment. The size of the patch could be measured in 22 rats: it was 1.82 cm.2 (standard deviation +/- 0.86) at operation and 2.30 cm.2 (standard deviation +/- 1.1) at sacrifice. In none of the rats did the patch decrease in size. The bladder capacity at a known pressure (mean 17 cm. water) could be measured in 26 animals: it was 2.35 ml. (standard deviation +/- 0.65) at operation and 5.18 ml. (standard deviation +/- 1.19) at sacrifice. Histological analysis was done in 40 rats. In all cases the serosal surface was lined with transitional epithelium, there was no fibrosis or inflammation and the structure of the muscular layer of the bowel remained intact. The earliest growth of uroepithelium in the serosal surface of the bowel was noted at 5 days. This model suggests that the seromuscular enterocystoplasty can be constructed successfully in the rat model. The seromuscular intestinal patch does not shrink. The bladder capacity increases and histology shows a uroepithelial lining of the augmentation."
-What are the key causes of obesity according to the given context?,"Obesity: types and treatments. Causes of obesity include a low resting metabolic rate, environmental factors, family behavior patterns, a poorly developed satiety response and reactive eating due to stress or anxiety. Morbid obesity is characterized by an increased number of adipocytes and a degree of irreversibility. Overeating increases the size of adipocytes; however, once adipocytes achieve their maximal size, proliferation is induced and massive, irreversible obesity may result. A syndrome of restrained eating produced by chronic dieting leads to hunger, frustration and rebound overeating. Treatment may be unsuccessful because of the failure to address specific causes of obesity in individual patients and the use of reducing regimens that are not designed to maintain weight loss. Recognition of the diverse clinical forms of obesity and their different etiologies permits treatment regimens to be more specific, increasing the likelihood of success. Even with this approach, treatment failure is common."
-What variations in transmembrane domain length were observed in the MHC class I genes of Peromyscus leucopus?,"Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes. The fifth exons of major histocompatibility complex (MHC) class I genes encode a transmembrane domain (TM) that is largely responsible for class I antigen cell-surface expression usually through conventional hydrophobic amino acid-membrane interactions or, less often, through phosphatidylinositol linkage. In this report we show that Peromyscus leucopus, a Cricetidae rodent, has MHC class I genes (Pele-A genes) encoding three distinct sizes of TMs. Increases in TM lengths were due to tandem duplications of sequences similar to human hypervariable minisatellite repeats and the lambda chi site. We discerned remnants of a similar duplication event in comparable rodent and primate MHC class I genes. Furthermore, several duplications and deletions appear to have occurred independently in H-2, RT1, Pele-A, and ChLA genes in near-identical positions. Accumulated data suggests that sequences in the fifth exon of MHC class I genes may, therefore, constitute a mutational or recombinational hot spot that is mediated by minisatellite- and chi-like sequences imbedded within the coding region. The MHC class I genes may thus have recruited ""selfish"" DNA in their evolution to encode cell surface proteins. Expression of Pele-A genes was examined by the polymerase chain reaction (PCR) using oligonucleotide primers specific for exon 4 and 5 sequences. The PCR product sizes indicated that genes encoding each TM domain length are ubiquitously transcribed."
-How does FDG-PET imaging help in detecting and assessing the prognosis of malignant lymphoma in the head and neck region?,"The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis. Twenty-one patients with untreated malignant lymphoma in the head and neck region were evaluated with positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) and gallium-67 SPECT imaging. Tumor-to-normal soft-tissue contrast ratios (TCRs) obtained 60 min after injection of FDG were higher than 2.6, and all malignant lymphomas were clearly visualized. In patients with poor prognosis, higher TCRs and glucose utilization rates (GURs) were observed, whereas low TCR and GUR were shown in a patient with low-grade malignancy. In comparison with 67Ga scintigraphy, patients with high TCRs and GURs were likely to show increased accumulation of gallium-67, but accumulation of gallium-67 was not increased as much as FDG in poor prognostic patients. FDG-PET may be useful in the detection and management of malignant lymphoma."
-Where and when did the Campylobacter enteritis outbreak occur in New Zealand?,"Campylobacter enteritis--New Zealand, 1990. In August-September 1990, an outbreak of Campylobacter enteritis occurred at a camp near Christchurch, New Zealand. This report provides a preliminary summary of the investigation of this outbreak by the New Zealand Communicable Disease Centre and the Canterbury Area Health Board."
-How effective was transesophageal echocardiography in diagnosing conditions in patients initially suspected of having aortic dissection?,"Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. Between September 1987 and April 1989, forty patients suspected to have aortic dissection were evaluated by transesophageal echocardiography. Aortic dissection was identified in 18 patients. This study evaluated the ability of transesophageal echocardiography in the assessment of the 22 patients in whom aortic dissection was not found. A range of pathologic conditions was diagnosed in these patients. Five patients had ischemic heart disease when they were initially seen. Among the remaining 17 only one patient had a normal aorta. Aortic disease was present in the other 16 patients with aortic dilatation in 10. Atheromas were detected in seven patients with concomitant aortic dilatation in five of them. An extrinsic aortic mass was present in two patients. Transesophageal echocardiography correctly identified an anastomotic leak at the site of left coronary artery implantation in a patient with a recent Bentall procedure, and a large mobile clot within the proximal descending aorta in a patient with blunt chest trauma. These findings obviated the need for other tests in 15 patients and led to surgery in four with no ancillary tests performed in three of them. Thus transesophageal echocardiography has an important role in assessing patients with suspected dissection. Aortic disease is common even in patients in whom aortic dissection is excluded, and some of the conditions can be just as life-threatening as dissection. Transesophageal echocardiography not only reliably identifies dissection but can also detect luminal and extraluminal diseases not adequately visualized by other modalities."
-How did the researchers measure local refractoriness during ventricular fibrillation in dogs?,"Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. In 18 dogs on total cardiopulmonary bypass, the average interval between local activations during artificially induced ventricular fibrillation (VF interval) was measured from extracellular electrograms, simultaneously recorded from up to 32 ventricular sites. VF intervals were used as an index of local refractoriness, based on the assumption that during ventricular fibrillation, cells are reexcited as soon as they have recovered their excitability. In support of this, microelectrode recordings in two hearts during ventricular fibrillation did not show a diastolic interval between successive action potentials. Refractory periods determined at a basic cycle length of 300 msec with the extrastimulus method correlated well with VF intervals measured at the same sites. Thus, this technique allows assessment of spatial dispersion of refractoriness during brief interventions such as sympathetic stimulation. The responses to left, right, and combined stellate ganglion stimulation varied substantially among individual hearts. This was observed both in dogs with an intact (n = 12) and decentralized (n = 6) autonomic nervous system. Individual ventricular sites could show effects of both left and right stellate ganglion stimulation (42% of tested sites) or show effects of left-sided stimulation only (31%) or right-sided stimulation only (14%). In 13% of sites, no effects of stellate stimulation were observed. Apart from these regional effects, the responses could be qualitatively different; that is, within the same heart, the VF interval prolonged at one site but shortened at another in response to the same intervention, although shortening was the general effect and prolongation the exception. Whenever sites responded to stellate ganglion stimulation with a shortening of VF interval, this shortening was approximately 10% for left, right, or combined stimulation, whether the autonomic nervous system was intact or decentralized. In six of 12 hearts in the intact group, there was a distinct regional effect of left stellate ganglion stimulation; in the other six hearts, the effects were distributed homogeneously over the ventricles. In three hearts, the effect of left stellate ganglion stimulation was strongest in the posterior wall, and in the other three hearts, in the anterior wall. The effects of right stellate ganglion stimulation were restricted to the anterior or lateral part of the left ventricle. Dispersion of VF intervals increased after left and combined stellate ganglion stimulation in the intact group and after right stellate ganglion stimulation in the decentralized group, but not significantly in every heart. This points to a marked individual variation with regard to the effects of sympathetic stimulation on electrophysiological properties of the heart."
-How does mitral valve replacement affect contractile function in a canine model of mitral regurgitation?,"Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload [published erratum appears in J Clin Invest 1991 Aug;88(2):723] It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload."
-What are the key hemodynamic characteristics of septic shock?,"Septic shock. Septic shock (SS) is the most common type of shock encountered by internists, and its prevalence appears to be increasing. SS complicates all types of infections. The hemodynamic characteristics of SS include a low systemic vascular resistance and an elevated, but relatively inadequate, cardiac output. A cardiomyopathy frequently occurs. The major endogenous mediator of SS is tumor necrosis factor, and interleukins-1 and -2 may also contribute. Important secondary phenomena include release of platelet activating factor, vasodilator prostaglandins, and upregulation of adhesion molecules on polymorphonuclear leukocytes and endothelial cells. Current therapy is often ineffectual, and potentially promising new therapeutic approaches are reviewed."
-What were the key findings of the study regarding cervical spine injuries in alert trauma patients?,"Clinical indications for cervical spine radiographs in alert trauma patients. Cervical spine fracture/dislocation is a potentially devastating injury that may be clinically difficult to diagnose. Therefore, a vast majority of trauma patients undergo cervical spine X rays when only a relatively small number of them will actually have a cervical spine injury. Because of the costly overuse of radiography, studies have been undertaken to define high yield criteria for evaluation of patients. This study examined the characteristics of acute cervical spine fracture/dislocation in alert trauma patients. Of 79 patients with this discharge diagnosis at St. Elizabeth Hospital Medical Center between 1982 and 1987, 47 met the criteria of Class I level of consciousness. All 47 patients complained of neck pain or demonstrated cervical tenderness to palpation. Other parameters (such as loss of consciousness, paresthesias, decreased sensation, weakness, cervical muscle spasm, decreased anal tone, and associated injuries) did not, individually or in combination with each other, consistently predict cervical spine injury. Although occult or painless cervical spine injuries have been reported in the literature, a careful review of these cases revealed that these injuries were not truly asymptomatic. Our study suggests that selected patients can be excluded from radiologic evaluation of the cervical spine. However, large prospective studies are needed to validate this finding."
-What precaution should be taken when using suxamethonium in a patient with a permanent pacemaker during anaesthesia?,"Pacemaker failure on induction of anaesthesia. A patient with a permanent pacemaker presented for repair of a strangulated hernia. During induction of anaesthesia, the pacemaker generator stopped discharging, thus causing cardiac arrest. The likely cause of the generator failure was inhibition by suxamethonium-induced muscle fasciculations. Following defibrillation, and increase in stimulation threshold necessitated urgent insertion of a transvenous pacing system. It is suggested that, when suxamethonium is to be used in a patient with a permanent pacemaker, consideration should be given to reprogramming the pacemaker to asynchronous mode before induction of anaesthesia. If a patient with a pacemaker requires defibrillation, an acute increase in stimulation threshold may result and cause loss of capture. Rapid insertion of a transvenous pacing system may be necessary."
-What potential complication can occur to the pancreas during extracorporeal shock wave lithotripsy (ESWL) for renal calculus fragmentation?,"Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed."
-What are the three different types of skew deviation described in the context?,"Different types of skew deviation. Although all manifest skew deviations appear the same for the clinician, skew deviation can result from different combinations of dysconjugate vertical ocular deviations. Evidence is presented for three different types of skew deviation when it occurs as a feature of an ocular tilt reaction. In type 1 (utricle) there is upward deviation of both eyes with different amplitudes, as described for otolith Tullio phenomenon in humans. In Type 2 (dorsolateral medulla oblongata) hypertropia of one eye occurs while the other eye remains in the primary position, the hypothetical mechanism of skew deviation in Wallenberg's syndrome. In Type 3 (midbrain tegmentum) there is simultaneous hypertropia of one eye and hypotropia of the other eye, as described for electrical stimulation of midbrain tegmentum in monkeys and observed in clinical cases with a paroxysmal ocular tilt reaction."
-What was the main objective of the study on P6 acupressure in children undergoing strabismus correction?,"Effect of P6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction. A prospective, double-blind study was conducted to compare the effect of pressure at the P6 (Neikuan) point with placebo as an antiemetic in children. Sixty-six patients, ages 3-12 yr, undergoing outpatient surgery for correction of strabismus, were allocated randomly to receive either bilateral P6 acupressure or placebo during the perioperative period. The study was designed to detect a 50% difference in the incidence of postoperative vomiting between the two groups, with a 90% power of achieving a statistically significant result at the 5% level (two-tailed). The incidence of postoperative vomiting for the placebo group was 58% before discharge from hospital, 73% at home and 82% in the first 24 h after surgery. The corresponding results for the acupressure group were 58% before discharge, 71% at home and 94% in the first 24 h. These differences were not significant; P6 acupressure did not reduce the incidence of postoperative vomiting in children undergoing strabismus surgery."
-What were the significant prognostic factors for recovery of awareness in patients with prolonged posttraumatic unawareness?,"Prognosis for recovery from prolonged posttraumatic unawareness: logistic analysis. This study reviews the course and outcome of 130 patients who remained in a state of prolonged unawareness 30 days after severe cranio-cerebral trauma. Prognostic indicators and outcome were fitted by a logistic model. The significant prognostic factors observable in the first week after trauma were found to be ventilatory status, motor reactivity and significant extraneural trauma. The significant prognostic factors after the first month of unawareness were early ventilatory status, early motor reactivity, late epilepsy and hydrocephalus. The estimated probability of recovery of awareness (that is, consciousness) ranged from 0.94 in patients with early decorticate posturing in the absence of both extraneural trauma and ventilatory disturbance to 0.06 in patients with flaccidity, extraneural trauma and ventilatory disturbance in the first week after injury."
-Which thrombolytic agent is most effective in restoring patency in coronary arteries according to clinical trials?,"Coronary artery thrombolysis: comparison of approved agents. Three agents approved for the lysis of thrombi in coronary arteries--alteplase, anistreplase and streptokinase--have undergone critical clinical experimental trials in Europe and the United States. Global comparison of their efficacy shows that alteplase is slightly more effective (71 percent) in restoring patency than anistreplase (60 percent) and streptokinase (58 percent). Streptokinase and anistreplase are allergenic, and repeat administration is not feasible in the short-term, a distinct advantage for alteplase. More accurate dosing of thrombolytic agents and skillful use of aspirin and heparin improve the efficacy of thrombolytic therapy but can also increase the risk of bleeding. A recanalization rate of 90 percent or more could be achieved if the thrombolytic agent is administered within the first hour after thrombosis. Administration this soon after the development of thrombosis may be possible if the agent is given outside the hospital by practicing physicians or, perhaps, paramedics."
-"What were the predictive values of digital rectal examination, transrectal ultrasound, and MRI for tumor confinement and extracapsular disease in prostate cancer?","Preoperative prediction of pathological tumor volume and stage in clinically localized prostate cancer: comparison of digital rectal examination, transrectal ultrasonography and magnetic resonance imaging. Accurate preoperative staging is important for proper selection of patients for radical retropubic prostatectomy. Preoperative staging by digital rectal examination, transrectal ultrasound, magnetic resonance imaging (MRI), Gleason grade and prostate specific antigen was compared to pathological stage for 25 patients who underwent radical retropubic prostatectomy. The predictive value for tumor confinement was 36% by rectal examination, 37% by ultrasound and 30% by MRI. The predictive value for extracapsular disease was 100% by rectal examination, 83% by ultrasound and 66% by MRI. Preoperative determinations of tumor volume by any modality did not correlate with pathological tumor volume. Digital rectal examination, ultrasound and MRI clinically understage the disease in most patients but they may be reliable to predict extracapsular disease."
-"What was the purpose of using sublaminar fixation in lumbosacral fusions, and what were the outcomes of the study?","Sublaminar fixation in lumbosacral fusions. Sublaminar fixation to stainless steel rectangles was employed in an effort to improve the fusion rate in lumbar and lumbosacral arthrodesis. Thirty-seven patients had spondylolisthesis, and 26 had other causes of pain secondary to lumbar mechanical instability. Of the 63 patients, 53 achieved fusion and 52 had relief of pain. No infections or neurologic complications were encountered. This fusion rate of 84% does not significantly differ from rates obtained with noninstrumented methods, and this construct is no longer used for lumbar fusions."
-What is the primary genetic mechanism behind Leber's hereditary optic neuropathy?,"Leber's hereditary optic neuropathy and Kearns-Sayre syndrome: mitochondrial DNA mutations. Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported."
-What was the main objective of the study on luteinizing hormone-releasing hormone agonist (LH-RH-a) treatment for uterine leiomyomata?,"Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women. OBJECTIVE: To evaluate the efficacy of luteinizing hormone-releasing hormone agonist (LH-RH-a) in the treatment of leiomyomata. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Twenty-five women, ages 36 to 54 years with symptomatic uterine leiomyomata, were divided into two groups according to the responsiveness to LH-RH-a: group A patients reached menopause after LH-RH-a, whereas resumption of menstruation occurred within 12 weeks after cessation of therapy in group B. INTERVENTIONS: Luteinizing hormone-releasing hormone agonist was administered intranasally three times a day with 150 micrograms insufflation of one spray in each nostril (total dose: 900 micrograms/d). MAIN OUTCOME MEASURES: Efficacies of treatment were assessed in terms of uterine volume, hemoglobin concentrations, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and bone density during and after treatment. RESULTS: In both groups, hemoglobin concentrations increased significantly after 16 weeks of treatment. A significant reduction in uterine volume was observed in both groups. After completing therapy, there was no further significant change in uterine volume in group A, whereas uterine volume in group B returned to pretreatment values. Serum LH and FSH concentrations were suppressed during treatment, but those gonadotropins in group A increased significantly up to the menopausal levels after treatment. Serum E2 concentrations in both groups showed consistent suppression by the end of the first treatment cycle. After cessation of therapy, serum E2 levels on group A remained in the castrate range, whereas E2 in group B returned to pretreatment levels, concomitant with the return of normal ovulation. CONCLUSIONS: Intranasal administration of LH-RH-a was successful in significantly decreasing uterine volume and increasing hemoglobin concentration in premenopausal women with leiomyomata."
-"What are the differences in the expression of Tn, sialosyl Tn, and T antigens across normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma?","Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis."
-What was the main finding of the study regarding epithelial migration in patients with unilateral cholesteatoma?,"Patterns of epithelial migration in the unaffected ear in patients with a history of unilateral cholesteatoma. Epithelial migration in a centrifugal manner is an established phenomenon in the normal human tympanic membrane. This pattern of migration is symmetrical in both ears of any one individual. We present a prospective study on the pattern of tympanic ink dot migration on the normal drum, in patients with a history of cholesteatoma in one ear. It was demonstrated that patients who develop cholesteatoma have a normal migratory pattern and rate in the unaffected ear. The conclusion from this study is that defective migration is not the initiating factor in the development of acquired cholesteatoma."
-Can CT scanning help determine which patients with minimal head injury can be safely discharged from the emergency department?,"The use of CT scanning to triage patients requiring admission following minimal head injury. Recent data have suggested that patients with both a normal cranial CT scan and normal neurologic examination following minimal head injury (MHI) have no risk of neurologic deterioration. This study prospectively examined the safety of discharging patients from the emergency department (ED) after MHI whether or not there was a responsible observer at home. MHI was defined as a history of loss of consciousness (LOC), a Glasgow Coma Scale (GCS) score of 14 or 15, and no focal neurologic findings. In a 4-month period 111 patients with MHI were evaluated. Fifteen (14%) patients had a CT scan which revealed an intracerebral injury; 96 patients had a normal CT scan; five patients with normal CT scans were admitted because of persistent lethargy; and one patient was admitted after his CT that demonstrated an old infarct; the remaining 90 patients were discharged. There were 71 men and 19 women with a mean age of 29 years. The mechanism of injury was assault in 55, MVA in 30, and falls in five. The initial GCS in was 15 in 79 and 14 in 11. Fifty-eight per cent of patients were intoxicated. Fifty-seven (63%) patients were successfully contacted by telephone; none had developed any neurologic symptoms. Thirty-one patients who could not be followed up gave fictitious phone numbers. These data suggest that CT can reliably triage patients who can be discharged from the ED following MHI, even in the absence of a responsible observer. Hospital admission can be avoided in more than 80% of patients sustaining MHI, better utilizing scarce hospital resources."
-How does the extent of coronary collateral circulation relate to the presence of viable myocardium in patients with recent myocardial infarction?,"Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction. The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area."
-What were the four radiological examinations investigated for acoustic neuromata in this study?,"Patient dose and associated risk due to radiological investigation of the internal auditory meatus. The radiation doses and associated somatic risks due to four radiological examinations for acoustic neuromata (AN) have been investigated. These examinations were (1) plain film radiography of the internal auditory meatus (IAM), (2) computed tomography (CT) of the IAM, (3) CT of the posterior fossa and (4) CT of the IAM with air contrast. Organ dose measurements were performed using lithium fluoride thermoluminescent dosemeters loaded in a patient equivalent phantom. Dose equivalents to various organs are presented, together with the effective dose equivalent and collective effective dose equivalent for each examination. Hypothetical fatal somatic risks for each examination studied here have been estimated from the effective dose equivalents. The estimated number of hypothetical fatal cancers induced by radiological examinations for AN is between approximately 110 and 820 times lower than the number of detected AN, depending on the method of assessing the radiation dose to the remainder organs. It is concluded that in this particular study the radiological examinations are of net benefit to this group of patients."
-What is the key finding regarding the origin of fetal tissue in the reported cases of repetitive hydatidiform mole?,"Hydatidiform mole and fetus with normal karyotype: support of a separate entity. Repetitive hydatidiform mole was observed in four pregnancies. The pregnancies presented with heavy bleeding and vomiting, but the post-evacuation courses were uncomplicated, with rapid regression of serum hCG levels. Cytogenetic investigations, analyses of restriction fragment length polymorphisms, and flow cytometry in three pregnancies were consistent with diploid, biparental conception as the origin of fetal tissue and molar and nonmolar villi. In one pregnancy, the analyses of cytogenetic markers suggested the coexistence of two different cell lines of dizygotic, biparental origin, whereas DNA analysis was consistent with a single conception. With incomplete genetic information, a hydatidiform mole with coexistent normal fetus is generally considered to result from dizygous twinning comprising an androgenetic complete mole and a normal conception. In the present gestations, the results based on several techniques applied on numerous samples from different tissues render this possibility unlikely. Some of the contradictions between histologic and cytogenetic classifications of hydatidiform mole may be explained by diploid, biparental partial mole, which seems to constitute a separate subgroup within hydatidiform mole. Following chorionic villus sampling or amniocentesis, continued pregnancy may be considered, depending on prenatal diagnosis including genetic marker analysis."
-What potential side effect did two siblings experience after receiving phenothiazine-containing medications?,"Phenothiazine-associated apnea in two siblings. A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed."
-What was the primary objective of using the miniaturized infrared end-tidal CO2 detector in this study?,"Confirmation of endotracheal tube placement: a miniaturized infrared qualitative CO2 detector. STUDY OBJECTIVES: A miniaturized, infrared, solid-state, end-tidal CO2 detector was used to confirm emergency endotracheal tube (ETT) placement. DESIGN: This prospective, clinical study used a miniature, infrared, solid-state end-tidal CO2 detector to confirm ETT placement in an acute setting. SETTING: The ICU, emergency department, and hospital floor. TYPE OF PARTICIPANTS: There were 88 consecutive adult patients requiring 100 emergency intubations. MEASUREMENTS AND MAIN RESULTS: The indication for airway intervention was considered urgent in 79% and under arrest conditions in 21%. The mean number of intubation attempts was 1.83 (range, one to five) with difficulty of intubation of 6.48 and confirmation of 7.75, on a linear scale from 0 (lowest) to 10 (highest). Determination of ETT position revealed intratracheal intubation in 96% and esophageal intubation in 4%. Placement was confirmed by direct visualization or radiography in all cases. Sensitivity and specificity for ETT localization was 100% (P less than .0001). CONCLUSION: This hand-held infrared capnometer reliably confirms ETT placement under emergency conditions."
-What is the primary aim of the modified lateral rhachotomy procedure for thoracic spinal lesions?,"Lateral rhachotomy for thoracic spinal lesions. Capener's ""Lateral Rhachotomy"" was modified by additional excision of the pedicle, articular facets, part of the lamina, and a posterior half of the vertebral bodies on one side through a transpleural approach to the thoracic spine, and a retroperitoneal approach to the lumbar spine. The aim was to excise a space-occupying lesion, which exists in front of the thoracic or lumbar spinal cord, safely. This modification enable the authors to expose more than 50% of the spinal canal, and decompress it from its anterior, lateral, and posterior compressing mass. The utmost important point of this procedure is the excision of the lesion under the direct visualization of the dura. In ossification of the posterior longitudinal ligament (OPLL), the dura is usually indented by the thick bony mass, and the lesion extends over a few segment with adhesion. Using ""Modified Lateral Rhachotomy,"" it was possible to explore three or four vertebral levels in continuity through the same skin incision. In the present report, the authors described their ""Modified Lateral Rhachotomy"" procedure, and reviewed the case material."
-How do Factor XIII subunits change in patients with ulcerative colitis during active and quiescent stages of the disease?,"Factor XIII subunits in relation to some other hemostatic parameters in ulcerative colitis. The hemostatic parameters, particularly with respect to F.XIII subunits, were examined in 48 untreated UC patients (22 at active and 26 at quiescent stage). UC active patients showed a significant decrease of F.XIII subunit ""a,"" compared with healthy subjects, as well as in UC patients in remission. In contrast, the level of F.XIII subunit ""b"" in each group was similar. Compared with normal subjects, UC active patients revealed a significant decrease in AT III concentration, prolonged ELT, and elevated fibrinogen level. In addition, the elevated titer of SDPS test for SFMC appeared in approximately 40% of those patients. However, no strict relationship was found between the presence of positive SDPS and diminution of AT III, as well as of F.XIIII subunit ""a"" in active UC state. In patients in remission, AT III level and ELT were similar to those as in the control group, but fibrinogen concentration was elevated. Such constellation of hemostatic parameters may indicate a tendency to blood hypercoagulability in UC active patients, whereas, in general, these changes are not associated with the stage of remission. The present data may also suggest that F.XIII behavior pattern should be taken into account in the clinical management of UC."
-What were the key differences in characteristics between palpable and mammographically detected breast lesions in this study?,"The prevalence of carcinoma in palpable vs impalpable, mammographically detected lesions. Concern over excessive numbers of false-positive mammograms, leading to unnecessary investigations and surgical interventions, has been cited as a barrier to mammographic screening for breast cancer. We compared the biopsy results from palpable vs impalpable, mammographically detected lesions from one experienced breast surgeon's practice from July 1980 through July 1989. Overall, there were 372 biopsies in 346 women. Of 143 biopsies for palpable abnormalities, 48 (34%) yielded a primary malignant lesion. The length of the palpable cancers averaged 3.7 cm (median, 2.8 cm). Sixteen (33%) of the 48 biopsies were in patients who had positive axillary lymph nodes, and five (10%) were in patients who had distant metastases at the time of biopsy. Of 229 biopsies for impalpable, mammographically detected lesions, 72 (31%) yielded a primary breast carcinoma. Excluding 34 carcinomas that had only calcifications, the length of the mammographically detected tumors averaged 2.0 cm (median, 1.5 cm). Eleven (15%) of the 72 biopsies were in patients who had positive axillary nodes, and none were in patients who had distant metastases at the time of biopsy. The positive predictive values (number of cancers detected divided by the number of biopsies recommended) were not significantly different when comparing biopsies indicated for palpable, clinically detected (34%) vs impalpable, mammographically detected (31%) abnormalities (p = .669). However, the mammographically detected cancers were smaller, more often noninvasive (32% vs 4%), less often associated with axillary metastases (15% vs 33%), and without distant metastases (0% vs 10%)."
-What is the significance of the modified endoscopic classification of burns in the management of corrosive ingestion?,"The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. We prospectively evaluated the role of fiberoptic esophagogastroduodenoscopy in the management of 81 patients with corrosive ingestion. A total of 381 endoscopic examinations were performed: 88 within 96 hours following corrosive ingestion, 108 between the third and ninth week, and 185 during the period of follow-up after bougie dilation of esophageal strictures. The customary endoscopic classification of burns (grades 0 to 3) was modified by subdividing grade 2 burns into 2a and 2b, and grade 3 burns into 3a and 3b for prognostic and therapeutic implications. There was no significant correlation between oropharyngeal and upper gastrointestinal tract injury. Early major complications and deaths were confined to patients with grade 3 burns. All patients with grade 0, 1, and 2a burns recovered without sequelae. The majority of patients (71.4%) with grade 2b injury and all survivors with grade 3 injury developed esophageal or gastric cicatrization, or both, which needed endoscopic or surgical treatment. There were no complications related to endoscopy. We conclude that early endoscopy is not only a safe, reliable, and accurate diagnostic tool in such patients, but also is of crucial importance in management and prognosis."
-How does corneal hypesthesia affect the duration of proparacaine anesthetic eyedrops?,"The effect of corneal hypesthesia on the duration of proparacaine anesthetic eyedrops. The duration of action of proparacaine is known in the normal cornea but not in the hypesthetic cornea. To determine this, we examined both eyes in seven patients with documented unilateral corneal hypesthesia associated with inactive herpetic disease. Cochet-Bonnet measurements were made in both eyes before and at two- to five-minute intervals after the instillation of one drop of 0.5% proparacaine until baseline corneal sensitivity levels were again achieved. Mean recovery time was 34.86 minutes in eyes with normal corneal sensitivity, compared to 45.43 minutes in hypesthetic corneas. In all patients, the recovery time was remarkably longer in the hypesthetic eye than it was in the normal fellow eye. These data demonstrate the need to wait up to one hour after the instillation of proparacaine in eyes suspected of having corneal hypesthesia if corneal sensitivity is to be determined accurately. Additionally, the duration of action of topically instilled anesthetic may be a useful method of discovering subtle differences in corneal sensitivity."
-What are the three hypotheses proposed to explain neurobehavioral impairments following cranial radiation therapy and intrathecal chemotherapy?,"Absence of synergistic effects of CNS treatments on neuropsychologic test performance among children. Three hypotheses are proposed to account for neurobehavioral impairments following treatment with cranial radiation therapy (CRT) and intrathecal (IT) chemotherapy: CNS treatments exert a synergistic effect (A x B), an additive effect (A + B), or a single-agent effect (A or B). Eighty-five long-term survivors of non-CNS cancers aged 6 to 16 years were classified into groups on the basis of CNS treatments: CRT-IT (n = 25), CRT-No IT (n = 11), No CRT-IT (n = 24), and No CRT-No IT (n = 25). Study I findings did not provide support for synergistic mechanisms; nonorthogonal analysis of variance showed interaction effects (CRT x IT) restricted to tactile-perceptual speed. However, main effects were significant for a single agent (CRT) across a wide range of measures. General intelligence, academic achievement, verbal knowledge and reasoning, and perceptual-motor abilities were found to be significantly lower among CRT-treated groups. Study II findings provided additional support for the role of CRT; Pearson correlations within the CRT-No IT group indicated significant negative associations between CRT dose estimates for cortical regions and perceptual-motor abilities."
-What percentage of lupus nephritis patients in the study were found to have renal vascular lesions (RVL)?,"Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the ""Gruppo Italiano per lo Studio della Nefrite Lupica"" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL."
-What is the significance of 99mTc-sestamibi in assessing myocardial area at risk during myocardial infarction?,"Perfusion imaging with 99mTc-sestamibi for the assessment of myocardial area at risk and the efficacy of acute treatment in myocardial infarction. There is a clear need to develop better measurement tools for assessment of the effect of acute therapy in myocardial infarction. Such tools must permit accurate measurement of the amount of myocardium that is initially at risk. 99mTc-sestamibi is a new radiopharmaceutical with unique properties that are well suited to the measurement of myocardium at risk without any delay in acute therapy. Tomographic imaging with this agent has been shown to provide accurate quantitative estimates of the myocardium at risk, which varies widely, even for patients with a similar coronary occlusion. For example, there is more than a threefold range in myocardium at risk for patients with a nonproximal occlusion of the left anterior descending coronary artery. The determination of the myocardium at risk before intervention and the change in this region after intervention constitute a promising measurement tool for the assessment of the effect of acute therapy. Initial studies with tomographic imaging have shown a significant improvement in a group of patients treated with thrombolysis, although the magnitude of improvement is highly variable in individual patients. Qualitatively similar results have been reported with planar imaging. Although it has a number of technical limitations, sequential imaging with 99mTc-sestamibi seems to have a clear advantage over those end points that have previously been used to assess acute therapy. This new measurement tool should facilitate future clinical trials of different treatments in acute myocardial infarction."
-What is the relationship between chronic pleural inflammatory disease and the development of soft tissue sarcoma in the pleural cavity?,"Soft tissue sarcoma of the pleural cavity. Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS."
-What changes in mucosal hemodynamics were observed in the canine model of gastric ulceration after ethanol injection?,"Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer. In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer."
-What are the two main clinical presentations of orbital lesions with granulomatous inflammation observed in the study?,"Orbital lesions with granulomatous inflammation. Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis)."
-What was the primary purpose of the clinical trial involving felbamate for complex partial seizures?,"Felbamate: a clinical trial for complex partial seizures. We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM."
-How do cytokines like interleukin-1 and tumor necrosis factor influence leukocyte-endothelial adhesion and contribute to inflammatory responses?,"Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. This paper reviews the evidence that cytokines induce a variety of functional and structural alterations in endothelium and that cytokine-endothelial interactions play important roles in the evolution of inflammatory and immune responses. The effect of cytokines, particularly interleukin-1 and tumor necrosis factor, on leukocyte-endothelial adhesion has led to the discovery of several endothelial adhesion molecules, and the molecular and biological characteristics of these are described. Finally, the review discusses the possible contribution of cytokine-induced activation to vascular injury in such pathological processes as septic shock, the Shwartzman reaction, delayed hypersensitivity, and immune-mediated vasculitis."
-What is central pontine myelinolysis and what causes it in burn patients?,Pontine myelinolysis after correction of hyponatremia during burn resuscitation. Central pontine myelinolysis is a neurologic disease produced by the rapid correction of hyponatremia. This report describes the occurrence of central pontine myelinolysis in a patient with burns. The natural history of this paralyzing condition and suggestions for its prevention are discussed. Severely burned and hyponatremic patients are at risk for this disorder because a large amount of sodium ion is typically required for the treatment of burn shock. Awareness of this phenomenon and avoidance of rapid correction of hyponatremia are essential to its prevention.
-What are the main endoscopic techniques used for palliation of tracheobronchial malignancies?,Endoscopic palliation of tracheobronchial malignancies. The prognosis for tracheobronchial tumours remains poor. Most patients can be offered only palliation. When the main symptom is breathlessness or refractory haemoptysis from a large airway tumour endoscopic treatment may be very effective. Over the last decade most attention has focused on the neodymium YAG laser. This often produces dramatic effects but has some important limitations. In the last few years better techniques for stenting and intrabronchial radiotherapy (brachytherapy) have also been developed. This article discusses the range of techniques now available and aims to help clinicians decide which patients may benefit from referral to centres providing these techniques.
-In how many primary brain lymphomas was Epstein-Barr virus (EBV) DNA detected?,"Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency. We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma."
-What factors are associated with increased delay in seeking treatment for acute myocardial infarction?,"Treatment-seeking behavior among those with signs and symptoms of acute myocardial infarction. Significant delays in seeking definitive treatment for the signs and symptoms of acute myocardial infarction increase morbidity and mortality. In most studies, delay times average more than 4 hours. The following variables are associated with increased delay: a medical history of angina, diabetes mellitus, or hypertension; older age; black race; seeking advice from a family member or a physician; symptom onset on a weekday; and attempts at self-treatment. Variables associated with reduced delay times are the following: pain recognized as cardiac in origin, hemodynamic instability, severe chest pain, younger age, and consultation with a coworker. Surprisingly, patients who have already experienced a myocardial infarction are just as likely to delay as patients who have not had this experience. These findings provide direction for developing and testing patient and family interventions, establishing community education programs, and reducing patient delay in response to the signs and symptoms of acute myocardial infarction."
-What are the characteristic features of nevoid basal cell carcinoma syndrome that pediatricians should be aware of?,"Cardiac tumors and the nevoid basal cell carcinoma syndrome. Nevoid basal cell carcinoma syndrome is a multisystem disease with a wide range of initial symptoms that can be seen at any age. The most characteristic features are vertebral or rib anomalies, intracranial falx calcification, multiple basal cell carcinomas, odontogenic keratocysts of the jaw, and palmar and/or plantar pits. Pediatricians need to be aware that if any one of these major anomalies is seen, this diagnosis should be considered. There now appears to be an established association between cardiac tumors and nevoid basal cell carcinoma syndrome. Primary cardiac tumors have been associated with cerebral tuberous sclerosis and neurofibromatosis, and evaluation of cardiac status is recommended when these genetically determined syndromes are diagnosed. This communication should serve to alert pediatricians to the need for complete cardiac evaluation and genetic counseling when a diagnosis of nevoid basal cell carcinoma is made."
-How rare is Hodgkin's disease involvement in the gastrointestinal tract according to the study?,"The surgical pathology of gastrointestinal Hodgkin's disease. The files of the National Cancer Institute were searched for all surgical specimens from the gastrointestinal (GI) tract with the diagnosis of Hodgkin's disease (HD) that were accessioned during the years 1953-1990; six patients with a histologically reconfirmed diagnosis were identified. Of these patients, four presented with GI HD and two had recurrent HD. Primary HD appeared in the stomach (three patients) and the duodenum (one patient); recurrent HD after diagnosis in a conventional nodal site appeared in the stomach (one patient) and the colon (one patient). One of the cases of primary gastric disease was a composite lymphoma consisting of HD and diffuse large cell lymphoma. In view of the rarity of GI tract involvement by HD, a diagnosis of primary GI HD should be viewed with skepticism; support for such a diagnosis may be provided by both classic histopathologic features of HD and immunostaining, but no single feature can be regarded as pathognomonic."
-What is the potential complication described in this medical case involving a saphenous vein graft and a native coronary artery?,Dislodgement of a vein graft thrombus by angiographic injection of native coronary artery. A case of retrograde dislodgement of thrombus in a saphenous vein graft during injection of the native right coronary artery is presented. Attention to this previously undescribed complication may allow for timely treatment with emergency surgery or thrombolysis.
-What is the recommended intervention for significantly increased plantar tissue pressure after a calcaneal fracture?,"Compartment syndrome of the foot after intraarticular calcaneal fracture. Seventeen patients with a total of 21 intraarticular calcaneal fractures were examined at up to 30 days after trauma for the development of tissue pressure in the central plantar muscle compartment. Twelve patients had a significant increase in tissue pressure with values greater than 30 mmHg because of primary fracture hematoma or interstitial fluid accumulation. This increase in pressure persisted for three to five days after trauma, so that ischemic damage to the short plantar foot muscles had to be suspected. Plantar muscle scarring and claw-toe formation were observed in seven patients with a total of 11 fractures during a mean observation period of 18 months. The plantar aponeurosis, which forms the constricting fascial envelope of the plantar muscles, is the anatomic structure responsible for the compartment syndrome that may develop after calcaneal fracture. Therefore, to avoid functional deficit, plantar compartmental pressures should be regularly measured after calcaneal fracture. Significantly increased plantar tissue pressure greater than 30 mmHg should be relieved by longitudinal incision of the plantar aponeurosis, preferably by a plantar incision as soon as the diagnosis is made."
-What percentage of patients with IgG antibody to hepatitis C virus also had IgM antibody to hepatitis C virus?,"IgM antibody to hepatitis C virus in acute and chronic hepatitis C. To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%)."
-What are the key challenges emergency physicians face when treating patients with headaches?,"Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache."
-How effective was desipramine in treating pain for patients with diabetic neuropathy in this clinical trial?,"Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect."
-"What is the treatment approach for cystoid macular edema in Coats' disease, and what potential side effects should patients be aware of?","Cystoid macular edema secondary to juxtafoveolar telangiectasis in Coats' disease. A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema."
-What were the key findings of the study on hypertonic saline resuscitation in burn patients?,"Hypertonic saline resuscitation: efficacy in a community-based burn unit. Many have discussed hypertonic saline for resuscitation in burned patients only to discourage its use or to emphasize it only as a research tool and not as standard resuscitation. We reviewed the records of 47 adults with burns over 20% or more of the total body surface area (TBSA) in whom hypertonic saline was used as standard resuscitation fluid in a large community burn unit. The solution consisted of sodium, 300 mEq/L, acetate, 200 mEq/L, and chloride, 100 mEq/L, with an osmolality of 600 mOsm/L. The mean TBSA burned was 37% and the mean patient age was 44.8 years. Eighteen patients (mean age 39.7 years, mean TBSA burned 27%) received hypertonic saline alone. They required an average of 75% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value over the first 48 hours was 44.2% and the mean serum sodium level was 141.6 mEq/L. Twenty-nine patients (mean age 51.8 years, mean TBSA burned 47.8%) received hypertonic saline plus colloid (albumin or fresh frozen plasma). Colloid was used in older patients with more serious burns. This group required 57% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value was 45.1% and mean sodium level was 143.8 mEq/L. The mean weight gain for both groups was 7.3% of the admission weight. None of the patients had changes in pH or renal function. All patients survived the resuscitation phase of their injury; the overall death rate was 49%. We conclude that hypertonic saline is a safe, effective means of resuscitation even in a community-based unit. It allows less fluid to be delivered for adequate resuscitation. The usual hyponatremia, hemoconcentration, and significant weight gain associated with administration of isotonic solutions was avoided. Colloid may further improve the resuscitation capabilities of hypertonic saline."
-What were the key findings of the TIMI II-B Study regarding the timing of beta-blocker therapy in patients with acute myocardial infarction?,"Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality."
-What was the effect of thoracic epidural analgesia on catecholamine levels during coronary artery bypass grafting in a patient with bilateral phaeochromocytoma?,"Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. A patient suffering from phaeochromocytoma and coronary artery stenoses needed coronary artery bypass grafting before adrenalectomy. High thoracic epidural analgesia (T1-T2) with bupivacaine and sufentanil in combination with general anaesthesia was used. Plasma adrenaline and noradrenaline concentrations decreased during the period before bypass grafting compared to the baseline value and no important haemodynamic changes were seen during this period. Thoracic epidural analgesia failed to suppress the release of catecholamine during the bypass period. After the operation, the plasma catecholamine concentrations returned to the baseline value. Excellent analgesia (visual analogue scale = 1-2) was achieved with a postoperative epidural, but the plasma catecholamine concentration increased considerably."
-What was the prevalence of antibodies to hepatitis C virus among patients with chronic hepatitis B virus infection in this study?,"The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection."
-How does amiodarone affect the mitochondrial beta-oxidation of fatty acids in mice?,"Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from [U-14C]palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of [14C]CO2 from [U-14C]palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of [U-14C]palmitic acid. One hour after 100 mg.kg-1, the exhalation of [14C]CO2 from [1-14C]palmitic acid, [1-14C]octanoic acid or [1-14C]butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of [14C]CO2 from [1-14C]palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice."
-How does DNA ploidy status and proliferative fraction correlate with the clinical behavior of atrial myxomas?,"DNA analysis of atrial myxomas. The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior."
-What psychological effects were observed in women undergoing different stages of breast screening?,"Assessment of the psychological impact of a breast screening programme. In order to assess the psychological effect of mammographic screening, questionnaires (which included psychometric tests) were sent to 750 women at invitation and, 6 weeks after screening, to 420 women normal after the first mammograph, to 240 women normal after special assessment, and to 68 women normal after open biopsy. Increasing degree of the investigation was associated both with increasing frequency of breast self examination (10% were practising breast self-examination at least once a week before screening compared with 24% for women after special assessment and 35% of women who had had an open biopsy (p less than 0.001)), and with greater confidence that any malignancy in the breast would have been found. Psychometric scores showed no increase of general levels of anxiety or depression in the screened groups. For anxiety, percentages abnormal were 5, 4, 2 and 6 for the four groups, respectively, and for depression the percentages abnormal were 5, 4, 4 and 6, respectively; 10% of screened women were more anxious about having breast cancer as a result of the screening. At least 10% of women proceeding to open biopsy of benign lesions require professional counselling and support. Psychological ill effects were not detected by the psychometric test among women who did not proceed to this final investigation. Behavioural changes did suggest a raised awareness or fear of potential cancer among the screened population."
-What percentage of infants with neonatal seizures experienced an unfavorable neurologic outcome in this study?,"Neurologic outcome after electroencephalographically proven neonatal seizures. Infants in whom neonatal seizures were confirmed by randomly recorded ictal electroencephalographic (EEG) tracings were retrospectively examined to determine their global neurologic outcome and the specific frequency of epilepsy, development delay, and cerebral palsy. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to the neurologic outcome. Forty infants with EEG documented seizures of diverse etiologies were studied. The 27 survivors were followed up at a mean of 31 months. The outcome was unfavorable in 70%. The rate of epilepsy was 56%, of developmental delay 67%, and of cerebral palsy 63%. The etiology of seizures was an important factor influencing the outcome. Other clinical factors that showed a significant relationship with global or specific aspects of the neurologic outcome included the age at the onset of seizures, birth weight, and neurologic examination results. The EEG parameters that significantly predicted the neurologic outcome were interictal EEG background, increased seizure frequency, and decreased seizure duration."
-What are the primary acute triggers for sudden cardiac death?,"Sudden cardiac death: management of high-risk patients Sudden cardiac death remains a leading cause of death in the United States, accounting for more than 350,000 deaths each year, and the survival rate of victims remains low. Most survivors face a significant risk for recurrence. The typical substrate is chronic--abnormal myocardium with fibrosis (often from previous myocardial infarction) and left ventricular dysfunction. Acute triggers for sudden cardiac death are primarily electrical, ischemic, metabolic, neurohormonal, and pharmacologic. In most electrocardiographically documented cases of sudden cardiac death, the trigger-substrate interaction appears to result in ventricular tachycardia and fibrillation. After initial resuscitation, survivors need a thorough cardiovascular evaluation, including definition of coronary anatomy, left ventricular function, and wall-motion abnormalities, as well as an electrophysiologic evaluation. An attempt must be made to determine what each survivor's correctable triggers are. Management should address all reversible triggers, such as acute ischemia and electrolyte abnormalities, and should include modifying or correcting the arrhythmogenic substrate. Empiric antiarrhythmic therapy offers no advantage in such modification. Pharmacologic therapy with antiarrhythmic drugs should be guided by an objective therapeutic endpoint, which is best accomplished through the use of programmed ventricular stimulation and serial electrophysiologic studies. Other therapeutic options include surgical suppression of ventricular tachycardia and implantation of a cardioverter defibrillator."
-What is the relationship between serum aminoterminal propeptide of type III procollagen levels and liver fibrosis in psoriasis patients?,"Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis. Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis."
-How did melatonin affect sleep onset and wake times in subjects with delayed sleep phase syndrome?,"Delayed sleep phase syndrome response to melatonin. The actions of melatonin on the sleep-wake cycle were investigated by means of a randomised, double-blind, placebo-controlled trial in 8 subjects with a delayed sleep phase syndrome attending a sleep disorders clinic. In randomised order the subjects received placebo or melatonin 5 mg daily for 4 weeks with a 1 week washout period between the treatments. Drug or placebo was given at 2200 h, 5 h before the mean time of sleep onset determined by pretrial sleep logs. In all 8 subjects sleep onset time (mean advance 82 [range 19-124] min; p less than 0.01) and wake time (117 [10-187] min; p less than 0.01) were significantly earlier during melatonin treatment than during placebo. Mean total sleep time was slightly less on melatonin (8 h 12 min) than on placebo (8 h 46 min). Alertness acrophase calculated from the subjects' ratings of alertness made every 2 h while awake was unaltered. Melatonin may act as a phase-setter for sleep-wake cycles in subjects with a delayed sleep phase syndrome."
-What were the two leading causes of overseas fatalities among US citizen travelers according to the study?,"Overseas fatalities of United States citizen travelers: an analysis of deaths related to international travel. STUDY OBJECTIVE: Studies of travel-related mortality and morbidity have been limited to nonfatal events. Causes of travel-related mortality may differ significantly from morbidity and thus have different prevention strategies. DESIGN: We examined the overseas fatalities of US citizen travelers for the years 1975 and 1984. The death certificates were abstracted; all deaths under age 60 and a 20% sample of deaths 60 and older were examined. SETTING AND TYPE OF PARTICIPANTS: All overseas travel fatalities of US citizens were examined excluding those occurring in Canada. INTERVENTIONS: None. RESULTS: Cardiovascular events (including myocardial infarctions and cerebrovascular accidents) and injuries accounted for 49% and 25% of the overseas deaths of US citizen travelers, respectively. Infectious diseases other than pneumonia accounted for only 1% of the deaths. Eighty percent of injury deaths occurred outside of hospitals. Injury death rates for male travelers were greater than US age-specific death rates. CONCLUSIONS: Greater emphasis on the prevention of fatal events, especially those resulting from injury, must be given by physicians and other individuals and organizations who advise travelers. Further studies are needed to explore the issues of preventable injury deaths, emergency medical services, and overseas travel."
-How did isradipine affect blood pressure control in patients with mild essential hypertension during a 24-hour period?,"Twenty-four-hour blood pressure control with isradipine in mild essential hypertension. The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine."
-What potential risks did the study find when using EMLA cream on wounds?,"Damage to tissue defenses by EMLA cream. EMLA is a new topical agent that safely anesthetizes intact skin. The purpose of this study was to determine if this cream could be safely used for anesthetizing wounds. This investigation evaluated the potential toxicity of EMLA cream in wounds by measuring its effect on host defenses and on the biology of wound repair. In contaminated wounds, EMLA cream elicited an exaggerated inflammatory response that damaged host defenses, inviting the development of infection. As a result of these investigations, we do not recommend the use of EMLA cream in wounds."
-What is a carotid cavernous fistula and how can it develop after minimal facial trauma?,"Carotid cavernous fistula after minimal facial trauma. Report of a case. The carotid cavernous fistula has historically been associated with extensive facial trauma as a result of direct or indirect forces. Most fistulas of traumatic origin develop as a result of a fracture through the base of the skull, which produces a force causing laceration of the internal carotid artery in the region where it approximates the cavernous sinus. We report a case in which apparently minimal head trauma resulted in the development of a carotid cavernous fistula. The rather innocuous presentation of this complication requires particular attention by the caregiver in assessing the patient sustaining maxillofacial trauma."
-What were the mortality rates for ischaemic heart disease and cerebrovascular disease among different ethnic groups in England and Wales during the 1970s and 1980s?,"Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade."
-What were the three protocols used to determine the effect of exercise supplementation on dipyridamole thallium image quality?,"Effect of exercise supplementation on dipyridamole thallium-201 image quality To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone."
-What is the connection between the patient's Creutzfeldt-Jakob disease and the cadaveric dural graft?,Creutzfeldt-Jakob disease in a patient with a cadaveric dural graft. We report a 26-year-old woman with Creutzfeldt-Jakob disease (CJD) who had received cadaveric dural material 33 months before the onset of neurologic symptoms. This is the fourth case in which a dural graft was the putative source of the CJD agent. All four cases had the grafting before changes in the sterilization procedure adopted in 1987 to inactivate the CJD agent.
-What was the main purpose of the retrospective study involving 498 women with 666 breast lesions?,"Mammographic follow-up of nonpalpable low-suspicion breast abnormalities: one versus two views. A retrospective study involving 498 women with a total of 666 breast lesions was undertaken to determine the relative efficacy of one- and two-view mammography in the follow-up evaluation of ""low-suspicion"" abnormal mammographic findings. These abnormalities consisted of well-defined masses (47.1%), well-defined punctate microcalcifications (20.9%), and parenchymal asymmetry (32.0%). Confidence in the adequacy of the single-view follow-up was high in 91% of cases. The addition of the second mammographic view changed the one-view interpretation in approximately 1% of all cases. Two cancers were detected during the initial follow-up period. Both cancers were detected with single-view and standard two-view follow-up examinations, with high confidence. In this controlled retrospective study, the single-view follow-up examination was adequate for follow-up of most low-suspicion mammographic abnormalities. Monitoring by physicians, however, would be necessary to prevent an unacceptable number of patient recalls, which could make the one-view follow-up study impractical to use in some practices."
-"What is the ""two week syndrome"" observed in patients receiving injection treatment for chronic pain?","The ""two week syndrome"" associated with injection treatment for chronic pain--fact or fiction? Many patients attending the pain clinic for regular injections of local anaesthetic state that the pain returned ""two weeks"" ago. This study demonstrates that 85% of these patients have a ""return of pain"" interval which coincides with the proximity of their next clinic appointment."
-What imaging techniques were used to diagnose choledochal cyst and biliary atresia in the neonates?,"Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management."
-How did the cardiac myocytes change in size and shape in rats with aortocaval fistulas at 1 week and 1 month after surgery?,"Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy. The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth."
-What is EXOSURF and how was it used in the clinical trials for treating hyaline membrane disease in neonates?,"Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease. EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial."
-What was the survival rate of patients who received defibrillation during the Heartstart Scotland initiative?,"""Heartstart Scotland""--initial experience of a national scheme for out of hospital defibrillation. OBJECTIVE--To determine the outcome of out of hospital defibrillation in Scotland during the year after the introduction of automated external defibrillators in October 1988. DESIGN--Retrospective analysis of ambulance service reports and hospital records. SETTING--Scottish Ambulance Service and acute receiving hospitals throughout Scotland. MAIN OUTCOME MEASURES--Delay from cardiac arrest to first defibrillator shock; vital state on arrival at hospital accident and emergency department; survival to hospital discharge. RESULTS--During the study period 268 defibrillators were purchased by public subscription and 96% of the 2000 ambulance crew underwent an eight hour training programme in cardiopulmonary resuscitation and defibrillation. A total of 1111 cardiac arrests were recorded, and defibrillation was indicated and undertaken in 602 (54%) patients, mean age 63 (range 14-92) years. A spontaneous pulse was present on arrival at hospital in 180 (30%) of the defibrillated patients, and 75 (12.5%) were subsequently discharged alive. As expected, the likelihood of survival was inversely related to the delay from the onset of cardiac arrest to the time of the first shock and was greater in the case of witnessed arrest. If ventricular fibrillation occurred after the arrival of the ambulance, survival to discharge was 33%. CONCLUSIONS--An effective scheme for out of hospital defibrillation can be introduced rapidly, and with limited training implications and costs, by the use of automated external defibrillators in ambulances."
-"What is the relationship between interleukin-2, interferon-alpha, and colonic ischemia in cancer patients?","Colonic ischemia complicating immunotherapy with interleukin-2 and interferon-alpha. Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI."
-What was the median patient survival time for patients with pancreatic cancer in this study?,"Carcinoma of the pancreas: a personal experience with 100 cases. One hundred patients with pancreatic cancer were evaluated between March 1981 and December 1989. This study showed that 61 were not candidates for definitive surgery because of nonoperability (28 patients) or nonresectability (33 patients). An additional 25 patients had cancers that were unresectable because of metastases (13 patients) or local spread of disease (12 patients) discovered at laparotomy. Fourteen patients had resectable cancers. Ten were treated by total pancreatectomy, three by distal pancreatectomy and one by pancreatoduodenectomy (Whipple). There were two operative mortalities. The median patient survival time was 20.5 months. Two patients survived 5 years. Five patients are alive at 3, 14, 18, and 47 months. Palliative surgical procedures performed in 18 patients included 10 biliary bypasses, 9 gastrojejunostomies, and 6 T-tube placements. This was associated with an operative mortality rate of 11%. The median survival time was 5 months. Other palliative measures included endoscopic placement of biliary and pancreatic stents (47 patients, 2.7% mortality rate), endoluminal radiation therapy, interstitial radiation therapy and external beam radiation therapy. The median survival time of patients so treated was 4.5 months."
-What treatment approach was used to successfully manage Candida endocarditis in the three critically ill infants described in the study?,"Successful medical treatment of presumed Candida endocarditis in critically ill infants. Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants."
-What clinical factors were independently associated with a positive response to esophageal balloon distension?,"Clinical correlates of abnormal sensitivity to intraesophageal balloon distension. Sixty-five patients with esophageal complaints were studied to determine clinical associations with abnormal sensitivity to intraesophageal balloon distension (esophageal sensory dysfunction). Associations were examined in four categories: motility, esophageal symptoms, recent psychological symptoms, and general clinical features. A positive response to balloon distension (pain with less than or equal to 8 ml volume) was found in 29 (45%) of the subjects. This response was associated with specific findings in each category except recent psychological symptoms. A multiple logistic regression analysis indicated that an increased frequency of multipeaked waves on motility testing, presence of dysphagia, and shorter height of the subject each had an independent association with positive response to balloon distension (P less than or equal to 0.05 for each). Further comparison of subjects with sensory dysfunction, motor dysfunction, or both (sensorimotor dysfunction) indicated that subjects with the combined disorder appeared more symptomatic than those with either finding alone. These observations indicate that: (1) esophageal motor and sensory dysfunction are partially associated, but both contribute to the symptomatic state; (2) dysphagia may be representative of sensory dysfunction in some cases; and (3) subject height should be taken into consideration when interpreting balloon distension results."
-How do smoking and oral contraceptive pills potentially contribute to the exacerbation of Crohn's disease?,"Smoking, the oral contraceptive pill, and Crohn's disease. Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease."
-What was the treatment approach and outcome for HIV-associated Kaposi's sarcoma patients using recombinant interferon alpha-2a?,"Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a. Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy."
-How can dual-energy CT help differentiate focal fatty infiltration of the liver from low-density masses?,"Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. Focal (irregular, partial) fatty infiltration of the liver may simulate neoplastic or other hypodense masses on CT. On the basis of previous observations of the phenomenon that differences in X-ray attenuation diminish with increasing energy of X-rays used, we performed a preliminary study to determine if dual-energy CT could be used to discriminate between fatty infiltration and hypodense liver masses. Dual-energy CT at 140 and 80 kVp was performed in 14 patients undergoing liver biopsy and in seven control subjects with presumedly normal liver. Attenuation measurements were taken, and the changes in attenuation between 140 and 80 kVp were calculated. The mean changes in attenuation were 3.5 H for normal liver (n = 7), 2.5 H for hypodense liver masses (n = 6), 13 H for fatty liver (n = 5), 0.3 H for fatty liver combined with hemochromatosis or hemosiderosis (n = 3), and 2 H for the spleen (n = 18). The change in attenuation increased as the fat content in the liver increased. Analysis of variance showed a statistically significant difference (p less than .001) between fatty liver and the other groups. A difference greater than 10 H was unique to fatty infiltration. These results suggest that dual-energy CT may help to differentiate focal fatty infiltration of the liver from low-density neoplastic or other lesions, but only if the iron content of the liver is not increased."
-What specific autoantibodies have been implicated in the pathogenesis of dilated cardiomyopathy (DCM)?,"Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy. Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM."
-What was the purpose of the randomized study involving nifedipine and nitroglycerin in patients undergoing coronary artery bypass grafting?,"Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS]."
-How does isradipine potentially protect the brain from damage in stroke models?,"Prevention of stroke and brain damage with calcium antagonists in animals. In a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery [MCAO]), various 1,4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isradipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addition, also protect the brain from damage engendered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antagonist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isradipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, appears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy."
-What was the relationship between inflammatory cells and metaplasia in asbestos workers?,"The relationship between large airway inflammation and airway metaplasia. To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers."
-What is the main finding of the study regarding the management of gallbladder in elderly patients after endoscopic sphincterotomy for bile duct stones?,"Risks of leaving the gallbladder in situ after endoscopic sphincterotomy for bile duct stones. There is controversy concerning the subsequent clinical course of patients whose gallbladder is left in situ following successful endoscopic removal of stones from their common bile ducts. A total of 191 patients (median age 76 years) were reviewed between 12 and 100 months (mean 38 months) after endoscopic sphincterotomy. Ten patients (5.2 per cent) had symptoms requiring cholecystectomy which was uneventful, nine in the first year. Cholangitis at presentation or failure to fill the gallbladder by endoscopic retrograde cholangiography were not helpful in identifying these patients. Forty-nine (25.6 per cent) patients died during the review period from non-biliary pathology (usually cardiovascular). Elective cholecystectomy is not required in elderly patients with symptomatic bile duct stones if the common bile duct can be cleared of stones after endoscopic sphincterotomy."
-What factors were found to be significantly associated with progression-free interval in the multi-variate analysis of cervical carcinoma patients treated with radiation therapy?,"Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant."
-What diagnostic techniques were used to identify and confirm the intrahepatic arterioportal fistula in this patient?,"Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed."
-What is the significance of the changing appearance of the cephalocele during transvaginal sonographic follow-up between 13-19 weeks of gestation?,"Transvaginal sonographic follow-up on the formation of fetal cephalocele at 13-19 weeks' gestation. An occipital meningocele was detected by transvaginal sonography in a fetus of 13 weeks' gestation. This changed at 14 weeks to a cephalocele, which disappeared at 15-16 weeks and was detected again at 19 weeks. It is possible that sliding backward and forward of the herniated brain tissue caused this sequence of events."
-How do anesthesiologists help prevent respiratory complications during and after surgery?,"Respiratory problems in emergence from anesthesia. In conclusion, anesthesia and mechanical ventilation have major effects on respiratory function, both intraoperatively and postoperatively. Recognition that mechanical ventilation represents a major departure from spontaneous ventilation should enable anesthesiologists to compensate for the increases in dead space ventilation and the propensity for alveolar collapse that accompany low volume mechanical ventilation. The use of postoperative regional analgesic techniques to alleviate respiratory compromise constitutes both current clinical practice and an area of active, ongoing investigation. Gone are the days when the anesthesiologist's responsibility stopped at the recovery room door. Today, anesthesiologists with expertise in postoperative pain management, cardiovascular physiology, and intensive ventilatory care are able to provide patients an improved likelihood of avoiding postoperative respiratory complications."
-How can red blood cell deformability index (DI) be used as an early indicator of infection in trauma patients?,"Red cell deformability is an early indicator of infection. Red blood cells (RBC) have been shown to become less deformable during infection. The RBC deformability index (DI) was measured within 24 hours of admission in 37 patients who had suffered trauma and every 48 to 72 hours thereafter while they were in the surgical intensive care unit to assess whether DI could be used as an early indicator of infection after injury. Infection was defined as a temperature of 101 degrees F or more and a white blood cell count of more than 12,000/cm3 associated with a positive culture. Eighteen patients developed an infection, and 19 patients did not. On day 1, both groups showed a significant decrease in DI, compared to controls (0.33 +/- 0.18 and 0.34 +/- 0.25 for patients with infection and patients with no infection vs 1.52 +/- 0.12 for control volunteers; p less than 0.05). In the group with no infection, the DI improved in 16 of 19 patients after injury; the DI in patients with infection continued to decrease in 17 of 18 patients. The decrease in DI occurred 4 +/- 2 days (range, 2 to 8 days) before the diagnosis of infection. No significant differences were apparent in the absolute white blood cell count between the group with infection and the group with no infection at any time after injury. Differences in maximal temperature were noted on day 3 and beyond; however, 30% of patients with no infection had a temperature of more than 101 degrees F for 7 days. These data show that trauma results in a significant decrease in RBC deformability and that serial changes in DI appeared to predict which patients would develop an infection and which patients would recover uneventfully. RBC deformability may be helpful in early detection of infection in patients who have suffered trauma."
-What was the main finding of the study regarding the sensitivity of the gastric mucosa in patients with nonulcer dyspepsia?,"Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents."
-What was the mean maximum temperature during an infection in the nursing home residents studied?,"Fever response in elderly nursing home residents: are the older truly colder? OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a ""blunted"" fever response (Tmax less than 101 degrees F). Of the 25 ""blunted"" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections."
-What percentage of primary neurogenous tumors arise from peripheral nerves in the head and neck region?,"Primary tumors of the facial (extracranial) nerve. Nearly 25% of all primary neurogenous tumors arise from peripheral nerves in the head and neck. The extracranial parts of the facial nerve, however, rank low as potential sites. Their tumors nonetheless pose diagnostic and management problems. In the intraparotid location the neurogenous tumors most often present as mass lesions, accompanied, in one third of patients, by various degrees of facial weakness. With the exception of a peculiar predilection of childhood plexiform neurofibromas to afflict the facial nerve, the majority of the tumors are neurilemomas. Recurrences are unusual after surgical removal of either neurilemomas or neurofibromas. The rare facial nerve sarcoma is a high-grade malignancy."
-What diagnostic challenges are associated with mucinous pancreatic tumors according to the ERCP findings?,"Mucinous pancreatic tumors: ERCP findings Mucin-producing tumors of the pancreas are rare and difficult to diagnose neoplasms. To further characterize the nature of these lesions, four such cases are described here in which the diagnosis was suspected at endoscopic retrograde cholangiopancreatography by the presence of ampullary or intraductal mucus. In one patient, pancreatoscopy directly visualized the tumor. Ultrasound and computed tomography failed to suggest the presence of a neoplasm in the majority of these cases, but endoscopic ultrasound was performed in one and correctly identified the multi-cystic tumor. A high incidence of acute pancreatitis was seen in these cases and was felt to be secondary to intermittent ductal obstruction by mucus. The characteristic appearance of intra-ductal mucus provides an important clue to the presence of this type of pancreatic neoplasia."
-What was the main purpose of the study on hepatitis C virus antibodies in blood donors?,"Antibody to hepatitis C virus and liver disease in volunteer blood donors. OBJECTIVE: To evaluate the specificity of antibodies to hepatitis C virus (anti-HCV) and their relation to liver disease in blood donors. DESIGN: Case series of consecutive blood donors found positive for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Patients were evaluated for antibody specificity using a recombinant immunoblotting assay (RIBA) and were evaluated for biochemical evidence of liver disease. Patients showing increased alanine aminotransferase (ALT) levels had a liver biopsy. SETTING: University hospital. PARTICIPANTS: Fifty consecutive blood donors found to be anti-HCV positive on both an initial and repeat ELISA. Inclusion criteria were as follows: an absence of hepatitis B surface antigens and non-organ-specific autoantibodies; a daily alcohol intake of less than 50 g; no history of recent hepatotoxic drug use; and normal serum levels of alpha 1 antitrypsin, ceruloplasmin, and copper. MAIN RESULTS: Anti-HCV positivity was confirmed by RIBA in only 13 of 50 donors (26%) who had positive ELISA results. These 13 donors had an elevated ALT level and histologic evidence of chronic hepatitis, which was active in 8 patients (62%) and had already produced cirrhosis in 2 patients (15%). In contrast, the 17 donors with an intermediate RIBA pattern had only mild and often nonspecific histologic liver abnormalities. The 20 patients with a negative RIBA result had normal ALT levels. CONCLUSION: In blood donors, the anti-HCV RIBA is not only more specific than the anti-HCV ELISA, but is also useful in identifying patients who have an underlying chronic liver disease."
-How does gadopentetate dimeglumine-enhanced magnetic resonance imaging improve the detection and staging of uterine carcinomas?,"Carcinoma of the uterus: use of gadopentetate dimeglumine in MR imaging. This prospective study assessed the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging in the detection and staging of carcinomas of the endometrium and cervix. Surgical-pathologic findings were used as the standard of reference. In the evaluation of endometrial carcinoma, contrast-enhanced imaging improved tumor detection and differentiation between viable tumor and retained debris. Use of contrast material significantly improved the staging accuracy. The ability to assess the depth of myometrial invasion was also improved. In the evaluation of cervical carcinoma, assessment of tumor location and size did not improve following contrast enhancement. Use of gadopentetate dimeglumine resulted in overestimation of stromal, parametrial, vaginal, and/or bladder wall invasion in eight patients. However, evaluation of intratumoral architecture and large lesions was easier with contrast-enhanced imaging. When only stage II and higher disease was analyzed, use of contrast material improved the evaluation of disease extent. The authors conclude that gadolinium enhancement adds to the accuracy of evaluation of endometrial carcinoma but is useful in only advanced cases of cervical carcinoma."
-What rare combination of tumors is described in this case report?,Osteogenic sarcoma arising adjacent to a long-standing ameloblastoma. A case report. Ameloblastoma is an uncommon odontogenic tumor usually occurring in the mandible. Rarely do other primary tumors occur with or arise from ameloblastoma. We describe a patient with simultaneous osteogenic sarcoma of the maxilla and recurrent ameloblastoma.
-What is the relationship between radiation therapy and the development of monomelic amyotrophy in the described cases?,"Postradiation lower motor neuron syndrome presenting as monomelic amyotrophy. Monomelic amyotrophy developed 16 months, nine and 12 years after irradiation of the lumbosacral spinal cord for seminoma in one patient and for Hodgkin's disease in two others. In two patients, involvement was clinically limited to one leg, with a subacute course followed by plateau in the first case and with progressive worsening in the second one. In the third patient, the course was progressive with involvement of the other lower limb occurring five years later. From clinical and electrophysiological data, it seems probable that the disease process was a result of a selective injury to the lower motor neuron in the lower spinal cord."
-How can transesophageal echocardiography help in diagnosing and managing cardiac tamponade with a patent foramen ovale?,"Right-to-left shunt across a patent foramen ovale caused by cardiac tamponade: diagnosis by transesophageal echocardiography. Cardiac tamponade can manifest as profound hypoxemia from intracardiac shunting across a patent foramen ovale. As a consequence, pulmonary embolus can be erroneously diagnosed. As demonstrated in the case described herein, transesophageal echocardiography can be useful in determining the correct diagnosis, especially if transthoracic echocardiography is technically limited. In our patient, the findings on transesophageal echocardiography also helped determine the appropriate treatment. The relative inaccessibility of the pericardial effusion to needle drainage prompted open surgical drainage."
-What was the primary finding regarding EMG activity in patients with chronic tension-type headache compared to healthy volunteers?,"EMG activity in pericranial muscles during postural variation and mental activity in healthy volunteers and patients with chronic tension type headache. EMG activity was recorded over frontalis, temporalis and trapezius muscles in a supine position, a standing position and during a mental task in 32 female patients suffering from chronic tension-type headache and in 20 healthy volunteers. Measurements in patients were made before and after biofeedback therapy. All EMG levels were on average significantly higher in patients than in controls. 62.5% of patients had at least one abnormal EMG level, but only 34% were beyond the normal range, if 1 muscle and 1 recording condition was considered. EMG levels were not correlated with headache severity, anxiety or response to biofeedback treatment. It is therefore suggested that pericranial EMG activity is not pathogenetic in chronic tension type headache, but merely one of several pathophysiologic changes, that are produced by a central dysfunction."
-What is the relationship between HLA B27 and the incidence of hypopyon in anterior uveitis?,"Anterior uveitis and hypopyon. We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective-tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis."
-What is the relationship between eosinophilic fasciitis and cutaneous T-cell lymphoma in this case study?,"Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms? Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms."
-What was the rate of adhesion formation after ovarian electrocauterization in the selective and unselective groups of patients with polycystic ovarian syndrome?,"Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. The rate of adhesion formation after ovarian electrocauterization has been described in two selective and unselective groups of patients with PCOS. The rate of this complication in the selective group was 0 from 16 ovaries and in the unselective group (5/25). However, the rate of major adnexal adhesion in the unselective group was 1 from 25 ovaries."
-How did the diagnosis of Asperger's syndrome impact the understanding of the children's emotional needs and their relationships with their parents?,"Asperger's syndrome: who is being abused? Six case histories of children referred and admitted to a psychiatric inpatient unit at a tertiary referral centre because of concerns about poor functioning and possible emotional abuse are presented. On initial assessment the children appeared to be well functioning and the impression was confirmed that their emotional needs were not being met by their parents. After detailed inpatient appraisal the diagnosis of Asperger's syndrome was made in all six cases, exemplified mainly by a formal concrete way of thinking and an inability to identify and understand human emotions and relationships. The impact of the diagnosis on the parents and their consequent relationships with their child and their willingness to work with professionals is discussed."
-How does the proportion of large molecular form of HBeAg relate to the severity of liver damage in chronic hepatitis B?,"Large molecular form of serum HBeAg in chronic hepatitis B virus infection: relation to liver cell damage. We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% +/- 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% +/- 27.8% in 32 patients with chronic persistent hepatitis and 65.6% +/- 23.3% in 21 patients with chronic active hepatitis (p less than 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B."
-"What neurological condition did the 39-year-old AIDS patient develop, and what was the underlying cause of his myelopathy?","Ischaemic myelopathy secondary to disseminated intravascular coagulation in AIDS. A 39-year-old patient with AIDS presented with a rapidly progressive myelopathy with a partial Brown-Sequard syndrome. He died, 9 weeks after onset of the first neurological signs, from diffuse encephalopathy. Neuropathological examination revealed multiple, usually small, frequently haemorrhagic, infarcts or various ages and numerous fibrin thrombi in medium and small penetrating vessels and capillaries of the brain and spinal cord, characteristic of disseminated intravascular coagulation. There were no inflammatory changes. Immunohistochemical studies for human immunodeficiency virus, cytomegalovirus, varicella zoster virus, herpes simplex virus type 1 and type 2 were negative. Ischaemic spinal cord lesions due to disseminated intravascular coagulation may represent an unusual cause of focal, non-inflammatory, non-tumoral, myelopathic syndrome in AIDS."
-How do mink cell focus-forming (MCF) viruses affect the interleukin-2 (IL-2) dependence of a rat T-cell lymphoma line?,"Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line. The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor."
-What are the key characteristics of pulmonary angiitis and granulomatosis syndromes in terms of clinical presentation and radiologic features?,"Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions."
-What is Acanthoma fissuratum and what is its primary cause according to the given context?,Acanthoma fissuratum. Acanthoma fissuratum secondary to the use of spectacles is a rare clinical finding associated with an ill-fitting frame. An interesting case is presented to highlight such a problem. Surgical excision of such lesions is recommended with advice to the patient regarding the suitable fitting of spectacles.
-What percentage of patients in the study had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex?,"Electrophysiologic and anatomic characteristics of ventricular tachycardia induced at the right ventricular outflow tract but not at the apex. The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex."
-How does sphincterotomy prevent gallstone formation in prairie dogs fed a high-cholesterol diet?,"Effect of bile diversion and sphincterotomy on gallbladder muscle contractility and gallstone formation. Feeding prairie dogs a diet rich in cholesterol induces gallstone formation that is preceded by a sustained decrease in gallbladder smooth muscle contractility. Sphincterotomy is known to prevent gallstone formation in cholesterol-fed prairie dogs. Experiments were designed to determine whether the effect of sphincterotomy is a consequence of hepatic bile diversion, and whether bile diversion prevents the altered contractility. Following sham operation, surgical biliary enteric bypass, or sphincterotomy, prairie dogs were fed a high-cholesterol or a regular diet. Gallbladder muscle contractility and the presence of crystals and stones were determined. In sham-operated animals, the cholesterol diet induced a decrease in gallbladder muscle contractility and caused the formation of cholesterol gallstones. In animals with bile diversion and sphincterotomy, the effects of cholesterol feeding were reduced or prevented. Thus, these procedures may prevent stone formation by preventing a reduction in gallbladder contractility. Contractility was depressed in animals with bile diversion fed a regular diet, compared with animals with a sham operation fed a regular diet. The mechanism for this depression may differ from that induced by the cholesterol diet. Diversion, and perhaps sphincterotomy, impairs gallbladder filling. Thus, gallbladder muscle is not stretched and does not contract against a load. This could result in a ""disuse atrophy."" If the results from our study apply to humans, sphincterotomy may reduce stone formation by preventing the effects of lithogenic bile on gallbladder muscle contractility and by enhancing the ability of the muscle to empty the lithogenic bile."
-What was the prevalence of hepatitis C antibodies among patients with alcoholic liver disease in this study?,"Antibody to hepatitis C is common among patients with alcoholic liver disease with and without risk factors. Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity."
-How did site-directed mutagenesis of the region around Cys-241 in human C2 affect its hemolytic activity?,"Site-directed mutagenesis of the region around Cys-241 of complement component C2. Evidence for a C4b binding site. We probed the functional significance of the region around Cys-241 in human C2 by testing the hemolytic activity of a series of mutant rC2. Mutant C2 cDNA were constructed by oligonucleotide-directed site-specific mutagenesis and expressed transiently in COS cells. Wild-type rC2 had threefold higher specific hemolytic activity than native serum C2. Substitution of Gly, Ala, or Ser for Cys-241 resulted in a slightly, but significantly, increased activity. In addition, I2 had no effect on the activity of these mutant C2. Substitution of Lys for Gln-243 increased the hemolytic activity by more than two-fold. Increased activity in all cases was due to slower decay rates of the C3 convertase. Finally, substitution of Leu or Ala for Asp-240 or Ser-244, respectively, resulted in more than 100-fold decrease of hemolytic activity. The results suggest that residues 240 to 244 of human C2 represent an important structural determinant of the C4b binding site of C2a. They also confirm that Cys-241 is the residue responsible for the increased activity of C2 reacted with I2."
-What is the main hypothesis tested in this study about Wolfram syndrome and psychiatric disorders?,"Psychiatric disorders in 36 families with Wolfram syndrome. OBJECTIVE: The purpose of this study was to test the hypothesis that heterozygous carriers of the gene for the Wolfram syndrome, who constitute about 1% of the population, are predisposed to significant psychiatric illness. The Wolfram syndrome is an autosomal recessive neurodegenerative syndrome in which 25% of the individuals who are homozygous for the condition have severe psychiatric symptoms that lead to suicide attempts or psychiatric hospitalizations. METHOD: The authors collected questionnaires, death certificates, and hospital records for blood relatives and their spouses in 36 families of individuals with the Wolfram syndrome and compared the proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness to the proportion of spouses with the same manifestations. RESULTS: The proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness significantly exceeded the proportion of spouses with the same manifestations. CONCLUSIONS: Since heterozygous carriers of the gene for the Wolfram syndrome are 50-fold more common among the blood relatives than among the spouses, the larger proportion among blood relatives is evidence that heterozygous carriers of the gene for the Wolfram syndrome are predisposed to significant psychiatric illness."
-How does sonography compare to chest radiography and CT in monitoring the therapeutic response of mediastinal lymphomas?,"Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT. The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas."
-"How does pyruvate kinase activity differ between normal fibrous tissue, benign proliferations, and malignant tumors?","Pyruvate kinase activity and isozyme composition in normal fibrous tissue and fibroblastic proliferations. Pyruvate kinase (PK) was studied in 57 fibroblastic and fibrohistiocytic proliferations and normal fibrous tissue (n = 10). The specific activity was significantly increased in malignant tumors (1.67 +/- 0.25) compared with normal tissue (0.26 +/- 0.04; P less than 0.001) and benign proliferations (0.52 +/- 0.05; P less than 0.005). Although an overlap exists between aggressive fibromatosis and the benign group, high values of PK activity are indicative of Grade 2 and 3 malignancy. Significant shifts in isozyme pattern, favoring the expression of K-type subunits were found in tumors with a metastasizing potential and aggressive fibromatosis. These changes in the isozyme pattern of PK in aggressive fibromatosis may act as another argument to place them in the category of malignant fibroblastic tumors."
-What method did the researchers use to detect mixed hematopoietic chimerism after allogeneic bone marrow transplantation?,"Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction. The influence of mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation remains unknown. Increasingly sensitive detection methods have shown that MC occurs frequently. We report a highly sensitive novel method to assess MC based on the polymerase chain reaction (PCR). Simple dinucleotide repeat sequences called microsatellites have been found to vary in their repeat number between individuals. We use this variation to type donor-recipient pairs following allogeneic BMT. A panel of seven microsatellites was used to distinguish between donor and recipient cells of 32 transplants. Informative microsatellites were subsequently used to assess MC after BMT in this group of patients. Seventeen of the 32 transplants involved a donor of opposite sex; hence, cytogenetics and Y chromosome-specific PCR were also used as an index of chimerism in these patients. MC was detected in bone marrow aspirates and peripheral blood in 18 of 32 patients (56%) by PCR. In several cases, only stored slide material was available for analysis but PCR of microsatellites or Y chromosomal material could be used successfully to assess the origin of cells in this archival material. Cytogenetic analysis was possible in 17 patients and MC was detected in three patients. Twelve patients received T-cell-depleted marrow and showed a high incidence of MC as revealed by PCR (greater than 80%). Twenty patients received unmanipulated marrow, and while the incidence of MC was lower (44%), this was a high percentage when compared with other studies. Once MC was detected, the percentages of recipient cells tended to increase. However, in patients exhibiting MC who subsequently relapsed, this increase was relatively sudden. The overall level of recipient cells in the group of MC patients who subsequently relapsed was higher than in those who exhibited stable MC. Thus, while the occurrence of MC was not indicative of a poor prognosis per se, sudden increases in the proportions of recipient cells may be a prelude to graft rejection or relapse."
-What was the impact of omentectomy on postoperative sepsis in patients undergoing proctocolectomy and ileoanal anastomosis?,"Let sleeping dogs lie: role of the omentum in the ileal pouch-anal anastomosis procedure. A surgical aphorism has long held that the omentum is the ""watchdog of the abdomen."" However, detractors believe that leaving the omentum behind after colectomy precipitates later small bowel obstruction. A retrospective comparison was made between a group of 406 patients (Group I) having omentectomy with proctocolectomy and ileoanal anastomosis and a group of 239 patients (Group II) having a similar procedure without omentectomy. Follow-up in this series of 645 patients was 4.3 +/- 2.1 years (mean +/- SEM). No difference was present in the rate of partial small bowel obstruction or complete small bowel obstruction between Group I patients (32 percent partial, 12 percent complete) and Group II patients (29 percent partial, 12 percent complete; P greater than 0.1). However, a better outcome with regard to postoperative sepsis and sepsis requiring operation was apparent in Group II patients retaining the omentum (4 percent and 3 percent, respectively) than in Group I patients (10 percent and 8 percent, respectively), in whom the omentum was removed (P less than 0.01). As this experience would support, we urge surgeons to ""let sleeping dogs lie"" and, when possible, retain the omentum when performing colectomy or proctocolectomy."
-What was the effectiveness of fluconazole in treating hepatosplenic candidiasis in patients who did not respond to previous antifungal treatments?,"Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy."
-How did colchicine affect renal function and fibrosis in a rabbit model of anti-glomerular basement membrane disease?,"Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit. A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis."
-What age groups were most affected by diarrheal deaths in the United States between 1979 and 1987?,"Diarrheal deaths in the United States, 1979 through 1987. A special problem for the elderly. OBJECTIVE.--Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal death among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States. DESIGN/SETTING/PARTICIPANTS.--We reviewed national mortality data complied by the National Center for Health Statistics, Hyattsville, Md, which consists of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a ""diarrheal death"" and included in the analysis. RESULTS.--We found that 28,538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children (younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin. CONCLUSION.--For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population."
-What are the acute and chronic hemodynamic effects of xamoterol in patients with mild to moderate congestive heart failure?,"Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure. Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment."
-What is the significance of using interphase cytogenetics with in situ hybridization in studying trisomy 12 in chronic lymphocytic leukemia?,"Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study. Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cells of conventional cytogenetic preparations from eight patients and on morphologically and immunologically classified cells of cytospin preparations from seven patients. The results show that trisomy 12 is more common than assumed on the basis of karyotype analysis of metaphase chromosomes: 2 of 13 patients with a normal karyotype in G-banding analysis were shown to have trisomy 12 by interphase cytogenetics. Immunophenotyping of the cells of one patient showed that the trisomy was restricted to cells with Ig light chain clonality. For the evaluation of the prognostic, therapeutic, and biologic significance of trisomy 12, in situ hybridization should be used in parallel with karyotype analysis because it allows the study of all cell populations of both interphase and mitotic cells, whether neoplastic or normal."
-What was the primary aim of the 10-year prospective screening study on multiple endocrine neoplasia type 1 (MEN 1)?,"Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified."
-What is the relationship between neurosurgical intervention and the risk of cerebral hemorrhage in patients with cerebral amyloid angiopathy?,"Surgical risk of hemorrhage in cerebral amyloid angiopathy. Cerebral amyloid angiopathy is increasingly recognized as a cause of lobar cerebral hemorrhage in normotensive elderly individuals. Isolated reports have suggested that neurosurgical intervention entails a high risk of precipitated hemorrhage. We identified 16 pathologically confirmed cases of cerebral amyloid angiopathy. Fourteen of these patients presented with lobar cerebral hemorrhage. Fifteen neurosurgical procedures in eight patients included eight clot evacuations, three abscess drainage procedures, two ventriculoperitoneal shunts, one biopsy, and one lobectomy. Recurrent postoperative cerebral hemorrhage was seen in four patients at 2 days, 9 days, 6 weeks, and 10 months, but surgery was thought to have precipitated the cerebral hemorrhage in only one patient. Recurrent cerebral hemorrhage also was seen in two of the eight nonoperated cases. Recurrent cerebral hemorrhage is characteristic of cerebral amyloid angiopathy, but we conclude that neurosurgical intervention, particularly evacuation of hematomas, is not associated with major risk of precipitated hemorrhage."
-What is the primary purpose of transvenous endomyocardial biopsy in cardiac transplant recipients?,"Ventricular fibrillation complicating endomyocardial biopsy of a cardiac allograft. Transvenous endomyocardial biopsy remains the most useful diagnostic aid in assessing rejection in the transplanted heart. Although invasive, the complications associated with endomyocardial biopsy are few, and the procedure is generally regarded as safe. We report a case of apparent ventricular fibrillation complicating transvenous endomyocardial biopsy. Histologic section revealed evidence of moderate acute rejection. This case represents the first report of a life threatening ventricular dysrhythmia following routine endomyocardial biopsy in a cardiac transplant recipient."
-What percentage of patients had an excellent result after catheter-less suprapubic cystolithotomy in children?,"Catheter-less suprapubic cystolithotomy in children. Bladder stones in children are common in developing countries and the procedure of choice for their removal is suprapubic cystolithotomy. It is standard practice to drain the bladder for a few days post-operatively to prevent urinary leakage. We have observed that, if the bladder is closed meticulously in 2 layers, bladder drainage by means of a catheter is not required. We have analysed 86 children treated by suprapubic cystolithotomy without a catheter. Size of the stones and intra-operative findings were noted and it was found that 85% of the patients had an excellent result; 10% had a satisfactory result and 4.7% were unsatisfactory. The advantages of the procedure and selection of the patients are discussed."
-What evidence suggests a potential link between HTLV-I and mycosis fungoides in the study?,"Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides."
-How does the pre-treatment PSA level correlate with treatment outcomes in prostate cancer patients receiving primary radiation therapy?,"Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy. The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures. Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence."
-What were the effects of DuP 753 and captopril on left ventricular end-diastolic pressure and volume in rats with heart failure?,"Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction."
-What are the major risk factors for coronary heart disease in the elderly?,"Preventive maintenance of the aging heart. Coronary heart disease (CHD) is the major cause of mortality in the elderly. Important risk factors include hypercholesterolemia, systolic and diastolic hypertension, cigarette smoking, hyperglycemia, and obesity. Elderly patients with existing CHD should be treated aggressively to control these risk factors, along with other medical therapies to treat myocardial ischemia. For elderly patients without recognized CHD, however, a more conservative approach is recommended and includes behavioral interventions when appropriate and pharmacologic therapy for higher risk patients with persistent, uncontrolled risk factors."
-"How many American women are expected to be affected by ovarian cancer this year, and what is the estimated mortality rate?","Screening in ovarian cancer. Ovarian cancer will affect 20,000 American women this year and some 13,500 will die of the disease. Most patients will have stage III or IV disease at the time of diagnosis. Because ovarian cancer may be initially without symptoms, attempts have been made to develop screening tests that would lead to an early diagnosis. Two tests, serum CA 125 and pelvic ultrasonography, have been suggested by some to be accurate enough to be included in yearly screening for ovarian cancer. Although further testing of these techniques is encouraged, data to date do not justify yearly screening with CA 125 or pelvic ultrasonography in all women."
-What factors were associated with less favorable crude survival in patients undergoing hepatic resection for colorectal secondaries?,"Indicators of prognosis after hepatic resection for colorectal secondaries. From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding ""high risk"" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control."
-What was the effectiveness of palliative radiation therapy in treating epidural compression caused by metastatic malignant melanoma?,"The effect of palliative radiation therapy on epidural compression due to metastatic malignant melanoma. The efficacy of palliative radiation therapy in the treatment of spinal cord and cauda equina compression due to metastatic malignant melanoma was evaluated in 38 sites in 35 patients treated between 1970 and 1990. All patients had radiographic documentation of epidural compression. The median dose of radiation therapy was 2850 cGy (range, 500 to 4000 cGy), with daily fractions ranging from 200 to 800 cGy. Twenty-eight sites in 26 patients were evaluable 1 month after completion of radiation therapy, and symptoms responded completely in 11 of 28 (39%) sites. Fourteen sites (46%) showed a partial response of symptoms. Response lasting until death was documented in 21 of 26 patients (81%). Patients receiving a total dose of 3000 cGy or greater were more likely to achieve a complete response than those receiving less than 3000 cGy (62% versus 20%) by univariate (P = 0.025) and multivariate (P = 0.048) analyses. A treatment program of radiation therapy and corticosteroids is effective in palliating the symptoms of epidural compression due to metastatic malignant melanoma. It is recommended to deliver an accelerated course of radiation therapy to a dose of 3000 cGy or greater without exceeding spinal cord tolerance (e.g., 3000 cGy in ten fractions at 300 cGy per fraction)."
-"What behavioral modification technique was used to help a patient with adipsia, diabetes insipidus, and memory impairment achieve independent drinking and be discharged from the hospital?","Management of adipsia by a behavioural modification technique. Adipsia combined with diabetes insipidus after hypothalamic damage may produce major difficulties in clinical management. If there is an associated memory impairment it may be impossible to teach self-regulation of fluid balance, necessitating long-term hospital supervision. The successful use of a behaviour modification technique to achieve independent drinking and allow discharge from hospital into the community is described in a patient with adipsia, diabetes insipidus and memory impairment resulting from the removal of a craniopharyngioma."
-What was the primary objective of the study involving thermal ablation of the gallbladder in dogs?,"Thermal ablation of the gallbladder. Gallbladder ablation by means of injection of hot contrast medium was attempted in 13 dogs. Room temperature contrast medium was injected into the gallbladders of two additional dogs (controls). After midline laparotomy was performed to expose the gallbladder, temperature probes were placed in the liver adjacent to the gallbladder, and on the surface and in the lumen of the gallbladder. A 7-F catheter with multiple side holes was placed into the gallbladder. The cystic duct was clamped during the procedure. After injection of boiling contrast medium, the mean temperature in the gallbladder lumen was 80 degrees C; in the adjacent liver, 43.5 degrees C; and on the gallbladder surface, 45.8 degrees C. After the procedure, the cystic duct was unclamped, temperature probes and catheter were removed, and the laparotomy was closed in standard fashion. In the hot contrast medium group, one dog each was sacrificed at 2, 4, 8, and 12 weeks, and at 6 months. Six animals were sacrificed at 1 year. The gallbladder was completely ablated in 11 of 13 animals in the hot contrast medium group. One dog was sacrificed at 8 days because of bile leakage, and another was sacrificed at 17 days because of gallbladder rupture. The two control animals were sacrificed at 12 and 13 weeks, and their gallbladders were normal at that time."
-What were the key predictors of breast cancer screening among women aged 40 and older in the Rhode Island study?,"A study guided by the Health Belief Model of the predictors of breast cancer screening of women ages 40 and older. In late 1987, a total of 852 Rhode Island women ages 40 and older were interviewed by telephone (78 percent response rate) to measure their use of breast cancer screening and to investigate potential predictors of use. Predictors included the women's socioeconomic status, use of medical care, a provider's reported recommendations for screening, and the women's health beliefs about breast cancer and mammography. The Health Belief Model guided the construction of the interview questions and data analysis. Logistic regression was used to identify leading independent predictors of breast cancer screening according to contemporary recommendations: reporting that a medical provider had ever recommended a screening mammogram (odds ratio [OR] = 18.77), having received gynecological care in the previous year (OR = 4.92), having a regular source of gynecological care (OR = 2.63), having ever had a diagnostic mammogram (OR = 2.32), and perceiving mammography as safe enough to have annually (OR = 1.93). The findings suggest that programs intended to increase the use of breast cancer screening should include ""inreach"" and ""outreach"" elements; inreach to patients with established patient-provider relationships, by assuring that physicians recommend screening to all eligible patients, and outreach to all eligible women, by helping them overcome barriers to effective primary care, and by promoting mammography, emphasizing its effectiveness and safety. The findings also suggest that socioeconomically disadvantaged women, who are less likely to be screened than other women, should become special targets of inreach and outreach interventions."
-What was the effectiveness of percutaneous drainage for traumatic pancreatic pseudocysts in children according to this study?,"Percutaneous drainage of traumatic pancreatic pseudocysts in children. To determine the effectiveness of percutaneous drainage of traumatic pancreatic pseudocysts, we reviewed the courses of 13 children. Six pseudocysts resolved on complete bowel rest and total parenteral nutrition. Seven required further therapy. Two pseudocysts were treated operatively; five were drained percutaneously with fluoroscopic guidance. These five ranged from 5 to 15 cm in diameter and were present for 10 to 42 days (mean, 26 days). In all cases, the cyst fluid was clear, had an amylase level of greater than 40,000 IU/L, and grew no organisms. The pigtail catheters left in place in four of the five children were removed when drainage stopped. Patients were followed by ultrasound while still in the hospital and 1 month after discharge. There were no complications nor any pseudocyst recurrence. Percutaneous drainage of traumatic pancreatic pseudocysts in children is an effective alternative to the standard operative therapy of pseudocystenteric anastomosis."
-What was the efficacy of continuous intravenous diltiazem infusion in controlling heart rate during atrial fibrillation and atrial flutter?,"A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem. Of the 47 patients, 44 responded to the bolus injection and were randomized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem (10 to 15 mg/h) (23 patients) or placebo (21 patients) for up to 24 h. Seventeen (74%) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h (p less than 0.001). Over 24 h, patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion (p less than 0.001). Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion. The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83% (34 of 41). Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients, those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg. However, intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter. No significant untoward effects were noted."
-What are histamine H2-receptor antagonists and how do they work to reduce gastric acid secretion?,"Histamine H2-receptor antagonists. In summary, histamine initiates acid secretion by stimulating the H2 subtype histamine receptor on parietal cells. Cimetidine, rantidine, famotidine, and nizantidine are histamine H2-receptor antagonists that block this action of histamine, reducing gastric acid output and concentration under both basal and stimulated conditions. These agents are used for treatment and prevention of peptic and stress ulcers as well as for hypersecretory states. Because of their effectiveness and low incidence of side effects, H2-antagonists have largely replaced more traditional antiulcer regimens."
-"What percentage of patients with parenchymal brain hemorrhage experience seizures, and in what stages do these seizures typically occur?","Seizures caused by nontraumatic parenchymal brain hemorrhages. Seizures occurred in 15% of patients with parenchymal brain hemorrhage (early in 12% and delayed in 3%). Seizures were most frequent with lobar hemorrhages and uncommon with deep subcortical hemorrhages. Lobar hemorrhages in the frontal, parietal, or temporal region were more commonly associated with seizures, whereas occipital hemorrhages were not. Seizures were most common if the hemorrhage was due to an aneurysm, angioma, or neoplasm and less common if hypertensive or spontaneous. If the patient had recurrent seizures or developed delayed seizures, CT showed that the hemorrhage evolved to a hypodense appearance; if the seizure did not recur, CT showed that the hemorrhage evolved to an isodense appearance."
-What diagnostic technique was found to be more sensitive in identifying patent ductus arteriosus in an infant with atrioventricular septal defect?,Patent ductus arteriosus in an infant with atrioventricular septal defect and pulmonary hypertension: diagnosis by transesophageal color flow echocardiography. An infant with complete atrioventricular septal defect (atrioventricular canal) was examined by standard transthoracic two-dimensional pulsed Doppler and color Doppler echocardiography. No evidence of ductus arteriosus was present. Preoperative transesophageal echocardiography identified a patent ductus: the left-to-right shunt seen by color Doppler echocardiography was enhanced by pharmacologic maneuvers aimed at decreasing pulmonary vascular resistance and increasing systemic vascular resistance. Transesophageal echocardiography was found to be more sensitive than transthoracic echocardiography even in a small infant.
-How did the study use ADL dependencies to determine long-term care eligibility for individuals with dementia in the Oregon Medicaid program?,"Using ADLs to establish eligibility for long-term care among the cognitively impaired. Using a database from the Oregon Medicaid program, we examined the differences in the potential insurance coverage of demented persons by using different formulations of ADL (activities of daily living) dependencies in which the definition of dependency did or did not include the need for supervision. For those with clear dementia, 81-88% of the persons with significant behavioral problems were correctly identified when a cut score of three or more ADLs was used; this percentage was even higher for two or more ADLs. This approach was not as effective in correctly discriminating those who had no behavioral problems."
-What neurological and musculoskeletal complications were observed in a 75-year-old woman with untreated primary hypothyroidism?,"Neuropathy, myopathy and destructive arthropathy in primary hypothyroidism. A 75-year-old woman with untreated primary hypothyroidism was found with peripheral neuropathy (including carpal tunnel syndrome), severe myopathy (high levels of creatine phosphokinase) and destructive arthropathy, affecting fingers, toes and the left knee. Radiographs of her knee showed destructive lesions of the tibial plateau similar to a pathologic compression fracture, while the joints of the fingers and toes showed all signs of severe erosive osteoarthritis (OA), radiographically documented over a period of 7 years. It is suggested that hypothyroidism is causally related to the development of erosive OA."
-What evidence suggests an autoimmune mechanism in the patient's neuromyotonia?,"Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome). Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases."
-What was the most common symptom among patients with lower esophageal mucosal rings in this study?,"Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring."
-What rare ictal phenomenon was investigated in two patients with epilepsy?,"Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions."
-What are the most common CT findings in patients with malignant pleural mesothelioma?,"Malignant pleural mesothelioma: CT manifestations in 50 cases. Malignant pleural mesothelioma, a rare and usually fatal neoplasm that is associated with asbestos exposure, is being encountered with increasing frequency. Pretreatment CT findings from 50 patients with malignant pleural mesothelioma are illustrated. Pleural thickening was found in 46 (92%) of the 50 patients, thickening of the pleural surfaces of the interlobar fissures in 43 (86%), pleural calcifications in 10 (20%), and pleural effusions in 37 (74%). The volume of the involved hemithorax varied appreciably. Contractions of the involved hemithorax was noted in 21 (42%) of 50 patients and contralateral mediastinal shift in seven (14%). Disease beyond the parietal pleura was found in the chest wall (nine patients), mediastinum, lymph nodes, and diaphragm."
-What was the clinical presentation and treatment of the 22-year-old patient with a prostatic mass?,"Pseudosarcomatous fibromyxoid tumor of the prostate. A case report with immunohistochemical, electron microscopic, and DNA flow cytometric analysis. A 22-year-old man presented with symptoms of urinary obstruction and was found to have a 5-cm mass protruding from the left side of the prostate into the prostatic urethra. The lesion was partially removed by transurethral resection (TURP). The patient's symptoms recurred, so he required another TURP four months later; at latest follow-up (four years later), there waas no evidence of disease. Light microscopy revealed a myxoid lesion characterized by an atypical fibroblastic proliferation associated with a prominent inflammatory component and granulation tissue-type vasculature. The lesion nearly replaced the prostatic parenchyma and invaded the bladder wall. Immunohistochemistry and electron microscopy showed a predominance of fibroblasts with occasional myofibroblasts. DNA flow cytometric analysis showed that the tumor cells had a diploid DNA content. Given these findings and the indolent clinical course, the authors think that this lesion represents a benign, reactive process consistent with a pseudosarcomatous fibromyxoid tumor, a recently described rare lesion of the genitourinary tract."
-What molecular weight of macrophage colony-stimulating factor (hM-CSF) was detected in serum and urine samples using immunoblot analysis?,"Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis. We characterized the molecular species of human macrophage colony-stimulating factor (hM-CSF) found in serum and urine, using immunoblot analysis after partial purification on an antibody-bound affinity column. Although antibodies were prepared using the recombinant product of the large form of hM-CSF with a molecular weight (MW) of 85 Kd as the antigen, this immunoblot system was also capable of detecting the small form of hM-CSF with a MW of 40 to 60 Kd. A single band with a MW of 43 Kd, which reacted with anti-recombinant hM-CSF IgG but not with control IgG, was found when serum and urine from normal adults underwent electrophoresis on reduced sodium dodecyl sulfate-polyacrylamide gel and subsequent immunoblotting. This band represented a subunit of the large form of hM-CSF, because the large form of hM-CSF is a homodimer of a subunit with a MW of 43 Kd and the small form of hM-CSF is a homodimer of a subunit with a MW of 20 to 30 Kd. Analysis of serum and urine from leukemic patients and pregnant women, who had higher serum levels of hM-CSF than normal adults, showed only a single band with a MW of 43 Kd as a hM-CSF-specific molecule. These results suggest that the large form of hM-CSF is the major species in human body fluids."
-What is the significance of a positive direct antiglobulin test (DAT) in multiple myeloma patients?,"Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance. Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis."
-What is the diagnostic value of mouse rosettes (M-rosette) and surface immunoglobulin (SIg) in differentiating B-chronic lymphocytic leukemia (B-CLL) from reactive lymphocytosis (RLC)?,"The importance of surface immunoglobulin, mouse rosettes, and CD5 in the immunophenotyping of chronic lymphocytic leukemia and reactive lymphocytosis. Peripheral blood from 167 B-chronic lymphocytic leukemia (B-CLL) and 119 reactive lymphocytosis (RLC) patients were analyzed to evaluate the immunophenotypic diagnostic value of mouse rosettes (M-rosette), and weak expression of monoclonal surface immunoglobulin (SIg). In B-CLL, 145 cases were M-rosette+ (86.83%), 135 surface immunoglobulin (SIg)+ (80.84%), and 117 M-rosette+ SIg+ (70.06%). Of 32 SIg- cases, 28 were M-rosette+; and of 22 M-rosette-cases, 18 were SIg+. By combining results of the two assays and accepting positivity of either one or both as sufficient for diagnosis, B-CLL was diagnosed in 163 cases (97.60%). CD5 was performed in 49 cases of the 167 with paired data for SIg and M-rosettes. By combining the results of the three assays and accepting positivity of any two or all three as sufficient for diagnosis, all 49 cases (100%) were diagnosed. Correlation analysis showed no significant association between M-rosette, SIg, and CD5 expression. The results demonstrate the independent expression of the three markers, and their complementary role in immunophenotyping B-CLL. In RLC, all 119 cases were T-lineage and SIg-, and 115 were M-rosette-, indicating the role of the two markers in differentiating B-CLL from RLC. Three of the four M-rosette+ T-RLC were subsequently diagnosed as B-CLL, suggesting the necessity of follow-up of such cases."
-How do different structural forms of hen egg lysozyme (HEL) affect its presentation by MHC class II molecules?,"Class II-restricted presentation of an endogenously derived immunodominant T-cell determinant of hen egg lysozyme. An in vitro model was used to investigate the potential for different structural forms of endogenous antigen to be processed and presented by major histocompatibility complex class II molecules. For this purpose the class II-restricted presentation of an immunodominant epitope of hen egg lysozyme [HEL-(46-61)] was studied in class II-positive B-lymphoma cells (M12.C3) transfected with genes encoding HEL molecules either (i) secreted in high (hi) or low (lo) amounts as soluble antigen [sHEL(hi/lo)], (ii) localized within the endoplasmic reticulum (ER)/salvage compartment (ER-HEL), or (iii) anchored on the cell surface as an integral membrane protein (mHEL). The corresponding sHEL, ER-HEL, and mHEL gene products were expressed as predicted except that HEL determinants accumulated in the culture supernatant as well as on the cell membrane of mHEL-transfected cells. Class II-positive cells endogenously expressing all three forms of HEL antigen constitutively presented the immunodominant HEL-(46-61) determinant with differential efficiency (mHEL, sHEL greater than ERHEL) to a class II-restricted T hybridoma. A second T hybridoma recognized endogenous HEL-(46-61) determinants constitutively presented on sHEL(hi) and mHEL transfectants but not on sHEL(lo) or ERHEL transfectants. The formation of HEL-(46-61)/I-Ak complexes in the ERHEL and sHEL(lo) transfectants was therefore limiting. Mixing experiments with different antigen-presenting cells indicated that the HEL-(46-61) determinant was derived from endogenous antigen rather than by reuptake of shed or secreted HEL determinants. We conclude that MHC class II molecules can present some antigenic determinants derived from endogenous proteins that are sequestered in the ER/salvage compartment as well as distally transported in the form of secretory or membrane antigens."
-What minimally invasive technique was used to successfully treat chylothorax after pneumonectomy when conservative therapy failed?,"Thoracoscopic diagnosis and treatment of chylothorax after pneumonectomy. Chylothorax after pneumonectomy was treated successfully by selective application of fibrin glue through a thoracoscope. Conservative therapy for 18 days failed to close the fistula. The site of leakage was identified during thoracoscopy, and fibrin glue was applied under direct vision. Leakage decreased immediately and eventually stopped completely. This technique is less invasive than standard surgical treatment and should be considered in all patients with postoperative chylothorax."
-What was the main strategy used for managing distal ileal Crohn's disease in this study?,"Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy."
-What modifications were made to the original T-shaped musculomucosal buccal flap method to improve cleft palate surgery outcomes?,"The modified buccal musculomucosal flap method for cleft palate surgery. We have reported previously on a palatoplasty method, called the T-shaped musculomucosal buccal flap method, for the primary repair of a cleft palate. This method has been used on more than 90 patients, and satisfactory outcomes have resulted in terms of maxillar development, the prevention of fistulation, and verbal functions. However, 14.3 percent of these patients exhibited a velopharyngeal incompetence that showed no potential improvement through training. In the majority of these patients, the entire raw surface of the oral cavity side could not be covered with a buccal musculomucosal flap, and as a result, postoperative contraction of the soft palate occurred. Thus a new surgical method has proven effective in which both buccal musculomucosal flaps are used as an oral lining, the nasal mucosa having been extended by Z-plasty. We have performed 25 operations using this new method and have observed no postoperative contractions of the soft palate, notwithstanding two cases (8.0 percent) of postoperative fistulation."
-What were the complete fragmentation rates and 3-month stone-free rates for the three different lithotripsy devices studied?,"Comparative studies of extracorporeal shock wave lithotripsy by Dornier HM3, EDAP LT 01 and Sonolith 2000 devices. During a 2-year period extracorporeal shock wave lithotripsy (ESWL) was done at our institution in 70 patients with the Dornier HM3, 113 with the EDAP LT 01 and 104 with the Sonolith 2000 lithotriptors. The size and location of stones were comparable in all 3 series, and all treatments were done by the same team of urologists. Complete fragmentation occurred in 79% of the patients treated by the Dornier, 82% treated by the EDAP and 79% treated by the Sonolith devices, with 3-month stone-free rates of 66, 67 and 58%, respectively. Auxiliary procedures were needed in 12% of the patients in the Dornier, 13% in the EDAP and 9% in the Sonolith groups. Repeat treatment was necessary in 4% of the Dornier group, 42% of the EDAP group and 26% of the Sonolith group. Therefore, all 3 lithotriptors are effective in stone disintegration and produce satisfactory results when selection criteria for ESWL are observed. The most significant difference among the 3 lithotriptors is the number of repeat treatments, which reflects the power and energy output of the lithotriptors. In conclusion, the Dornier HM3 device has the advantage of low repeat treatment rate and easier stone localization. The EDAP LT 01 unit has the advantage of lower treatment costs and anesthesia-free treatment with no irradiation. The Sonolith 2000 device has features of the other 2 lithotriptors with a superior ultrasound image."
-What were the key findings from linking the Illinois AIDS and Cancer Registries regarding neoplasia in people with AIDS?,"A systematic consideration of the neoplastic spectrum of AIDS: registry linkage in Illinois. To examine unexplored aspects of the association between AIDS and neoplasia, the Illinois AIDS and Cancer Registries were linked. The method integrated use of a personal computer to find exact matches on names and dates of birth with manual review to assure satisfaction of a match definition. Of the factors examined, white race and homosexuality predicted Kaposi's sarcoma (KS) among people with AIDS (PWAs), and white race predicted non-Hodgkin's lymphoma (NHL). Earlier reports of a declining proportion of PWAs with KS were confirmed. Lymphoma (mixed lymphocytic/histiocytic type), while not currently diagnostic of AIDS, occurred more frequently among PWAs than in the Illinois population. For the first time, rates of cancers other than KS and NHL were demonstrated to be significantly increased among PWAs compared with general populations. In the light of these findings, reconsideration of current neoplastic definitions may be useful."
-What treatment was used for children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and what were its outcomes?,"Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin. We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients."
-What were the two-year clinical success rates for the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups?,"Experience with laser-assisted balloon angioplasty and a rotary angioplasty instrument: lessons learned. Favorable early results with mechanical angioplasty devices and laser-assisted balloon angioplasty have resulted in aggressive marketing and a rapid increase in the use of these devices for the treatment of femoropopliteal occlusive disease. Recent reports, however, have questioned the durability of these less invasive procedures. Since 1986 we have been involved in the clinical investigation of the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty. One hundred two balloon angioplasty procedures assisted by the Nd:YAG laser (n = 56) and the Kensey dynamic angioplasty instrument (n = 46) were performed for the treatment of femoropopliteal occlusive lesions. Both Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups were similar with regard to age, operative indication, preoperative ankle-brachial index, lesion length, and distal runoff. Mean follow-up was 19 months in the Kensey dynamic angioplasty instrument group and 15 months in the laser-assisted balloon angioplasty group. Technically successful recanalization was achieved in 67% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 82% of laser-assisted balloon angioplasty procedures. Early hemodynamic and clinical improvement was obtained in 59% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 57% of laser-assisted balloon angioplasty procedures. Two-year clinical success by life-table analysis was 37% in the Kensey dynamic angioplasty instrument group and 19% in the laser-assisted balloon angioplasty group. The level of subsequent surgical revascularization was not altered in any patient by Kensey dynamic angioplasty instrument-assisted balloon angioplasty or laser-assisted balloon angioplasty."
-What was the impact of long-term passive anti-HBV immunoprophylaxis on HBV reinfection and survival in liver transplant patients?,"Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. 110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation."
-How does the diaphragmatic activity differ between slow-wave sleep and rapid-eye-movement (REM) sleep in cats?,"Differential activation within costal diaphragm during rapid-eye-movement sleep in cats. Simultaneous recordings of the diaphragmatic electromyogram (EMG) were made from two separate regions of the costal diaphragm in six normal cats. The diaphragmatic activities were always synchronous and the amplitudes and rates of rise were similar during slow-wave sleep. In contrast, during natural rapid-eye-movement (REM) sleep, different activity was often present in the two leads. These differences were in the time of onset and offset, as well as in the amplitude and spike patterns, and occurred in approximately 5-20% of the diaphragmatic bursts averaged over the entire REM sleep period. With respect to eye movement density, the rate of differential activation was higher during periods of high density (26%) than in the absence of eye movements (1%) in the four animals for which these data were available. Differential activation of portions of the costal diaphragm is apparently a normal event of REM sleep. This could result from descending state-specific phasic neuronal activity that bypasses the medullary respiratory generator. Differential activation of portions of the diaphragm could contribute to disordered ventilation during REM sleep."
-What symptoms are commonly associated with posttraumatic headache as part of the postconcussion syndrome?,"Posttraumatic headache and the postconcussion syndrome. Although headache is the most common sequelae of head injury, the posttraumatic headache is associated frequently with dizziness, irritability, lack of concentration, and intolerance to alcohol ingestion as a part of a symptom complex known as the postconcussion syndrome. This article clarifies the definitions of acute traumatic headache, posttraumatic headache, and the postconcussion syndrome and improves diagnostic ability, making the assessment and treatment of patients with these three conditions more accurate and effective."
-What are the two bacterial factors identified as important in enteropathogenic Escherichia coli (EPEC) infection?,"Characterization of interactions of enteropathogenic Escherichia coli O127:H6 with mammalian cells in vitro. Previous studies have identified two bacterial factors involved in enteropathogenic Escherichia coli (EPEC) infection. A plasmid-mediated EPEC adherence factor (EAF) is responsible for initial and localized adherence. A chromosomally encoded E. coli attachment and effacement factor (eae) is involved in effacement of the eukaryotic cell surface and characteristic ""pedestal"" formation. By using isogenic strains deficient in either EAF, eae, or both, the process of EPEC adherence and entry in vitro was examined. While EAF proved necessary and sufficient for efficient bacterial association with HEp-2 cells, both EAF and eae were required for efficient effacement of and entry into these cells and other cultured cell lines. Invasion mediated by eae was markedly inhibited by cytochalasin D and colchicine. Afimbrial adhesion or type I pili from uropathogenic strains of E. coli substituted for EAF in EAF-Eae+ strains to provide initial adherence to HEp-2 cells and to facilitate actin condensation."
-What are the key initiatives proposed to address the shortage of trained eye care professionals in sub-Saharan Africa?,"Who will operate on Africa's 3 million curably blind people? About half the 6 million blind people in sub-Saharan Africa have surgically curable cataract. The available manpower and resources can only provide services for less than 10% of the new blind cataract patients each year, and little is being done for the estimated 3 million ""cataract backlog"". A serious limiting factor to the development of prevention of blindness programmes is lack of trained manpower. Despite an increase in the number of ophthalmologists trained in cataract surgery (which varies greatly from country to country), this number is not keeping pace with increased demand for eye-care services, especially in large rural populations. Initiatives that will help to overcome this dilemma are specific post-graduate courses in community ophthalmology in Africa, plans to develop a one-year diploma in ophthalmology course for English-speaking West African countries, and a proposal to upgrade a similar course in Zimbabwe. Additionally there is a need for the training of more ophthalmic assistants, cataract surgeons, and nurses in the diagnosis and management of common ophthalmic disorders. Experienced expatriate ophthalmologists also have an important role in the teaching of doctors and ophthalmic assistants how to select patients and carry out successful inexpensive cataract surgery with appropriate technology and limited facilities."
-What unique characteristics were observed in this case report of a pituitary adenoma?,"Ectopic pituitary adenoma in the suprasellar cistern: case report. The case of a 56-year-old man with an ectopic pituitary adenoma is reported. Neurological examinations, neurodiagnostic imaging, surgical observation, endocrinological evaluation, histological examination, and immunohistological study demonstrated evidence of ectopic prolactinoma in the suprasellar cistern and the presence of a normal pituitary in the sella turcica. The patient underwent total removal of the suprasellar mass by a pterional approach, leading to a surgical and endocrinological cure."
-What is neoplastic angioendotheliomatosis (NAE) and how did it manifest in the two described cases?,"Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months."
-What was the main finding of the study comparing low and high doses of ethanolamine oleate in treating esophageal varices?,"Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant."
-How do the responses of pial arterioles to bradykinin differ between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive (WKY) rats?,"Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP."
-What rare condition was reported in this medical case involving the gasserian ganglion?,Primary malignant melanoma of the gasserian ganglion associated with neurofibromatosis. A case of primary intracranial malignant melanoma of the left gasserian ganglion associated with temporal lobe gliosis in a patient suffering from von Recklinghausen's disease is reported. The association of primary malignant melanoma of the trigeminal nerve and neurofibromatosis is discussed.
-What was the average number of lymph nodes found in stations 1-11 and 1-16 in the cadaveric study?,"Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma."
-How does gamma-interferon influence astrocyte proliferation and reactive gliosis?,"Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to gamma-interferon (IFN). Recombinant IFN alone can induce proliferation of human adult astrocytes in vitro and increase the extent of trauma-initiated gliosis in the adult mouse brain. The astrocyte proliferation-inducing activity of supernatants of glial cultures treated with IFN can be completely blocked with IFN-neutralizing antibody, suggesting that the proliferative effect does not require intermediary cytokines or cells. These results implicate IFN as an important mediator of the gliosis observed in pathologic conditions of the adult central nervous system associated with infiltrating lymphocytes."
-What was the incidence of clinically significant pneumatosis intestinalis in patients who underwent abdominal operations or bariatric procedures with needle catheter jejunostomy?,"Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication. We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics."
-What are the typical symptoms and clinical presentation of medially invasive petrous bone cholesteatoma?,"Facial nerve and medially invasive petrous bone cholesteatomas. Eight patients with extensive petrous bone cholesteatomas that invaded the labyrinth and fallopian canal are presented. The eight cases are added to a tabulation of prior literature reports to elucidate concepts of routes of extension of medially invasive temporal bone cholesteatoma. Medially invasive petrous bone cholesteatoma develops insidiously, often without symptoms other than facial palsy and/or unilateral deafness. Typically, a history of chronic ear disease can be obtained. While hearing is unlikely to be preserved in this group of patients, facial nerve function can usually be preserved, and a facial nerve graft was not necessary in our series. Acute facial nerve palsy or facial nerve paresis progressing to palsy in patients with a history of chronic ear disease should be studied radiographically for petrous bone cholesteatoma, even if there is no physical evidence of cholesteatoma."
-What were the four different 6-month chemotherapy regimens used in this study for treating pulmonary tuberculosis?,"Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Hong Kong Chest Service/British Medical Research Council In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at random to four 6-month regimens of chemotherapy, all given three times weekly from the start and all containing isoniazid (H) and rifampin (R) throughout. Three contained streptomycin (S) for the first 4 months and pyrazinamide (Z) for 2 months (Z2), 4 months (Z4), or 6 months (Z6); the fourth contained pyrazinamide for 6 months but no streptomycin (Z6noS). Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis. During the later part of the intake patients were allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide, or as the three drugs separately. Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment, bacteriologic failure during chemotherapy occurred in 4, all Z6noS (2% of 224; p less than 0.005 for the comparison with the S-containing regimens). During 30 months of follow-up after the end of chemotherapy, bacteriologic relapse occurred in 2 (3%) of 71 Z2, 2 (3%) of 72 Z4, 4 (6%) of 66 Z6, and 6 (9%) of 64 Z6noS patients allocated to Rifater, and in 4 (3%) of 149 Z2, 8 (6%) of 133 Z4, 2 (1%) of 142 Z6, and 6 (4%) of 135 Z6noS patients allocated to separate drugs. In the relapse rates there were no significant differences between the Rifater and separate drug regimens, the different durations of pyrazinamide, or the regimens with and without streptomycin."
-Does 24-hour esophageal pH monitoring predict the response of reflux esophagitis to standard medical therapy?,"Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis. Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy."
-What were the key findings of the morphometric study on gastric endocrine cells after 6 months of omeprazole treatment in duodenal ulcer patients?,"Ultrastructural morphometry of gastric endocrine cells before and after omeprazole. A study in the oxyntic mucosa of duodenal ulcer patients. Long-term toxicological experiments with inhibitors of acid secretion were found to induce hyperplasia and eventually carcinoid tumors of the enterochromaffin-like cells of the oxyntic mucosa. To evaluate the effects of 6 months' treatment with omeprazole in humans, the oxyntic endocrine cells were morphometrically investigated at the ultrastructural level in five patients with active duodenal ulcer. No omeprazole-induced changes were found in the volume density of the total endocrine cell population and specific cell types (including the enterochromaffin-like cell) as well as in the other cytological parameters investigated (number of cell profiles per unit area, mean cross-sectional area of cell profiles, nuclear-cytoplasmic ratio, and density of cytoplasmic secretory granules). Both pretreatment and post-treatment values in our patients with duodenal ulcer significantly differed from those of a previous investigation of healthy volunteers with regard to the volume density of enterochromaffin-like cells and non-granulated cells, which increased, and of D cells, which markedly decreased. The latter result may provide a cellular basis for impairment in the paracrine release of fundic somatostatin in peptic ulcer disease. Finally, morphometric data on endocrine cell volume density provided by electron microscopy were found to correlate with those obtained in the same patients using light microscopy techniques (Grimelius silver impregnation and chromogranin A immunostaining). It is concluded that 6 months' treatment with pharmacological doses of omeprazole is devoid of appreciable trophic effect on endocrine cells of human oxyntic mucosa."
-What were the key differences in outcomes between patients with thrombolysis-mediated patency and those with patency achieved by angioplasty in acute myocardial infarction?,"Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy."
-How do deletions in different domains of the dystrophin gene affect the clinical presentation of Becker muscular dystrophy?,"Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels."
-What are the typical symptoms associated with anterior urethral polyps in male patients?,"Anterior urethral polyp associated with hematuria in six-year-old child. Anterior urethral polyps are rare, occur only in male patients, and have been associated with obstruction, terminal hematuria, and enuresis. We believe this is the fifth reported case of anterior urethral polyp associated with terminal hematuria. The radiographic findings, treatment, and pathology are reviewed."
-What is the purpose of the study on percutaneous stimulation of the cauda equina?,"Percutaneous stimulation of the cauda equina. A new diagnostic method in spinal stenosis. A study to determine the feasibility of measurement of conduction velocities through the lumbosacral nerve roots by direct percutaneous stimulation of the cauda equina is reported. The technique was applied to a series of normal volunteers and its reliability and reproducibility confirmed. An electrophysiologic defect was demonstrated in most patients with surgically proven lateral recess stenosis. Electrophysiologic recovery was shown in patients examined after surgery. Although the technique can be refined, these early results are encouraging."
-What are the key noninvasive strategies to reduce stroke risk in elderly patients?,"Reducing the risk of stroke: identifying patients to refer for carotid endarterectomy. The most common causes of stroke are two diseases of aging: hypertension and atherosclerosis. Therefore, although stroke may occur at any age, the incidence is highest among the elderly population. Noninvasive efforts to reduce the risk of stroke in the elderly include control of hypertension and diabetes, smoking cessation, low-cholesterol dietary habits, and moderate exercise. Routine low-dose aspirin also provides some protective effect. High-risk patients (with asymptomatic high-grade stenosis, TIAs, or prior stroke) should be considered candidates for carotid endarterectomy in the absence of contraindications to surgery."
-"What was the effect of different doses of interferon alfa-2b on alanine aminotransferase levels in patients with chronic non-A, non-B hepatitis?","Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond."
-What is the primary medical intervention discussed for managing retroperitoneal hemorrhage from renal angiomyolipoma in a patient with polycystic kidney disease?,"Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited."
-"What medical condition caused paraplegia in the pregnant thalassemic woman, and how was she successfully treated?","Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions. The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed."
-What percentage of hemodialysis patients in the study developed hypertension after receiving recombinant human erythropoietin (rHuEpo) therapy?,"Hypertension following erythropoietin therapy in anemic hemodialysis patients. Recombinant human erythropoietin (rHuEpo) corrects the anemia of end-stage renal disease. However, hypertension has been observed as an adverse effect of increasing red cell mass. In our study, 44 of 63 patients (70%) treated with rHuEpo had an increase in mean arterial pressure greater than 10 mm Hg or required new or additional hypertensive medications. Retrospective analysis disclosed that increasing blood pressure was associated with pretreatment hematocrit level less than or equal to 0.20 (P = .05) and dependency on red cell transfusions (P less than .01). Factors not associated with hypertension included the rate of rise of the hematocrit, the net rise in hematocrit, age, sex, the number of years on dialysis, the presence or absence of kidneys, smoking, or the presence of pretreatment hypertension. Noninvasive hemodynamic studies in eight normotensive patients before and after improvement of the anemia demonstrated a normalization of the decreased peripheral vascular resistance and a reduction toward normal in the elevated cardiac output. In three of these patients, clinical hypertension subsequently evolved. Follow-up hemodynamic studies in nine other patients receiving new or additional antihypertensive medications were difficult to interpret. Although the hypertension can be controlled with routine medication, hypertensive encephalopathy may occur if the blood pressure increases rapidly when the hematocrit increases with rHuEpo therapy."
-What were the survival rates for children with malignant intracranial ependymomas based on different radiation treatment approaches?,"Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas? Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory."
-How can the measurement of free light chains in urine potentially help in monitoring multiple sclerosis disease activity?,"Increased free light chains in the urine from patients with multiple sclerosis. We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity."
-How do monoclonal antibodies help identify interaction sites of Plasminogen Activator Inhibitor 1 (PAI-1) with tissue-type plasminogen activator (t-PA) and fibrin?,"The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: localization of interaction sites and physiologic relevance. Plasminogen activator inhibitor 1 (PAI-1), an essential regulatory protein of the fibrinolytic system, harbors interaction sites for plasminogen activators (tissue-type [t-PA] and urokinase-type [u-PA]) and for fibrin. In this study, anti-PAI-1 monoclonal antibodies (MoAbs) were used to identify interaction sites of PAI-1 with these components. The binding sites of 18 different MoAbs were established and are located on five distinct ""linear"" areas of PAI-1. MoAbs, binding to two distinct areas of PAI-1, are able to prevent the inhibition of t-PA by PAI-1. In addition, two interaction sites for fibrin were identified on PAI-1. The area located between amino acids 110 and 145 of PAI-1 contains a binding site for both components and its significance is discussed in the context of the t-PA inhibition by fibrin-bound PAI-1. Subsequently, the MoAbs were used to assess the role of platelet-PAI-1 in clot-lysis. An in vitro clot-lysis system was used to demonstrate that clot-lysis resistance is dependent on the presence of activated platelets and that PAI-1 is a major determinant for lysis-resistance. We propose that, upon activation of platelets, PAI-1 is fixed within the clot by binding to fibrin and retains its full capacity to inhibit t-PA and u-PA."
-What is unique about the reported case of pulmonary zygomycosis in this medical report?,Granulomatous pulmonary zygomycosis in a patient without underlying illness. Computed tomographic appearances and treatment by pneumonectomy. Pulmonary zygomycosis rarely occurs in the absence of underlying disease. We report a patient with granulomatous pulmonary zygomycosis without underlying disease who presented with a pulmonary mass. We present the computed tomographic findings that we believe have not been described previously. We also report the successful treatment by pneumonectomy.
-What was the main finding regarding dysplasia and carcinoma in ulcerative colitis patients who underwent ileorectal anastomosis (IRA) in this follow-up study?,"Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a defined patient group. In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955-1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n = 22, one postoperative death) or owing to dysplasia (n = 3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low."
-What did the study suggest about the relationship between erythrokeratoderma variabilis (EKV) and progressive symmetrical erythrokeratoderma (PSEK)?,"Is erythrokeratoderma one disorder? A clinical and ultrastructural study of two siblings. Two sisters with erythrokeratoderma are described. In the younger sister the clinical appearance corresponded to erythrokeratoderma variabilis (EKV), whereas in the older sister it corresponded to progressive symmetrical erythrokeratoderma (PSEK). Ultrastructural findings in both cases were identical. We suggest that EKV and PSEK are different manifestations of a single condition."
-How do oral contraceptive pills affect insulin-like growth factor binding protein-1 (IGFBP-1) concentration in women with polycystic ovarian disease (PCOD)?,"Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease. Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD."
-What is the significance of CD23 expression on lymphocytes in chronic inflammatory conditions?,"Immunohistochemical demonstration of CD23 expression on lymphocytes in rheumatoid synovitis. The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate."
-What unique medical condition did the patient develop in her surgically reconstructed neovagina?,"Ulcerative colitis in the autotransplanted neovagina. A 33-year-old woman had undergone a radical surgical excision for carcinoma of the vagina at age 11. Vaginal reconstruction using a pedicled transplant of the sigmoid colon was successfully accomplished at age 19. Fourteen years later she developed vaginal bleeding, and a biopsy of the neovagina revealed changes consistent with ulcerative colitis. Within 2 weeks the patient developed bleeding per ano, and a rectal biopsy also revealed changes consistent with ulcerative colitis. Symptoms responded to sulfasalazine. This is believed to be the first case report of ulcerative colitis developing in colonic tissue used for a neovagina. The etiology, natural history, and surveillance of ulcerative colitis in relation to this unique case are reviewed. This case argues against the hypothesis that chronic ulcerative colitis is causally related to direct exposure to alimentary antigens."
-How did the administration of atrial natriuretic factor (ANF) affect the vasoconstrictor response during lower body negative pressure in patients with hypertension?,"An atrial natriuretic factor analogue at low doses attenuates forearm reflex vasoconstriction to cardiopulmonary receptor deactivation in patients with hypertension. Contrasting data exist about a possible modulation of the autonomic function by atrial natriuretic factor (ANF) in human beings, particularly at low, biologically, significant concentrations. We have evaluated that possibility by increasing plasma ANF levels through the infusion of a synthetic analogue (WY-47,663, anaritide) in five male patients with mild to moderate uncomplicated hypertension. Nonhypotensive lower body negative pressure (-10 mm Hg x 5 min) was used to selectively deactivate cardiopulmonary receptors and to stimulate sympathetic efferent tone reflexogenically. ANF was given at either a low rate (0.005 micrograms/kg/min x 60 min, which was previously shown to increase plasma ANF in a range compatible with physiologic stimuli) or at a high rate (0.05 micrograms/kg/min x 60 min, each). Administration of ANF was preceded and followed by vehicle infusion (Haemacell x 30 min). Forearm blood flow (venous plethysmography), intraarterial blood pressure, and heart rate were monitored continuously, and venous immunoreactive ANF, plasma renin activity, aldosterone level, and venous hematocrit were measured at the end of both control and infusion periods. Arterial norepinephrine values, an indirect index of sympathetic discharge, were measured at rest and during lower body negative pressure conditions. Graded systemic ANF infusion increased immunoreactive ANF and venous hematocrit, decreased aldosterone level and plasma renin activity, whereas resting norepinephrine levels, blood pressure, and heart rate did not change. Lower body negative pressure decreased forearm blood flow during vehicle infusion, but it lost its vasoconstrictor effect during infusion of ANF. To identify the site of that inhibitory action, ANF was also infused into the brachial artery at rates that raised local but not systemic levels of immunoreactive ANF."
-What immunological evidence suggests the co-existence of Lambert-Eaton myasthenic syndrome and myasthenia gravis in the two patients described?,"Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. Two patients are described in whom a clinical and electromyographic diagnosis of the Lambert-Eaton myasthenic syndrome (LEMS) was made. Serum antibodies to voltage-gated calcium channels (VGCCs), the antigenic target in LEMS and to acetylcholine receptors (AChRs), the antigen in myasthenia gravis, were detected at raised titres in both cases, using radioimmunoassays based on 125I-omega-Conotoxin labelled VGCCs and 125I-alpha-Bungarotoxin labelled AChRs. These data provide immunological evidence for the coexistence of the two disorders in these patients."
-What was the sensitivity and specificity of fine-needle aspiration biopsy in this pediatric head and neck masses study?,"Fine-needle aspiration biopsy: application to pediatric head and neck masses. Fine-needle aspiration biopsy cytology is widely used to screen masses in adults. The authors present a series of 89 fine-needle aspiration biopsies performed between January 1973 and December 1988 on 86 pediatric patients with clinically significant head and neck masses. All fine-needle aspiration diagnoses were confirmed by subsequent surgical biopsy, autopsy, or clinical follow-up for a minimum of 18 months. Of 21 tumors identified, 19 were malignant. Of the 89 aspirations performed, 67 required no subsequent surgical biopsy. In 11 of these cases, metastatic or recurrent tumor was diagnosed and appropriate therapy instituted. Fifteen of the 89 aspirates revealed previously undiagnosed tumors requiring surgical intervention. One false-negative and two false-positive results were obtained. No radical treatment resulted from the false-positive diagnoses, and no patient delay in treatment occurred because of the false-negative result. The sensitivity was 94.4%, and the specificity was 97.1%. The usefulness and cost-effectiveness of fine-needle aspiration is stressed."
-What medical procedure did the two patients with previous malignancy undergo to treat their congestive cardiomyopathy?,Orthotopic cardiac transplantation in two patients with previous malignancy. This report presents 2 patients with previous malignancy in whom congestive cardiomyopathy developed secondary to doxorubicin toxicity. Both patients underwent orthotopic cardiac transplantation 3 and 5 years ago and are now in functional class I with no evidence of malignant recurrence.
-What is priapism and how can it be related to vasculitis?,"Priapism as a manifestation of isolated genital vasculitis. Vasculitis may affect virtually any organ system in the body. We describe a patient who presented with priapism due to isolated genital vasculitis. This responded promptly to oral corticosteroids. In patients presenting with priapism, a possible underlying vasculitis should be considered in the differential diagnosis; the treatment for this may be nonsurgical."
-What symptoms were significantly more common in patients with infectious mononucleosis during the acute phase of illness?,"Acute and chronic symptoms of mononucleosis. BACKGROUND. The clinical symptoms and durations of illness of patients with infectious mononucleosis (IM) are variable and are poorly documented in the scientific literature. METHODS. Patients who presented for care at the Student Health Service of a Canadian university between September 1985 and May 1988 and had been diagnosed as having IM were surveyed. Health experience during the acute and convalescent phases of IM was compared with that of a group of patients matched for age, sex, date of diagnosis, and year of study, who had suffered acute upper respiratory tract infections (URI), other than Epstein-Barr virus (EBV)-induced, during the same period. RESULTS. Students were sicker for longer after IM than after non-EBV-induced URI. During the acute phase of illness, the symptoms of fatigue (P = less than .000001), night sweats (P = .000001), and painful neck swelling (P = .00003) were seen significantly more often in the IM group. The severity and duration of these symptoms were also significantly worse in IM patients. Getting tired easily (P = .002), diurnal somnolence (P = .002), and depression (P = .002) were significantly more common postacute symptoms. Eleven percent of IM patients reported persistence of symptoms longer than 100 days, and in 6% of patients the symptoms had persisted after 1 year. Convalescent cases showed a trend toward reduced alcohol intake and, perhaps, reduced alcohol tolerance. CONCLUSIONS. IM involves excessive morbidity in a student community compared with URI that was other than EBV-induced, during both the acute and the postacute phases of infection."
-How do plasma atrial natriuretic peptide (ANP) levels change during dynamic exercise in patients with effort angina pectoris?,"Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris. We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise."
-How does acute appendicitis present differently in patients with AIDS/HIV infection compared to immunocompetent patients?,"Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality."
-How has the use of antihypertensive agents changed in different age groups in the United States?,"Changes in hypertension treatment and in congestive heart failure mortality in the United States. The use of antihypertensive agents has increased in recent years and has been more marked among individuals in older age groups (65-74 years) than in middle-aged groups (45-54 years). Because hypertension is a strong risk factor for the development of congestive heart failure, more common use of antihypertensive agents would be expected to reduce the incidence of congestive heart failure. Examination of the national death statistics reveals decreases in congestive heart failure mortality at younger ages with mortality increases at older ages. The reasons for these divergent trends in congestive heart failure mortality in different ages and the apparent inconsistency with respect to the changes in the use of antihypertensive drugs are explored. We speculate that antihypertensive treatment does not completely prevent congestive heart failure but merely postpones its development by several decades."
-What was the most common cause of death among patients with tuberous sclerosis complex (TSC) in the Mayo Clinic study?,"Causes of death in patients with tuberous sclerosis. Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications."
-What imaging technique is recommended for diagnosing sigmoid sinus thrombosis?,"Sigmoid sinus thrombosis diagnosis by contrasted MRI scanning. Septic thrombosis of the transverse-sigmoid sinuses and the jugular bulb is a highly lethal condition. The presenting signs and symptoms of this disease entity are subtle and not in proportion to the magnitude of the problem. Later in the disease course, sudden fulminant findings appear. A high index of suspicion, combined with scanning techniques of either enhanced MRI or CT, allows prompt diagnosis and treatment. MRI enhanced with gadolinium-DTPA (Gd) is a valuable adjunct that confirms the diagnosis and delineates the extent of suspected pathology."
-What is the prevalence of transverse aortic arch hypoplasia in infants undergoing coarctation repair?,"Coarctation and hypoplasia of the aortic arch: will the arch grow? Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to-end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25."
-"How does the left atrial pump function differ between normal subjects, patients with essential hypertension, and patients with healed myocardial infarction?","Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation. To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 +/- 3 mm) and in those with myocardial infarction (32 +/- 4 mm) than in normal subjects (28 +/- 3 mm) (p less than 0.01, p less than 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 +/- 3 mm Hg.mm, p less than 0.01) and in subjects with myocardial infarction (29 +/- 10 mm Hg.mm, p less than 0.05), compared with normal subjects (20 +/- 8 mm Hg.mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p less than 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p less than 0.01, p less than 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p less than 0.01)."
-What are the potential benefits and complications of using small-diameter flexible fiberscopes for visual diagnosis of spinal canal diseases?,"Observation of spinal canal and cisternae with the newly developed small-diameter, flexible fiberscopes. Small-diameter (0.5-, 0.9-, and 1.4-mm) flexible fiberscopes were developed for visual diagnosis of spinal canal diseases. The fiberscopes were introduced via a Tuohy needle into the subarachnoid and epidural spaces of ten patients with various pain syndromes. Clear visualization of the subarachnoid space was achieved using the fiberscopes. The epidural space could be visualized only during withdrawal of the fiberscope. In five cases, the fiberscope could be advanced up to the level of the cisternae without causing the patient any discomfort. A slight headache and transient fever were noted after the examination in five and two cases, respectively, but no other complications occurred. Interestingly, preexisting pain diminished (two cases) or disappeared (one case) after the myeloscopy in three of five cases in which the myeloscopy revealed aseptic adhesive arachnoiditis. Further studies should be carried out to evaluate the usefulness of this technique."
-"What is the ""cuff sign"" in the context of sonographic evaluation of pancreatic cancer and superior mesenteric artery involvement?","Thickening at the root of the superior mesenteric artery on sonography: evidence of vascular involvement in patients with cancer of the pancreas. Thickening of the root of the superior mesenteric artery (SMA) was studied by using preoperative sonography in 23 patients with pancreatic cancer and in 10 healthy control subjects. Of the 23 with cancer, 11 had neoplastic involvement of the SMA and 12 did not. Prominent thickening of the area around the SMA with (six patients) or without (five patients) decreased echogenicity compared with the adjacent retropancreatic connective tissue was observed in patients with involvement of the SMA, a finding called the ""cuff sign."" Mean thickness of the periarterial area in the cancer patients with and without involvement of the SMA and in control subjects were 8.5 mm, 4.0 mm, and 2.9 mm, respectively. With an upper limit of normal of 7.0 mm for the thickness of the SMA, the sensitivity, specificity, and overall accuracy of this sign in the evaluation of involvement of the SMA were 91%, 100%, and 96%, respectively. Decreased echogenicity of the periarterial area was not observed in patients without involvement of the SMA or in control subjects. Our results show that sonographic evidence of periarterial thickening of the root of the SMA (cuff sign), especially with decreased echogenicity, is a reliable finding of tumor infiltration of the SMA in patients with pancreatic carcinoma."
-What is the incidence of masseter muscle spasm (MMS) in children during anesthesia with succinylcholine?,"Masseter muscle spasm in children: implications of continuing the triggering anesthetic. This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique."
-How does unilateral brain damage in the left hemisphere affect decision-making accuracy compared to right hemisphere damage?,"Hemisphere asymmetry in decision making abilities. An experimental study in unilateral brain damage. Thirty control subjects and 60 unilateral brain-damaged patients, 30 with left hemisphere (LH) damage and 30 with right hemisphere (RH) disease, underwent a disjunctive 4-choice reaction time study. Speed of reaction (as defined by the reciprocal of reaction time (RT), movement time (MT) and total response time (TRT] and accuracy of response (as represented by the sum of errors in selecting the correct response key) were investigated comparatively as a function of side of lesion and of performance on Raven's Coloured Progressive Matrices (PM47). In contrast to movement speed (1/MT), reaction speed (1/RT) as well as total response speed (1/TRT) showed a lesion effect independent of side of damage. Conversely, accuracy was differentially impaired, LH damage being associated with a significantly higher number of errors. Speed and accuracy had different relationships with the performance on the PM47 in the two hemisphere groups. Speed was affected in parallel with changes in PM47 performance both in the LH and in RH groups, whereas accuracy was altered only in LH patients. It was concluded that speed of motor reaction is affected by unilateral brain lesions irrespective of their side, whereas decision making processes, as expressed by accuracy of response, seem to be specifically impaired by LH damage."
-"What were the key findings of the study comparing cisplatin and etoposide (PE) with cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for metastatic breast carcinoma?","Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research. In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research."
-What is idiopathic colonic perforation in a neonate and how is it typically diagnosed?,"Idiopathic colonic perforation in the neonate. We describe a premature infant in whom spontaneous perforation of the colon was initially detected on routine abdominal films. There was no clinical evidence of necrotizing enterocolitis, peritonitis, or bowel obstruction. Surgical and pathologic findings confirmed the diagnosis of idiopathic bowel perforation. Since spontaneous gastrointestinal perforation in the neonate is often difficult to diagnose clinically, radiographic evaluation may allow earlier diagnosis and prompt surgical treatment of this life-threatening condition."
-What were the key determinants of outcome in the cervical cerclage study?,"Prognostic factors and complication rates for cervical cerclage: a review of 482 cases. Charts from 482 singleton pregnancies undergoing cerclage placement in patients over a 6-year period were reviewed. Cervical dilatation at time of surgery, number of previous spontaneous losses, and gestational age at placement were key determinants of outcome. The most frequent complication, premature rupture of the membranes, ultimately occurred in 38% of patients. The 6.6% infection rate was increased in patients undergoing emergent versus elective surgery (12.7% vs 4.7%, p less than 0.005) and in patients at increased dilatation at time of surgery (5.7% for less than or equal to 2 cm vs 41.7% for greater than 2 cm, p less than 0.005). McDonald and Shirodkar procedures had similar obstetric outcomes in patients undergoing their first cerclage. The subgroup of patients with prior cerclage surgery showed improved birth weight when the Shirodkar procedure was performed instead of the McDonald cerclage (mean birth weight 3020 vs 2470 gm, p less than 0.005). An increased rate of primary cesarean section was found in the Shirodkar group (31% vs 17%, p less than 0.005). Complication rates and pregnancy outcome appear to reflect cervical dilatation more than gestational age at time of surgery."
-What diagnostic tests were found to be most useful in identifying extraspinal causes of lumbosacral radiculopathy in this study?,"Extraspinal causes of lumbosacral radiculopathy. Twelve of 12,125 patients who had been referred during a seven-year period to a specialist in spinal disorders were found to have an extraspinal cause of radiculopathy or neuropathy of the lower extremity. The records of these twelve patients were reviewed retrospectively. The average age of the twelve patients was sixty-five years (range, forty-two to seventy-seven years). The cause of the symptoms was an occult malignant tumor in nine patients and a hematoma, an aneurysm of the obturator artery, or a neurilemoma of the sciatic nerve in the others. The average time from the onset of symptoms to the final diagnosis was eight months (range, one month to two years). The most useful test for determination of the correct diagnosis was computed tomography or magnetic resonance imaging of the abdomen and pelvis. Computed tomography or magnetic resonance imaging of the spine and bone-scanning of the whole body were of little help in localizing the disease. In four of the twelve patients, an operation was performed on the basis of an incorrect diagnosis. In dealing with elderly patients who have radiculopathy, one should be suspicious that the cause is outside the spine."
-What percentage of patients in the study were confirmed to have hepatitis A and hepatitis B through IgM antibody testing?,"Hepatotoxicity of rifampin and isoniazid. Is it all drug-induced hepatitis? Serologic markers for hepatitis viruses were studied in 40 children who developed acute hepatitis during antituberculosis therapy with rifampin and isoniazid, with the aim of assessing the contributory role of these viruses toward producing hepatic injury. Hepatitis A and B were confirmed in 7.5 and 35% patients, respectively, by IgM antibodies. Epidemiologic evidence suggested the possibility of non-A, non-B hepatitis in at least a few of the remaining 23 children. Hepatitis B was seen more often in children with severe tubercular disease (72%) and was largely (92.8%) parenterally transmitted. The study highlights that the endemicity of viral hepatitis in developing countries, among other factors, could also be responsible for the reported higher incidence of hepatotoxicity from developing countries and also for the increased risk of hepatotoxicity seen in severe tubercular disease."
-What are the key differences observed between women with single and multiple admissions for hyperemesis gravidarum in this study?,"Hyperemesis gravidarum. A comparison of single and multiple admissions. Recurrent hyperemesis gravidarum is a frustrating and poorly studied complication of early pregnancy. Between 1979 and 1987, 140 women with emesis severe enough to require parenteral fluid and electrolyte replacement were admitted to the Medical University of South Carolina Hospital, Charleston, on 220 occasions. Thirty-nine of the 140 women were admitted on multiple occasions. A comparison of clinical characteristics of women with single and multiple admissions revealed no significant differences except that women admitted repeatedly for hyperemesis gravidarum were more likely to be nulliparous (P less than .05). Ptyalism (59% vs. 9%) and persistent vomiting for greater than 24 hours after admission (69% vs. 23%) were significantly more common among women who were admitted repeatedly (P less than .05). Despite published reports that hyperemesis gravidarum has no impact on ultimate perinatal outcome, this study indicated that women admitted repeatedly have a more severe nutritional disturbance, associated with significantly reduced maternal weight gain and neonatal birth weight. These risks argue for more aggressive antenatal treatment and increased fetal surveillance in pregnancies complicated by recurrent hyperemesis gravidarum."
-What was the main finding of the study regarding the use of vancomycin in empirical antibiotic therapy for febrile granulocytopenic cancer patients?,"Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group [published erratum appears in J Infect Dis 1991 Oct;164(4):832] A total of 747 febrile granulocytopenic patients with cancer were randomized to receive ceftazidime plus amikacin (CA) with or without vancomycin (V) as initial empirical therapy. Single gram-positive bacteremias responded in 29 (43%) of 68 patients treated with CA and in 48 (72%) of 67 treated with CAV (P = .001). For single gram-negative bacteremias and clinically documented and possible infections the response rates of CA and CAV were 80% and 63% (P = .17), 55% and 75% (P = .009), and 74% and 81% (P = .16), respectively. However, for patients with gram-positive bacteremia and for all other patients, there were no differences by treatment regimens in the proportion of febrile patients on each trial day (P = .85, P = .82, respectively) or in the duration of fever (P = .22, P = .93, respectively). Moreover, no patient with gram-positive bacteremia died during the first 3 days of true empirical therapy. Antibiotic-associated nephrotoxicity was more frequent in patients treated with vancomycin (6% vs. 2%, P = .02). These results do not support the empirical addition of vancomycin to initial antibiotic therapy in cancer patients with fever and granulocytopenia."
-What are the key enzymes involved in the bioconversion of primaquine's side chain?,"The conversion of primaquine into primaquine-aldehyde, primaquine-alcohol, and carboxyprimaquine, a major plasma metabolite. Although efficacy and toxicity of primaquine (PQ) depend on bioconversion, the process is poorly understood, even for carboxyprimaquine (CPQ), the major plasma metabolite. Earlier work to clarify drug metabolism showed that PQ could be converted quantitatively into CPQ, in vitro, with human erythroleukemic K562 cells or nonleukemic bone marrow supplemented with calf serum. We have now found--using systems with serum only, as well as with K562, bone marrow, and adult or embryonic liver cells--that the bioconversion of the side chain of PQ involves a branched pathway with at least three separate enzymes and two derivatives other than CPQ. An oxidase activity in serum converted PQ first into a novel side chain aldehyde (Y). Aldehyde dehydrogenase transformed PQ-aldehyde into CPQ in cell-free systems and in K562, bone marrow, and adult liver cells. Embryonic hepatocytes or bone marrow treated with 1,3-bis(2-chloroethyl)-1-nitrosourea did not produce CPQ; instead, they made a metabolite (Xc) that we could synthetize via PQ-aldehyde and identify as PQ-alcohol. PQ-alcohol replaced CPQ as the final product whenever alcohol-dehydrogenase prevailed over aldehyde dehydrogenase. These enzymes operated in intact cells and controlled the biotransformation of PQ absolutely. Unless both dehydrogenase were absent, inhibited, or deprived of coenzyme, potentially cytotoxic PQ-aldehyde intermediate did not accumulate. Some of the unique tissues schizonticidal and gametocidal effects of PQ may depend on the distribution pattern and relative activities of PQ oxidase, aldehyde dehydrogenase, and alcohol dehydrogenase in human subjects and in parasites."
-What is an inflammatory pseudotumor of the liver and how was it treated in this case report?,"Inflammatory pseudotumor of the liver causing biliary obstruction. Treatment by biliary stenting with 5-year follow-up. Inflammatory pseudotumors of the liver are rare lesions that are becoming increasingly recognized, possibly because of frequent use of abdominal computed tomography (CT) and ultrasonography. Most previously reported cases have been treated by hepatic resection. For this reason, we describe a patient with obstructive jaundice secondary to an inflammatory hepatic pseudotumor in the porta hepatis. Bilateral internal biliary stents were inserted, and the patient remains well 5 years later. The clinicopathologic features of inflammatory pseudotumors of the liver are described, as are the implications of accurate diagnosis. There have been no previous reports of biliary stenting in management of inflammatory hepatic pseudotumors."
-What percentage of patients with syncope were found to have orthostatic hypotension in this study?,"Syncope and orthostatic hypotension. PURPOSE: The purpose of this study was to determine the postural blood pressure response over time, the prevalence of orthostatic hypotension in patients with syncope, and the relationship of orthostatic hypotension to recurrence of symptoms. PATIENTS AND METHODS: We prospectively evaluated 223 patients with syncope in a standardized manner. Orthostatic responses were measured in a standardized fashion at 0, 1, 2, 3, 5, and 10 minutes or until symptoms occurred. Follow-up was obtained at 3-month intervals. Causes of syncope were assigned by predetermined criteria. RESULTS: Orthostatic hypotension (20 mm Hg or greater systolic blood pressure decline) was found in 69 patients (31%). The median time to reach minimal standing systolic blood pressure was 1 minute for all subjects. In patients with orthostatic hypotension (20 mm Hg or greater), mean time to reach minimum blood pressure was 2.4 minutes. The vast majority of patients with significant orthostatic hypotension had this finding within 2 minutes of standing. Orthostatic hypotension was common in patients for whom other probable causes of syncope were assigned. The recurrence of syncope was not related to the degree of orthostatic hypotension; however, the recurrence of dizziness and syncope as end-points was lower in patients with 20 mm Hg or greater systolic blood pressure reductions as compared with patients with lesser degrees of orthostatic blood pressure declines. CONCLUSION: Orthostatic hypotension is common in patients with syncope and is detected in the vast majority of patients by 2 minutes. Although symptom recurrence on follow-up was lower in patients with more severe orthostatic hypotension, the clinical significance of this finding needs to be further defined by future studies."
-What did the meta-analysis reveal about the effectiveness of prophylactic antibiotics in head and neck surgery?,"A meta-analysis of prophylactic antibiotics in head and neck surgery. Although it is generally agreed that prophylactic antibiotics are necessary for the prevention of postoperative wound infection, the choice of antibiotic regimen is controversial. In an attempt to determine the most effective antibiotic regimen, a meta-analysis of published clinical trials of prophylactic antibiotics for head and neck surgery was undertaken. The meta-analysis revealed a relative difference in infection rates of 43.7 percent in favor of the use of antibiotics versus placebo, of 8.3 percent in favor of multiple antibiotics versus a single antibiotic, of 13.7 percent in favor of multiple antibiotics versus cefazolin, and of 4.1 percent in favor of multiple-day prophylaxis versus single-day prophylaxis. This meta-analysis suggests that a 1-day course of clindamycin may be the most effective prophylactic antibiotic regimen for head and neck surgery."
-What are the key immunohistochemical and electron microscopic findings of the ossifying fibromyxoid tumor of soft parts?,"Ossifying fibromyxoid tumor of soft parts. Additional observations of a distinctive soft tissue tumor. The author studied four subcutaneous soft tissue tumors, similar to those recently described by Enzinger and associates (Am J Surg Pathol 1989;13:817) by the name ""ossifying fibromyxoid tumor,"" by immunohistochemistry and electron microscopy to further understand the cellular nature of this lesion. The four tumors were composed of uniform round cells often surrounded by a lacunar space. The tumors often contained a peripheral zone of metaplastic bone. The cellularity was high, but the mitotic rate was low, suggesting a benign or borderline nature of the lesion. Longer follow-up was available for three cases, showing recurrence-free survival times of 11, 8, and 3 years. Immunohistochemistry studies revealed that all tumors were strongly positive for S-100 protein and focally positive for Leu-7, whereas melanoma-specific marker HMB45 was negative. Vimentin was the main type of intermediate filament protein, and one case also contained scattered glial fibrillary acidic protein-positive cells. Epithelial markers (keratins, epithelial membrane antigen), desmin, and muscle actins were negative. Electron microscopic examination showed partial, sometimes reduplicated, basal lamina surrounding many cells. Complex cell processes were also present. No myofilaments were found. The immunohistochemical and electron microscopic results may suggest that this tumor has Schwann's cell differentiation."
-What changes in colonic mucosal blood flow were observed after exposure to 10% acetic acid in the rat study?,"Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. The hypothesis that a significant reduction in colonic mucosal perfusion, and hence ischemic injury, precedes the development of mucosal ulceration and inflammation is tested in this report. The microcirculatory changes in the rat colonic mucosa within 1 hr of topical exposure to 10% acetic acid were assessed. Colonic mucosal blood flow signals measured by laser Doppler flowmetry were significantly reduced to 61 +/- 8, 52 +/- 10, and 37 +/- 13% (mean +/- SEM) of baseline values at 1 min, 4 min, and 10 min after the colonic mucosa was exposed to 10% acetic acid, respectively, but not in controls exposed to saline. After the start of application of 10% acetic acid (for 4 min), in vivo microscopy studies demonstrated that colonic mucosal ischemia (stasis of the red blood cells in the mucosal capillaries) occurred at 9 +/- 5 min (mean +/- SEM). Evidence of endothelial cell death (failure to exclude a fluorescent dye, propidium iodide, by endothelial cells) developed at 25 +/- 10 min (mean +/- SEM). These findings indicate that within minutes after contact of the colonic mucosa with 10% acetic acid, colonic mucosal ischemia develops, followed shortly by death of endothelial cells. The data do not establish a cause-and-effect relationship between the reductions in mucosal blood flow and loss of endothelial cell viability in response to acetic acid. Nevertheless, because these events occur at such an early time point, they may play a pathogenetic role in the development of the subsequent inflammatory and ulcerative changes in this animal model of colitis. Further studies to define the potential causal relationships between these parameters are warranted."
-What alternative agents were used in epidural infusions for patients with intractable non-cancer pain?,"Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or vertebral body compression fracture were treated with alternative solutions in an epidural route. For maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used, and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5% bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache, nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also advantageous for programmable pumps because it is 100 times more potent than morphine and therefore allows longer pump refill times and higher infusion doses. Although this study was done on a limited number of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for non-cancer patients provide significant alternative drug combinations and routes."
-How does the HIV-1 protease affect the processing of the NF-kappa B precursor (p105) during infection?,"Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. Transcription of the human immunodeficiency virus type-1 (HIV-1) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells. T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat. This factor consists of two DNA-binding subunits of relative molecular mass 50,000 (50K) associated with two 65K subunits. It is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex. External stimuli, including those that activate T cells, result in nuclear translocation of active NF-kappa B. The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor (p105) (V.B., P.K. and A.I., manuscript submitted). The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105. Because HIV-1 requires active NF-kappa B for efficient transcription, we tested the effect of HIV-1 infection on the processing of the human 105K precursor. We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex."
-How does Trichinella spiralis infection affect small intestinal motor activity and transit time?,"Trichinella spiralis infection alters small bowel motor activity in the fed state. The effect of Trichinella spiralis infection on small intestinal transit and motor activity in the fed state during the intestinal phase of infection was studied. Contractions were recorded by strain gauge transducers, and mean transit time was measured by marker dilution technique. The mean amplitude and area of individual phasic contractions decreased, but no change occurred in their mean duration during trichinosis. The total amplitude and area of phasic contractions also decreased; this was caused by a decrease in the frequency of contractions as well as a decrease in the mean parameters. The reduction in the total duration was entirely caused by the decrease in frequency. The reduction in the total parameters of all contractions was the result of a reduction in the same parameters for both propagating and nonpropagating contractions. However, the decrease in the parameters of propagating contractions was much greater. Also, there was a decrease in the distance of propagation of phasic contractions. The transit time as a result of phasic contractions increased during T. spiralis infection. Additionally, T. spiralis infection induced giant migrating contractions in the fed state that were never observed during control. Chyme was propelled very rapidly and effectively by giant migrating contractions. The findings of the present study suggest that during diarrhea induced by T. spiralis infection, the phasic contractions may act to decrease transit and, hence, allow more contact time for absorption of water and nutrients. However, this response may be counter-balanced by giant migrating contractions that rapidly propel chyme into the colon and compound the diarrhea associated with T. spiralis infection."
-What is the significance of the STRO-1 monoclonal antibody in identifying stromal cell precursors in human bone marrow?,"Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM], erythroid bursts [BFU-E], and mixed colonies [CFU-Mix]). Fibroblast colony-forming cells (CFU-F) are present exclusively in the STRO-1+ population. Dual-color cell sorting using STRO-1 in combination with antibody to glycophorin A yields a population approximately 100-fold enriched in CFU-F in the STRO-1+/glycophorin A+ population. When plated under long-term BM culture (LTBMC) conditions, STRO-1+ cells generate adherent cell layers containing multiple stromal cell types, including adipocytes, smooth muscle cells, and fibroblastic elements. STRO-1+ cells isolated from LTBMC at later times retain the capacity to generate adherent layers with a cellular composition identical to that of the parent cultures. The STRO-1-selected adherent layers are able to support the generation of clonogenic cells and mature hematopoietic cells from a population of CD34+ cells highly enriched in so-called long-term culture-initiating cells. We conclude that antibody STRO-1 binds to BM stromal elements with the capacity to transfer the hematopoietic microenvironment in vitro."
-What was the success rate of the percutaneous posterolateral lumbar discectomy procedure in this study?,"Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise."
-What factors contribute to the varying prevalence of obesity across different population groups?,"Obesity in minority populations: policy implications of research. Obesity is a major health problem for many Americans, with an overall prevalence for adults of approximately 25% and a range for specific subgroups of 24-75%. This range is striking and reflects many factors shown to influence the development and maintenance of obesity, including physical activity, diet, ethnicity, income, education, and genetic susceptibility. Many minority populations have higher prevalences of obesity and, thus, experience its adverse health consequences disproportionately. Research in diverse populations indicates that the relative importance of risk factors for cardiovascular disease varies in many populations. Data characterizing the profile of risk factors, including obesity and physical activity, for various special populations are limited and some, such as obesity, are based on standards developed in the general population. For public health policy and interventions to succeed, they must address the needs of special populations and of the overall population. This paper discusses some of the relevant broader social and research issues."
-What method was used to evaluate body composition in alcohol-induced migraine patients?,"Bioelectrical impedance assay (BIA) of total body composition in alcohol-induced migraine patients. Preliminary report. ""Whole body composition"" was investigated in 30 people subject to alcohol-induced migraine. The control group was 30 people matched for age, sex, height and weight, who were not subject to migraine and who consumed moderate amounts of alcohol. The following were evaluated: anthropometric data, alcohol intake in grams per day, total body water, fat-free mass, fat mass, and body mass index (kg/m2). Two methods of measurement were used: skin fold thickness evaluation, and bioelectric impedance assay (BIA). BIA is a non-invasive method based on the principle that lean tissues conduct a low frequency alternating current of electricity better than do fatty tissues. Body mass index was increased in the alcohol-induced migraine patients (p less than 0.04), as was fat mass, (p less than 0.03) as evaluated by skin fold measurements. Bioelectric impedance assay demonstrated a slight total body water increase in alcohol-induced migraine patients (p less than 0.07). Possibly, if this total body water increase was reflected at the neuronal level, the bioelectric properties of the migrainous brain may be altered, thus creating a hypothetical link with the phenomenon of spreading depression."
-What percentage of families with alcohol-related problems were identified by physicians in the study?,"Detection of alcoholism in hospitalized children and their families The study sought to measure provider recognition of family alcohol-related problems among hospitalized children and to identify characteristics distinguishing ""positive"" families. The study sample (N = 147) was drawn from admissions to the general pediatric medical service of a metropolitan teaching hospital. Positivity was assessed through parent and patient interviews that included standard alcohol abuse screening instruments. Provider recognition was assessed through record review and physician interview. Of the 22 families screened positive, only one was so identified by the child's attending or resident physician. Positive and ""negative"" families were similar in most respects, although parents in positive families were more likely to report stress and sleeping problems and adolescents were more likely to report being troubled by a parent's drinking. The similarity of positive and negative families and the low pediatrician recognition rate suggest that alcohol problems are likely to go unnoticed without a conscious screening effort."
-What is Generalized Resistance to Thyroid Hormone (GRTH) and how was it detected in this case study?,"Neonatal detection of generalized resistance to thyroid hormone [published erratum appears in JAMA 1991 Feb 20;265(7):869] Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. We detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L (normal, 84 to 232 nmol/L). Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels (liothyronine sodium, 21 micrograms/kg per day, and levothyroxine sodium, 44 micrograms/kg per day) were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH."
-What were the clinical results and Harris hip ratings for different types of hip prostheses in this study?,"Total hip replacement with cemented, uncemented, and hybrid prostheses. A comparison of clinical and radiographic results at two to four years. One hundred and thirty-one patients who had 144 cemented or uncemented hip prostheses were followed prospectively for two to four years. A cemented or a hybrid prosthesis (consisting of a cemented femoral component and an uncemented acetabular component) was used in men older than seventy years, in women older than sixty years, and in younger patients in whom adequate initial fixation could not be obtained without cement. Uncemented, porous-surfaced implants were used in all other patients. The over-all clinical results were similar for the three groups. For the fifty-two hips that had a cemented prosthesis, the mean total Harris hip rating was 91 points and the score for pain, 42 points; for the twenty-seven hips that had a hybrid prosthesis, 90 and 43 points; and for the sixty-five hips that had an implant allowing ingrowth of bone in both the acetabulum and the femur, 95 and 43 points. Two prosthetic stems that were designed to allow ingrowth of bone had aseptic loosening; one was revised. Pain in the thigh, usually slight and not disabling, occurred at one year in 24 per cent of the patients in whom a femoral component allowing ingrowth had been used; the prevalence of pain then declined. The incidences of migration of the components and of radiolucent lines were greater in the acetabula that had a cemented component than in those that had a cup allowing ingrowth of bone."
-What was the effect of oral nitroglycerin on portal blood velocity in cirrhotic patients according to this study?,"The effect of oral nitroglycerin on portal blood velocity as measured by ultrasonic Doppler. A double blind, placebo controlled study. We studied the effect of oral nitroglycerin on portal blood velocity (PBV) in 20 cirrhotic patients by a double blind, placebo controlled method using noninvasive Doppler sonography. After we obtained baseline Doppler in the fasting state, 0.6 mg nitroglycerin or placebo was given orally and the mean of 3 s averaged mean PBVs was repeated at 5 min intervals for 60 min. Ten patients each received nitroglycerin or placebo. Portal vein flows were antegrade in all. Of the 10 patients receiving nitroglycerin, seven (P = 0.002) showed a greater than 10% fall in the mean PBVs for at least 15 min. Of these seven ""responders,"" five patients had a 10% decrease in mean systemic blood pressure for at least 15 min. None of the ""nonresponders"" had systemic hypotension. Our study suggests that the PBV-reducing effect of nitroglycerin in cirrhotics may be explained in part by systemic hypotension."
-What factors were considered in determining the safety of vaginal delivery for the second twin?,"Twin delivery: influence of the presentation and method of delivery on the second twin. To ascertain the perinatal mortality and morbidity in the second twin as related to its presentation and method of delivery, we reviewed the data on 578 sets of twins delivered from 1980 to 1987 and included 397 sets in whom both twins were greater than or equal to 1000 gm, without lethal anomalies, and in whom the first twin presented as a vertex. The perinatal outcome comparing twin A (all vertex) with twin B (vertex or nonvertex) with cesarean section or vaginal delivery was analyzed. No statistically significant difference in perinatal mortality or morbidity was found in comparing the nonvertex second twin delivered vaginally or by cesarean section. The one perinatal death and significant perinatal morbidity occurred in infants weighing less than 1500 gm or at less than 32 weeks' gestational age. It is concluded that vaginal delivery, irrespective of the position of the second twin, is valid in selected cases as long as fetal weight is greater than 1500 gm and the gestational age is greater than or equal to 32 weeks."
-What was the objective response rate of menogaril in patients with cisplatin-refractory advanced ovarian carcinoma?,"A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic. Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment."
-What were the key findings of the study comparing calcium channel receptors in normal and myelodysplastic bladders?,"The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders. The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function."
-What did the study reveal about the relationship between IgA2 allotypes and IgA nephropathy in Black patients?,"IgA nephropathy in blacks: studies of IgA2 allotypes and clinical course. The prevalence of IgA nephropathy (IgAN) varies among racial groups, being most common among Caucasians and Orientals and rare in Blacks. Other investigators have hypothesized that the risk for IgAN may be influenced by the IgA2 allotype. It has been suggested that the rare Black patients with IgAN may be homozygous for the A2m(1) allele which predominates in Whites, but is less common in Blacks. In a multicenter study, 27 Black IgAN patients were enrolled to investigate this hypothesis and analyze the clinical course of disease in Blacks. The IgA2 allotypes of 18 Black patients and 14 controls were determined using restriction fragment length polymorphism analysis. Three patients were homozygous for the A2m(1) allele, four were homozygous for A2m(2) and 11 were heterozygous. The respective allelic frequencies of A2m(1) and A2m(2) were 0.47 and 0.53 and did not differ significantly from Black controls. Most clinical manifestations of disease did not significantly differ with respect to distribution of the two alleles, although the gender ratio differed between the homozygous A2m(1) and heterozygous patients. The presence of the A2m(1) allele did not increase the risk for IgAN, and the presence of the A2m(2) allele or homozygosity for this allele did not protect Blacks from the development of IgAN."
-What diagnostic tests were performed on patients with angina pectoris-like pain and normal coronary angiograms?,"Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms. Twenty patients with angina pectoris-like pain, normal coronary angiography and abnormal exercise 201Tl scans were investigated by means of haemodynamic, coronary sinus blood flow and lactate determinations before and after cold provocation, pacing and dipyridamole infusion. Radionuclide angiography, a new exercise 201Tl scan and noninvasive hyperventilation and ergonovine tests were performed. Intracoronary infusions of acetylcholine were given in increasing doses and a second coronary angiogram in combination with a 201Tl scintigram was performed. Despite a previously pathological 201Tl scintigram, with reversible perfusion defects, only ten of the patients had reversible perfusion defects at the second investigation. Hyperventilation and ergonovine tests did not result in ECG signs indicative of coronary spasm. Intracoronary infusion of acetylcholine resulted in a diffuse coronary constriction in 3 of 14 patients, and in one patient a perfusion defect was observed on thallium scintigram. In conclusion, although most of the common methods for inducing coronary vasospasm were used, no consistent pattern of reaction was found to explain the chest pains experienced in this group of patients."
-What are the key pathological characteristics of Erdheim-Chester disease?,"Erdheim-Chester disease. Case report with autopsy findings. Erdheim-Chester disease is a rare pathologic entity characterized by symmetrical radiodensities in the metaphyseal and the diaphyseal portions of the long bones. Fibrosis, osteoblastic cortical bone deposition, and fibroxanthomatous granulomas with lipid-laden macrophages and multinucleated giant cells, which have a particular tropism for connective and adipose tissues, are the pathologic hallmarks. To our knowledge, 27 cases have been reported in the literature since the entity was first described in 1930. Protean clinical features range from a focal and asymptomatic process to a multisystemic infiltrative disease. We describe the clinical course of a new case and review the extensive pathologic findings at autopsy, including those demonstrated by light and electron microscopy and cytochemical and immunocytochemical studies."
-What were the minor complication rates for different trocar insertion methods in this laparoscopic study?,"Comparison of direct insertion of disposable and standard reusable laparoscopic trocars and previous pneumoperitoneum with Veress needle. A randomized prospective study was conducted to evaluate the ease of use and safety of direct insertion of laparoscopic trocars. Comparison of previous pneumoperitoneum by Veress needle insertion with direct insertion of the reusable conventional laparoscopic trocar and direct insertion of the disposable shielded trocar revealed minor complication rates of 22, 6 and 0%, respectively. No major complications occurred in this series of 200 patients."
-What percentage of acoustic tumors showed no detectable growth or apparent regression in this conservative treatment study?,"Conservative treatment of patients with acoustic tumors. Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy."
-What is the rare medical condition described in this case report involving a plasmacytoma and superior vena cava syndrome?,"Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described."
-How does hypoxic ventilation affect the pulmonary arterial pressure-flow relationship in a canine preparation?,"Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation. We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure."
-What is the significance of detecting antineutrophil cytoplasmic antibodies (ANCA) in classifying patients with necrotizing arteritis?,"Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. PURPOSE: Assessment of the value of determination of antineutrophil cytoplasmic antibodies (ANCA) and its specificities for classification of patients with biopsy-proven necrotizing arteritis. PATIENTS AND METHODS: The serum samples of 28 consecutive patients with biopsy-proven vasculitis involving medium- and/or small-sized arteries were tested for ANCA by an indirect immunofluorescence technique, by neutrophil extract enzyme-linked immunosorbent assay (ELISA), and by catching ELISA. RESULTS: Eight patients had Churg-Strauss syndrome; six had myeloperoxidase (MPO) antibodies, and in the other two patients, ANCA were not detected. Six patients had polyarteritis nodosa (PAN) limited to the skin and the musculoskeletal system; ANCA were not detected in these patients. Two patients had systemic PAN and both had MPO antibodies. The remaining 12 patients had overlapping clinical features of the different forms of vasculitis. Five patients had polyarteritis in combination with chronic nasal inflammation and glomerulonephritis compatible with Wegener's granulomatosis (WG) but without granulomas in the respiratory tract. All five patients had 29-kd serine protease antibodies. Two patients had polyarteritis in combination with nasal polyposis and asthma compatible with Churg-Strauss syndrome, but eosinophilia was not detected. Both patients had MPO antibodies. Three patients with unclassified granulomatous arteritis had either elastase antibodies or ANCA of unknown specificity. One patient with unclassified systemic vasculitis had 29-kd serine protease antibodies, and one patient with necrotizing arteritis of the bowel in combination with Schonlein-Henoch purpura was negative for ANCA. CONCLUSION: Determination of ANCA and its specificities is a useful adjunct to the classification of patients with biopsy-proven necrotizing arteritis. Within the spectrum of idiopathic vasculitides, 29-kd serine protease antibodies are associated with WG, MPO antibodies are associated with Churg-Strauss syndrome and systemic PAN, and PAN limited to the skin and the musculoskeletal system is not associated with ANCA."
-What are the current challenges in lung transplantation despite its improved success rates?,"Current status of lung transplantation. Techniques and indications for single and bilateral lung transplantation have evolved significantly in the past several years. Lung transplantation has entered a new era in which transplantation can be achieved with the same degree of success as that achieved with other major organ transplants. Many problems, common to organ transplantation remain to be solved including availability of suitable donor organs, improved immunosuppressive regimens, and the ability to properly diagnose and effectively treat organ rejection."
-What percentage of patients experienced complications in this five-year vascular audit?,"Five-year vascular audit from a district hospital. Vascular patients under the care of one surgeon over a 5-year period have been reviewed, from computer-based discharge records, with regard to in-hospital measures of outcome to determine whether or not surgery was being performed to an acceptable standard. Out of 466 procedures, 30 per cent of patients had at least one complication, 14 per cent had further surgery and 9 per cent died. Outcome was examined within the following treatment groups: aorto/iliac aneurysm, aortofemoral bypass, femoroproximal popliteal bypass, femorodistal popliteal bypass, femorocrural bypass, embolectomy and percutaneous transluminal angioplasty. Patients having below-knee bypass surgery were found to have an unacceptably high rate of complications, reoperations and amputations. An overall rate of reoperation for postoperative bleeding of 5 per cent was also considered to be high. With these exceptions, it was concluded that the surgery was being performed to an acceptable standard, but that comparative audit of this type remained difficult while there was a deficiency of national statistics against which the work of individual surgeons could be judged."
-What were the most common causes of persistent vegetative state (PVS) among the patients in this study?,"Clinical characteristics of patients in the persistent vegetative state Little is known concerning the specific clinical characteristics of patients in persistent vegetative states (PVS). Fifty-one patients from four nursing homes, approximately 3% of the total patients, were identified as being in a PVS. The mean age of the patients was 64.8 +/- 3.2 years (range, 19 to 96 years) and the mean duration of the PVS was 3.3 +/- 5.0 years (range, 1 to 16.8 years), with 13 patients' PVS being longer than 5 years. Cerebrovascular accidents and dementia were the most common causes of the PVS, accounting for 32 of the cases (63%). In the younger patients cerebral trauma secondary to motor vehicle accidents was the most common cause. All 51 patients were fed via tube feeding and 35 patients had urinary catheters (75%). All patients were receiving daily medications, with greater than 50% taking daily vitamins. Over 30% were taking digitalis and/or diuretics and over 32% were taking H2 blockers. Transfer of patients to an acute care hospital was not uncommon, with 31 patients (61%) requiring 63 acute care hospitalizations during their stay in the nursing home. As expected, infections were the most common reason for acute care hospitalization, although 15 of the patients were hospitalized for surgical procedures. Another common problem encountered by the patients was pressure sores, with 78% of patients requiring specific therapy for at least one pressure sore. Surprisingly, only 27 (53%) of 51 patients had a specific resuscitation status designation in the medical chart, and neither presence of a chart designation nor specific resuscitation order was related to the patient's age or the cause or duration of PVS. From these data it would appear that clinical characteristics of patients in PVS are variable. Some patients are young, others are old. The cause varies from cerebrovascular accidents to cerebral trauma. Survival may be prolonged; complications are not uncommon, with some patients requiring acute care hospitalization."
-What was the distribution of ischemic episodes in patients with stable angina pectoris during a 24-hour period?,"Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia. The circadian variation of total ischemic activity was examined during 3289 hours of ambulatory ECG monitoring in 101 patients with stable angina pectoris and proved coronary artery disease, who were not receiving any prophylactic antianginal therapy. The 101 patients displayed 411 episodes of ischemia, 312 (76%) of which were silent; a circadian rhythm was noted for the occurrence of total and silent ischemia. Thirty-eight percent of the ischemic episodes occurred between 6 AM and 12 noon, and total and silent ischemia were significantly more frequent during this period compared with the other three 6-hour periods (p less than 0.01); a lesser peak was noted in the evening. The effects of metoprolol and combined therapy with metoprolol and nifedipine on the circadian variation of ischemic activity were studied in two subgroups of patients in a random, double-blind study design (31 patients receiving metoprolol and 42 receiving combined therapy). During therapy with metoprolol the morning increase in ischemic activity was attenuated, and the highest frequency of ischemia was then noted in the evening (6 AM to 12 noon compared with 6 PM to 12 midnight; p less than 0.05). Combined therapy abolished the morning peak as did metoprolol monotherapy, but even the evening increase in ischemic activity was attenuated (p less than 0.05). The diurnal distribution of the mean heart rate at the onset of ischemia, when patients were off therapy, showed a morning increase similar to the increase in ischemic activity but no second peak in the evening."
-What is lymphedema-distichiasis syndrome and why is it important for ophthalmologists to be aware of it?,Hereditary lymphedema and distichiasis. Two patients with lymphedema-distichiasis syndrome illustrate that both Milroy's disease and late-onset hereditary lymphedema are sometimes associated with distichiasis. It is important for ophthalmologists to be aware of the lymphedema-distichiasis syndrome because of its ophthalmic manifestations and the associated systemic abnormalities that can be potentially life threatening.
-What is the primary goal of rapidly controlling severe hypertension?,"Management of hypertensive emergencies: changing therapeutic options. Rapid lowering of severe hypertension is essential to prevent irreversible damage to vital organs. The patient's clinical status should be evaluated, noting particularly cardiac, neurologic, and renal functions. Choice of treatment should be based on speed and efficacy of action and on hemodynamic, vascular, and renal consequences. It is also important to preserve circulatory homeostasis and vital organ function. Sodium nitroprusside, labetalol, diazoxide, and hydralazine have been used parenterally for rapid control of severe hypertension, but they do not always produce optimal, balanced hemodynamic effects. Calcium antagonists have been advocated because of their beneficial circulatory effects. Nicardipine, a new dihydropyridine calcium antagonist, produces significant antihypertensive effects, and when given intravenously, results in a rapid fall in blood pressure. Studies have confirmed that nicardipine is effective and safe in the management of severe hypertension and hypertensive crises. Because the aim of rapidly controlling severe hypertension is to prevent target organ dysfunction, nicardipine therapy offers a useful additional option in the clinical management of severe hypertension and hypertensive crises."
-How did the picture book help children cope with venous blood sampling in the study?,"Preparing children for venous blood sampling. A convenience sample of 100 children, aged 6-12 years, attending Kuwait government hospital laboratories for venous blood sampling was studied. A picture book was used to prepare half of the children for the procedure. Preparation was carried out just prior to sampling and took less than 5 min. The story provided a simple description of venous blood sampling, and why it is carried out; it stressed that the pain is noticeable but not unbearable, and that children will experience less pain if they relax their arm and cooperate with the technician. Prepared children reported significantly less pain, and radial pulse rates confirmed that they were less distressed by the procedure. Observers' and parents' evaluations also indicated that prepared children coped better. Various explanations for the benefits observed are discussed, together with requirements for managing the pain, fear and stress experienced by children during medical treatment."
-How does outlet obstruction constipation affect urinary flow parameters in women?,Relationship between outlet obstruction constipation and obstructed urinary flow. Ten women with symptoms and radiological features of outlet obstruction constipation underwent urodynamic bladder studies. The results were compared with ten age- and sex-matched controls. The mean (s.e.m.) peak flow rate for patients was 19.4 (6.4) ml/s compared with 32.1 (7.2) ml/s for controls (P less than 0.05). The mean (s.e.m.) voiding time for patients was 62.9 (23.7) s against a corresponding value of 15.6 (6) for controls (P less than 0.05). The mean (s.e.m.) bladder volume in patients was 482 (80) ml compared with a control value of 254 (112) ml (P less than 0.03). The mean (s.e.m.) detrusor pressure during the voiding phase was 53.3 (12) cmH2O. These results demonstrate that patients with outlet obstruction constipation have a generalized pelvic floor disorder resulting in obstructed urinary flow.
-What are the key characteristics of peritoneal cystic mesothelioma based on the three reported cases?,"Cystic mesothelioma of the peritoneum. A report of three cases. Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis."
-"What were the three surgical techniques used for treating chronic ear disease in this study, and how did their post-operative outcomes compare?","Surgery for chronic ear disease in a non-university hospital: open cavity, obliteration and intact canal wall techniques. The long-term results of surgery for chronic suppurative middle ear disease at a non-university ENT-clinic (Vasa Central Hospital, Finland) are reported. The material consisted of 273 ears, 65 of which had been operated on by open cavity techniques, 178 by the original Palva obliteration method, and 30 by the intact canal wall method. Post-operative cholesteatoma occurred equally frequently with the two canal wall down methods (7.7 and 7.3%, respectively) but was more frequent after intact canal wall surgery (23.3%). Hearing was better and the infection rate lower with obliteration than with open cavity techniques. Post-operative infection was the least frequent and the hearing result best in the intact canal wall ears, but compared to the other two groups the extent of disease found at surgery was considerably less in this group. The obliteration operation proved to be a safe method in the hands of a practising otologist outside university clinics."
-What unique technique was used to establish the DuPro-1 human prostate adenocarcinoma cell line?,"Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer."
-How does induced hypertension affect neuronal injury and edema formation after temporary middle cerebral artery occlusion in rats?,"Induced hypertension during restoration of flow after temporary middle cerebral artery occlusion in the rat: effect on neuronal injury and edema. The effect of hypertension instituted during restoration of flow after focal ischemia was studied. After the middle cerebral artery (MCA) of 12 rats was occluded for 2 hours, the ligatures were released and flow was restored for a period of 2 hours. In the control group, mean arterial pressure (MAP) was not manipulated. In the hypertensive group, the MAP was elevated by 25-30 mm Hg immediately after reestablishment of MCA patency. The area of neuronal injury, determined by 2,3,5-triphenyltetrazolium staining, was significantly smaller in the hypertensive group. Specific gravity, determined by microgravimetry, did not differ between groups. The data demonstrate that modest hypertension, when induced during reperfusion after 2 hours of MCA occlusion, reduces neuronal injury and does not exacerbate edema formation."
-What percentage of breast reconstructions performed at the University of Texas M.D. Anderson Cancer Center experienced some degree of flap necrosis?,"The early management of flap necrosis in breast reconstruction. Flap necrosis is a potential complication of any type of breast reconstruction. Of 302 breast reconstructions performed by the author at the University of Texas M.D. Anderson Cancer Center, some degree of flap necrosis occurred in 59 (19.5 percent). Small areas of flap necrosis can be managed with simple observation, but secondary healing may not be complete for months. Early and aggressive excision of the ischemic tissue with immediate primary closure often can achieve rapid primary healing. In addition, early revision and reshaping of the breast may, in selected patients, permit achievement of a significantly better final result. This is true not only for TRAM and latissimus dorsi flaps, but also for the mastectomy flap necrosis sometimes encountered in immediate reconstruction with simple implants or tissue expanders."
-How did monthly pulses of vincristine and prednisone impact the relapse-free survival of children with low-risk acute lymphoblastic leukemia in the CCG-161 study?,"Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group. On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX."
-How did the researchers find that IGFBP-3 gene expression is increased in renal adenocarcinoma tissues?,"Expression of the insulin like growth factor-binding protein 3 (IGFBP-3) gene is increased in human renal carcinomas. After we had established that the IGFBP-3 gene is expressed in normal human kidney we examined renal adenocarcinoma tissue for alterations of the expression of this gene. For this purpose we prepared poly(A)+ RNA from normal kidney tissue and adjacent renal adenocarcinoma of 18 adult patients and compared the levels of IGFBP-3 mRNA by Northern analysis in both samples. The mean content by densitometry was markedly increased in the carcinoma tissues; in 17 of 18 patients the carcinoma contained significantly more IGFBP-3 mRNA than the normal kidney sample. The highest mRNA levels were found in patients with N2 and N3 lymph node extensions. Comparative Southern analysis of paired samples of four of these patients did not reveal amplification of the gene as the cause of these increased mRNA levels. In one patient, however, we identified a restriction fragment length polymorphism (RFLP) present in normal and malignant cellular DNA. This suggests a participation of the IGFBP-3 gene in the development of human renal cell cancer."
-What differences in mortality and kernicterus were observed between the jaundiced RHA/N-j and ACI/N-j rat strains?,"A difference in mortality between two strains of jaundiced rats. Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. Two new, inbred rat strains that carry the Gunn mutation are described. These were developed by breeding the mutant Gunn gene (j) into the RHA/N and ACI/N strains, producing the new lines, which were designated RHA/N-j and ACI/N-j. Liver assay confirmed the absence of transferase activity in jaundiced rats from both of the new strains, but marked differences in mortality between the strains were observed. The mortality of jaundiced RHA/N-j rats through 8 weeks was the same as that of their nonjaundiced littermates (20%). In contrast, mortality of jaundiced ACI/N-j rats was distinctly greater than that of their nonjaundiced littermates (81% vs 34%, P less than .001). Signs of kernicterus such as ataxia were much more frequent in jaundiced ACI/N-j rats than in jaundiced RHA/N-j rats (73% vs 11%, P less than .001). Both strains had comparable albumin concentrations through 8 weeks of age. Serum bilirubin concentrations were also comparable, except for a small but significant difference at 20 days of age (ACI/N-j = 294 mumols/L, RHA/N-j = 248 mumols/L, P less than .01). Similarly, the bilirubin-to-albumin ratios were comparable except for a significantly higher ratio at 20 days of age in the ACI/N-j rats (ACI/N-j = 0.70, RHA/N-j = 0.51, P less than .01). Thus, the RHA/N-j strain is unusual in that the jaundiced animals remain healthy. Conversely, the ACI/N-j animals demonstrate a high incidence of kernicterus with mortality."
-What is asymptomatic bacterascites and how does it differ from spontaneous bacterial peritonitis?,"Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required."
-What was the primary objective of the study on fetal sheep?,"Fetal hypertension induced by norepinephrine infusion and umbilical artery flow velocity waveforms in fetal sheep. This study was designed to examine the effects of fetal hypertension on the umbilical artery pulsatility index. Fetal arterial blood pressure and umbilical venous pressure were measured in eight sheep, 3 to 5 days after surgery. Umbilical blood flow was measured with an electromagnetic flowmeter around the common umbilical vein. Umbilical artery flow velocity waveforms were obtained either by an indwelling 5 MHz pulsed Doppler device (n = 4) or transcutaneously by a 4 MHz continuous-wave Doppler device (n = 4). Fetal blood pressure was raised by intravenous infusion of norepinephrine 10 micrograms/min during 5 minutes. Norepinephrine infusion resulted in elevated arterial and umbilical venous pressures, accompanied by a bradycardia during the first 3 minutes. Umbilical blood flow, calculated placental vascular resistance, and umbilical artery pulsatility index did not change. After atropine administration, the norepinephrine-induced elevated arterial and umbilical venous pressures were accompanied by tachycardia, increased umbilical blood flow, and no change in placental vascular resistance and umbilical artery pulsatility index. It is concluded that fetal arterial hypertension provoked by norepinephrine infusion has no effect on placental vascular resistance, umbilical blood flow, and umbilical artery pulsatility index."
-What makes this case of prolactin-producing pituitary carcinoma unique in medical literature?,"Prolactin-producing pituitary carcinoma with pulmonary metastases. Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34-year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed."
-What potential complication occurred during the ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma?,Renal pelvic explosion during conservative management of upper tract urothelial cancer. Ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma is a relatively new and limited procedure. We present a case of intrarenal explosion during ureteroscopic fulguration.
-What are the five response subtypes observed in the cutaneous test examining the flushing response to ethanol and acetaldehyde among Chinese of Han ethnicity?,"Cutaneous vasomotor sensitivity to ethanol and acetaldehyde: subtypes of alcohol-flushing response among Chinese. A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol-induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers."
-What were the key findings regarding parental occupational exposures and childhood leukaemia risk in this study?,"Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead OBJECTIVE--To determine whether parental occupations and chemical and other specific exposures are risk factors for childhood leukaemia. DESIGN--Case-control study. Information on parents was obtained by home interview. SETTING--Three areas in north England: Copeland and South Lakeland (west Cumbria); Kingston upon Hull, Beverley, East Yorkshire, and Holderness (north Humberside), and Gateshead. SUBJECTS--109 children aged 0-14 born and diagnosed as having leukaemia or non-Hodgkin's lymphoma in study areas during 1974-88. Two controls matched for sex and date and district of birth were obtained for each child. MAIN OUTCOME MEASURES--Occupations of parents and specific exposure of parents before the children's conception, during gestation, and after birth. Other adults living with the children were included in the postnatal analysis. RESULTS--Few risk factors were identified for mothers, although preconceptional association with the food industry was significantly increased in case mothers (odds ratio 2.56; 95% confidence interval 1.32 to 5.00). Significant associations were found between childhood leukaemia and reported preconceptional exposure of fathers to wood dust (2.73, 1.44 to 5.16), radiation (3.23, 1.36 to 7.72), and benzene (5.81, 1.67 to 26.44); ionising radiation alone gave an odds ratio of 2.35 (0.92 to 6.22). Raised odds ratios were found for paternal exposure during gestation, but no independent postnatal effect was evident. CONCLUSION--These results should be interpreted cautiously because of the small numbers, overlap with another study, and multiple exposure of some parents. It is important to distinguish periods of parental exposures; identified risk factors were almost exclusively restricted to the time before the child's birth."
-What is L-tryptophan-induced eosinophilia-myalgia syndrome and what symptoms did the patients in this study experience?,"L-tryptophan-induced eosinophilia-myalgia syndrome. This report describes three Belgian cases of the eosinophilia-myalgia syndrome associated with the use of L-tryptophan-containing products. Three women, aged 51, 53 and 73 years, were taking L-tryptophan for 2 months to 2 years, at 500, 1500, and 2250 mg d-1, respectively. All developed disabling myalgias, fatigue, and a variable skin rash, in association with marked eosinophilia. In one patient, symptoms and eosinophilia reappeared after rechallenge with L-tryptophan. Discontinuation of the drug resulted in gradual disappearance of the symptoms, signs and laboratory abnormalities in two patients. One patient was treated with corticosteroids because of persisting myalgias. Because of the non-specific clinical manifestations, clinicians from all subspecialties of internal medicine might be confronted with such patients and should be aware of this new entity."
-What are the common symptoms shared by mitral valve prolapse and panic disorder?,"Mitral valve prolapse, panic disorder, and chest pain. Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS)."
-How do nitrone free-radical spin traps affect c-fos induction and ATP recovery in a rat model of hepatic ischemia and reperfusion?,"Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents. Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction."
-Where is the translocation breakpoint located in the patient with Menkes syndrome?,"Localization of the translocation breakpoint in a female with Menkes syndrome to Xq13.2-q13.3 proximal to PGK-1. Menkes syndrome is a rare X-linked recessive disorder characterized by an inability to metabolize copper. A female patient with both this disease and an X; autosome translocation with karyotype 46,X,t(X;2)(q13;q32.2) has previously been described. The translocation breakpoint in Xq13 coincides with a previous assignment of the Menkes gene at Xq13 by linkage data in humans and by analogy to the mottled mutations which are models for Menkes disease in the mouse. Therefore, this translocation probably interrupts the gene for Menkes syndrome in band Xq13. We describe here experiments to precisely map the translocation breakpoint within this chromosomal band. We have established a lymphoblastoid cell line from this patient and have used it to isolate the der(2) translocation chromosome (2pter----2q32::Xq13----Xqter) in human/hamster somatic cell hybrids. Southern blot analyses using a number of probes specific for chromosomes X and 2 have been studied to define precisely the location of the translocation breakpoint. Our results show that the breakpoint in this patient--and, therefore, likely the Menkes gene--maps to a small subregion of band Xq13.2-q13.3 proximal to the PGK1 locus and distal to all other Xq13 loci tested."
-What are the key findings from the report of five cases of solitary extradural cavernous hemangiomas in the spinal canal?,"Solitary extradural cavernous hemangiomas in the spinal canal. Report of five cases. Five cases of solitary extrathecal cavernous hemangioma in the spinal canal are reported. In one case, two coexistent massive cerebral venous medullary malformations were found. The symptomatology and prognosis of extrathecal spinal cavernous hemangiomas are discussed, as is the significance of various diagnostic measures. The patient material further permitted a rough calculation of the incidence of symptomatic extrathecal cavernous hemangiomas in the spinal canal."
-What is the accuracy of transesophageal echocardiography in evaluating the patency of ventriculoatrial shunts?,"Transesophageal echocardiography: a simple method for monitoring the patency of ventriculoatrial shunts. Technical note. A new method for evaluating the patency of a ventriculoatrial shunt is described, and early experience with it is reported. Transesophageal echocardiography can demonstrate a cerebrospinal fluid leak in the right atrium through the atrial tip of a shunting device. This capability was an incidental discovery, and since then the accuracy of the technique in evaluating the patency of a ventriculoatrial shunt has been prospectively studied in 20 observations of 16 patients. The method proved to be accurate in 90% to 100% of cases. It is concluded that transesophageal echocardiography offers a rapid and accurate assessment of ventriculoatrial shunt function, is well tolerated, and is easy to perform."
-What is heterotopic ossification and how can it potentially impact peripheral nerves?,"Heterotopic ossification and peripheral nerve entrapment: early diagnosis and excision. Heterotopic ossification can occur in neurologic disorders, burns, musculoskeletal trauma, and metabolic disorders. In addition to producing the complications of contracture, skin breakdown, and pain, it can cause peripheral nerve entrapment. Nerve entrapment due to heterotopic ossification may be misdiagnosed, and it is difficult to evaluate and treat without recurrence. Computed tomography is especially useful in localization before surgical release of the entrapped nerve. Resection of heterotopic ossification can be successful using disodium etidronate to decrease the risk of recurrence, and resection can improve range of motion and nerve function. Two case studies of nerve entrapment due to heterotopic ossification are presented with the results of computed tomography localization, successful resection, and long-term follow-up. Clinicians should be aware of this complication and the potential for rapid nerve injury. If heterotopic ossification is causing clinically significant peripheral nerve entrapment, early surgical treatment may be indicated, and may be successful."
-How does a multidisciplinary approach help in managing chronic orthopedic infections?,"The effect of chronic orthopedic infection on quality of life. The patient with chronic orthopedic infection presents a unique challenge to the orthopedic surgeon. The orthopedic surgeon must not only possess an expertise in constantly evolving diagnostic and treatment techniques but also be able to identify numerous related problems and direct the patient in receiving the most appropriate treatment. This demands a commitment of time by the treating surgeon to the individual patient to properly assess the need for support, the extent of psychologic distress, the intensity of pain, and the requirement for medication management. The effective utilization of a multidisciplinary team of health care providers (e.g., specialists in infectious disease, physical medicine and rehabilitation, psychiatry, nursing, pharmacology) can provide an optimal treatment program for this multifaceted problem and maximize the potential for a favorable outcome."
-How do cells generate ATP during hypoxic conditions when aerobic metabolism is compromised?,"Cellular energy metabolism during hypoxia. Tissue hypoxia is frequently seen in critically ill patients and it perhaps predisposes these patients to development of multiple system organ failure. In cellular terms, hypoxia is characterized by decreases in the intracellular concentration of oxygen, leading to a decline in aerobically produced adenosine triphosphate (ATP). The deficit arising from unequal levels of cellular ATP requirements and aerobic ATP production is partially satisfied by anaerobic sources of ATP, including glycolysis, the creatine kinase reaction, and the adenylate kinase reaction. These reactions can set in motion cellular mechanisms that ultimately may lead to cellular dysfunction and death. A clear understanding of the relative importance of these reactions is impossible to acquire from global measures of oxygen delivery and oxygen consumption; therefore, the clinical monitoring of tissue oxygenation also should include the measurement of metabolically relevant, organ-specific variables."
-What was the perioperative mortality rate in the acoustic neuroma surgery series from Manchester Royal Infirmary between 1978 and 1990?,"Acoustic neuroma (schwannoma) surgery 1978-1990. A series of 151 patients with 154 acoustic schwannomas have been operated upon in Manchester Royal Infirmary by a joint Otological and Neurosurgical team, employing either the translabyrinthine or the suboccipital approach. The perioperative mortality rate was 3 per cent. Anatomical preservation of the facial nerve was achieved in 89 per cent of tumour removals and a good to normal functional result in 79 per cent of cases. Attempts at hearing preservation have been unsuccessful, largely because of the small number of patients in the series in whom useful hearing was present preoperatively. Complications included major brain stem ischaemia (1.2 per cent), CSF fistula (5 per cent) and facial dysaesthesia (7 per cent). The incidence of mortality and morbidity is directly related to tumour size and to the experience of the surgeons. A number of patients experienced an unusual type of post-operative dreamlike state which appeared to be a form of hypnagogic hallucination, and the possible neurophysiological mechanism responsible for this phenomenon is discussed. The continuing failure to attain the ideal of early diagnosis is lamented, and the importance of a flexible bidisciplinary surgical approach emphasized."
-What are the main syndromes of mitochondrial encephalopathies observed in children during the 1984-1988 study?,"Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders."
-What medical condition did the 2-year-old boy have that led to difficulty swallowing and spasticity due to compression of the medulla and cervical spine?,Cervicomedullary junction decompression in a case of Marshall-Smith syndrome. Case report. The case is reported of a 2-year-old boy born with Marshall-Smith syndrome who had difficulty in swallowing and who exhibited spasticity and quadriparesis due to compression of the medulla and cervical spine. This is the first child with this rare condition reported to have brain-stem compression from bone abnormalities at the craniovertebral junction and who has required surgery.
-"What morphometrical parameters were found to be most useful in distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis?","Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma. Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well-differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid-sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well-differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue."
-What is pure akinesia and how does it relate to progressive supranuclear palsy (PSP)?,"Pure akinesia: an atypical manifestation of progressive supranuclear palsy. Two patients with ""pure akinesia"" who showed the characteristic changes of progressive supranuclear palsy (PSP) at necropsy are described. They had akinesia but no rigidity or tremor, and ophthalmoplegia was not observed during the course of illness. The symptoms of ""pure akinesia"" was not improved by levodopa therapy but was considerably improved by L-threo-3,4-dihydroxy-phenylserine. At necropsy, pathological findings were not different from those reported for PSP. It is suggested that ""pure akinesia"" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP."
-What unusual characteristic was observed in the Listeria monocytogenes isolate from the patient's cerebrospinal fluid culture?,"Catalase-negative listeria monocytogenes causing meningitis in an adult. Clinical and laboratory features. A 63-year-old previously healthy woman presented with acute meningitis. Cultures of the cerebrospinal fluid yielded a serotype 1/2a isolate of Listeria monocytogenes that was biochemically typical in all respects, other than the reproducible lack of catalase production. During therapy, the patient developed oculomotor dysfunction that was attributed to an abscess in the internal capsule. This case report documents the existence of catalase-negative L. monocytogenes indicating that catalase production should not be a strict criterion for identification of Listeria. Furthermore, this clinical experience extends in vitro and experimental animal studies indicating that catalase production is not a necessary virulence factor for invasion by Listeria."
-What percentage of patients achieved complete thrombolysis based on the duration of their limb ischaemia symptoms?,"Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected."
-What were the key selection criteria for surgical resection in cirrhotic patients with liver cancer in this study?,"Limited hepatic resection for selected cirrhotic patients with hepatocellular or cholangiocellular carcinoma: a prospective study. From 1 January 1983 to 1 January 1989 123 cirrhotic patients with hepatocellular cancer (n = 122) or cholangiocarcinoma (n = 1) were screened using liver function tests, alpha-fetoprotein determination, ultrasonography with biopsy (and in selected cases computed tomography or nuclear magnetic resonance), laparoscopy and angiography, Child-Pugh classification and urea-nitrogen synthesis rate. Twenty-three patients were selected for surgical resection because the tumour was smaller than 5 cm, not centrally located and at least 1 cm away from main structures; there was no evidence of multicentricity or metastatic disease; and the Child-Pugh classification was A or B and the urea-nitrogen synthesis rate at least 6 g/day. Upper gastrointestinal endoscopy was used routinely to identify oesophageal varices which were present in 17 cases; ten patients with a history of variceal haemorrhage (43 per cent) had preoperative endoscopic sclerotherapy. In cases with recurrent haemorrhage, surgery was used to prevent intraoperative and postoperative bleeding. Tumour resection was carried out using controlled hypotension and hepatoduodenal ligament clamping. Twelve bisegmentectomies, ten segmentectomies and one atypical resection were performed. The operative mortality rate was 13 per cent with liver failure and sepsis as the causes of death. The 'recurrence rate' was 26 per cent and the late mortality rate for the whole group up to 1 January 1990 was 30 per cent; 13 patients were still alive. The 12-month survival rate was 77 per cent and after 5 years it was 49 per cent. Thus, surgical resection of small liver tumours is the treatment of choice in this selected group of patients."
-What are the key clinical features associated with T-cell ALL cases having the t(11;14) translocation?,"Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations."
-What imaging technique was found to accurately demonstrate the spread of disease in a case of spinal leptomeningeal metastasis from cerebral glioblastoma?,"Spinal leptomeningeal metastasis from cerebral glioblastoma. Appearance on magnetic resonance imaging. A case of circumferential leptomeningeal metastasis to the spinal cord from an intracranial glioblastoma multiforme (spinal meningeal gliomatosis) is presented. The clinical, radiographic, and pathological features are described. Spinal magnetic resonance imaging with gadolinium-diethylenetriaminepentaacetic acid accurately demonstrated the spread of disease when compared with autopsy findings. The value of spinal magnetic resonance imaging in patients with symptoms attributable to cerebrospinal fluid metastases is discussed."
-What surgical approaches were used to treat localized and diffuse supravalvar aortic stenosis (SVAS) in this study?,"Supravalvar aortic stenosis: a 29-year review of surgical experience Between February 1960 and August 1989, 73 consecutive patients underwent surgical correction for supravalvar aortic stenosis (SVAS) at the Texas Heart Institute. There were 43 male (59%) and 30 female patients (41%) ranging in age from 5 days to 27 years (mean age, 12 years). Preoperatively, 8 patients were in New York Heart Association functional class I, 43 in class II, 18 in class III, and 4 in class IV. Of the 73 patients, 62 had localized SVAS and 11 (15%), diffuse SVAS. For all procedures, patients were placed on cardiopulmonary bypass. Those with localized SVAS were successfully treated with patch aortoplasty, whereas those with diffuse SVAS required either an apicoaortic conduit or extensive end-arterectomy with extended patch aortoplasty. There were eight early deaths (less than or equal to 30 days postoperatively) (11%) and four late deaths (greater than 30 days postoperatively) (6%) in a follow-up period ranging from 2 months to 28 years. Sixteen patients (25%) underwent one or more additional operations in the follow-up period. Postoperatively, there were 44 patients in New York Heart Association functional class I and 17 in class II. Preoperative functional class III and class IV (p less than 0.0005), diffuse SVAS (p = 0.05), and the presence of associated congenital defects (p less than 0.01) were important determinants of death."
-How did the visual evoked potentials change in patients after transurethral resection of the prostate using glycine as an irrigating fluid?,"Visual evoked potentials and visual acuity after transurethral resection of the prostate. Changes in visual evoked potentials, visual acuity, blood ammonia levels and serum electrolytes (Na+ and K+) after transurethral resection of the prostate using glycine as an irrigating fluid performed under subarachnoid block were studied in 12 patients, in the pre-operative and immediate postoperative periods. Visual evoked potentials (p100 latency), recorded by shift of a checkerboard pattern, increased significantly from a pre-operative value of mean (SEM) 101.18 (1.63) msec in the right eye, and 102.5 (1.47) msec in the left eye to 108.91 (1.8) msec (p less than 0.01) and 108.08 (2.53) msec (p less than 0.01) respectively in the postoperative phase. There were no changes in visual acuity as assessed by a Snellen's chart, blood ammonia levels and serum electrolyte concentrations. The amount of glycine used intra-operatively for irrigation ranged from 3 to 31 litres."
-How do delusions and hallucinations impact the progression and neuropsychological characteristics of Alzheimer's disease patients?,"Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates. We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality."
-What is the specific anesthesia-related complication observed in the 4-year-old boy with Williams syndrome?,Williams syndrome: masseter spasm during anaesthesia. A 4-year-old boy with Williams syndrome developed masseter spasm after halothane and suxamethonium. He did not develop malignant hyperthermia; the surgery was accomplished with a nontriggering anaesthetic and no further problems.
-What was the concern regarding the use of transillumination for breast cancer screening in Wisconsin in 1990?,"Inappropriate use of transillumination for breast cancer screening--Wisconsin, 1990. The overall effectiveness of early breast cancer detection efforts requires the appropriate use and maintenance of dedicated radiographic mammography systems. However, the effectiveness of early detection efforts can be compromised if proven technology is improperly used and/or maintained or if ineffective technology is successfully marketed as an equivalent or superior alternative to mammography. This report summarizes state and federal responses to the inappropriate use of a nonradiographic imaging technique in a breast cancer screening service advertised and used in Wisconsin in 1990."
-What was the purpose of the study on thallium stress testing in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation?,"Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. PURPOSE: This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. PATIENTS AND METHODS: The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressions on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). RESULTS: Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test (10 of 64 versus 27 of 77, chi 2 = 6.66, p less than or equal to 0.025). Forty-three percent (26 of 61 in Group B) of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients (p less than 0.001). Thallium stress testing was less expensive than cardiac catheterization ($1,000 versus $4,000 to $5,000). CONCLUSIONS: Thallium stress testing allowed 45% of patients to avoid cardiac catheterization before renal transplantation. Discontinuing beta-blockers before thallium stress tests may improve exercise performance. The risk of perioperative cardiac events after transplantation was low and not different among patient groups. The relatively low predictive value of thallium stress testing for significant coronary artery disease and perioperative cardiac events in diabetic patients with end-stage renal disease suggests the need for the development of a more cost-effective, noninvasive screening test for this patient population."
-What is the sensitivity and specificity of color Doppler imaging in detecting portal vein thrombosis according to this study?,"Diagnosis of portal vein thrombosis: value of color Doppler imaging. This study was undertaken to determine the accuracy of color Doppler imaging in the diagnosis of portal vein thrombosis. Two hundred fifteen patients were studied with color Doppler imaging to determine patency of the main portal vein. Sonographic findings were confirmed in 75 patients, aged 19 to 66 years. Correlation with angiography was obtained in 13 patients, and surgical correlation was obtained in the remaining 62. Nine patients had portal vein thrombosis on the basis of these gold standards. Sonograms were classified as showing either patency or thrombosis, depending on the ability to show color flow within the main portal vein. Agreement between sonography and angiography or surgery was found in 69 patients (61 patent, eight thrombosed). One patient with a patent portal vein at sonography was found to have a thrombosed vessel at surgery, whereas five patients without portal venous flow at sonography had patent vessels at angiography (one patient) or surgery (four patients). Overall sensitivity and specificity for detection of portal vein thrombosis were 89% and 92%, with an accuracy of 92%, a false-negative rate of 0.11, a negative predictive value of 0.98, and a positive predictive value of 0.62. We postulate that the majority of errors in our study occurred in vessels that, although patent, had only sluggish flow, which could not be resolved because of technical limitations. We conclude that color Doppler imaging is a valuable screening procedure for the assessment of portal vein patency. If the sonogram shows a patent portal vein, no further studies are required. However, a lack of demonstrable flow does not always indicate thrombosis, and other imaging studies should be performed for confirmation."
-How has aggressive chemotherapy impacted the cure rate and treatment of osteosarcoma?,"Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable."
-What was the incidence rate of posterior wall left ventricular rupture during mitral valve replacement surgeries between 1970 and 1989?,"Rupture of the posterior wall of the left ventricle after mitral valve replacement. During a 20 year period from 1970 to 1989, 1100 patients underwent mitral valve replacement. Rupture of the posterior wall of the left ventricle occurred in seven patients (0.6%); four in the operating room and three in the postoperative room. It was possible to institute CP bypass in six patients and in all of them bleeding was controlled successfully, with repair by an external approach. Only one patient survived. We believe that institution of CP bypass and reinfusion of cardioplegic solution is a major determinant of the outcome."
-What technique was used to detect and differentiate heat-labile enterotoxins from enterotoxigenic Escherichia coli strains of human origin?,"Heterogeneity of immunotypes of heat-labile enterotoxins of enterotoxigenic Escherichia coli of human origin. A new technique, checkerboard immunoblotting (CBIB), has been applied to detect and to differentiate heat-labile enterotoxins, (LTs), from enterotoxigenic strains of Escherichia coli of human origin using polyclonal and monoclonal antibodies. Optimal conditions of production and release of LTs were defined using CBIB. LT release was enhanced when E. coli cells were treated with 8 M urea. LT production was highest when E. coli strains were incubated with shaking (200 rpm) at 37 degrees C for 12 h in CAYE-2 medium. Two hundred and five strains of E. coli, isolated from patients with diarrhea in Japan, Thailand, the United States, Mexico, and Brazil, were examined for LT. Of 133 LT-positive strains, 4 (3%) produced an LT that reacted like H-LT-1 (originally isolated from E. coli strain H-74-114) while 126 strains (94.7%) produced LT that reacted like H-LT-2 (originally isolated from strain H-10407) or H-LT-3 (from strain H-240-3). Three strains of human origin (2.3%) produced an LT that reacted like P-LT (produced by E. coli strains of porcine origin). This study shows that CBIB, a simple, efficient, and practical assay, might be useful for epidemiologic surveys and for evaluation of serologic responses to LTs and antitoxic vaccines."
-How does von Willebrand factor (vWF) influence platelet activation and occlusive arterial thrombosis in normal and von Willebrand disease pigs?,"Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs. With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis. Two methods of arterial injury have been used to determine the thrombotic response of flowing blood in vivo. The first involves balloon catheter injury. After superficial denudation of endothelium from coronary intima, platelets adhere to the subendothelium in a monolayer. Similar numbers of adherent platelets are found in both phenotypes, but platelets in vWD pigs have impaired pseudopod formation and are less well spread morphological indexes of limited platelet activation. Deeper injury, which involves the media, produces nonocclusive platelet-fibrin microthrombi. The second injury method involves pinching the artery at a site of superimposed stenosis, a procedure that almost always exposes media. This procedure induces platelet-fibrin microthrombi in normal and vWD pigs, but only normal pigs develop occlusive thrombosis. Both methods of arterial injury have also been performed in normal and vWD pigs with diet-induced hypercholesterolemia and atherosclerosis. Atherosclerosis promotes platelet spread in vWD pigs but does not abolish the protection from stenosis and injury-induced occlusive thrombosis. In addition, neutralization of vWF activity in normal pigs by a monoclonal antibody prevents the induction of occlusive thrombosis by the stenosis and pinch-injury procedure. This monoclonal antibody also causes performed platelet aggregates to break up. These experimental models of inducing arterial thrombosis have been used in normal and vWD pigs to demonstrate interactions between normal and atherosclerotic vessel wall constituents, circulating platelets and vWF that are fundamental in the process of arterial thrombosis."
-How do serum zinc levels differ between patients with active inflammatory bowel disease and healthy controls?,"Serum zinc, copper, and selenium levels in inflammatory bowel disease: effect of total enteral nutrition on trace element status. Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed."
-How did tranexamic acid help in treating hemothorax in patients with malignant mesothelioma?,Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma. Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of transfusion requirements.
-What was the most commonly involved nerve in peripheral nerve lesions among hemophilia patients at the Nuffield Orthopaedic Centre?,"Peripheral nerve lesions in hemophilia. Between 1962 and 1986, eighty-one of the 1351 admissions of patients who had hemophilia to the Nuffield Orthopaedic Centre were for peripheral nerve lesions. Eighty-eight such lesions were identified in fifty-four patients, and thirty-nine of these patients (sixty-one lesions) had adequate follow-up (mean, 8.4 years; range, four months to eighteen years). The femoral nerve was most commonly involved, but involvement of other peripheral nerves also occurred. In thirty (49 per cent) of the sixty-one lesions, the nerve had full motor and sensory recovery; in twenty-one (34 per cent), a residual sensory deficit; and in ten (16 per cent), both a persistent motor and sensory deficit. Patients who had antibodies to factor VIII were significantly less likely to recover full motor or sensory function than were those who did not have such antibodies, and the time to full motor recovery in these patients was significantly longer."
-How did mammography impact the treatment approach for patients with small breast cancers in this study?,"Mammography in the management of patients with small breast cancers. Findings on mammography resulted in a change of treatment policy in 17 of 200 patients with small breast cancers (T1/T2 less than 4 cm, N0/N1, M0). Twelve patients were considered unsuitable for conservation therapy because of mammographic evidence of either extensive in situ carcinoma or more than one focus of invasive carcinoma. These patients were treated by mastectomy and histology confirmed widespread in situ carcinoma or multifocal/multicentric invasive carcinoma. Seven patients were found to have unsuspected contralateral lesions on mammography, of which five were subsequently shown to be malignant. Routine preoperative mammography is essential in the management of patients with small breast cancers."
-"How does metformin treatment affect insulin resistance and metabolic risk factors in non-obese, non-diabetic men with hypertension?","Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease."
-What are the key neuropathologic features of generalized cortical dysplasia observed in the three children studied?,"Generalized cortical dysplasia. Clinical and pathologic aspects. Three children with profound mental retardation and intractable seizures died at ages 10 months, 3 years, and 7 years, respectively. Complete examination of their brains showed generalized cortical dysplasia, without any major malformation of the external gyral pattern. The neuropathologic features of cortical dysplasia include abnormally thickened cortex with indistinct demarcation of the gray-white matter junction. In many areas, the cortex contained increased numbers of large neurons with disordered cortical lamination. Heterotopic neurons were scattered throughout the white matter with decreased myelination of the underlying white matter. To our knowledge, these cases represent the first fully detailed neuropathologic study of diffuse cortical dysplasia--a newly recognized entity of abnormal neuronal migration."
-How does alcohol affect ferritin expression in the HepG2 human hepatoblastoma cell line?,"Alcohol induction of ferritin expression in a human hepatoblastoma cell line (HEP G2). Hyperferritinemia, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression."
-What was the relationship between preoperative dipyridamole perfusion scintigraphy findings and intraoperative transesophageal echocardiography in identifying myocardial ischemic risk?,"Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk. The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed."
-What diagnostic method is recommended for identifying Clostridium septicum abscesses in immunosuppressed patients?,"Recognition, management, and prevention of Clostridium septicum abscess in immunosuppressed patients. Spontaneous gas gangrene due to Clostridium septicum is a rapidly progressing disease that usually ends in fatal toxemia. We report three cases of asymptomatic C septicum abscesses to document the clinical course of this entity and to establish guidelines for its prevention and treatment. In contrast to previously reported data, C septicum infections can produce abscesses in solid organs, the retroperitoneum, and the extremities. These lesions often occur in patients with cancer, producing liver abscesses without gas formation that may be misinterpreted as metastatic carcinoma. Symptoms may be minimal or nonspecific before fulminant toxemia. Asymptomatic bacteremia should prompt a search for unsuspected cancer and an abscess. Computed tomography is the diagnostic modality of choice. The treatment consists of surgical debridement of necrotic tissue in concert with an appropriate course of antibiotics. We have found recurrences after adequate debridement and short-term antibiotic therapy, suggesting that prolonged and even lifelong prophylactic oral penicillin G potassium may be necessary to prevent further recurrences."
-How does endotoxin (LPS) infusion affect hypoxic pulmonary vasoconstriction in unanesthetized sheep?,"Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep. Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS."
-How did damage to the fornix affect memory function in the two patients after colloid cyst removal?,"Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans."
-How do nasal and pharyngeal resistances change during progressive normocapnic hypoxia in normal men?,"Changes in upper airway resistance during progressive normocapnic hypoxia in normal men. The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia."
-What were the predictive factors for thrombotic complications in venous coronary bypass graft angioplasty?,"Long-term angiographic follow-up after angioplasty of venous coronary bypass grafts. From April 1981 to June 1987, 57 patients underwent venous coronary bypass graft percutaneous angioplasty and had a minimal follow-up of 18 months. The procedure was elective for 28 patients, urgent for 19, and was considered as an emergency for 10. A total of 64 grafts were dilated that had been bypassed 58 +/- 48 months previously (range 2 to 184 months); lesions were located on the aortic anastomosis in 12 grafts, on the body in 38, and on the coronary anastomosis in 14. Technical success was 95.3% (61 of 64) per lesion; clinical success was 84.4% (54 of 64) per lesion and 82.5% (47 of 57) per patient. Thrombotic complications with images of a lacunar defect occurred in 11 grafts (17.2%). Predictive factors for these complications were: age of grafts 38.5% for greater than 60 month grafts versus 2.6% for less than 60 month grafts (p less than 0.01); site of lesion, body lesion 28.9% versus anastomosis none (p less than 0.01); type of lesion, concentric and short 6% versus other 29% (p less than 0.05); and recent fibrinolysis in 66% versus 10.6% (p less than 0.05). Long-term follow-up is available in the 47 successful patients and the three limited non-Q wave myocardial infarction patients. Two patients died at 13 and 17 months. Long-term angiographic follow-up is available in 45 of 48 patients or 94%. At the end of the study, 35 of 57 (61.4%) venous bypass grafts in 32 patients (64%) were patent after one or more percutaneous transluminal angioplasties."
-What differences were observed in the expression of primary response genes between renal compensatory hypertrophy (uninephrectomy) and renal hyperplasia (folic acid injection)?,"Differences in ""primary response"" gene expression in renal compensatory hypertrophy and hyperplasia. The induction of a family of primary response genes (ie, genes whose transcription is not dependent on new protein synthesis) occurs within minutes after stimulation of quiescent 3T3 cells by phorbol esters and growth factors. A similar pattern of gene expression is seen in PC-12 pheochromocytoma cells induced to differentiate by nerve growth factor (NGF), suggesting that a common set of activating signals occur in different forms of cell growth. To determine whether the same ""activation"" process occurs in renal hypertrophy, we measured mRNA levels in mice subjected to uninephrectomy (UNX) or sham operation. Regenerative renal hyperplasia was induced by intraperitoneal folic acid (FA) injection with vehicle as control. Northern blots showed induction of these genes by FA with elevated mRNA levels persisting for up to 24 to 48 hours. UNX and sham operation demonstrated a slight and transient elevation of mRNA levels, with a prompt return to basal levels by 60 minutes."
-How did the long-term psychological stress of patients with congenital heart disease compare to normative data in this 25-year follow-up study?,"Long-term psychologic implications of congenital heart disease: a 25-year follow-up. Patients with various types of congenital heart disease were contacted 25 years after their original examination at the Mayo Clinic. In addition to providing their current health status, level of education achieved, and current occupation, they were asked to complete a detailed standardized questionnaire to assess their degree of psychologic stress. Of the original 463 patients, 168 completed and returned the psychologic questionnaires. These patients had evidence of psychologic stress in excess of that expected on the basis of normative data. Furthermore, the degree of stress was unrelated to the clinical severity of the original cardiac defect. In addition, the psychologic stress occurred despite ""success"" as defined by educational achievement and occupational level. One can speculate that as children these patients were exposed to environmental stresses that may well have been colored by parental attitudes and perceptions."
-What is the most serious complication of thrombolytic therapy that can limit its usefulness?,"Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy. Bleeding is the most serious complication of thrombolytic therapy and limits its usefulness. We have reported a case of epidural hematoma, a rare occurrence after combined therapy with tissue plasminogen activator (TPA) and heparin. We emphasize that in patients treated with thrombolytic agents, any trauma may increase the risk of bleeding. The sudden onset of back pain and neurologic deficits should alert the clinician to the possibility of spinal hematoma with cord compression."
-What is the primary cause of death in children with maple syrup urine disease (MSUD) as described in this context?,"Cerebral edema causing death in children with maple syrup urine disease. Four children with the classic form of maple syrup urine disease (MSUD) died of cerebral edema during an intercurrent infection that caused severe dehydration and acidosis. The diagnosis of MSUD had been established during the neonatal period in all four patients, on day 1 of life in three of them. All were in satisfactory control before the intercurrent illness. Two patients underwent peritoneal dialysis. Signs of brain-stem compression occurred after treatment, when biochemical abnormalities were improving. Computed tomography of the head, which was done in two patients, revealed cerebral edema; one of these patients also had subarachnoid hemorrhage. Autopsy in one case revealed cerebral edema with herniation. Our experience documents that cerebral edema may occur in the older child with MSUD as well as in the neonate. The pathogenesis of cerebral edema in MSUD remains unclear. Early treatment of dehydration and acidosis may prevent the catastrophic consequences that we have observed."
-How do personality traits and life events relate to the frequency of headaches in adults?,"The association of frequent headaches with personality and life events. The associations between personality traits, life events and frequent headaches were studied in a sample of 5766 adult subjects between 20 and 65 years of age from the general population. Subjects with at least weekly headaches had more life events and higher inadequacy, social inadequacy, rigidity and injuredness than subjects with less frequent headaches. These relationships were not observed in subjects of 50 years of age and older, with the exception of the association with inadequacy. From the traits measured, inadequacy had the highest odds ratios for frequent headaches and showed a modest interaction with the presence of a life event. These findings are in agreement with Sarason's interactional model."
-What inflammatory changes were observed at the neuromuscular junction in patients with myasthenia gravis?,"Inflammation at the neuromuscular junction in myasthenia gravis. To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG."
-What is the significance of lowering cholesterol levels in patients with coronary heart disease (CHD)?,"On lowering lipids in the post-infarction patient. In patients with coronary heart disease (CHD) elevated serum cholesterol levels, like other classical risk factors, remain predictive of further coronary events. The excess risk attributable to raised cholesterol levels is considerable, and greater than that in subjects without CHD. A recent meta-analysis of all eight qualifying trials of secondary prevention of CHD by cholesterol lowering is reviewed. There were significant reductions in recurrent non-fatal and fatal CHD, with a downward trend in total mortality. Mechanisms underlying the relationship between cholesterol lowering and secondary prevention are reviewed. The implication of this analysis of trials for clinical practice is that hypercholesterolaemia should be sought and effectively treated in patients with CHD, unless contraindications are present."
-What was the clinical outcome for children with glutathione peroxidase deficiency after discontinuing anticonvulsant medication and receiving selenium substitution?,"Glutathione peroxidase deficiency and childhood seizures. 4 children with intractable seizures, repeated infections, and intolerance to anticonvulsants had evidence of glutathione peroxidase deficiency. 2 had low intracellular enzyme activity but normal blood selenium and high plasma glutathione peroxidase concentrations. The other 2 had low intracellular glutathione peroxidase activity with low circulating glutathione peroxidase and selenium concentrations. The clinical state of the children improved after discontinuation of anticonvulsant medication and selenium substitution."
-How does polysialic acid help distinguish small cell lung carcinoma from carcinoids?,"Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. The neural cell adhesion molecule (NCAM) exists in various types of neuroendocrine cells and their tumors. A typical feature of NCAM is polysialic acid, of which the chain length is developmentally regulated. The authors have performed a comparative immunohistochemical study on small cell lung carcinomas and bronchial as well as gastrointestinal carcinoids with the monoclonal antibody (MAb) 735 reactive with the long-chain form of polysialic acid. The small cell lung carcinomas, irrespective of their histological type, were positive for polysialic acid. Metastatic tumor cell complexes also exhibited immunostaining. The tumor cell-surface-associated immunostaining for polysialic acid was sensitive to endoneuraminidase. The mature and atypical bronchial and gastrointestinal carcinoids were not immunoreactive for polysialic acid. Cytoplasmic staining in groups of cells of carcinoids (2 of 28 cases) was due to nonspecific antibody binding, which could be prevented by increased ion strength. These data indicate that neuroendocrine tumors of the lung can be distinguished by their content of highly sialylated NCAM."
-What are the potential consequences of malignant eye tumors in geriatric patients?,"Malignant tumors of the eye in geriatric patients. The ocular tissues can be the site of a number of malignant tumors in adults and geriatric patients. In addition to posing a threat to the patient's life, these tumors can cause severe visual loss or blindness. Therefore, the primary care clinician should be capable of prompt diagnosis of the various malignant ocular tumors and be prepared to refer the patient for appropriate management. This article provides a photographic guide to the most common primary and secondary malignancies that can affect the eyelid, conjunctiva, intraocular structures, and orbit in the geriatric patient."
-What factors were found to have the strongest univariate relations to the restenosis rate in this study?,"Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators. The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and ""optimal"" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis."
-What diagnostic techniques were used to identify the left ventricular aneurysm in the fetus?,"Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review. Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented."
-What was the main objective of the study on community obstetric care in West Berkshire?,"Community obstetric care in West Berkshire OBJECTIVE--To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN--Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING--West Berkshire Health District. SUBJECTS--All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES--Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS--Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION--Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife."
-How do the outcomes of psychogenic seizures differ between children/adolescents and adults according to the study?,"Outcome of psychogenic seizures in children and adolescents compared with adults. We compared outcome of psychogenic seizures documented by video-EEG in 18 nonepileptic children and adolescents (ages 8 to 18; median, 14.5 years old) and 20 adults (ages 25 to 56; median, 34.0 years old). Outcome was significantly better for the younger patients at 1 year, 2 years, and 3 years after diagnosis. At these follow-up times, the percentages of children and adolescents free of psychogenic attacks were 73%, 75%, and 81%; at the same follow-up times, the percentages of adults free of psychogenic attacks were only 25%, 25%, and 40%. Factors leading to better outcome for younger patients may have been different psychological mechanisms at different ages of onset and greater effectiveness with earlier intervention."
-What are the proposed criteria for diagnosing migraine without aura in clinical practice?,"Criteria for the diagnosis of migraine in clinical practice. Criteria for the diagnosis of migraine have evolved from generalized descriptions to specific rules designed to ensure the selection of homogenous groups of patients for research studies. For clinical practice, the former are insufficiently specific and the latter are too complex. For care of headache patients by primary care physicians, we propose that the diagnosis of migraine without aura (common migraine) is warranted if any two of the following symptoms are present: unilateral site, throbbing quality, nausea, photophobia or phonophobia. These criteria are derived from a study comparing the features of 100 patients with migraine without aura and 100 patients with chronic daily headache. The proposed criteria for the diagnosis of migraine without aura were highly sensitive and adequately specific in discriminating groups. These simple criteria should facilitate the diagnosis of migraine by primary care physicians."
-What was the main finding regarding secondary prophylactic drug use for patients after myocardial infarction in the study?,"Use of secondary prophylaxis against myocardial infarction in the north of England OBJECTIVE--To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. DESIGN--Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. SETTING--The nine family practitioner committee areas within the Northern Regional Health Authority. PATIENTS--Patients who had had a myocardial infarction and were discharged to their general practitioner. MAIN OUTCOME MEASURE--Whether beta blockers or aspirin, or both, were given on discharge. RESULTS--Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. CONCLUSIONS--Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary."
-How does the MELAS mutation affect mitochondrial RNA transcription termination?,"Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products."
-How do thromboxane A2 synthase inhibition and thromboxane A2/prostaglandin endoperoxide receptor antagonism differently affect occlusive thrombosis in canine coronary arteries with varying degrees of vascular damage?,"Differential effects of thromboxane A2 synthase inhibition, singly or combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on occlusive thrombosis elicited by endothelial cell injury or by deep vascular damage in canine coronary arteries. In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n = 24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16 +/- 0.16/hr; n = 6; p less than 0.05) or by a comparatively modest degree of TXA2/prostaglandin endoperoxide receptor antagonism on top of TXA2 synthase inhibition (5 mg/kg i.v. ridogrel; CFR, 0.22 +/- 0.1/hr; n = 10; p less than 0.05). By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-microA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1 +/- 13.9 minutes; n = 7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n = 7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n = 7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg + 10 mg/kg/hr i.v. sulotroban for 300 minutes; n = 5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion greater than 300 minutes, n = 7; incidence of occlusion within 300 minutes, one of seven experiments; p less than 0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel."
-What were the main outcome measures in comparing dual chamber pacing (DDD) and ventricular rate adaptive pacing (VVIR) in patients with complete heart block?,"Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block. OBJECTIVE--To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block. DESIGN--Double blind crossover comparison with one month in each pacing mode. PATIENTS--10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers. MAIN OUTCOME MEASURES--Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline. RESULTS--No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes. CONCLUSIONS--In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing."
-How does Epstein-Barr virus infection impact liver transplant patients and their graft function?,"Epstein-Barr virus and persistent graft dysfunction after liver transplantation. Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection."
-What surgical procedure was used to treat scaphoid pseudarthrosis in this long-term review study?,"Pseudarthrosis of the scaphoid treated by the Matti-Russe operation. A long-term review of 77 cases. We report the long-term results of the Matti-Russe operation for pseudarthrosis of the scaphoid in 100 cases, reported previously by Mulder in 1968. Clinical results for 77 patients and radiographic data for 74 were reviewed at 22 to 34.8 years after surgery. In general, there was satisfactory relief of pain and stiffness but some patients had limitation of motion and reduced grip-strength, with usually slight osteoarthritic changes. There was poor correlation between subjective, objective, and radiographic results but 88% of the patients were satisfied with their results."
-What is the significance of the reported case of hydroureteronephrosis secondary to perforated Meckel's diverticulum?,"Hydroureteronephrosis secondary to perforated Meckel's diverticulum. Complications related to Meckel's diverticulum are not unusual. However, involvement of the urinary tract is extremely rare. To our knowledge this is the first reported case of ureteral obstruction due to perforation of Meckel's diverticulum."
-What are the key risk factors that contribute to excess morbidity and mortality from influenza infections in children in developing countries?,"Pathogenesis of respiratory infections due to influenza virus: implications for developing countries. The influenza viruses have an important and distinctive place among respiratory viruses: they change antigenic character at irregular intervals, infect individuals of all ages, cause illnesses characterized by constitutional symptoms and tracheobronchitis, produce yearly epidemics associated frequently with excess morbidity and mortality, and predispose the host to bacterial superinfections. Much is known about influenza viruses, but their role in respiratory infections among children in developing countries is poorly understood, and the risk factors that lead to the excess morbidity and mortality have not been identified clearly. Among the many risk factors that may be important are alterations in host immunity, malnutrition, prior or coincident infections with other microorganisms, inhaled pollutants, and lack of access to medical care. There is a great need for research that can establish more precisely the role these and other unidentified factors play in the pathogenesis of influenza infections in children in the developing world."
-What did the study reveal about the presence of atrial natriuretic factor in the human ventricle in relation to ventricular dilation?,"Expression of atrial natriuretic factor in the human ventricle is independent of chamber dilation This study investigated the presence of atrial natriuretic factor in ventricular tissue obtained from humans with dilated or restrictive heart disease. In 17 patients with ventricular dilation and impaired systolic function and in 8 patients with restrictive heart disease and preserved systolic function, the presence of ventricular atrial natriuretic factor was investigated in tissue obtained by ventricular endomyocardial biopsy. The objective of the study was to determine if the ventricular presence of atrial natriuretic factor is dependent on ventricular dilation. Left ventricular end-diastolic volume index was greater in the group with dilated cardiomyopathy than in the group with restrictive cardiomyopathy (134 +/- 13 versus 78 +/- 5 ml/m2, p less than 0.05); end-diastolic pressure was elevated in the two groups (20 +/- 2 versus 25 +/- 4 mm Hg, p = NS). With the use of immunohistochemical techniques, ventricular atrial natriuretic factor was clearly detected in 15 of the 17 patients with dilated cardiomyopathy and in 6 of the 8 patients with restrictive cardiomyopathy. This study demonstrates the high prevalence of ventricular atrial natriuretic factor in living patients with either systolic or diastolic dysfunction. Whereas in the atria, stretch or dilation may be an important stimulus, atrial natriuretic factor in the ventricular chamber occurs independent of dilation."
-What is the primary purpose of the knowledge-based computer system described in the context?,"Knowledge-based computer system to aid in the histopathological diagnosis of breast disease. A knowledge-based computer system, designed to assist pathologists in the histological diagnosis of breast disease, is described. This system represents knowledge in the form of ""disease profiles"" and uses a novel inference model based on the mathematical technique of hypergraphs. Its design overcomes many of the limitations of existing expert system technologies when applied to breast disease. In particular, the system can quickly focus on a differential problem and thus reduce the amount of data necessary to reach a conclusion. The system was tested on two sets of samples, consisting of 14 retrospective cases and five hypothetical cases of breast disease. Its recommendations were judged ""correct"" by the evaluating pathologist in 15 cases. This study shows the feasibility of providing ""decision support"" in histopathology."
-What changes were observed in the high-frequency peak power of heart rate variability in patients not taking beta blockers during the 24-hour period after acute myocardial infarction?,"Diurnal variations of neurocardiac rhythms in acute myocardial infarction. To determine the diurnal pattern of cardiac autonomic tone in acute myocardial infarction (AMI), this study examined the power spectrum of heart rate (HR) variability in 24 patients during a single 24-hour segment within 4 days of AMI. Patients were nonrandomly allocated to a group (n = 14) without autonomic drugs and to a group (n = 10) already receiving beta blockers at the time of AMI. With use of autoregressive modeling, the power spectrum of HR variability was computed from continuous 1-hour electrocardiographic segments recorded at equally spaced intervals; 7 to 8 A.M., 3 to 4 P.M., and 11 to 12 P.M. All patients were supine, awake and pain free during recordings. There were no differences in HR, HR variance or the low-frequency peak power (0.06 to 0.1 Hz) from one temporal sequence to another. For the patients not taking beta blockers, the high-frequency peak power (0.2 to 0.36 Hz) or vagal component increased significantly from 3 P.M. to 11 P.M. (28 +/- 11 to 45 +/- 20 beats/min2.Hz-1, p less than 0.01). There was a significant decrease in the low- to high-frequency peak power and area ratios from 3 P.M. to 11 P.M. All power spectral parameters in the patients taking beta blockers remained unchanged over 24 hours. There was significantly heightened vagal modulation of sinus node activity in those receiving beta blockers, especially at 7 A.M. and 3 P.M. The data suggest that under steady-state wakeful conditions in the early recovery phase after an AMI, vagal tone is more pronounced during the late evening hours with a possible shift to relative sympathetic dominance during early morning and midafternoon hours."
-What are the three types of adenomatous hyperplasia (AH) identified in the study?,"Argyrophilic nucleolar organizer regions and alpha-fetoprotein in adenomatous hyperplasia in human cirrhotic livers. Recently, adenomatous hyperplasia (AH) of the liver has been suspected as a precancerous lesion in human hepatocarcinogenesis. The authors examined 75 cases of AH from 42 cirrhotic livers, using staining of argyrophilic nucleolar organizer regions (AgNORs). These reflect proliferative cell activity. Findings in AH were compared with those seen in hepatocellular carcinoma (HCC) and other chronic liver diseases. Expression of alpha-fetoprotein (AFP) was also examined immunohistochemically. The authors classified AH into three types: ordinary (OAH), atypical (AAH), and AH with focal malignancy (FM). OAH implies a lack of atypia; AAH represents AH with structural and cellular atypia but without the features of overt carcinoma; and FM denotes AH with foci of overt HCC. Forty of the 75 cases of AH were categorized as OAH, 19 as AAH, and 16 as FM. The noncancerous areas of FM had features of AAH. The mean number of AgNORs in AH was intermediate between that seen in cirrhosis (2.93) and HCC (6.18) and showed a step-wise increase in the following order: OAH (2.95), AAH (3.89), noncancerous areas in FM (4.58), and malignant foci in FM (5.71). There was no significant difference in AgNOR counts between OAH and cirrhosis. AgNOR counts in AAH and FM were significantly higher than those of OAH, and lower than those of HCC. AFP was positive in 12 of 25 HCCs and in malignant foci of 3 FM lesions, but it was absent in OAH and AAH. These data suggest that OAH has a limited capacity for proliferation but that AAH and FM are much more replicative. The latter two conditions are probably preneoplastic lesions or early forms of HCC."
-How does repetition priming differ from explicit memory in patients with depression?,"Explicit memory and repetition priming in depression. Preliminary findings. Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia."
-How does Lupron affect the cell cycle of the ovarian cancer cell line 2774?,"Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment."
-How effective was zidovudine (ZDV) treatment in preventing Friend virus (FV) progression in mice?,"Early-initiated zidovudine therapy prevents disease but not low levels of persistent retrovirus in mice. An F1 hybrid mouse strain containing the Rfv-3r/s genotype was inoculated with Friend virus complex (FV) and treated with zidovudine (ZDV) intraperitoneally three times daily for 20 days beginning as early as 10 min after initial viral exposure. This strain of mice develops FV-specific neutralizing antibodies that aid in reducing viremia and splenic virus titers but do not prevent splenomegaly and eventual FV-associated death. The virally exposed mice treated with ZDV did not develop splenomegaly or have detectable viremia after the last drug treatment. On day 21, a single animal had demonstrable virus in the spleen as determined by a focal immunoenzyme assay; 57% had detectable virus at 5 weeks, but non displayed splenic virus after 35 weeks. None of the animals died after the 35-week holding period, compared to 38% dying in placebo-treated mice. To detect low levels of the virus, or potentially latent virus, splenocytes were cocultivated with a cell line known to readily propagate FV, and the cells were subsequently passaged four times to amplify replication of the virus. After amplification, a significant increase was seen in the number of mice testing positive for virus. Thus, ZDV treatment initiated early after virus exposure was effective in preventing FV-induced splenomegaly and death, but did not prevent low levels of persistent retrovirus in the mice."
-What diagnostic technique was used to detect minute lesions in patients with Crohn's disease during the sigmoidoscopy procedure?,"Minute lesions of the rectum and sigmoid colon in patients with Crohn's disease. Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease."
-How did cardiac myocyte size and volume change in different heart regions of rats with aortocaval fistulas after 5 months?,"Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects. Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass."
-What were the main findings of the study regarding the effects of microsurgical DREZ-otomy (MDT) on somatosensory function?,"Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity. The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a ""retuning"" of the dorsal horn as the mode of action of MDT is presented."
-"How do neutrophils, PAF, and thromboxane contribute to the decrease in local blood flow during pulmonary inflammation?","Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane. The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response."
-What role does echocardiography play in diagnosing and evaluating mitral and tricuspid stenosis?,"Role of echocardiography in the diagnosis and evaluation of severity of mitral and tricuspid stenosis. The presence, severity, and hemodynamic consequences of mitral and tricuspid stenosis can be determined by echocardiographic techniques. In mitral stenosis two-dimensional echocardiographic imaging allows definition of leaflet anatomy and dynamics, subvalvular disease, ventricular function, and involvement of other valves. Spectral and color Doppler echocardiographic techniques permit accurate measurement of transvalvular gradient, determination of functional orifice area, evaluation of associated valvular regurgitation, and assessment of pulmonary artery pressures. These approaches are of recognized clinical value, and they provide additional diagnostic information that is unavailable from clinical assessment alone in a significant number of patients. Compared with available invasive diagnostic standards of reference, echocardiographic data have been found to be comparable in accuracy. In tricuspid stenosis echocardiographic imaging and Doppler techniques provide an assessment of valve morphology and function that should be similarly useful in clinical management decisions, although rigorous comparative studies have not been performed. Currently, carefully done echocardiographic studies are a definitive means of establishing the presence and significance of mitral stenosis and tricuspid stenosis, thereby obviating the need for invasive evaluation in many patients, reducing risk, and potentially decreasing the cost of diagnostic assessment."
-What was the impact of graft diameter on patency in this study of Dacron aortobifemoral bypass grafts?,"Lack of diameter effect on short-term patency of size-matched Dacron aortobifemoral grafts. This study examined the relationship between graft diameter and subsequent patency in 79 patients who received Dacron aortobifemoral bypass grafts for aortoiliac occlusive disease between 1985 and 1989. Sixty-five percent of these patients were men, 25% were diabetic, and 94% were smokers, with an average age of 62 years. Patients were followed for a mean interval of 24 months. Life-table survival was 92% at 3 years. All surviving patients showed ""significant"" postoperative improvement by use of Society for Vascular Surgery/International Society for Cardiovascular Surgery combined clinical and vascular laboratory criteria. There were three early and five late graft thromboses. Primary and secondary life-table patencies were 85% and 92%, respectively, at 3 years. Dacron bifurcation grafts were selected to match the size of native arteries. Patients receiving small diameter grafts, defined as 12 mm (n = 9) and 14 mm (n = 39), were compared with patients receiving large diameter grafts of 16 mm (n = 26) and 18 mm (n = 5). Small diameter grafts were more likely to be used in women (p less than 0.01), but patient groups were otherwise comparable with respect to age, smoking history, diabetes, outflow status, operative indications, type of proximal anastomosis (end-to-end or end-to-side), location of distal anastomosis (common femoral vs deep femoral), type of graft construction (knitted vs woven), and functional result. Graft diameter did not influence life-table patency, which was 84% for small and 87% for large diameter grafts at 3 years (p = 0.74). Furthermore, none of the other variables listed above influenced graft patency."
-How did patients with fornix damage perform on nonverbal memory tests compared to patients with other brain lesions?,"Amnesia following damage to the left fornix and to other sites. A comparative study. Two memory-impaired patients, who had suffered damage to the left or both fornix columns during removal of a ventricular cyst, were compared with 3 others having left-sided hippocampal or thalamic lesions, and with normal controls. The tests used were nonverbal--scene recognition, delayed matching-to-sample and concurrent pattern and object discrimination learning. The last two are differentially sensitive to fornix transection and to hippocampal or thalamic ablations in monkeys; however, the patients with fornix damage did not show a distinctive pattern of impairment. The reasons for this discrepancy are discussed. The study adds to the evidence that fornix transection can cause wide-ranging memory disturbances in man."
-"How did the DNA ploidy status of cervical carcinoma tumors change after radiation therapy, and what was its relationship to tumor response?","DNA ploidy analysis of effectiveness of radiation therapy for cervical carcinoma. Cellular DNA content from 30 patients with cervical carcinoma was determined using flow cytometry before and after radiation therapy (RT). The authors attempted to correlate changes in DNA content, tumor response to RT, and post-RT pathologic findings. Before RT, tumors from eight of 30 patients (26.7%) were diploid or near-diploid; tumors from 22 patients (73.3%) were aneuploid. After RT, diploid or near-diploid tumors were found in 23 patients (76.7%), and aneuploid tumors were observed in seven patients (23.3%). Aneuploidy disappeared in 15 of the patient tumors, and complete tumor response (CR) was observed in 13 of these 15 patients (86.7%). Pathologic examinations were negative in 12 of 15 cases and suspicious in one of 15 cases. Of the seven patients whose tumor aneuploidy did not change after RT, CR was observed in only two (28.7%). Pathologic examinations were positive in five of seven cases and suspicious in one of seven cases. The CR for the 22 patients with pre-RT aneuploid tumors was 15 of 22 (68.2%); the CR for the eight patients with pre-RT diploid tumors was two of eight (25%, P less than 0.01). From these data the authors conclude there is a direct correlation between DNA content and radiosensitivity in cervical carcinoma. Aneuploid tumors from these patients were more radiosensitive than diploid tumors, and they patients had a better clinical tumor response and improved pathologic findings."
-How does enhanced GABAergic inhibition impact neuronal death and cognitive function in an epilepsy model?,"Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy. The excitotoxic hypothesis of epileptic cell death [Olney, J. W. (1978) in Kainic Acid as a Tool in Neurobiology, eds. McGeer, E., Olney, J. W. & McGeer, P. (Raven, New York), pp. 95-121; Olney, J. W. (1983) in Excitotoxins, eds. Fuxe, K., Roberts, P. J. & Schwartch, R. (Wenner-Gren International Symposium Series, Macmillan, London), Vol. 39, pp. 82-96; and Rothman, S. M. & Olney, J. W. (1986) Ann. Neurol. 19, 105-111] predicts an imbalance between excitation and inhibition, which occurs probably as a result of hyperactivity in afferent pathways or impaired inhibition. In the present study, we investigated whether the enhancement of gamma-aminobutyric acid (GABA)-mediated (GABAergic) inhibition of neurotransmission by blocking the GABA-metabolizing enzyme, GABA transaminase, could influence the histopathological and/or the behavioral outcome in this epilepsy model. We demonstrate that the loss of pyramidal cells and hilar somatostatin-containing neurons can be abolished by enhancing the level of synaptically released GABA, and that the preservation of hippocampal structure is accompanied by a significant sparing of spatial memory as compared with placebo-treated controls. These results suggest that enhanced GABAergic inhibition can effectively block the pathophysiological processes that lead to excitotoxic cell death and, as a result, protect the brain from seizure-induced cognitive impairment."
-What percentage of children with acquired cortical blindness had a poor visual outcome in the study?,"Cortical blindness in children: a study of etiology and prognosis. Thirty-four children (20 boys, 14 girls) with congenital and acquired cortical blindness were analyzed for visual outcome in relation to etiology, visual evoked potentials, electroencephalography, and cranial computed tomography. All 7 children with congenital cortical blindness remained blind on subsequent examination. Of the 27 children with acquired blindness, 16 (59%) had poor visual outcome. Poor visual outcome occurred in those with cardiac arrest, hypoxia, status epilepticus, intracranial hemorrhage, cerebral thrombosis, and head trauma. Good visual outcome occurred in children with hypotensive episodes after cardiac surgery. Of the 12 children with recovery of vision, the interval from acute loss of vision to partial or total recovery was 2 weeks to 5 months. Seven children had complete recovery of vision with no residual visual field defect. The majority of children (87%) had focal or multifocal spike-and-waves and slow sharp-wave discharges on electroencephalography. None had photic recruitment response or occipital spike-and-wave discharges. Flash visual evoked potential studies performed during acute episodes of cortical blindness documented 11 with absent response, 10 with bilateral increases in latency, and 6 with normal responses. There was no correlation between normal visual evoked potentials and a good visual outcome. Only 2 of 6 children with normal responses had normal vision. Abnormal or absent responses are more predictive of a poor recovery of vision because only 3 of 21 (14%) had normal vision on subsequent examination. Abnormal electroencephalographic findings with focal or multifocal spike-and-wave discharges or cerebral atrophy on cranial computed tomography are also poor prognostic signs."
-What factors beyond physical swallowing ability influence a patient's capacity to resume oral nutrition in oropharyngeal dysphagia?,"Factors affecting ability to resume oral nutrition in the oropharyngeal dysphagic individual. Successful oral intake of nutrition depends not only on the patient's ability to swallow efficiently and safely but also a number of cognitive, neurolinguistic, and behavioral variables. This paper reviews these competencies as they are integrated into the act of oral feeding and describes the types of disorders that affect these abilities. Methods of evaluating and treating the abilities needed for successful oral intake are described."
-What is the significance of screening for Wilson disease in cases of unexplained recurrent abortion?,"Recurrent abortion and the diagnosis of Wilson disease. We describe the first patient with Wilson disease and recurrent abortion who was effectively treated with oral zinc for both conditions. Between the ages of 21-26, this patient experienced seven successive unexplained abortions. At age 27, neurologic signs and liver function disturbances appeared. Wilson disease was diagnosed when Kayser-Fleischer rings were detected in the cornea. Decoppering therapy was instituted with zinc sulfate per os. By the age of 31, hepatic and neurologic signs had vanished. The patient conceived, and after an uncomplicated eighth pregnancy she delivered her first healthy child. Two years later, a ninth pregnancy was equally successful. The chance that Wilson disease may be the cause of recurrent abortion is small. However, because the disease is fatal if left untreated and because it is an underdiagnosed disease, we recommend screening for Wilson disease in cases of unexplained recurrent abortion when family history demonstrates consanguinity or neurologic, psychiatric, and/or liver disorders. A strategy to this end is proposed."
-How does Ki-67 immunostaining correlate with nuclear grade and clinical outcome in node-negative breast carcinoma?,"Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity."
-How was DNA typing used to determine paternity in the case of a putrefied fetus during a forensic investigation?,"A forensic application of DNA typing. Paternity determination in a putrefied fetus. Using minisatellite DNA probes that hybridize to a variable number of tandemly repeated loci, an individual-specific DNA fingerprint can be determined. In the case reported here, we succeeded in extracting high-molecular-weight DNA from a 3-month-old fetus discovered during the autopsy of a murdered 28-year-old pregnant woman reported missing 10 days earlier. The results of analysis of restriction-fragment-length polymorphisms showed that all bands present in the fetus's pattern, but absent in the mother's, matched only those of the putative father. Thus, the paternity of the victim's husband was ruled out."
-What drugs showed the greatest influence on clinical outcomes in the treatment of metastatic neuroblastoma?,"Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma."
-What was the primary purpose of performing palliative amputations in this study?,"Major amputations done with palliative intent in the treatment of local bony complications associated with advanced cancer. Palliative amputations were performed on 11 patients (7 men, 4 women) with disseminated disease to control local bony complications. The average patient age was 54 years (range 14-78 years). The primary diseases were melanoma/sarcoma (seven patients) and carcinoma (four patients). All had pain; eight had intractable pain that could not be controlled by analgesics. All 11 patients had additional severe local complications, which included recurrent pathological fracture (4), sepsis (2), hemorrhage (2), radiation necrosis (2), and iliofemoral thrombosis secondary to tumor (1). Previous attempts of palliation had been made in all 11 patients, and 8 had undergone previous operative procedures (5 had undergone two or more) prior to amputation. Three anterior hemipelvectomies, five posterior hemipelvectomies, two hip disarticulations, and one forequarter amputation were performed. All patients survived the surgery, and there were no intraoperative complications. All patients received dramatic relief of pain. Postoperative complications included two cases of flap necrosis and two infections; all resolved satisfactorily. The six patients who were nonambulatory before surgery ambulated postoperatively, and two eventually ambulated with a prosthesis. Six of 11 patients survived 1 year or longer, with a median postoperative survival period of 13 months (average 16 months). Although major amputations are viewed at times as offering little to already-compromised patients, they can improve dramatically the quality of life in selected patients."
-What did the confirmatory factor analysis reveal about the theoretical structure of the McGill Pain Questionnaire in acute pain scenarios?,"Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain. Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain."
-What specific areas of medical knowledge must cardiologists possess when treating adults with congenital heart disease?,"The physician's responsibilities: residua and sequelae. Cardiologists assuming responsibility for adults with congenital heart disease must have knowledge of electrophysiologic, valvular (native valves), prosthetic (valves, patches and conduits), ventricular (especially chamber function), vascular (especially elevated pulmonary vascular resistance) and noncardiovascular residua and sequelae. Acquired cardiac and noncardiac diseases coexist in older adults with postoperative congenital heart disease and add to the physician's responsibilities."
-"How did the Mini Shah grommet compare to the conventional Shah grommet in terms of extrusion, effusion recurrence, and tympanosclerosis?","The mini-grommet and tympanosclerosis. One hundred and sixteen children with otitis media with effusion underwent myringotomy and insertion of a conventional pattern of Shah grommet in one ear and the much smaller Mini Shah grommet in the other. Close observation post-operatively determined the comparative rate of extrusion, recurrence of effusion, and of onset and degree of tympanosclerosis. At one year review, the Mini Shah shows a significantly earlier extrusion and a greater tendency to recurrence of otitis media with effusion. However, this is compensated by a decreased incidence of tympanosclerosis and reduced severity in those affected. This tends to support the view that shear forces produced by heavier patterns of ventilation tube promote tympanosclerosis."
-What is the rare complication observed in this patient with mixed connective tissue disease?,Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease.
-What unique medical findings were discovered in the autopsy of this 62-year-old world record marathon runner?,"A world record marathon runner with silent ischemia without coronary atherosclerosis. A 62-year-old world record marathon runner was found to have silent ischemia manifested by a very abnormal stress test, whereas at autopsy nine months later, there was virtually no coronary atherosclerosis nor other disease of the coronary microvasculature. However, there was focal fibrosis of the papillary muscles consistent with remote ischemia secondary to possible CV. It is postulated that endurance-related high catecholamine levels might have been responsible."
-What were the findings of the study regarding the potential ototoxic effects of ciprofloxacin when applied ototopically?,Lack of ciprofloxacin ototoxicity after repeated ototopical application. The possible side effects of ototopically applied ciprofloxacin on inner ear function were investigated. The hearing function of pigmented guinea pigs was evaluated by daily frequency-specific evoked response audiometry after repeated application of the drug to both ears. Ciprofloxacin appeared to have no statistically significant effect on the hearing thresholds of the experimental animals.
-What are the key risk factors for tunnel infections in continuous peritoneal dialysis?,"Risk factors for tunnel infections in continuous peritoneal dialysis. Little data are available about risk factors for peritoneal catheter subcutaneous tunnel infection. Therefore, we analyzed tunnel infections occurring in our program over a 10.5-year period. One hundred twenty-nine tunnel infections occurred in 92 of 411 patients (22%) on peritoneal dialysis for a mean of 19 +/- 19 months. Tunnel infection rate was 0.19 per year. By 1 year, 15% of patients had a tunnel infection, and by 2 years, 23%. Tunnel infection rates decreased with increasing time on peritoneal dialysis: 2.4 per year for patients on peritoneal dialysis less than 1 year, 0.8 per year for patients on dialysis 1 to 2 years, and 0.4 per year for patients on dialysis greater than 2 years (all different at P less than 0.01). Organisms were cultured in 109 tunnel infections: gram-positive cocci in 77 episodes (71%) [Staphylococcus aureus 57, 52%], and gram-negative bacilli in 24 episodes (22%). Tunnel infection rates were higher in diabetics than in nondiabetics (0.27 per year v 0.16 per year, respectively; P less than 0.001 by life-table analysis of time to first infection) and also higher in women than in men (0.23 per year v 0.17 per year, P less than 0.001). Tunnel infection rates were 0.35 per year for diabetic women, 0.20 per year for diabetic men, 0.18 per year for nondiabetic women, and 0.15 per year for nondiabetic men (groups different, P less than 0.001). Race and age were similar in patients with and without tunnel infections. Catheter loss was 80% when tunnel infection was associated with peritonitis and 40% when tunnel infection alone was present (P less than 0.001). We conclude that the risk of tunnel infection is highest early in the course of peritoneal dialysis and that diabetic women, for unclear reasons, are at the highest risk."
-How does color Doppler flow sonography help in assessing erectile function in normal and abnormal cases?,"Assessment of normal and abnormal erectile function: color Doppler flow sonography versus conventional techniques. The penile arteries were studied with color Doppler flow sonography in 10 subjects with normal and 39 patients with abnormal erectile function. The relationships of systolic and diastolic velocities to spectral waveform changes in the penile arteries in response to tumescence were studied before and after intracorporal injection of vasoactive medications that induce erection. In normal subjects, a characteristic spectral waveform pattern corresponded to increasing intracorporal pressure. Patients with abnormal arterial inflow and/or abnormal venous sinusoidal leakage demonstrated deviation from the patterns noted in normal subjects. Patients with abnormal arterial inflow had lower mean peak systolic velocities than normal subjects. Patients with severe venous sinusoidal incompetence had an arrest of waveform progression with evolution to but not beyond phases 1 or 2 (diastolic flow remained positive). Patients with abnormal arterial inflow and abnormal venous sinusoidal outflow had waveform changes that reflected both processes. Systolic/diastolic velocity and waveform relationships can be used to define the integrity of both the cavernosal artery inflow and venous sinusoidal outflow occlusion mechanisms."
-What percentage of women with metastatic breast cancer develop eye metastases?,"Breast cancer metastatic to the eye is a common entity. Breast cancer metastatic to the eye is a common entity occurring in up to 30% of women with metastatic disease. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs. The diagnosis should be suspected in any women with a history of breast cancer and any visual symptoms, particularly metamorphopsia and scotomata. A thorough ophthalmologic evaluation, aided by ultrasonography, computed tomography, or magnetic resonance scanning, usually confirms the diagnosis. Early treatment with radiation therapy can alleviate symptoms and control local disease. The recognition and treatment of this disorder is important in maximizing the quality of life in patients with metastatic breast cancer, especially because newer treatment regimens prolong survival and thereby increase the chances for ocular metastasis."
-What are the two major types of cystic pancreatic neoplasms mentioned in the context?,"Incidental detection of a microcystic adenoma of the pancreas. Cystic neoplasms of the pancreas are uncommon. The two major types of cystic pancreatic neoplasms are microcystic (serous) cystadenoma and mucinous cystic lesions (mucinous cystadenoma and mucinous cystadenocarcinoma). The two types differ substantially in the long-term mortality. Symptoms and signs do not distinguish between the two types, and small lesions are often asymptomatic. The neoplasms may be discovered during imaging procedures for unrelated complaints. Computerized tomography may suggest the diagnosis of microcystic adenoma or mucinous cystic neoplasm when the features are typical, but the final diagnosis must be established by surgical biopsy. Characteristic gross findings, light microscopic findings, and immunohistochemical staining patterns distinguish between the two types. When preliminary open biopsy confirms microcystic adenoma, extensive unnecessary surgery can be avoided."
-How does dobutamine affect left ventricular isovolumic relaxation in patients with congestive heart failure compared to normal subjects?,"Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle. BACKGROUND. We tested the hypothesis that beta-adrenergic receptor-stimulated acceleration of left ventricular (LV) isovolumic relaxation (i.e., positive lusitropic response) is attenuated in patients with severe congestive heart failure (CHF) compared with patients without LV dysfunction or CHF. METHODS AND RESULTS. The beta-adrenergic agonist dobutamine was infused by the intracoronary route in 14 subjects (normal group, six; CHF patients, eight) and by the intravenous route in a second group of 14 subjects (normal group, four; CHF patients, 10). The positive inotropic response to intracoronary or intravenous dobutamine was substantially and significantly reduced in the patients with CHF. LV isovolumic relaxation rate was determined by the methods of Weiss (TL), Mirsky (T1/2), and by a nonlinear regression technique (TNL). LV isovolumic relaxation assessed by all three methods was significantly prolonged in CHF patients compared with normal subjects. Intracoronary and intravenous infusions of dobutamine caused significant acceleration of LV isovolumic relaxation in both normal subjects and patients with CHF. The magnitude of the dobutamine-stimulated acceleration of isovolumic relaxation in patients with CHF was comparable with that in normal subjects. CONCLUSIONS. These data demonstrate that beta-adrenergic receptor stimulation causes significant acceleration of LV isovolumic relaxation in both normal subjects and patients with severe CHF. Coronary to our hypothesis, the lusitropic response to beta-adrenergic stimulation is well preserved in patients with severe CHF despite substantial attenuation of the beta-adrenergic positive inotropic response. These findings have potentially important implications regarding the physiology and pharmacology of adrenergically mediated LV relaxation in humans."
-What is the significance of dystrophin-positive fibers (revertants) in Duchenne muscular dystrophy patients?,"Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group. The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript."
-What is the relationship between dimethylformamide (DMF) exposure and liver enzyme levels among synthetic leather workers?,"Dimethylformamide-induced liver damage among synthetic leather workers. Prevalence of liver injury associated with dimethylformamide (DMF) exposure was determined. Medical examinations, liver function tests, and creatine phosphokinase (CPK) determinations were performed on 183 of 204 (76%) employees of a synthetic leather factory. Air concentrations of solvents were measured with personal samplers and gas chromatography. The concentration of DMF in air to which each worker was exposed was categorized. High exposure concentrations of DMF (i.e., 25-60 ppm) were significantly associated with elevated alanine aminotransferase (ALT) levels (ALT greater than or equal to 35 IU/l), a result that did not change even after stratification by hepatitis B carrier status. Modeling by logistic regression demonstrated that exposure to high concentrations of DMF was associated with an elevated ALT (p = .01), whereas hepatitis B surface antigen (HBsAg) was slightly but independently associated with an elevated ALT (p = .07). In those workers who had normal ALT values, there occurred still significantly higher mean ALT and aspartate aminotransferase (AST) activities, especially among those who were not HBsAg carriers. A significant association existed between elevated CPK levels and exposure to DMF. However, an analysis of the CPK isoenzyme among 143 workers did not reveal any specific damage to muscles. This outbreak of liver injury among synthetic leather workers is ascribed to DMF. It is recommended that the occupational standard for DMF and its toxicity among HBsAg carriers be evaluated further."
-What is Parathyroid Hypertensive Factor (PHF) and how does it contribute to hypertension?,"Parathyroid hypertensive factor, a circulating factor in animal and human hypertension. A new circulating hypertensive factor (parathyroid hypertensive factor; PHF) was shown to exist in the plasma of spontaneously hypertensive rats (SHR) but not in that of normotensive rats. PHF produced a delayed increase in blood pressure with a peak response at 45 min (bolus injection) or 60 to 90 min (continuous infusion). This increase in blood pressure was coupled with an in vitro increase in calcium uptake in rat tail artery with a similar time course. The involvement of calcium in the mechanism of action was supported by the inhibitory effect of calcium antagonists on the vascular action of PHF. Furthermore, PHF increased the intracellular free calcium concentration in cultured smooth muscle cells from rat tail artery. Parathyroidectomy and parathyroid transplant experiments indicated the parathyroid origin of PHF. A culture of parathyroid glands from SHR, but not from normotensive rats, produced in the medium a factor which has the same biological property and HPLC retention time as plasma PHF. A novel cell type was described in the parathyroid gland of SHR, but not normotensive rats, and the percent of these cells correlated significantly with plasma PHF level and blood pressure. In some hyperparathyroid patients, plasma PHF and hypertension were found, both of which disappeared after surgical removal of the parathyroid gland. In both animal models and human studies, PHF seems to be associated with low or normal plasma renin and salt-sensitive type of hypertension."
-How accurately can radiographers triage x-ray films in accident and emergency departments?,"How well can radiographers triage x ray films in accident and emergency departments? [published erratum appears in BMJ 1991 Mar 23;302(6778):696] OBJECTIVE--To assess the ability of radiographers to identify abnormal radiographs of patients attending accident and emergency departments. DESIGN--Prospective study over six weeks. SETTING--Teaching hospital casualty x ray department. PATIENTS--3394 consecutive patients referred for radiography. INTERVENTIONS--Radiographs were assessed by radiographers who were offered a four point triage scheme: normal, abnormal, insignificantly abnormal, or further advice required. MAIN OUTCOME MEASURES--Comparison of radiographers' assessments with an assessment made independently by the reporting radiologists. RESULTS--Overall disagreement between the radiographers and radiologists was 9.4%. There were 7% false positives and 14% false negatives. Most errors occurred in assessing radiographs of the skull, facial bones, chest, abdomen, and soft tissues. CONCLUSION--Unselected radiographers can offer useful advice on radiographs to casualty officers, but their high rate of false positive diagnoses indicates that they cannot triage casualty radiographs sufficiently accurately to allow them to extend their current reporting role."
-What was the primary objective of the nicardipine study in ischemic stroke patients?,"Early treatment of ischemic stroke with a calcium antagonist. We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified."
-Is intravenous immunoglobulin G recommended as a first-line treatment for acute thrombotic thrombocytopenic purpura?,"Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature. Acute thrombotic thrombocytopenic purpura (TTP) is a rare and serious disease. Treatment with prednisone, anticoagulation, antiplatelet drugs, splenectomy, exchange transfusions, vincristine, and plasmapheresis may be effective in some patients, but the response to these therapies is inconsistent and all carry the potential for serious side effects. We, and others, have recently seen dramatic responses to intravenous (IV) immunoglobulin G (IgG) when other treatments have failed. Although IV IgG is expensive, its costs are low compared with those extended plasmapheresis regimens. Since the response to treatment can usually be evaluated within a few days and the side effects appear less than with other treatments, we believe a strong case can be made for the use of IV IgG as first-line therapy for acute TTP. Continued multicenter studies are necessary to finally solve the problem of competing and confusing treatment attempts and synergism of treatment in acute TTP."
-What were the key findings regarding the prognostic value of tumor grade and DNA ploidy status in stage D2 prostate cancer patients?,"The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma. This study was designed to compare the prognostic potential of tumor grade and ploidy status in patients with stage D2 prostate cancer. Two outcome groups were selected on the basis of survival after orchiectomy: a bad outcome group consisting of 66 patients who died of the disease within 12 months and a good outcome group comprising 37 patients who survived beyond 5 years. Tumors were classified histologically as well (17%), moderately (17%) or poorly (66%) differentiated. Tumor grade was a significant predictor of outcome, with 76% of poorly differentiated tumors in the bad outcome group and 65% of well differentiated tumors in the good outcome group (p less than 0.005). Deoxyribonucleic acid (DNA) ploidy analysis was performed on formalin fixed, paraffin embedded samples of the primary tumor to yield 97 final tracings that were classified using set criteria for DNA ploidy status. Over-all, 54% of the tumors were nondiploid (33% aneuploid and 21% tetraploid) and the remaining 46% were diploid. DNA ploidy status was a significant indicator of outcome (p less than 0.001), with 64% of diploid tumors in the good outcome group and 88% of the nondiploid tumors in the poor outcome group. Tetraploid tumors behaved no differently from other nondiploid tumors. We conclude that DNA ploidy status and tumor grading are significant independent predictors of outcome after orchiectomy and when combined yield important additional prognostic information."
-How does milrinone affect left ventricular remodeling after an acute myocardial infarction in rats?,"Effects of milrinone on left ventricular remodeling after acute myocardial infarction. BACKGROUND. Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS. Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION. Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation."
-What percentage of women with chronic pelvic pain were found to have occult somatic pathology after a negative laparoscopy?,"Nongynecologic somatic pathology in women with chronic pelvic pain and negative laparoscopy. One hundred eighty-three women with chronic pelvic pain were referred to a multidisciplinary chronic pelvic pain clinic after negative laparoscopy. One hundred twenty-two of them completed a thorough medical and psychologic evaluation and were followed for a minimum of six months after completion of therapy. Occult somatic pathology was diagnosed in 57 women (47%), including 19 in whom coexistent psychopathology was diagnosed. Myofascial pain was the most common somatic diagnosis, followed by atypical cyclic pain (dysmenorrhea or mittelschmerz); gastroenterologic, urologic and infectious diseases; and pelvic vascular congestion. No plausible somatic etiology was apparent in the remaining 65 (53%) of the 122 referrals. Nongynecologic somatic pathology accounted for 34 (29%) and gynecologic pathology for 23 (19%) of the referrals, only 6 (5%) of whom ultimately required hysterectomy. Women with a somatic diagnosis were found to be significantly older than the remainder of the referral population. Long-term symptomatic improvement or resolution of pain was obtained in 43 (75%) of the 57 patients with somatic diagnoses. Coexistent psychopathology was found to correlate with a poorer long-term prognosis. Our findings underscore the importance of a multidisciplinary approach to evaluating and treating chronic pelvic pain in women and confirm that hysterectomy is indicated in this setting only rarely."
-What was the efficacy of teicoplanin in treating osteomyelitis and vascular-access-associated bacteremias in this study?,"Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin. Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed."
-"How did nicardipine affect glucose tolerance, insulin secretion, and blood lipid levels in the study?","Effect of the calcium antagonist nicardipine hydrochloride on glucose tolerance and insulin secretion. The calcium antagonist nicardipine was administered to 42 patients at a dose of 60 or 120 mg/day for an average of 7.8 weeks to determine its effects on glucose tolerance and insulin secretion. Glucose tolerance and immunoreactive insulin levels were essentially unchanged by nicardipine regardless of the preexisting level of glucose tolerance. Mean systolic and diastolic blood pressures decreased in all patients. Concentrations of triglycerides decreased and high-density lipoprotein cholesterol levels increased significantly (p less than 0.05) in association with nicardipine administration. Therefore it is concluded that, regardless of the preexisting level of glucose tolerance, nicardipine exerted hypotensive effects without significant adverse effects on glucose tolerance or insulin secretion."
-How did the monitoring of somatosensory evoked potentials (SEPs) help predict and potentially prevent neurological deficits during middle cerebral artery aneurysm surgeries?,"Monitoring of somatosensory evoked potentials during surgery for middle cerebral artery aneurysms. Somatosensory evoked potentials (SEPs) were monitored during 53 procedures for aneurysms of the middle cerebral artery (MCA). ""Significant"" changes were reported to the surgeon, who took corrective action when possible. Changes in the SEPs were categorized as follows: Type I, no change; Type II, significant change with complete return to baseline; Type III, significant change with incomplete return to baseline; Type IV, complete loss with no return; and Type V, no response at baseline. Only 1 of 37 patients with a Type I SEP had a new neurological deficit, and this was a patient who could not be examined for several days after surgery because he was in a pentobarbital coma. All 4 patients with Type III and IV changes had new postoperative neurological deficits. Perhaps of greater importance, 4 of 5 patients with Type II changes had no new deficit. These patients all had changes in SEPs that were completely reversible by clip adjustment (2), prompt removal of temporary clips (1), and inducing hypertension after aneurysm trapping (1). These cases may, therefore, represent instances in which SEP monitoring allowed the clinicians to prevent a neurological deficit. The MCA supplies the area of the somatosensory cortex that controls the hand. Median nerve SEPs are, therefore, a theoretically ideal monitor during surgery for MCA aneurysms. This study suggests that the results of MCA aneurysm surgery may be accurately predicted and improved with SEP monitoring."
-What diagnostic values were studied in patients with spinal metastasis from adenocarcinoma of unknown origin?,"Clinical diagnosis for metastatic adenocarcinoma of spine of unknown origin. A comparative study. The diagnostic values of the presence of Virchow's node (VN) or rectal shelf (RS) in spinal metastasis from adenocarcinoma of unknown origin were studied prospectively in 60 patients during 1986-1988. These were compared with 14 cases with other malignancies of the spine and 37 controls with nonneoplastic spinal lesions. The diagnosis was confirmed by histologic study in all malignant cases. The results were analyzed by diagnostic test analysis and McNemar chi 2 testing. This yields 18.3-21.6%, 97.2-100%, and 92.8-100% sensitivity, specificity, and predictive value, respectively, for a positive test for VN and RS to differentiate significantly adenocarcinoma from other malignancies and control patients (P less than 0.005). These findings may thus be considered as a simple and economic guide for physicians to determine the proper approach to patients with a spinal lesion suspected to be malignant."
-What is the primary purpose of using botulinum toxin in the treatment of spasmodic dysphonia?,"Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia. Spasmodic dysphonia is a focal dystonia that causes a loss of the fine control of intrinsic laryngeal muscles and produces a strained staccato voice. Temporary relief from symptoms has been reported in patients treated with botulinum toxin percutaneously injected into the thyroarytenoid muscle. A newly developed method of treatment differs from reported methods by increasing the accuracy of botulinum toxin placement, reducing soft tissue trauma, and applying basic scientific information about the functional histology of intrinsic laryngeal musculature. Sixteen patients with primarily adductor spasmodic dysphonia were treated. Initial assessment included laryngeal examination by indirect laryngoscopy, videoendoscopy, and stroboscopy, neurology examination (including laryngeal EMG), and vocal function studies with acoustic analysis and aerodynamic studies. A device originally designed for collagen injection allowed the precise microdelivery of toxin to the thyroarytenoid muscle. Indirect laryngoscopy was used to direct the needle, in an attempt to cover a broad area of motor end plates. The minimally effective dose was titrated for each patient, to avoid paralysis and preserve laryngeal function. All patients showed improved voices after treatment. There were no major complications. The basic technique can be performed in the otolaryngologist's office and does not require electromyography equipment or expertise."
-What is the main purpose of the new approach described in the study for differentiating between supraventricular tachycardia with aberrant conduction and ventricular tachycardia?,"A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. BACKGROUND. In the differential diagnosis of a tachycardia with a wide QRS complex (greater than or equal to 0.12 second) diagnostic mistakes are frequent. Therefore, we investigated the reasons for failure of presently available criteria, and we identified new, simpler criteria and incorporated them in a stepwise approach that provides better sensitivity and specificity for making a correct diagnosis. METHODS AND RESULTS. A prospective analysis revealed that current criteria had a poor specificity for the differential diagnosis. The value of four new criteria incorporated in a stepwise approach was prospectively analyzed in a total of 554 tachycardias with a widened QRS complex (384 ventricular and 170 supraventricular). The sensitivity of the four consecutive steps was 0.987, and the specificity was 0.965. CONCLUSIONS. Current criteria for the differential diagnosis between supraventricular tachycardia with aberrant conduction and ventricular tachycardia are frequently absent or suggest the wrong diagnosis. The absence of an RS complex in all precordial leads is easily recognizable and highly specific for the diagnosis of ventricular tachycardia. When an RS complex is present in one or more precordial leads, an RS interval of more than 100 msec is highly specific for ventricular tachycardia. This new stepwise approach may prevent diagnostic mistakes."
-What percentage of patients in the study experienced otolaryngic complications during cancer chemotherapy?,"The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed."
-How did rice bran treatment affect stone formation rates in hypercalciuric patients?,"Results of long-term rice bran treatment on stone recurrence in hypercalciuric patients. A series of 182 calcium stone formers with idiopathic hypercalciuria underwent treatment with rice bran for 1 to 94 months. Urinary calcium excretion was considerably reduced, but there was some increase in urinary phosphate and oxalate. Urinary excretion of magnesium and uric acid, serum calcium, magnesium, phosphate, uric acid, parathyroid hormone (PTH) and ALP was unaffected. There were no obvious changes in serum iron, zinc and copper even when patients were treated for long periods. Rice bran was well tolerated in almost all cases and there were no serious side effects; 49 patients have undergone treatment for more than 3 years (average duration of administration 5.09 years). The frequency of new stone formation was drastically reduced (individual stone formation rate (no./year) from 0.720 +/- 0.533 to 0.125 +/- 0.204; group stone formation rate (no./patient-year) from 0.721 to 0.120) compared with the 3-year period before treatment. During treatment, 61.2% of patients remained in remission. Although rice bran therapy should be effective in correcting absorptive hypercalciuria, there may be limits to the overall ability of rice bran monotherapy to prevent recurrence."
-What was the primary objective of this Phase II trial involving intraperitoneal mitoxantrone in epithelial ovarian cancer?,"Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer. Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation)."
-How does the presence of the S-allele in Dahl rats affect their alcohol consumption?,"The influence of the renin gene on alcohol consumption in Dahl rats. A rat renin allele (the S-allele) has been identified in Dahl rats which cosegregates with increases in blood pressure. Rats with a double dose of the allele--the salt-sensitive hypertensive rats--have low renin activity compared with the salt-resistant hypertensive rat that does not have this S-allele. Alcohol consumption in rats has also been shown to vary with renin activity, and the possible involvement of renin activity in the genetics of alcohol consumption was suggested by previous work showing that the alcohol-preferring P line of selected rats had low renin levels. In the present study we examined alcohol consumption in a group of inbred Dahl rats, which have a double dose of the S renin allele, and in a group of selected Dahl rats, which have only a single dose of this S-allele. After an initial acclimation period, these two groups were first given daily 1-hr access to ascending concentrations of alcohol (3%, 6%, 8% w/v) over a 34-day period followed by continuous access to alcohol for a further 10 days. Water and food were always available. Regardless of whether alcohol was rationed or continuously available, the rats with the double dose of the S-allele drank significantly more alcohol than the rats that had only a single dose of this allele. These findings suggest that genetically mediated alterations in the renin gene may exert a significant influence on alcohol consumption and may be a component in the etiology of alcoholism."
-What was the clinical outcome of treating 15 patients with high-risk intracranial saccular aneurysms using electrolytically detachable coils?,"Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. Fifteen patients with high-risk intracranial saccular aneurysms were treated using electrolytically detachable coils introduced via an endovascular approach. The patients ranged in age from 21 to 69 years. The most frequent clinical presentation was subarachnoid hemorrhage (eight cases). Considerable thrombosis of the aneurysm (70% to 100%) was achieved in all 15 patients, and preservation of the parent artery was obtained in 14. Although temporary neurological deterioration due to the technique was recorded in one patient, no permanent neurological deficit was observed in this series and there were no deaths. It is believed that this new technology is a viable alternative in the management of patients with high-risk intracranial saccular aneurysms. It may also play an important role in the occlusion of aneurysms in the acute phase of subarachnoid hemorrhage."
-"How did the National Health Service Corps physicians contribute to reducing perinatal mortality rates in Dade County, Florida between 1987 and 1989?","The impact of National Health Service Corps physicians in the lowering perinatal mortality rate in Dade County, Florida. In some parts of Dade County, Florida, perinatal mortality rates have revealed serious problems in the delivery of health care to poor pregnant women. From 1982-1985, the reported perinatal mortality rates varied from 32-36 per 1000 live births, more than double the national average. Under the leadership of the Primary Health Care Consortium of Dade County (a federation of community health centers and other primary care providers), National Health Service Corps obstetricians and pediatricians served inner-city, medically needy patients as part of a coordinated perinatal plan from 1987-1989. Data on fetal and neonatal deaths, collected from census tracts adjacent to the community health centers, were used to study the impact of Corps obstetrician and pediatrician placement. The respective perinatal mortality rates were compared with those of 1986 as historic controls. Within a year, the overall perinatal mortality rate was reduced by 45%. As a result, an estimated 320 lives were saved between 1987-1989. This public health achievement represents a measurable impact due to assignment of National Health Service Corps physicians and can be used as a working model to reduce perinatal mortality in medically underserved communities in the United States."
-How does smoking affect ambulatory systolic blood pressure in hypertensive patients over 50 years old?,"Elevation of ambulatory systolic blood pressure in hypertensive smokers. A case-control study. Although smoking raises blood pressure, the office blood pressure measurements of smokers are the same as, or lower than, those of nonsmokers. To resolve this paradox, we compared the office and 24-hour ambulatory blood pressures of 59 untreated hypertensive smokers with 118 nonsmoking hypertensives matched for age, sex, and race. The office blood pressures of the smoking and nonsmoking groups were 141/93 and 142/93 mm Hg, respectively. The awake ambulatory systolic blood pressure was significantly higher in the smokers (145 vs 140 mm Hg). This difference was greater among patients over the age of 50 years (153 vs 142 mmHg), and absent among patients under 50 years (140 vs 139 mm Hg). Blood pressures during sleep did not differ between the two groups (121/76 vs 123/77 mm Hg). We conclude that, among white hypertensives above the age of 50 years, smokers maintain a higher daytime ambulatory systolic blood pressure than nonsmokers even though blood pressure measured in the office is similar."
-What rare underlying condition was found in a 46-year-old obese and mildly hypertensive patient with bilateral central retinal vein occlusions?,"Bilateral central retinal vein occlusion as an initial manifestation of pseudotumor cerebri. Pseudotumor cerebri, or benign intracranial hypertension, is known to produce visual symptoms. Central retinal vein occlusion has been linked with pseudotumor cerebri but rarely as an initial manifestation. We describe a 46-year-old patient--who was obese and mildly hypertensive with bilateral central retinal vein occlusions--who was subsequently diagnosed as having pseudotumor cerebri. In patients with simultaneous bilateral central retinal vein occlusions, unusual underlying systemic conditions such as pseudotumor cerebri should be considered in the diagnostic evaluation."
-What were the outcomes of laser laparoscopic management for patients with endometriomas in terms of fertility and pelvic pain?,"Laser laparoscopic management of large endometriomas. Forty-seven patients underwent laser laparoscopic management of endometriomas from 3 to 12 cm in diameter. Eighteen patients had infertility, 15 had pelvic pain, and 14 had both. The types of laser used were the carbon dioxide, argon, and potassium-titanyl-phosphate. There were no surgical complications. Twelve of 32 patients with infertility achieved pregnancy after the initial procedure. Subsequently, 2 patients conceived after a second-look procedure. Twenty-three of 30 patients with pelvic pain reported improvement or resolution. We confirm the efficacy of operative laparoscopy using lasers in the management of large ovarian endometriomas."
-What were the key findings regarding family practice residents' attitudes and behaviors towards serum cholesterol screening and management?,"Serum cholesterol: attitudes and behavior of family practice residents BACKGROUND. Given the current health promotion efforts regarding coronary artery disease, more information is needed about residents' attitudes and behaviors that relate to identification and management of patients with elevated serum cholesterol levels. METHODS. Family practice residents from eight US programs (N = 128) were surveyed in 1989 to assess their attitudes and reported practice patterns. Resident survey data were compared, when feasible, to published data from 1986 and 1990 surveys of practicing physicians performed by the National Heart, Lung, and Blood Institute. RESULTS. The use of faculty ""key contacts"" resulted in a 90% response rate (N = 115). Both residents and practicing physicians attributed a high degree of importance to cholesterol as a risk factor. Residents reported more frequent routine screening of middle-aged men than the routine screening rate of practicing physicians in 1986 (P less than .01). Residents reported less frequent screening of younger and older adults than of middle-aged men (P less than .001). Residents' threshold for the use of cholesterol-lowering medication was lower than that of practicing physicians surveyed in 1986, but higher than that of physicians surveyed in 1990. Compared with practicing physicians, residents did not believe they were as well prepared to counsel patients about dietary change or as successful when they tried to help patients make changes; residents reported a significantly higher rate of referral to dietitians (P less than .01). CONCLUSIONS. Residents may need more education regarding screening guidelines for children and young adults. A health promotion skills gap may exist that explains reported discrepancies between self-report and actual behavior and indicates that residency educators may need to pay more attention to fostering dietary assessment and counseling skills in their residents."
-What were the key findings regarding the relationship between calcitonin gene-related peptide (CGRP) concentrations and blood pressure in patients with mild to moderate essential hypertension?,"Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension. Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease."
-How does interleukin-1 (IL-1) contribute to the autocrine growth regulation of the B1 leukemic cell line?,"Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line. A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation."
-"How do cephalometric measurements differ between patients with sleep apnoea, non-apnoeic snorers, and non-snoring control subjects?","Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age."
-What were the four major sources of artifactual staining identified in the study of intermediate filament antibodies in human brain and brain tumors?,"Unexpected immunoreactivities of intermediate filament antibodies in human brain and brain tumors. Immunoreactivities of 35 different monoclonal antibodies (MAbs) that detect intermediate filaments were studied systematically on serial cryostat sections of 14 well-defined human gliomas (five astrocytomas, three oligodendrogliomas, six glioblastomas) and on normal brain. Glial fibrillary acidic protein (GFAP), vimentin, desmin, neurofilaments, and broad-specificity keratin MAbs, as well as MAbs that recognize several or only single keratin polypeptides, were used. Unexpected reactivities were surprisingly frequent. As these may lead to diagnostic confusion and misinterpretation on this material, the authors investigated these phenomena more thoroughly. Four major sources of artifactual staining were found: 1) positive staining attributable to the rabbit gamma G immunoglobulins used in the alkaline phosphatase anti-alkaline phosphatase technique; 2) certain desmin and keratin MAbs cross-reacted with astrocytic glia and with other brain-specific epitopes; 3) technical difficulties; 4) some MAbs directed against neurofilaments and keratins showed unexpected reactivities only on individual anaplastic gliomas. The implications of these findings for intermediate filament typing of neuropathologic material are discussed."
-What behavioral and sensory changes were observed in rats after partial sciatic nerve injury?,"A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Partial nerve injury is the main cause of causalgiform pain disorders in humans. We present here a novel animal model of this condition. In rats we unilaterally ligated about half of the sciatic nerve high in the thigh. Within a few hours after the operation, and for several months thereafter, the rats developed guarding behavior of the ipsilateral hind paw and licked it often, suggesting the possibility of spontaneous pain. The plantar surface of the foot was evenly hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized. There was a sharp decrease in the withdrawal thresholds bilaterally in response to repetitive Von Frey hair stimulation at the plantar side. After a series of such stimuli in the operated side, light touch elicited aversive responses, suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a companion report, we show that these abnormalities critically depend on the sympathetic outflow. Based on the immediate onset and long-lasting perpetuation of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the resemblance of the contralateral phenomena to 'mirror image' pains in some humans with causalgia, we suggest that this preparation may serve as a model for syndromes of the causalgiform variety that are triggered by partial nerve injury and maintained by sympathetic activity."
-Which viruses demonstrated the most significant ability to infect and persist in human joint tissue according to the research?,"Susceptibility of normal human joint tissue to viruses. A model system has been developed to investigate the comparative ability of different viruses to replicate and persist intraarticularly. The viruses chosen for study were rubella, mumps, Coxsackie B4, adenovirus and varicella zoster, a selection of viruses with different degrees of association with joint symptoms in clinical studies. Our results showed that these viruses demonstrated a range of abilities to infect and persist in human joint tissue cultured in vitro. The most arthritogenic viruses, rubella, and to a lesser extent mumps, replicated and penetrated deeply into the synovial membrane. In contrast, the other 3 viruses were much less arthrotropic, and may only induce arthritis by immunopathological mechanisms."
-What is the relationship between intermittent claudication and silent myocardial ischemia in the study?,"Intermittent claudication as a manifestation of silent myocardial ischemia: a pilot study. One hundred consecutive patients with intermittent claudication were screened noninvasively with electrocardiography chest wall mapping stress test and transcutaneous aortovelography during bicycle ergometry. Electrocardiographic chest wall stress testing indicated three-vessel coronary disease in 25 patients and left anterior descending plus circumflex (left main stem equivalent) disease in seven. In these 32 patients transcutaneous aortovelography demonstrated a decrease in stroke distance (an index of cardiac stroke volume) (median, -28%; 90% range, +5% to -48%), and coronary angiography confirmed the presence and severity of the disease. The claudication distance ranged between 50 and 250 meters. After myocardial revascularization or medical therapy a significant increase occurred in the stroke distance after exercise (median, +20; 90% range, +40% to -25%); also a significant increase in the postexercise pressure index and a reduction in the recovery time (p less than 0.01). No change occurred in the ankle/pressure index at rest. Twelve patients were able to walk without being limited by claudication; 15 reported improvement with a two to tenfold increase in claudication distance. No change occurred in three. The results indicate that silent myocardial ischemia is a common finding in patients with intermittent claudication. It produces left ventricular dysfunction and a decrease in stroke volume leading to a large fall in ankle pressure and early onset of claudication during exercise. Niltrates and myocardial revascularization tend to reverse this."
-What unique characteristics were observed in the five children with intractable ulcerating enterocolitis of infancy?,"Intractable ulcerating enterocolitis of infancy. Five children (three boys, two girls) presenting in the first year of life with intractable diarrhoea had a number of features in common. All had ulcerating stomatitis, four had partial villous atrophy on small intestinal biopsy, all had colitis characterised by large ulcers with overhanging edges, and four had severe perianal disease; no stool pathogens were detected. Treatment with steroids, sulphasalazine, and azathioprine was unsuccessful. All five required subtotal colectomy. Four were children of consanguinous marriages, two were siblings of Pakistani origin, two were cousins of Arab origin, and the fifth was Portuguese. Although the diagnoses of Behcet's disease and Crohn's disease were considered, it appears that these children represent a distinct inherited condition affecting the whole gastrointestinal tract, particularly the colon."
-What trend was observed in operative mortality rates for gastric cancer surgery from 1970 to 1990?,"Improving survival in gastric cancer: review of operative mortality in English language publications from 1970. In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner."
-What evidence suggests a potential link between anal cancer and cervical cancer in this study?,"Aetiological parallel between anal cancer and cervical cancer. It has been postulated that an infectious agent and/or specific sexual behaviour is involved in the aetiology of anal cancer, in analogy with the aetiology established for cancer of the cervix. A case-control study of 29,648 women with cancers registered in the Danish Cancer Registry during 1968-87 tested the hypothesis that anal cancer patients were more likely than patients with colon, stomach, or vulva cancer to have had a previous diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cervical cancer. The odds ratio of CIN, adjusted for age and year of diagnosis, for anal vs colon cancer was 5.2 (95% confidence interval [CI] 3.3-8.3), that for anal vs stomach cancer 3.6 (2.1-6.0), and that for anal vs vulva cancer 1.6 (0.9-2.9). The median time from diagnosis of CIN to diagnosis of the registered cancer was 151 months for anal, 112 months for vulva, 114 months for colon, and 126 months for stomach cancer. The association with previous invasive cervical cancer was also investigated; no patient with cervical cancer in this second analysis had been included in the CIN analysis. The odds ratios were similar. In addition, anal cancer patients were significantly more likely to have had cervical cancer than were patients with vulva cancer (odds ratio 1.8 [1.0-3.9]). The strong association between anal cancer and CIN/invasive cervical cancer suggests that these cancers share common risk factors. The association is at least as strong as that between cervical and vulva cancer."
-How did two-dimensional echocardiography and continuous-wave Doppler help diagnose the pseudo-tricuspid stenosis in this case?,Reversible tricuspid stenosis. Demonstration with two-dimensional echocardiography and continuous-wave Doppler. We report a case of pseudo-tricuspid stenosis as a result of extrinsic compression of the tricuspid valve by a large right-sided pericardial effusion. Two-dimensional echocardiography and continuous-wave Doppler enabled accurate noninvasive diagnosis and hemodynamic assessment.
-What did the study reveal about the relationship between Helicobacter pylori antibodies and tissue staining in subjects with atrophic body gastritis?,"Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Helicobacter pylori is rarely found in gastric biopsy specimens from individuals with atrophic gastritis of the body mucosa. To determine if subjects with atrophic body gastritis have evidence of previous infection with H. pylori, immunoglobulin G antibody to H. pylori was measured by enzyme-linked immunosorbent assay in sera of 399 Finnish subjects. In 124 subjects, multiple biopsy specimens from body and antrum had been evaluated for the presence of H. pylori by Giemsa staining. Antibody correlated well with H. pylori staining except in the subgroup with atrophic body gastritis, in whom the prevalence of seropositivity (86%) was significantly greater than the prevalence of positive staining (33%) (P less than 0.001). Twenty-five subjects had positive antibody and negative staining. This group had a significantly higher prevalence of atrophic body gastritis (80%), lower maximal acid output, lower serum pepsinogen I levels, and higher serum gastrin concentrations than did seropositive subjects with H. pylori. These data suggest that most patients with atrophic body gastritis, despite having a low incidence of current overt infection, have been infected with H. pylori at some point in their lives."
-How does the superoxide anion production of neutrophils in Crohn's disease patients differ from that of healthy subjects when stimulated by PMA1 and PMA2?,"Superoxide production by Crohn's disease neutrophils. Neutrophil superoxide anion production was measured in healthy subjects and in patients with quiescent and active Crohn's disease using superoxide dismutase inhibitable cytochrome C reduction. Three stimuli were used: phorbol 12-myristate 13-acetate (PMA1), phorbol 20-oxo-20-deoxy 12-myristate 13-acetate (PMA2), and Candida albicans in serum. Normal neutrophils produced significantly more superoxide anion than Crohn's disease neutrophils with both PMA1 (mean (SD) 9.6 (2.2) v 8.6 (1.8) nmol/10(6) cells/5 minutes, p = 0.04) and PMA2 (1.8 (0.8) v 0.8 (0.77) nmol/10(6) cells/5 minutes, p = 0.00004). With C albicans in serum, normal and Crohn's disease neutrophils produced similar amounts of superoxide anion (4.4 (1.5) v 4.3 (1.7) nmol/10(6) cells/30 minutes, not significant). Results were independent of disease activity. Superoxide anion production by PMA-stimulated Crohn's disease neutrophils is significantly lower than by normal neutrophils."
-What changes were observed in the circulating levels of the N-terminus of the atrial natriuretic factor (ANF) prohormone in patients with pheochromocytomas?,"Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas. To investigate the possible relationship of hypertension and the N-terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas."
-What is the purpose of using human recombinant erythropoietin in the preoperative setting described in this case report?,"Use of human recombinant erythropoietin to correct severe preoperative anemia. The risks of homologous blood transfusion are well known. Herein, we describe the successful preoperative use of human recombinant erythropoietin to correct severe anemia in a patient refusing transfusion. This case report emphasizes the important perioperative role human recombinant erythropoietin may play in the future."
-How do staging procedures and tumor stage differ between academic and community hospitals for lung cancer patients?,"Cancer staging may have different meanings in academic and community hospitals. We investigated differences in lung cancer care and outcome between academic and community settings for all lung cancer patients diagnosed during 1973-1976 in New Hampshire and Vermont. Trained abstracters reviewed hospital charts to record personal, diagnostic, and clinical information, and survival was determined for all patients through the end of 1979. Patients diagnosed in university hospital cancer centers underwent more staging procedures and tended to be assigned to a higher stage than similar patients diagnosed in community hospitals. When tumor stage was considered as a covariable in a survival analysis, these patients appeared to have a lower mortality rate both for non-small cell tumors (mortality rate ratio, 95% confidence interval = 0.81, 0.71-0.91) and for small cell tumors (0.71, 0.55-0.91). When functional status rather than tumor stage was used to adjust for disease severity, there was no apparent survival advantage for university patients with non-small cell cancer (0.96, 0.85-1.09) and the lower mortality for small cell cancers (0.76, 0.59-0.97) was attenuated, although still statistically significant. We conclude that inconsistently-collected data on clinical stage can complicate comparisons of prognosis between cancer patients from different types of hospitals and that measures of performance status may be more useful indicators of disease severity in population based studies."
-How does lumbar puncture affect intracranial cerebrospinal fluid (CSF) volume and its relationship to post-lumbar puncture headache?,"Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. Post-lumbar puncture (LP) headache may be due to ""low CSF pressure"", leading to stretching of pain sensitive intracranial structures. The low intracranial pressure is secondary to net loss of intracranial CSF. It has, however, not been possible to measure intracranial CSF volume accurately during life until recently. Intracranial CSF volume can now be measured non-invasively by a MRI technique. The changes in intracranial CSF volume were studied in 20 patients who had LP. Total intracranial CSF volume was reduced in 19 of the 20 patients 24 hours after LP (range -1.8 mls to -158.6 mls). Most of the CSF was lost from the cortical sulci. Very large reductions in intracranial CSF volume were frequently related to post-LP headache but some patients developed headache with relatively little alteration in the intracranial CSF volume. There was not a measurable change in position of the intracranial structures following LP."
-What is the prognostic significance of proliferating cell nuclear antigen (PCNA) in gastric carcinoma according to the study?,"Prognostic value of proliferating cell nuclear antigen in gastric carcinoma. A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising."
-What is the recommended approach for treating renal oncocytomas based on the Australian experience described in the context?,"Renal oncocytomas--an Australian experience. A review was made of 24 cases of renal oncocytoma seen between 1978 and 1989. There was considerable overlap between the clinical presentation of renal oncocytomas and renal carcinomas. Although pre-operative radiological, cytological and pathological investigations may suggest the presence of an oncocytoma, these studies cannot make a definitive diagnosis. We recommend that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise."
-What were the key findings of the study comparing the effectiveness of metoprolol and nifedipine in patients with mixed angina?,"Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine. The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve."
-What are the primary indications for liver transplantation according to the context?,"Liver transplantation for alcoholic liver disease, viral hepatitis, and hepatic neoplasms. In closing, it is important to note that the indications for liver transplantation are not static but rather are remarkably dynamic and capable of change over time. Thus yesterday's major indications can become relative contraindications, while yesterday's absolute contraindications have become today's nuisances. The goal for physicians who care for individuals with problems such as alcoholic liver disease, viral hepatitis, and hepatic cancer should be to develop new strategies of care that will ultimately eliminate these diseases as problems, rather than eliminating individuals with such health problems from currently available health options. In other words, physicians who accept the responsibility for a patient's life should be searching for the best form of therapy available for their patient rather than examining the reasons that exist for limiting one's choice in health care."
-Which drug was more effective in converting paroxysmal atrial fibrillation to sinus rhythm: propafenone or flecainide?,"The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainide (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p less than 0.02). If atrial fibrillation was present less than or equal to 24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p less than 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS). Mean time to conversion was 16 +/- 10 min in the propafenone group versus 18 +/- 13 min in the flecainide group (p = NS). QRS lengthening (83 +/- 15 to 99 +/- 20 ms) was observed only in the patients treated with flecainide (p less than 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p less than 0.01). In conclusion, at a dose of 2 mg/kg in 10 min, flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter."
-What potential complication can tissue plasminogen activator (t-PA) cause during treatment of acute myocardial infarction?,"Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable."
-What are the primary early mechanical features observed in cemented femoral components of hip arthroplasties?,"The initiation of failure in cemented femoral components of hip arthroplasties. We studied 16 femora retrieved at post-mortem from symptomless patients who had a satisfactory cemented total hip arthroplasty from two weeks to 17 years earlier, with the aim of delineating the initial mechanisms involved in loosening. Only one specimen showed radiographic evidence of loosening; the other 15 were stable to mechanical testing at 17.0 Nm of torque. In all 16 specimens, the cement-bone interface was intact with little fibrous tissue formation. By contrast, separation at the cement-prosthesis interface and fractures in the cement mantle were frequent. The most common early feature was debonding of the cement from the metal, seen at the proximal and distal ends of the prosthesis. Specimens which had been in place for longer also showed circumferential fractures in the cement, near the cement-metal interface, and radial fractures extending from this interface into the cement and sometimes to the bony interface. The most extensive cement fractures appeared to have started at or near sharp corners in the metal, or where the cement mantle was thin or incomplete. Fractures were also related to voids in the cement. The time relationship in this series suggested that long-term failure of the fixation of cemented femoral components was primarily mechanical, starting with debonding at the interface between the cement and the prosthesis, and continuing as slowly developing fractures in the cement mantle."
-"What was the purpose of studying the vasomotor response of coronary artery segments in patients with syndrome X, chronic stable angina, and control subjects?","Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X) The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments."
-What is Henoch-Schonlein purpura and how does it affect children according to the surgical evaluation in this study?,"Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived."
-What were the key findings of the study regarding peritoneal factors in rabbits with surgically induced endometriosis?,"Surgically induced endometriosis does not alter peritoneal factors in the rabbit model. OBJECTIVE: It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN: Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS: There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS: These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue."
-What are the two distinct patterns of venous pulse observed in patients with dilated cardiomyopathy?,"Jugular venous 'a' wave in dilated cardiomyopathy: sign of abbreviated right ventricular filling time. OBJECTIVE--To study the mechanisms underlying the high venous pressure often seen in patients with dilated cardiomyopathy. DESIGN--Retrospective and prospective examination of the pattern of flow in the superior vena cava, cardiac echo-Doppler studies, and recordings of the jugular venous pulse. SETTING--A tertiary referral cardiac centre. PATIENTS PARTICIPANTS--23 patients with dilated cardiomyopathy, all with functional mitral and tricuspid regurgitation. RESULTS--Two patterns of venous pulse were seen: a dominant 'a' wave and 'x' descent, with systolic flow in the superior vena cava (group 1, n = 11), and a dominant 'v' wave with 'y' descent and diastolic flow in the superior vena cava (group 2, n = 12). A comparison of group 1 and group 2 showed: age (mean (SD] 58 (12) v 61 (6) years, left ventricular end diastolic dimension 7.0 (0.7) cm in both groups, right ventricular short axis 3.3 (0.6) v 3.6 (0.5) cm and long axis 7.3 (0.5) v 7.1 (0.7) cm, and duration of tricuspid regurgitation 350 (65) v 370 (50) ms. The RR interval (550 (100) v 680 (80) ms) and right ventricular filling time (150 (30) v 290 (50) ms) were significantly shorter in group 1. In all patients in group 2 right ventricular filling time was more than 200 ms with separate E and A waves on the tricuspid Doppler echocardiogram, while in all group 1 patients it was less than 200 ms with a single summation peak. In nine patients in group 1, the right ventricular filling time was limited by prolonged tricuspid regurgitation and in the remaining two by prolonged isovolumic relaxation time (215 (80) ms), so that it was consistently significantly less than that of the left ventricle. CONCLUSION--In patients with dilated cardiomyopathy, right ventricular filling time may be so short that it limits stroke volume. Such patients can be recognised by a dominant 'a' wave on the jugular venous pulse. Patients in whom the right ventricular filling time was longer showed a dominant 'v' wave. Both groups can present as ""congestive heart failure""."
-How does the response of atrial natriuretic factor (ANF) differ between patients with and without right ventricular (RV) infarction after volume expansion?,"Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction. To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction."
-Which virulence characteristics were independently associated with Escherichia coli strains causing acute pyelonephritis according to the multivariate statistical analysis?,"Relative importance of eight virulence characteristics of pyelonephritogenic Escherichia coli strains assessed by multivariate statistical analysis. We have previously reported univariate statistical analysis of the prevalences of putative virulence determinants in Escherichia coli isolated from children and adults with acute pyelonephritis. The expression of P-fimbriae, cell surface hydrophobicity, mannose resistant haemagglutination, haemolysin synthesis, cytotoxic necrotizing factor production and aerobactin mediated iron uptake occurred more often in a collection of 115 Escherichia coli strains isolated from children and women with acute non-obstructive pyelonephritis compared to 96 strains isolated from the commensal fecal flora. With the aim to study which of these virulence markers were independently associated with strains causing infection we performed a multivariate statistical analysis with the data from these strains. The previously proposed virulence factors, expression of type 1 fimbriae and adhesion to HeLa cells were also included in the analysis. P-fimbriae, mannose resistant haemagglutination and the production of haemolysin were, in the multivariate analysis, associated with strains isolated from patients with acute pyelonephritis."
-What was the mean time to sensation of warmth in the spinal and extradural groups during the study?,"Sensitivity, specificity and predictive value of the sensation of warmth as a method of detecting inadvertent subarachnoid injection of local anaesthetic when performing extradural blocks. In order to test if the rate of onset of sensation of warmth in the legs after the injection of 0.5% bupivacaine might discriminate between subarachnoid and extradural injection, 150 urological patients were allocated randomly to receive either spinal anaesthesia with isobaric (IS) or hyperbaric (HS) 0.5% bupivacaine, or extradural anaesthesia with isobaric 0.5% bupivacaine. The volume of the local anaesthetic for spinal anaesthesia and for the extradural test dose was 3-4 ml. The patients were asked to report at once if they had a sensation of warmth in the legs during or after injection of local anaesthetic. The mean time to the sensation of warmth was significantly shorter in the spinal groups (80 (SEM 10) s in IS and 76 (8.0) s in HS) than in the extradural group (558 (38) s). However, six patients in the IS and two in the HS group had no sensation of warmth."
-What is the purpose of the document developed by the Centers for Disease Control (CDC) regarding HIV and hepatitis B virus transmission?,Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. This document has been developed by the Centers for Disease Control (CDC) to update recommendations for prevention of transmission of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in the health-care setting. Current data suggest that the risk for such transmission from a health-care worker (HCW) to a patient during an invasive procedure is small; a precise assessment of the risk is not yet available. This document contains recommendations to provide guidance for prevention of HIV and HBV transmission during those invasive procedures that are considered exposure-prone.
-What was the main purpose of the study regarding pancreatic pseudocyst amylase concentration?,"The value of pancreatic pseudocyst amylase concentration in the detection of pseudocyst communication with the pancreatic duct. The aims of the study were to compare the results of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous cystopancreatography (PCP) in the detection of the communication between the pancreatic pseudocyst and the pancreatic duct, and to assess the reliability of the increased amylase concentration in the pseudocyst content as an indicator of the existence of communication between the pancreatic pseudocyst and the pancreatic duct system. Forty-three patients were included in the study. Pseudocystic fluid content was obtained by percutaneous aspiration. Twenty-four patients had pseudocyst amylase concentrations above 64 Wolgemuth units (WU), and 19 patients had less than 64 WU. The communication between pseudocyst and the pancreatic duct was determined in 22 patients by ERCP and in 13 patients by PCP, all in the group with increased pseudocyst amylase concentration. Due to high sensitivity and specificity of pseudocyst amylase concentration for the existence of pseudocyst communication with the pancreatic duct, we conclude that guided percutaneous aspiration of the pancreatic pseudocyst with the determination of amylase concentration in the fluid can replace ERCP as a method of choice for the detection of pseudocyst communication with the pancreatic duct."
-What are the key findings from the review of lumbar discectomies regarding intestinal injury?,"Intestinal injury after lumbar discectomy. In a review of 5,200 lumbar discectomies performed from 1974 to 1989, two patients sustained a ventral perforation of the disc space followed by isolated small intestinal injury. Both patients underwent lumbar discectomy at the lumbosacral junction and presented with signs and symptoms of acute abdominal distress within three days after the operation. At surgical laparotomy, small tears were noted in the ileum, which were closed primarily. The patients had an uneventful recovery. The results of a review of 11 instances reported in the literature suggest that isolated intestinal injuries usually occur postoperatively at the lumbosacral junction and involve the small intestine. Factors, such as body habitus, surgical experience, patient positioning and types of instruments, as well as the use of a surgical microscope, do not appear to modify the risk of intestinal injury. After discectomy, patients may present with acute abdominal signs and symptoms or chronic wound infections. Work-up studies include evaluation of vascular structures and ureters either roentgenographically or at abdominal exploration. A high index of suspicion and adequate disc space visualization during discectomy may reduce the incidence of this complication."
-What percentage of patients achieved union in the salvage operations for nonunion following total ankle arthrodesis?,"Salvage of nonunion following ankle arthrodesis for failed total ankle arthroplasty. Revision operations for nonunion following total ankle arthrodesis for total ankle arthroplasty (TAA) were reviewed in ten patients. Operations averaged 2.0 years after prior arthrodesis attempts and featured external fixation in seven, internal fixation in one, percutaneous pin fixation in one, and cast immobilization only in one. Bone graft was used in seven. Union was achieved in 78%. The one complication was an infection in a patient with prior sepsis. The results were considered excellent in three, good in one, fair in three, and poor in two of the nine patients with adequate follow-up evaluation (average, 7 years). Despite successful arthrodesis, residual symptoms were common because of factors such as hindfoot degenerative arthritis and malalignment."
-What was the main finding of the study regarding the effects of low to moderate lead exposure on vitamin D metabolism and bone mineral content in young children?,"Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure. One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure."
-What was the overall response rate and median survival time in this Phase II pilot study of weekly cisplatin-based induction regimen for extensive non-small cell lung cancer?,"A weekly cisplatin-based induction regimen for extensive non-small cell lung cancer. A Southwest Oncology Group study. The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach."
-What is the significance of intercellular adhesion molecule 1 expression in primary biliary cirrhosis and primary sclerosing cholangitis?,"Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis. It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis."
-What technique is described for salvaging thrombosed forearm polytetrafluoroethylene (PTFE) vascular access grafts?,"Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting. A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction."
-How did dopexamine compare to dopamine in preventing renal impairment in patients undergoing orthotopic liver transplantation?,"A comparison of dopexamine and dopamine to prevent renal impairment in patients undergoing orthotopic liver transplantation. The efficacy of low-dose dopamine as a renal protective agent was compared with that of dopexamine in patients who underwent orthotopic liver transplantation. Twelve patients who received a continuous infusion of dopexamine (1-3 micrograms/kg/minute) were matched for age, diagnosis, pre-operative creatinine clearance and blood loss with 12 patients who received a low-dose infusion of dopamine (2 micrograms/kg/minute). The catecholamine infusion was started after induction of anaesthesia and continued for 48 hours after surgery. Patients in the dopexamine group had less evidence of renal impairment and failure than those in the dopamine group during 7 days after the operation, although the differences between groups did not achieve statistical significance. Similarly there were no significant differences between the two groups in peri-operative urine output, urine/plasma osmolality ratio or creatine clearance. Dopexamine is at least as effective as dopamine for renal protection in patients who undergo liver transplantation."
-How does sodium benzoate administration affect the urinary carnitine profile?,"Alteration of urinary carnitine profile induced by benzoate administration. To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia."
-What are the key findings of magnetic resonance imaging (MRI) in patients with spinal trauma within 3 weeks and more than 3 weeks after injury?,"Magnetic resonance imaging of spinal trauma. A retrospective series of 118 magnetic resonance examinations of 110 patients who had sustained previous spinal trauma is reported. Examinations performed within 3 weeks of trauma showed extraspinal soft tissue (including ligamentous) injury in 48% and intraspinal lesions in 61% (mostly consisting of extradural haematoma and spinal cord contusion). In examinations performed more than 3 weeks after injury intraspinal abnormalities were shown in 51% and these represented spinal cord compression, atrophy, myelomalacia and syringohydromyelia. Magnetic resonance imaging has the unique capability of displaying non-invasively the late sequelae of spinal trauma permitting simultaneous evaluation of the extra-spinal soft tissues, vertebral column and spinal cord. It is therefore recommended as the technique of choice in the investigation of patients who have sustained previous spinal injury, particularly those with neurological deficit. In the acute phase potentially remediable causes of neurological impairment such as disc herniation or extradural haematoma can be identified. Signal changes in the cord may allow the prognosis for neurological recovery to be established. In the later stages sequelae such as cord atrophy, myelomalacia and syringohydromyelia are accurately identified and surgical therapy may be guided, where appropriate."
-What changes were observed in the density of glomerular atrial natriuretic factor binding sites in bile duct-ligated rats with ascites?,"Altered density of glomerular binding sites for atrial natriuretic factor in bile duct-ligated rats with ascites. The renal response to atrial natriuretic factor is blunted in cirrhosis with ascites. This might be due to alterations of renal receptors for atrial natriuretic factor. Therefore density and affinity of glomerular atrial natriuretic factor binding sites of bile duct-ligated rats with ascites (n = 10) and of sham-operated controls (n = 10) were determined. Glomerular atrial natriuretic factor binding sites were identified to be of the B-(""biologically active"") and C-(""clearance"") receptor type. Discrimination and quantitative determination of B and C receptors for atrial natriuretic factor were achieved by displacement experiments with atrial natriuretic factor(99-126) or des(18-22)atrial natriuretic factor(4-23), an analogue binding to C receptors only. Density of total glomerular atrial natriuretic factor binding sites was significantly increased in bile duct-ligated rats (3,518 +/- 864 vs. 1,648 +/- 358 fmol/mg protein; p less than 0.05). This was due to a significant increase of C-receptor density (3,460 +/- 866 vs. 1,486 +/- 363 fmol/mg protein; p less than 0.05), whereas density of B receptors was not significantly different in bile duct-ligated rats (58 +/- 11 vs. 162 +/- 63 fmol/mg protein). Affinity of atrial natriuretic factor to its glomerular binding sites did not differ significantly between both groups. These data suggest that an altered glomerular atrial natriuretic factor receptor density could be involved in the renal resistance to atrial natriuretic factor in cirrhosis with ascites."
-"How did the treatment approach for medulloblastoma change between 1970-1983 and 1984, and what impact did this change have on patient outcomes?","The change in patterns of relapse in medulloblastoma. The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases."
-What type of graft was used for venous reconstruction in the superior vena cava replacement during mediastinal and pulmonary tumor resections?,"Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors. The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease."
-"What is the purpose of using a free gastric mucosal flap with microvascular transfer in the reconstruction of malignant lesions in the oral cavity, base of tongue, and oropharynx?","Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered."
-What was the purpose of the study on intravenous heme-albumin in acute intermittent porphyria?,"Intravenous heme-albumin in acute intermittent porphyria: evidence for repletion of hepatic hemoproteins and regulatory heme pools. The purpose of this study was to assess effects of heme administered intravenously, complexed to human serum albumin, on activities of the hepatic hemoproteins, cytochrome(s) P-450, and tryptophan pyrrolase, and on the size of the heme pool that regulates activity of 5-aminolevulinate synthase. Effects were compared in six normal women and four women with acute intermittent porphyria. All porphyric subjects over-excreted heme precursors and had histories of acute neurovisceral porphyric attacks. All subjects were placed on a constant daily diet that included at least 3 g carbohydrate/kg body weight and sufficient total intake to provide 1.4 times the estimated resting energy expenditure. Urinary excretions of 5-aminolevulinate, porphobilinogen, porphyrins, and metabolites of tryptophan were measured daily before, during, and after infusions of heme-albumin. In the porphyric subjects, intravenous heme [4 mg (6.1 mumol)/kg body weight (BWt) with equimolar albumin], given daily for 4 days, markedly reduced overexcretion of 5-aminolevulinate, porphobilinogen, and porphyrins, indicating repletion of the regulatory heme pool. The heme infusions also decreased mean urinary excretion of 5-hydroxyindoleacetic acid from 4.9 to 2.9 mg/g creatinine per day, suggesting increased activity of hepatic tryptophan pyrrolase, the rate-controlling enzyme for metabolism of tryptophan to products not in the serotonin-5-hydroxyindoleacetic acid pathway. Heme-albumin infusions were without detectable effects on excretions of heme precursors or tryptophan metabolites in normal subjects. In contrast, in both normals and porphyrics, heme-albumin infusions significantly increased rates of antipyrine metabolism (by 159% and 330%, respectively), suggesting increased activities of cytochrome(s) P-450 were produced by the infusions. The infusions were well tolerated; no subject developed thrombophlebitis or bleeding. We conclude that such infusions are safe and effective in repleting deficient heme pools and hemoproteins in patients with acute porphyria, and that activities of cytochrome(s) P-450 in normal subjects may also be increased by heme administration. The therapeutic effect of heme in acute porphyria probably relates to its ability to decrease overproduction of precursors of heme or serotonin, as the result of its increasing critical cellular heme pools."
-How did the researchers use anti-V region antibodies to study cutaneous T cell lymphomas and leukemias?,"Anti-V region antibodies as ""almost clonotypic"" reagents for the study of cutaneous T cell lymphomas and leukemias. Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an ""almost clonotypic"" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL."
-What was the effect of recombinant human erythropoietin (rHuEPO) on anemia correction in predialysis patients with chronic renal failure?,"Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group [published erratum appears in Am J Kidney Dis 1991 Sep;18(3):420] One hundred seventeen patients with anemia related to chronic renal failure not severe enough to require maintenance dialysis were randomly assigned to receive recombinant human erythropoietin (rHuEPO; 50, 100, or 150 U/kg body weight) or placebo intravenously (IV) three times a week for 8 weeks or until their anemia was corrected. Correction of anemia (hematocrit of 40% for males, 35% for females) occurred in 87% of those given 150 U/kg, 64% of those given 100 U/kg, 46% of those given 50 U/kg rHuEPO and in 3% of the placebo group. Energy levels and work capacity improved significantly in the group with corrected anemia compared with the group with uncorrected anemia. rHuEPO appeared to be well tolerated. There was no evidence that rHuEPO therapy accelerated the deterioration of renal function as measured by serum creatinine and reciprocal of serum creatinine compared with placebo treatment. However, it is essential that blood pressure and hematocrit be carefully monitored, particularly in hypertensive patients, to prevent the development of complications associated with hypertension."
-How has the understanding and diagnosis of preeclampsia changed over time according to the given context?,"Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased."
-What is the relationship between non-cirrhotic portal hypertension and IgA nephropathy in the reported case?,IgA nephropathy in non-cirrhotic portal hypertension. Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease.
-What are the four types of diarrheal illnesses identified in rural Bangladesh according to folk terminology?,"Folk terminology for diarrhea in rural Bangladesh. Diarrhea, a descriptive term used in medical science for a variety of clinical diseases, denotes an illness that is categorized differently and known by numerous terms in various cultures. These diversified classifications and terminologies are based on the symptoms of diarrheal disorders, their perceived etiology, and their treatment. In Bangladesh, four types of illnesses with names derived from folk terminology have been identified for which the clinical symptoms resemble those of diarrhea. These include dud haga, which is due to ingestion of breast milk by infants; ajirno, which is due to overeating; amasha, a mucoid diarrhea; and daeria, which is severe watery diarrhea or cholera. Use of the word diarrhea in epidemiologic evaluations was discovered to be problematic; people confused this term with daeria, which accounted for only 5% of all episodes of diarrhea. The implications of such epidemiologic information for a large-scale program of oral rehydration therapy are also discussed."
-What is the significance of using 31P localized magnetic resonance spectroscopy in the assessment of head and neck tumors?,"31P localized magnetic resonance spectroscopy of head and neck tumors--preliminary findings. Magnetic resonance imaging (MRI) is a powerful tool for accurate assessment of the anatomic extent of head and neck neoplasms. The development of methods for spatial localization by use of multiply tuned radio frequency coils that permit the measurement of multiple nuclear MR spectra (1H and 31P) from precisely defined volumes of interest has provided a basis for integrating spectroscopy into the clinical MRI examination. This offers a means for noninvasive monitoring of relative concentrations of mobile metabolites within a tumor. With the use of imaging to determine proper coil placement, a test-retest variance of about 17% is seen on MR spectroscopy. Data are presented from MRI/MRS studies for four head and neck lesions: (1) a squamous cell carcinoma of the lip; (2) a juvenile angiofibroma extending into the nasal cavity; (3) a massive chondrosarcoma of the nasal septum; and (4) a cervical nodal metastasis of a squamous cell carcinoma of the pharynx. Spectra are evaluated by comparison of relative concentrations of phosphorus compounds. The concentrations of phosphomonoesters and phosphodiesters are significantly higher in the neoplasms studied than in normal skeletal muscle. The developing role of integrated MRI/MRS to monitor the response of malignant neoplasm to radiation therapy is discussed."
-How did Streptococcus pneumoniae infection affect the metabolic responses and performance capacity of rats during swimming exercise?,"Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats. The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection."
-What are the current challenges in treating congestive heart failure and its high mortality rate?,"Congestive heart failure. New frontiers. Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome."
-How was leuprolide acetate used to manage symptoms of severe fibrocystic breast disease in the study?,Management of severe fibrocystic disease of the breast with leuprolide acetate. Symptoms of severe fibrocystic disease of the breast were successfully ameliorated in two patients as a result of treatment with daily subcutaneous LA without adverse effects. A state of drug-induced hypogonadotropic hypogonadism appears to be responsible for the clinical effect and is further suggestive of the hormonal dependence of this common disorder.
-Are surgical procedures performed by residents as safe as those performed by attending staff?,"Safety of surgical procedures performed by residents. The outcome of surgical procedures on the gallbladder performed by surgical residents in a university hospital was compared with the outcome of those performed by the attending staff. More than 60% of the operations (643/1084) were done by residents under the direct supervision of the attending surgeon. We found no differences in the rate of technical complications, postoperative morbidity and mortality, or length of hospitalization between the two groups. Thus, resident surgery under appropriate guidance is safe and does not compromise the quality of patient care or operative outcome."
-What complications did the patients with chickenpox pneumonia experience in this case report?,"Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation."
-How does acetylcholine influence pancreastatin secretion in the QGP-1N cell line?,"Acetylcholine regulates pancreastatin secretion from the human pancreastatin-producing cell line (QGP-1N). Studies were made of pancreastatin (PST) secretion from a human PST-producing cell line (QGP-1N) in response to various secretagogues. Cells with immunoreactivity for PST were observed in monolayer cultures of QGP-1N cells. Carbachol stimulated PST secretion and the intracellular Ca2+ mobilization concentration dependently in the range of 10(-6)-10(-4) M. The PST secretion and Ca2+ mobilization induced by carbachol were inhibited by atropine. The calcium ionophore (A23187) stimulated PST secretion. However, cholecystokinin and gastrin-releasing peptide did not stimulate either PST secretion or Ca2+ mobilization. Secretin also did not stimulate PST secretion. The glucose concentration in the culture medium had no effect on PST secretion. These results suggest that PST secretion is mainly regulated by acetylcholine through a muscarinic receptor, and that an increase in intracellular Ca2+ plays an important role in stimulus-secretion coupling in QGP-1N cells."
-What are the potential causes of delayed visual loss following head trauma according to the study?,"Delayed visual loss due to trauma of the internal carotid artery. The group of six patients in this study experienced delayed visual loss following head trauma. Visual loss occurred from 1 day to 13 years after the initial injury. All patients suffered indirect trauma to the internal carotid artery resulting in formation of either an aneurysm or pseudoaneurysm or a carotid-cavernous fistula. Review of the radiologic and clinical findings was performed in six patients. The diagnosis was established by computed tomography, magnetic resonance imaging, and angiography. All patients had follow-up clinical evaluation and imaging studies. Treatment by neurosurgical or interventional neuroradiologic procedures resulted in significant visual improvement in five patients. Different pathophysiologic mechanisms could be correlated with the delayed visual loss produced by the two types of lesions. The pathologic changes associated with the aneurysms/pseudoaneurysms included direct compression of optic nerves and/or chiasm and intracranial hematoma. A carotid-cavernous fistula caused delayed visual loss by either hematoma at the orbital apex or compression of the chiasm and/or optic nerves by saccular dilatation of the cavernous sinus. The delayed onset of decreased vision following head trauma should alert the physician to the possibility of a traumatic aneurysm/pseudoaneurysm or a carotid-cavernous fistula. Different neuro-ophthalmologic symptoms can usually be correlated with the pathologic changes demonstrated by neuroimaging procedures."
-What were the key findings regarding exercise-related sudden ischemic death in the study of 17 resuscitated victims?,"Clinical and angiographic observations on resuscitated victims of exercise-related sudden ischemic death. The clinical and angiographic findings of 17 resuscitated victims of exercise-related sudden ischemic death are reported in an attempt to elucidate the mechanism(s) of these deaths. Ten survivors developed cardiac arrest during or after sporting activities (group A) and 7 others during or after an exercise stress test (group B). There were 15 men and 2 women. The mean age of group A was 46 years and of group B 55 years. Coronary risk factors, as well as previous angina and myocardial infarction, were more frequent in group B. Only 3 of the 17 survivors had anginal symptoms before sudden death. Sudden death in group A was associated with acute myocardial infarction in 8 and unstable angina in 2 and was associated in group B with acute myocardial infarction in 2, unstable angina in 3 and silent ischemia in 2. Coronary angiography was acutely performed in 15 patients. In most patients the ischemia-related coronary artery was totally or subtotally occluded. Clinical and angiographic findings indicate that exercise-related sudden ischemic death was due to an acute coronary event--in most cases unexpected and unpredictable. It is suggested that exercise-induced intracoronary changes were probably responsible for the development of acute coronary (sub)occlusion and sudden death."
-What is the significance of the Shope papilloma-carcinoma complex in rabbits for understanding human papillomavirus-associated malignancies?,"Establishment from Shope carcinoma induced in an inbred rabbit of culture cell lines with various potentials for differentiation and tumorigenicity. Shope papillomas induced by cottontail rabbit papilloma-virus (CRPV) in domestic rabbits frequently regress spontaneously or, failing to do so, convert into squamous cell carcinomas at a high rate. This papilloma-carcinoma complex in rabbits provides an experimental model for human papillo-mavirus-associated malignancies. The aim of this study was to prepare an experimental system in inbred rabbits by establishing culture cell lines of the tumor. Squamous cell carcinoma developed from a Shope papilloma that had been induced 6 months previously by inoculating CRPV into an inbred B/J rabbit. By in vitro culturing of the tumor cells, cell lines with potentials for terminal differentiation and tumorigenicity were established. Cloning yielded sublines that varied in these potentials and possessed episomal and integrated CRPV genomes as revealed by Southern hybridization in both one- and two-dimensional electrophoresis. Major CRPV-specific transcripts were similarly observed both in well-differentiated and in poorly differentiated sublines. Immunofluorescence with syngeneic rabbit antibody against tumor-specific antigens localized such antigens mainly in the nuclei of the cells of these sublines. This experimental system allows experiments that were not feasible in randomly bred rabbits."
-How do limited access to healthcare and cultural barriers impact neurological care for minority populations in the United States?,"Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies."
-What is xeroderma pigmentosum (XP) and how does it affect patients neurologically?,"Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system."
-What morphometric findings were observed in the brain stems of patients with Joseph disease using computed tomography?,"Brain stem atrophy in Joseph disease: a morphometric study using two-dimensional (area) measurement by computed tomography. Eight Japanese patients with Joseph disease were studied using computed tomography (CT). Morphometric analysis using the two-dimensional (area) measurement by CT was performed in the infratentorial region. The brain-stem index, an index of brain-stem atrophy or pontine atrophy, revealed a significant decrease (P less than 0.01), with a mean of 66.7% when compared with 16 control subjects. The patients showed a significant increase (P less than 0.01), with a mean of three times that of the controls in the fourth ventricular index, an index of fourth ventricular dilatation. There were no differences in the cerebellar index, an index of cerebellar atrophy, between these patients and the controls, although the patients had an increased number of visible cerebellar vermian (2.0, SD 0.7) and hemispheric sulci (2.6 SD 0.6) as compared with the controls (vermian sulci: 0.4, SD 0.7: hemispheric sulci: 0). These data indicate severe pontine atrophy, fourth ventricular dilatation with mild involvement of the cerebellum and correlate well with the common pathological features of Joseph disease. The present morphometric evaluation by CT may be useful in the clinical diagnosis of Joseph disease."
-How does the day of the menstrual cycle affect the incidence of postoperative nausea and vomiting in women undergoing laparoscopy?,"The incidence of postoperative nausea and vomiting in women undergoing laparoscopy is influenced by the day of menstrual cycle. Postoperative nausea and vomiting is a major cause of postoperative morbidity. It can lead to increased recovery time, delaying patient discharge and an increase in hospital costs. Past studies have shown that postoperative nausea and vomiting is more frequent in women than men, appears to elevate around the time of menarche and is reduced around the time of menopause. This retrospective review of a one-year experience of laparoscopic tubal ligation at our institute examined the effect of menstrual cycle on postoperative nausea and vomiting. The anaesthetic and surgical techniques were consistent for all patients. Patient data included age, weight, last day of menstrual cycle, the length of anaesthetic, the dose of inhalational agent, the dose of narcotic, emesis on emergence and whether or not droperidol was used. Of the the 235 patients in the study, the incidence of nausea and vomiting was 28%. One hundred fifty-eight had had no preoperative antiemetic and 77 had received droperidol. These two groups were analyzed separately. The incidence in the group not receiving droperidol was 33.5% and in the droperidol group, 16.9% (P less than 0.01). The incidence of nausea and vomiting was higher on the first eight menstrual days (51.6 vs 21.6, P less than 0.001), was highest on day five of the menstrual cycle and lowest on days 18, 19, and 20 where there was no nausea and vomiting. Droperidol reduced the incidence of postoperative nausea and vomiting but the variation in postoperative nausea and vomiting during the cycle persisted."
-What percentage of patients survived long-term after receiving the Bio-Medicus ventricular assist device during cardiac surgery?,"Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients."
-What are the key applications of PET scanning in clinical oncology?,"The applications of PET in clinical oncology. With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology."
-What were the key findings regarding the response of patients with systemic sclerosis to nifedipine and captopril in this study?,"Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril. PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed ""borderline"" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder."
-How did oral administration of myelin antigens affect the progression of experimental autoimmune encephalomyelitis in Lewis rats and strain 13 guinea pigs?,"Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the Lewis rat and strain 13 guinea pig. Oral administration of proteins is a long-recognized method of inducing antigen-specific peripheral immune tolerance. We previously showed that oral administration of myelin basic protein suppresses monophasic experimental autoimmune encephalomyelitis in the Lewis rat when it is given in association with immunization and prior to disease onset. As a potential therapy for human autoimmune disease, it is crucial to determine whether oral tolerance can ameliorate an ongoing immune response. We therefore asked whether oral administration of myelin antigens, after sensitization and disease expression has occurred, could affect immunological, clinical, or pathological features of experimental autoimmune encephalomyelitis. Chronic relapsing experimental autoimmune encephalomyelitis was induced in the Lewis rat and strain 13 guinea pig by immunization with whole guinea pig cord homogenate, complete Freund's adjuvant, and Mycobacterium tuberculosis. Following recovery from the first attack, animals were orally given bovine myelin, guinea pig myelin, or guinea pig myelin basic protein three times per week for up to 3 months. Animals receiving myelin products orally had decreased severity and frequency of clinical relapses, decreased delayed-type hypersensitivity responses to myelin antigens, diminished inflammation in the central nervous system (CNS), and decreased areas of CNS demyelination. In the rat, guinea pig myelin basic protein was as effective as guinea pig myelin in ameliorating the disease and also resulted in decreased serum anti-myelin basic protein antibody levels. No exacerbation of disease or worsening of pathological findings occurred in the animals given myelin products. These results demonstrate that oral administration of myelin antigens can suppress chronic relapsing experimental autoimmune encephalomyelitis and have direct relevance to therapy of human demyelinating disorders such as multiple sclerosis."
-What diagnostic techniques were used to identify and confirm the intrahepatic arterioportal fistula in this patient?,"Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed."
-What characteristics of focal hepatic lesions can help differentiate between benign and malignant tumors using MR imaging?,"Focal hepatic lesions: differentiation with MR imaging at 0.5 T. Magnetic resonance (MR) examinations of 43 patients with 95 focal hepatic lesions (diameter, greater than 1 cm) were analyzed for lesion shape, homogeneity, and relative signal intensity compared with normal liver parenchyma, spleen, and skeletal muscle. On T1-weighted, balanced, and T2-weighted images, most metastases (74%), cavernous hemangiomas (76%), and cysts (82%) were smooth and round or oval, while the hepatocellular carcinomas all had irregular borders (40%) or were lobulated (60%). All lesions with irregular borders were malignant. Seventy percent of metastatic lesions, 85% of cavernous hemangiomas, and 100% of simple hepatic cysts were of homogeneous signal intensity, while 60% of hepatocellular carcinomas were inhomogeneous. Logistic regression analysis of multiple lesion characteristics showed that inhomogeneous lesions had a high likelihood of malignancy, while markedly hyperintense lesions had a very low probability of being malignant, regardless of other traits. Homogeneous lesions that were isointense or hyperintense compared with spleen on balanced images but were not markedly hyperintense on T2-weighted images also had a high likelihood of malignancy."
-What percentage of stage I testicular cancer patients experienced recurrence in the Testicular Cancer Intergroup Study?,"Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study. The Testicular Cancer Center Intergroup Study entered surgically staged patients with nonseminomatous tumor and metastases limited to the regional lymph nodes into a previously reported cooperative trial of immediate versus delayed therapy for positive retroperitoneal node disease. Patients with negative nodes (stage I) were placed in an observation registry with specified treatment strategy upon relapse. Of 264 stage I cancer patients 27 (10.2%) had recurrence: 5 of these 27 patients died after recurrence of the testicular malignancies, while 4 other nontumor-related deaths have occurred. Pre-lymphadenectomy staging characteristics observed to predict significantly node positivity are the results of radiological examinations, presence of tumor invasion, vascular invasion and tumor histology. In a multiple logistic regression analysis with these variables, misclassification still occurs in more than a fourth of the patients. Future refinements in diagnosis may allow for better prediction of these patients at risk to have positive lymph nodes and ultimately recurrence. Presently, if assessment of nodal involvement is the objective, noninvasive procedures are not an adequate substitute for surgical staging with modified lymphadenectomy."
-What distinctive features of crackling lung sounds were found in patients with different respiratory conditions?,"Crackles in patients with fibrosing alveolitis, bronchiectasis, COPD, and heart failure. We have studied the crackling lung sounds of ten patients with cryptogenic fibrosing alveolitis, ten with bronchiectasis, ten with chronic obstructive pulmonary disease, and ten with heart failure by analyzing frequency, waveform, and timing of crackles. The upper frequency limit of inspiratory sounds was higher in CFA than in COPD or in HF. The period of crackling was shorter in COPD than in CFA or BE. Inspiratory crackling terminated significantly earlier in COPD than in CFA, BE, or HF. The initial deflection width and the two-cycle duration of the expanded waveforms of crackles were smaller in CFA than in BE, COPD, or HF. The largest deflection width was smaller in CFA than in BE, HF, or COPD and smaller in BE than in HF. The results indicate that crackling lung sounds in different diseases have distinctive features and that their analysis can be of diagnostic value."
-What novel treatment strategies have been explored for Parkinson's disease?,"Parkinson's disease: new treatment strategies. Recent interest has focused on two novel approaches to the treatment of Parkinson's disease-medications to slow or arrest disease progression, and cerebral transplantation. Two recent studies have demonstrated that selegiline can slow, although not halt, the progression of recent-onset Parkinson's disease. The data are sufficiently compelling to justify the use of this drug in most new patients. It also seems reasonable to extrapolate from the data and offer this medication to all patients but those with the most advanced Parkinson's disease. The current focus on excessive oxidative stress as a causative factor has led some investigators to recommended treating patients with the antioxidant tocopherol (vitamin E). There is no clinical evidence demonstrating its effectiveness, but a current multicenter study is being conducted, with the results expected within the next 2 years. High-dose vitamin E (such as 800 to 2000 U/d), taken for a number of months, is probably harmless. It is probably reasonable, therefore, to allow patients to take this over-the-counter compound until more definitive evidence is available. Another antioxidant, vitamin C, has also been advocated as a means of slowing the progression of Parkinson's disease. There are no studies that demonstrate any clinical effectiveness, and there are also no ongoing studies investigating this issue in patients with Parkinson's disease. The excitement surrounding the initially favorable results of adrenal-brain transplantation has waned with the failure of numerous institutions to replicate the original dramatic success. While mild or occasionally moderate improvement has been noted in subsequent patients undergoing adrenal-brain transplantation, the improvement has not been sufficient to justify the risk and expense of this surgery."
-What was the impact of switching from body ventilators (BVs) to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP) on patients with obstructive sleep apnea?,"Obstructive sleep apnea complicating negative-pressure ventilatory support in patients with chronic paralytic/restrictive ventilatory dysfunction. The purpose of this study was to determine the incidence and severity of obstructive events and oxyhemoglobin desaturation (dSaO2) in 37 patients with paralytic/restrictive ventilatory insufficiency during use of nocturnal ventilatory assistance provided by means of negative-pressure body ventilators (BVs). Thirteen of the 37 patients had mean oxyhemoglobin saturation (SaO2) less than 95 percent and a mean of ten or more episodes per hour when the dSaO2 was greater than or equal to 4 percent (4%dSaO2/h). In all, 26 of the 37 patients had evidence of significant multiple episodes of dSaO2 while asleep on BVs. Polysomnography performed on three of these patients substantiated the obstructive nature of the dSaO2. Twenty-two of the 37 patients who had a mean SaO2 of 90.6 +/- 7.2 percent and a mean of 17.7 +/- 16.1 4%dSaO2/h on BVs were switched to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP). Their mean SaO2 improved to 96.0 +/- 2.2 percent, and the 4%dSaO2/h decreased to 1.2 +/- 1.8 per hour. All symptoms similar to those of obstructive sleep apnea were relieved. We conclude that BV use is associated with significant dSaO2 in over 50 percent of patients. The dSaO2 is predominantly obstructive in nature but may be due to chronic underventilation in patients using less effective BVs. Patients with a mean SaO2 less than 95 percent or 10 or more 4%dSaO2/h may benefit from conversion to NV-PAP via the nose, the mouth, or an oral-nasal interface."
-What significant changes have occurred in rehabilitation approaches for patients with rheumatic diseases over the past decade?,"Rehabilitation in rheumatic diseases. What's new. In the past decade, considerable change has occurred in concepts of rehabilitation in patients with rheumatic diseases. This includes approaches to functional assessment and outcome, new concepts in exercise, and new orthotics."
-How does a family history of coronary artery disease affect hemodynamic responses to exercise in young black boys?,"Family history of myocardial infarction and hemodynamic responses to exercise in young black boys. The influence of family history of coronary artery disease on children's hemodynamic responses to exercise was examined with 25 black boys aged 7 to 10 years. Blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance were evaluated during preexercise, peak exercise, and recovery stages. Children with a family history of CAD exhibited greater systolic blood pressure and total peripheral resistance during preexercise and peak exercise stages than did those without a family history of coronary artery disease. After controlling for preexercise differences, the group with a family history of coronary artery disease exhibited greater increases in systolic blood pressure and less attenuation of total peripheral resistance to peak exercise than the group without a family history of coronary artery disease. Cardiac output indexed by body surface area and stroke volumes were higher at all times in the group without a family history compared with the group with a family history of coronary artery disease. Findings are compared with those of adult studies in terms of influence of family history of coronary artery disease on cardiovascular reactivity to stress."
-What evidence suggests that the chronic lymphocytic leukemia and lymphoblastic lymphoma in this patient originated from the same malignant cell?,"Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed."
-How does the degree of headache relief impact psychological changes in chronic headache patients?,"Psychological changes accompanying non-pharmacological treatment of chronic headache: the effects of outcome. Several prior studies suggest that non-drug treatment for chronic headache is accompanied by concomitant reductions in patients' anxiety, depression and somatization. It is currently unclear, however, whether such beneficial side effects are a function of degree of headache relief or are due simply to receiving treatment. Most work to date in this area has treated outcome as a dichotomous variable. The present report employed a regression approach which treats outcome (degree of headache relief) as a continuous variable in the study of 149 chronic headache patients and their accompanying psychological changes. Anxiety and depression were significantly reduced for headache patients regardless of degree of headache relief. With somatization, however, degree of headache relief had a significant effect; the greater the reduction in headache, the fewer somatic concerns were expressed, especially for mixed headache."
-What was the main purpose of the study on exocrine pancreatic function in children with coeliac disease?,"Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal."
-What is the significance of left atrial spontaneous echo contrast in patients undergoing transesophageal echocardiography?,"Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement."
-What was the main finding regarding resting energy expenditure (REE) in patients with newly detected gastric and colorectal cancers?,"Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients."
-What was the main finding of the study comparing short-term and long-term cefoxitin prophylaxis after radical hysterectomy?,"Comparative efficacy of short-term versus long-term cefoxitin prophylaxis against postoperative infection after radical hysterectomy: a prospective study. We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy."
-What was the response rate and median time to progression for patients with recurrent malignant glioma treated with intravenous carboplatin?,"Intravenous carboplatin for recurrent malignant glioma: a phase II study. Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate."
-What are the bactericidal properties of fibrin gel against different bacterial species in a contaminated hepatic injury model?,"Autologous fibrin gel: bactericidal properties in contaminated hepatic injury. Fibrin glue is an effective hemostatic agent in a variety of clinical situations; its utility is limited by potential transmission of viral infection. We studied the bactericidal properties of fibrin gel (FG) in a murine contaminated hepatic injury model and in vitro by agar plate culture method. Intra-abdominal abscess formation and adhesion rate were assessed following controlled liver injury in association with abdominal contamination with 10(7) Bacteroides fragilis and hepatorrhaphy (H, n = 15) or FG (n = 12). Animals treated by hepatorrhaphy had a significantly greater intra-abdominal abscess rate (15/15 vs. 4/12, p less than 0.05) and adhesion rate (14/15 vs. 6/12, p less than 0.05) than animals treated with FG. Fibrin gel is bactericidal to Bacteroides fragilis, Enterobacter faecium, Escherichia coli, and Staphylococcus aureus but has no effect against Klebsiella pneumoniae or Pseudomonas aeruginosa; the plasma component appears active. Fibrin gel demonstrates significant improvement in adhesion formation and intra-abdominal abscess rate when compared with suture hepatorrhaphy. Fibrin gel appears protective in contaminated hepatic injury."
-What rare ictal phenomenon was investigated in two patients with epilepsy?,"Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions."
-What medical condition was observed in a 16-month-old infant with congenitally-acquired HIV infection?,Acute hemiplegia associated with HIV infection. An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia.
-What is moricizine hydrochloride and what is its primary medical application?,"Moricizine: a new agent for the treatment of ventricular arrhythmias. Over the last several years, a number of new antiarrhythmic agents have come into use. One of these promising new drugs, moricizine hydrochloride (Ethmozine), is now available for use in this country. Although similar in some aspects to both quinidine and lidocaine, Moricizine hydrochloride is in many ways unique. The purpose of this review is to summarize the pharmacologic and physiologic effects of moricizine and to outline its clinical use."
-What was the mortality rate during the initial admission for neonates with oesophageal atresia and/or tracheo-oesophageal fistula in this surgical study?,"Success and failure with neonatal tracheo-oesophageal anomalies. In seven and a half years, one surgical team treated 67 consecutive neonates with oesophageal atresia and/or tracheo-oesophageal fistula. According to Waterston's classification, 28 were in group A, 12 in group B and 27 in group C. The mortality rate during the initial admission was 10 per cent, all seven deaths being unavoidable in infants in group C with multiple anomalies. Birthweight alone had no bearing upon the chances of survival. Primary oesophageal repair, including one suture-fistula procedure and one delayed primary repair, was attempted in 54 (84 per cent) of the 64 patients with atresia and was successful in 46 (85 per cent). All three H-type tracheo-oesophageal fistulae were successfully divided in infants in group A. Recurrent tracheo-oesophageal fistula developed in four (7 per cent) infants, one of whom (group A) underwent successful repair. One disrupted anastomosis was successfully resutured (group A), so an intact oesophagus was finally achieved in 51 patients, of whom six (12 per cent) developed anastomotic strictures and 21 (41 per cent) underwent surgery for gastro-oesophageal reflux. Of the 60 early survivors, 10 (17 per cent) underwent aortopexy for tracheomalacia. Whenever possible, primary repair is advocated in all infants. Even for those in group C with multiple, severe associated anomalies, the combined early and late mortality was no greater following primary repair (7 died of 12 operated) than after staged repair (4 died of 7 operated), but major anastomotic complications were more common in infants in group C (5 out of 19) than in those in groups A and B (3 out of 38)."
-How did the quality of life differ between patients taking atenolol and nifedipine GITS during the 20-week antihypertensive therapy trial?,"Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system. To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation."
-What was the significance of culturing the calcified lymph nodes in this patient's case?,"Esophagobronchial fistula and mediastinal tuberculosis. A 59-year-old man was seen with what preoperatively was thought to be an acquired esophagobronchial fistula secondary to an old burned-out infection with tuberculosis. At operation the gross and microscopic findings were most compatible with a congenital H-shaped esophagobronchial fistula. However, cultures of calcified lymph nodes grew Mycobacterium tuberculosis. The need for culturing calcified tissue to assure proper treatment is emphasized."
-How does acute appendicitis present differently in patients with AIDS/HIV infection compared to immunocompetent patients?,"Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality."
-What was the success rate of antitachycardia pacing in treating tachycardia episodes in this study?,"Reduction in defibrillator shocks with an implantable device combining antitachycardia pacing and shock therapy. Implantable defibrillators reduce the risk of sudden death in patients with malignant ventricular arrhythmias, but significant restriction in quality of life can occur as a result of frequent device activation. To determine if a device that provides both antitachycardia pacing and shock therapy can safely reduce the frequency of shocks after implantation, 46 consecutive patients undergoing initial implantation of a defibrillator were studied. In all patients, the implanted device provided antitachycardia pacing and shock therapy. Detected tachycardia characteristics and the results of therapy were stored in the device's memory. There were 42 men and 4 women, aged 26 to 71 years (mean 58.7 +/- 13.5). Left ventricular ejection fraction ranged from 13% to 67% (mean 32.2 +/- 13.4%) and 31 patients had experienced one or more episodes of cardiac arrest. Induced arrhythmias included sustained monomorphic ventricular tachycardia in 38 patients, nonsustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. Over a total follow-up period of 255 patient-months (range 1 to 13, mean 6.1), 25 patients experienced spontaneous arrhythmic events. In 22 patients, 909 episodes of tachycardia were treated by antitachycardia pacing, which was successful on 840 occasions (92.4%). Acceleration of ventricular tachycardia by pacing therapy was estimated to have occurred 39 times. Syncope occurred once during pacing-induced acceleration of ventricular tachycardia. Forty-four episodes of tachycardia in seven patients were treated directly by shocks because of short tachycardia cycle length; 88% of all detected tachycardias were treated without the need for shocks. Four patients died from cardiorespiratory failure and one patient died suddenly without any detected tachyarrhythmia."
-What are the primary methods for treating active esophagogastric variceal bleeding and preventing its recurrence?,"Bleeding esophagogastric varices. Ways to treat active episodes and prevent recurrence. Bleeding from esophagogastric varices carries a high mortality rate. Active variceal bleeding can usually be temporarily controlled medically with a combination of intravenous vasopressin and nitroglycerin, with balloon tamponade, or with endoscopic sclerotherapy. Because of the high likelihood of recurrence, long-term treatment, such as repeated sclerotherapy, propranolol therapy, or shunt surgery, is necessary. The proper selection of such measures requires consideration of the site of variceal bleeding, local availability of specialized techniques, and patient factors. Only liver transplantation reverses the liver damage and offers hope of improved long-term survival. As success at identifying high-risk patients by endoscopic features improves, propranolol or other pharmacologic prophylaxis may become an acceptable treatment."
-What method is described for reorienting the left ventricular long-axis from myocardial transaxial tomographic data?,"Reorientation of the left ventricular long-axis on myocardial transaxial tomograms by a linear fitting method. A method is described for reorientating the left ventricular (LV) long-axis from myocardial transaxial tomographic data. On a midventricular transverse slice and on a midventricular sagittal slice, the apical and basal limits are selected successively by the operator. The linear activity profiles between these two limits are plotted line by line. In each profile, the two points with the maximum counts in the septal and lateral walls on the transverse slice, or in the anterior and inferior walls on the sagittal slice, are detected. The intermediate point with the minimum counts is then determined. The set of points with minimum counts are fitted by a straight line using the least squares method. This line is taken as the LV long-axis. In a series of 15 cases with stress-delayed 201Tl SPECT, the reproducibility of the reorientation with this semi-automatic method was compared with manual selection of the LV long-axis. In all patients, a successful reorientation was obtained with the present method. The reproducibility was significantly better with the semi-automatic method than with the manual selection of the LV long-axis."
-What was the primary finding of the study regarding nocturnal airflow obstruction in children with allergic asthma?,"Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma. A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine without (group 2) nocturnal airflow obstruction, and an age matched control group. All drugs were withheld for three days before and during the study. On day 4 each child was admitted to hospital and a series of measurements was made every four hours for 24 hours. These included measurements of the forced expiratory volume in one second (FEV1), heart rate and sinus arrhythmia gap from an electrocardiogram (an indirect measure of parasympathetic activity) and urine sampling for determination of catecholamine and N'-methylhistamine concentrations (measures of sympathetic activity and histamine release respectively). Urinary N'-methylhistamine excretion was significantly higher over the 24 hours in children in group 1 than in children in group 2, and overnight values were also significantly higher in children in group 1 than those in group 2. Mean (SEM) values (mumol/mol creatinine) were 154.6 (11.2) in group 1 and 110 (11.2) in group 2 for 2400-0400 hours samples and 139.2 (13.1) and 101.2 (10.6) 0400-0800 hours samples. There was no evidence of decreased sympathetic or increased parasympathetic activity in association with the nocturnal airflow obstruction; noradrenaline concentrations were increased in group 1. These observations indicate that nocturnal airflow obstruction is associated with increased release of histamine overnight."
-What was the main finding regarding regional cerebral blood flow in patients after cardiac arrest?,"Regional cerebral blood flow after human cardiac arrest. A hexamethylpropyleneamine oxime single photon emission computed tomographic study. We studied 30 patients 24 hours after out-of-hospital cardiac arrest and 13 age-matched normal controls with the use of technetium Tc 99m-hexamethylpropyleneamine oxime single photon emission computed tomography. All patients were followed up for 12 months or until death. Frontal hypoperfusion (anteroposterior perfusion ratio, less than 0.90) was observed in 23 patients (77%). In eight patients who remained comatose and died, the total size of perfusion defects was larger (38% +/- 20%) than in the 21 patients who recovered consciousness (24% +/- 14%), but the anteroposterior ratio was similar in both of these patient groups (0.83 +/- 0.09) and significantly lower than in the controls (0.96 +/- 0.03). During follow-up, both the anteroposterior perfusion ratio and the relative defect size improved, but frontal hypoperfusion was still observed in seven of 13 patients. After cardiac arrest, regional cerebral blood flow is characterized by frontal hypoperfusion that tends to improve over time but that persists in most patients."
-How do nitrendipine and removal of extracellular calcium ions affect tetanic responses in frog toe muscles?,"Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle. The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the ""late negative afterpotential"" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers."
-What percentage of splenic lesions were found to be hypoechoic in the sonographic study?,"Sonography of focal lesions of the spleen. The sonographic appearances of benign and malignant splenic lesions in 154 patients are illustrated. Sixty-six of the 154 patients had malignant splenic lesions; 55 of these had malignant lymphoma and 11 had splenic metastatic lesions. The lesions were hypoechoic in 64 cases (97%), including all cases of malignant lymphoma, and were hyperechoic in two. Eighty-eight patients had benign splenic lesions; findings included cysts, infarcts, abscesses, hemangiomas, and calcifications."
-What was the outcome of the prospective assessment of the rebound tenderness test in patients with abdominal pain?,Rebound tenderness test. The usefulness of the rebound tenderness test in indicating peritonitis was prospectively assessed in 142 unselected patients admitted as emergencies with abdominal pain and tenderness. It was found to be of no predictive value.
-What rare complication can occur after local steroid injection of a ganglion cyst on the hand?,"Localized depigmentation after steroid injection of a ganglion cyst on the hand. Presented is the case of a man who had localized depigmentation after local injection of triamcinolone diacetate. Search of the literature indicates that this is a rare complication of such therapy. Localized depigmentation may have important cultural implications for dark-skinned patients. There is some experimental evidence that less-potent and shorter-acting steroid preparations have a lower likelihood for depigmenting side effects, and such agents may be more appropriate when injecting subcutaneous structures to prevent this complication."
-What are the key diagnostic challenges associated with identifying Enterobius egg granuloma in medical pathology?,"Enterobius egg granuloma of the vulva and peritoneum: review of the literature. Two cases of Enterobius granuloma containing eggs only are reported. The first case involved the vulva, where no such granuloma has been reported previously. The coexistence of peritoneal granuloma and rectal adenocarcinoma in the second case suggests the possibility of direct penetration of the damaged colonic wall by the parasite, as emphasized by several previous reports of neoplastic involvement and perforation of the intestinal wall in cases of ectopic infections. The diagnostic criteria of Enterobius eggs granuloma, which might be a diagnostic dilemma for pathologists who are not familiar with such criteria, are described herein."
-What is the significance of thiamine deficiency in chronic hemodialysis patients according to the case report?,"Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report. We report the case of a patient with terminal renal disease on chronic hemodialysis who developed acute thiamine deficiency as confirmed by erythrocyte transketolase determinations. The patient presented with a confusional state and severe memory disturbances, but other classical features of Wernicke's encephalopathy were absent. Almost all central nervous system symptoms rapidly disappeared after thiamine therapy. Therefore the possibility of thiamine deficiency must be considered in patients on chronic dialysis who present with central nervous system disturbances, even if all of the classical features of Wernicke's encephalopathy are not present."
-What was the primary objective of the study on transjugular intrahepatic portosystemic shunt?,"Percutaneous transjugular portosystemic shunt. OBJECTIVE.--To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension. DESIGN.--Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months. PATIENTS.--All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids. MAIN OUTCOME MEASURES.--Shunt patency and recurrent variceal hemorrhage. RESULTS.--Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up. CONCLUSION.--Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage."
-What was the percentage of true histiocytic neoplasias found among malignant lymphoma and related conditions in this Japanese study?,"Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan. Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%."
-What factors in childhood can predict future high blood pressure?,"Childhood predictors of future blood pressure. Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults."
-What is the relationship between anemia and postoperative apnea in former preterm infants undergoing inguinal hernia repair?,"Anemia and postoperative apnea in former preterm infants. To examine the association between anemia and postoperative apnea in former preterm infants, 24 former preterm infants of less than 60 weeks postconceptual age undergoing inguinal hernia repair were studied. A hematocrit of at least 25% was required for study participation. General endotracheal inhalational anesthesia, supplemented with neuromuscular blockade and controlled ventilation, was used. No barbiturates or opioids were administered. Respiratory pattern and heart rate were recorded for at least 12 h postoperatively using an impedance pneumograph. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the hematologic profile of the infant. Nineteen patients had a hematocrit of 30% or greater (group 1). Their mean (+/- standard deviation [SD]) gestational age was 33.5 +/- 2.7 weeks and postconceptual age 45.5 +/- 4.6 weeks. Five infants had a hematocrit less than 30% (group 2). Their mean gestational age (+/- SD) was 32.4 +/- 3.2 weeks and postconceptual age 43.6 +/- 5.5 weeks. Anemic infants had an 80% incidence of postoperative apnea versus 21% in infants with a normal hematocrit (P less than .03). In the infants who developed postoperative prolonged apnea and/or bradycardia, a prior history of apnea was equally present in both groups (21% in group 1 and 20% in group 2). This study shows that anemia in former preterm infants can be associated with an increased incidence of postoperative apnea."
-What are the general characteristics and treatment approaches for haemangiomas in different parts of the urinary tract?,"Haemangioma of the urinary tract: review of the literature. General features. Haemangiomas are benign vascular tumours. They can regress spontaneously as a result of fibrosclerosis, suggesting a conservative approach wherever possible. Asymptomatic haemangiomas do not require treatment. Renal haemangioma. In all, 198 cases have been reported. The lesion is usually solitary and unilateral and occurs most often in the pyramid, and in the mucosa or subepithelial tissue of the pelvis. In some cases a tentative diagnosis of haemangioma has been made by means of selective renal angiography and pre- or per-operative renoscopy. Partial nephrectomy is recommended in cases of minor haemangioma. Ureteric haemangioma. Six cases have been described. When haemangioma is suspected a conservative operation is recommended. Bladder haemangioma. A total of 106 cases have been reported. Many of the tumours had the characteristics of an iceberg, with considerable extravesical extension making endoscopic management less suitable because of the possibility of massive haemorrhage or recurrence. Consequently, many authors prefer local excision. In the case of endoscopic treatment the patient should be prepared for open surgery. Urethral haemangioma. Twenty cases have been described. The lesions often extend further than is immediately apparent. Endoscopic management is recommended for small lesions and, in the case of more extensive lesions, open exploration is advised followed by appropriate urethral reconstruction."
-What was the most common gastrointestinal complication in patients who underwent cardiopulmonary bypass surgery?,"Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group."
-What is the key finding in the histologic examination of the small intestine in this case of familial enteric neuropathy?,"Familial enteric neuropathy with pseudoobstruction. We report a case of autosomal dominant chronic intestinal pseudoobstruction secondary to a familial enteric neuropathy. Esophagogastrointestinal manometry studies in the index case showed decreased postprandial contractile frequency with normal amplitude of pressure activity in the stomach and small bowel. Pupillary function and autonomic reflexes were all normal, excluding an extrinsic autonomic neuropathy of the viscera. Histologic examination of the small intestine by hematoxylin and eosin stains revealed normal smooth muscles but a reduced number of neurons in the myenteric plexus without inflammatory cells or neuroNal intranuclear inclusions. Histologic examination of the myenteric plexus using the sections taken along the longitudinal axis of the intestine, stained with silver by the Smith technique, disclosed decreased numbers of argyrophilic neurons and degeneration of neurons and axons; however, there was no reactive increase in the number of glial cell nuclei. The patient's mother had suffered from chronic intestinal pseudoobstruction, which did not abate following extensive small bowel resection. This is the third family reported with an autosomal dominant enteric neuropathy unassociated with evidence of extrinsic autonomic or peripheral neuropathy. Subtotal resection of the small bowel was followed by recurrence of the pseudoobstruction syndrome in both affected members of the family."
-Does the anatomical position of the vermiform appendix impact the clinical presentation and outcomes of acute appendicitis?,"Does the retrocecal position of the vermiform appendix alter the clinical course of acute appendicitis? A prospective analysis. Ninety-four adult patients undergoing appendectomy for acute appendicitis were prospectively studied during a 2-year period. Patients were divided into retrocecal (group 1; n = 27 [29%]) and anterior (group 2; n = 67 [71%]) groups according to the position of the appendix. There was no statistical difference between the two groups in duration of symptoms, presenting signs and symptoms, and initial white blood cell count. Furthermore, retrocecal appendicitis was not associated with a higher rate of perforation or increased morbidity. We conclude that the retrocecal position of the appendix does not alter the presentation of appendicitis."
-What was the healing rate of transmetatarsal amputations in different patient groups based on revascularization?,"Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized."
-What was the purpose of the isotopic examination of the stomach in patients with chronic nausea and/or vomiting?,"Idiopathic gastroparesis in patients with unexplained nausea and vomiting. Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation."
-How did the researchers correct the human beta S-globin gene in the mouse-human hybrid cell line BSM?,"Correction of a human beta S-globin gene by gene targeting. As a step toward using gene targeting for gene therapy, we have corrected a human beta S-globin gene to the normal beta A allele by homologous recombination in the mouse-human hybrid cell line BSM. BSM is derived from a mouse erythroleukemia cell line and carries a single human chromosome 11 with the beta S-globin allele. A beta A-globin targeting construct containing a unique oligomer and a neomycin-resistance gene was electroporated into the BSM cells, which were then placed under G418 selection. Then 126 resulting pools containing a total of approximately 29,000 G418-resistant clones were screened by PCR for the presence of a targeted recombinant: 3 positive pools were identified. A targeted clone was isolated by replating one of the positive pools into smaller pools and rescreening by PCR, followed by dilution cloning. Southern blot analysis demonstrated that the isolated clone had been targeted as planned. The correction of the beta S allele to beta A was confirmed both by allele-specific PCR and by allele-specific antibodies. Expression studies comparing the uninduced and induced RNA levels in unmodified BSM cells and in the targeted clone showed no significant alteration in the ability of the targeted clone to undergo induction, despite the potentially disrupting presence of a transcriptionally active neomycin gene 5' to the human beta A-globin gene. Thus gene targeting can correct a beta S allele to beta A, and the use of a selectable helper gene need not significantly interfere with the induction of the corrected gene."
-"What was the relationship between DNA ploidy, N-myc gene amplification, and clinical outcome in stage IVS neuroblastoma?","N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required."
-What were the long-term surgical outcomes for patients who underwent lateral cranial base surgery between 1970 and 1987?,"Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis."
-How does the intracerebral temperature compare to the rectal temperature in neurosurgical patients?,"Intracerebral temperature in neurosurgical patients. Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper-constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment."
-What are the three processes related to leukotrienes that are observed during the immediate reaction in bronchial asthma?,"The potential roles of leukotrienes in bronchial asthma. Leukotrienes (LTs), in particular LTC4, LTD4, and LTE4, have been shown to be capable of participating in the induction of three related processes observed during the immediate reaction in bronchial asthma: edema formation, mucus secretion, and muscle contraction. Despite impressive evidence potentially implicating the LTs, the role of LTs in asthma is still unproved, and a positive answer to their critical actions in causing airflow obstruction will require studies with specific antagonists."
-What is the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft (CABG) surgery?,"Functional recovery of hibernating myocardium after coronary bypass surgery: does it coincide with improvement in perfusion? To determine the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft surgery (CABG), 49 patients were studied. Radionuclide angiography was performed before, 1 month after, and 6 to 12 months after CABG to evaluate regional wall motion. Exercise thallium-201 myocardial perfusion imaging was done before and 1 month after CABG to assess regional perfusion. Preoperative asynergy was observed in 108 segments, and 74 of them showed an improvement in wall motion 1 month after CABG (segment A). Sixty-six of these segments (89%) were associated with an improvement in perfusion. Eight segments that had not improved 1 month after CABG demonstrated a delayed recovery of wall motion 6 to 12 months after CABG (segment B). However, seven of eight segments (88%) already showed an improvement in perfusion 1 month after CABG. A total of 82 segments exhibited functional recovery after CABG and were considered hibernating segments. In the preoperative study segment B more frequently had areas of akinesis or dyskinesis than segment A (75% vs 34%, p less than 0.05). The mean percent thallium-201 uptake in segment B was lower than that in segment A (74% +/- 9% vs 83% +/- 8%, p less than 0.05). Functional recovery of hibernating myocardium usually coincided with an improvement in perfusion. However, delayed functional recovery after reperfusion was observed in some instances. Severe asynergy and severe thallium-201 defects were more frequently observed in these segments with delayed recovery. Hibernating myocardium might remain stunned during those recovery periods."
-What are the key challenges patients with HIV infection face in rehabilitation medicine?,"Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine. Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder."
-How does the extent of small bowel resection in Crohn's disease patients affect the absorption of cholecalciferol and 25-hydroxycholecalciferol?,"Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome."
-What alternative treatment was used for the patient with Wilson's disease when low-dose D-penicillamine caused severe neurological deterioration?,"Zinc sulphate therapy for Wilson's disease after acute deterioration during treatment with low-dose D-penicillamine. A 30-year-old woman with Wilson's disease was treated with low-dose D-penicillamine. After 12 days, treatment was changed to zinc sulphate because of severe neurological deterioration. The patient subsequently improved within a few days. During a follow-up period of 20 months, the effectiveness of therapy was evaluated by measuring copper and zinc levels in plasma and urine, and by 64Cu-loading tests. We conclude that sulphate therapy may be a satisfactory alternative, even when rapid deterioration occurs in the early stages of D-penicillamine treatment."
-What were the key findings of the 15-year follow-up study on cardiovascular risk factors in primary hyperparathyroidism?,"Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases. The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT."
-How do the reflex responses of airway smooth muscle in piglets change between 2 and 10 weeks of age?,"Maturation of respiratory reflex responses in the piglet. Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation."
-What complication occurred after platelet transfusion following a successful PTCA procedure?,Abrupt vessel closure following platelet transfusion post-PTCA. A successful PTCA was complicated by abrupt closure following a platelet transfusion which was given for control of local bleeding. Possible mechanisms of abrupt closure are discussed. Recommendation is made to avoid giving platelet transfusion following PTCA.
-What is a porencephalic cyst and how can it potentially occur during fetal intravascular transfusion?,"Porencephalic cyst: a complication of fetal intravascular transfusion. A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication."
-What was the 5-year patency rate for different types of grafts used in infrapopliteal bypass surgery?,"Infrapopliteal bypass for severe ischemia: comparison of autogenous vein, composite, and prosthetic grafts. Results of 253 consecutive bypass grafts to infrapopliteal arteries were reviewed. Most (92%) were placed for rest pain (103) or tissue loss (130). Autogenous veins were used in 175 (69%) cases, composite vein-prosthetic grafts were used in 45 (18%), and prosthetic grafts alone were used in 33 (13%). Follow-up ranged from 0 to 101 months (mean, 19 months); 37 grafts (15%) were lost to follow-up. The operative mortality rate was 4%, and 5-year patient survival rate was 44%. Limb salvage was 82% at 5 years. The 5-year patency of vein grafts (63%) exceeded that of both composite (28%) and prosthetic (7%) grafts (p = 0.005 and p = 0.00007, respectively); but the patency of composite and prosthetic grafts did not differ significantly (p = 0.29). The patency of reversed vein (59%) and in situ vein grafts (74%) was not significantly different at 5 years (p = 0.34). Patency was also not affected by the site of the proximal or distal anastomoses or diabetes. The major determinant of long-term patency in infrapopliteal reconstructions continues to be graft material. Composite grafts offered no clear advantage over prosthetic grafts, and both should be used only when there is no other alternative to amputation."
-What were the common problems and rehabilitation interventions encountered in patients with AIDS?,"Experience with rehabilitation in the acquired immunodeficiency syndrome. Patients with the acquired immunodeficiency syndrome (AIDS) represent a novel referral population for rehabilitation services. Limited information about the rehabilitation needs of individuals with human immunodeficiency virus infection is available. We reviewed 51 consecutive patients with AIDS referred to a rehabilitation consult service. Common problems encountered included generalized deconditioning (27%) and neurologic dysfunction (45%). Neurologic presentations were diverse and included hemiparesis, diffuse cognitive dysfunction and dementia, myelopathy, myopathy and peripheral neuropathy. Other patients were referred for wound care as well as the management of the local effects of Kaposi's sarcoma, various musculoskeletal syndromes and new onset blindness. Problems identified included impaired mobility (76%), difficulty with self-care (57%), impaired cognition (29%) and uncontrolled pain (37%). Among the rehabilitation interventions utilized were therapeutic exercise (73%), gait aids (45%), bathroom and safety equipment (45%), orthotics (29%), vocational counseling (4%), pain management (29%) and whirlpool treatments (10%). Five patients were too ill or refused treatment. We conclude that AIDS patients referred for rehabilitation have a wide variety of physical deficits, demonstrate a considerable degree of functional impairment and may require multiple rehabilitation interventions."
-What are the typical symptoms and diagnostic challenges of adnexal torsion in postmenopausal women?,"Adnexal torsion. An unusual cause of abdominal pain in postmenopausal women. Adnexal torsion is a rare cause of abdominal pain in older women. Because the presenting symptoms and signs are vague, the diagnosis is not often considered. Lower abdominal pain with nausea and vomiting are usual in patients with torsion. Ultrasonography or computed tomography are useful diagnostic tests. Two case reports of older patients with adnexal torsion are presented to emphasize the diagnostic features of this entity, including lower abdominal pain, nausea and vomiting, and abdominal mass. Although the condition is uncommon, adnexal torsion should be considered in the differential diagnosis of acute abdominal pain."
-Which two genes have been identified as influencing the onset of autoimmune type 1 diabetes in nonobese diabetic mice?,"Genetic analysis of autoimmune type 1 diabetes mellitus in mice Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17."
-Does Helicobacter pylori infection increase the severity of mucosal injury caused by naproxen or aspirin?,"Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin."
-What is the origin of the extra chromosome 21q in Down syndrome cases with de novo Robertsonian translocation t(14q;21q)?,"Down syndrome due to de novo Robertsonian translocation t(14q;21q): DNA polymorphism analysis suggests that the origin of the extra 21q is maternal. Down syndrome is rarely due to a de novo Robertsonian translocation t(14q;21q). DNA polymorphisms in eight families with Down syndrome due to de novo t(14q;21q) demonstrated maternal origin of the extra chromosome 21q in all cases. In seven nonmosaic cases the DNA markers showed crossing-over between two maternal chromosomes 21, and in one mosaic case no crossing-over was observed (this case was probably due to an early postzygotic nondisjunction). In the majority of cases (five of six informative families) the proximal marker D21S120 was reduced to homozygosity in the offspring with trisomy 21. The data can be best explained by chromatid translocation in meiosis I and by normal crossover and segregation in meiosis I and meiosis II."
-What are the key differences in oxygen transport patterns between cardiogenic and septic shock patients in this study?,"Oxygen transport in cardiogenic and septic shock. OBJECTIVE: To review clinical studies of oxygen transport in cardiogenic and septic shock. DESIGN: Descriptive and prospective studies. SETTING: University hospital multi disciplinary ICU. PATIENTS: Critically ill cardiogenic and septic shock patients greater than 18 and less than 80 yrs of age. INTERVENTIONS: The responses to volume loading with colloid or crystalloid and infusion of catecholamines are documented with baseline hemodynamic and oxygen transport measurements before and after administration of catecholamines. MEASUREMENTS AND MAIN RESULTS: Nineteen patients in cardiogenic shock were studied. In three patients, invasive systemic mean arterial pressure was greater than 80 mm Hg and cardiac index was greater than 2.0 L/min.m2. In all patients, there were increases in oxygen extraction ratio that averaged 48 +/- 18 (SD) %. However, in 30 septic shock patients, extraction ratio was 24 +/- 2%. In both groups, the response to therapy was an increase in mixed venous oxygen saturation from 54 +/- 16% to 69 +/- 8% in cardiogenic patients (p less than .001) and from 75 +/- 2% to 80 +/- 1% in septic shock (p less than .01). CONCLUSIONS: There are widely differing oxygen transport patterns in cardiogenic and septic shock that may have implications for therapy."
-"What medical condition did the 35-year-old man have, and how was it treated?","Repair of a cerebrospinal fluid perilymph fistula primarily through the middle ear and secondarily by occluding the cochlear aqueduct. A 35-year-old man had a 5-year history of fluctuating hearing loss in his only hearing ear. History and diagnostic tests indicated a perilymph fistula, a diagnosis subsequently confirmed by exploration. Primary and secondary repairs temporarily ameliorated symptoms. A spinal fluid to middle ear fluid pathway was identified by radioactive tracer. A patent cochlear aqueduct indicated on computed tomography scan was found and repaired through a posterior cranial fossa approach. Hearing was preserved, remaining relatively stable during the 2-year follow-up period."
-What are the new therapies for gallstone management that have been developed in the past decade?,New trends in gallstone management. Many new therapies for the management of gallstone disease have been pioneered in the past decade. The object of this review is to equip the surgeon with the answers to all of the questions a patient will ask about gallstone therapy; the review is therefore didactic as well as comprehensive.
-What was the main finding regarding pulmonary artery wedge pressure (PAWP) and cardiac performance in patients with aneurysmal subarachnoid hemorrhage?,"Cardiac performance indices during hypervolemic therapy for cerebral vasospasm. The effect of hypervolemic preload enhancement on cardiac performance was systematically analyzed in nine patients following aneurysmal subarachnoid hemorrhage. The patients ranged in age from 34 to 63 years, and none had a history of cardiac disease. Each patient underwent placement of a flow-directed balloon-tipped catheter and the following measurements were taken during hypervolemic therapy: pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), cardiac index (CI), stroke volume index (SVI), and left ventricular stroke work index (LVSWI). After baseline measurements were recorded, hetastarch or plasmanate was infused intravenously at 300 cc/hr. Thermal output determination and pressures were measured every 15 minutes. The PAWP did not correlate in a statistically significant fashion with the CVP in the ranges recorded; however, a statistically significant correlation did exist between PAWP increases and increases in CI, SVI, and LVSWI (p less than 0.01). There was no statistical correlation between PAWP increases above 14 mm Hg and improvement in cardiac performance as evidenced by CI, SVI, and LVSWI measurements. It is concluded that CVP is an unreliable index of cardiac performance during hypervolemic therapy and that, in previously healthy individuals, a PAWP of 14 mm Hg is associated with maximum cardiac performance."
-What were the key histologic and ultrastructural findings observed in the Leeds-Keio prosthetic anterior cruciate ligament after 18 months of implantation?,"Histologic and ultrastructural findings of tissue ingrowth. The Leeds-Keio prosthetic anterior cruciate ligament. A light and electron microscopy investigation was performed on a Leeds-Keio ligament removed because of rupture 18 months after implantation to repair an anterior cruciate ligament. The investigation showed fibrous connective tissue on the plane of the main stress force. There was elastin and adequate vascularization interspersed with Type I collagen fibrils in the area most distant from the ligament. The tissue near the Dacron fibers was highly cellular with a matrix of infrequent, thin collagen fibrils and abundant fine granular material. The growth of the host tissue occurred in and around a Leeds-Keio ligament in response to tensile stresses."
-What surgical technique was used to treat syndactyly with osseous fusion of the distal phalanges?,"Surgical method for treatment of syndactyly with osseous fusion of the distal phalanges. For the interdigital space plasty to correct a syndactyly with fusion of the distal phalanges, we adopted a new operative procedure, covering the exposed distal bone with local rectangular flaps designed transversely on both dorsal and volar surfaces. A full-thickness skin graft from the groin region covers the remaining raw surface. The procedure was performed in six patients, and the flaps measured 6 mm (width) x 12 to 16 mm (length) in four patients, 5 x 15 mm in one patient, and 5 x 18 mm in one patient. Partial necrosis was observed in only one patient, in whom a narrow flap of 5 x 18 mm was used. In the other five patients, however, the results were satisfactory on both external appearance and function during the follow-up period of 3 to 6 years."
-How many patients preferred ultrasound over flexible cystoscopy in the detection of recurrent bladder tumours?,"Flexible cystoscopy compared with ultrasound in the detection of recurrent bladder tumours. A combination of transrectal and transabdominal ultrasound was compared with flexible cystoscopy as a means of detecting recurrent bladder tumours. The study group comprised 50 patients who had previously had rigid cystoscopy. They underwent combination ultrasound in the out-patient department 1 week before flexible cystoscopy. Combination ultrasound identified 25 patients with recurrent tumours and flexible cystoscopy identified 26. Thirty-four patients (68%) preferred ultrasound, 10 (20%) preferred flexible cystoscopy, 3 (6%) preferred general anaesthesia and rigid cystoscopy and 3 (6%) had no preference. The main objection to ultrasound was the use of the transrectal probe."
-What is the key advantage of stab evulsion phlebectomy for treating truncal varicose veins compared to traditional surgical methods?,"Ambulatory stab evulsion phlebectomy for truncal varicose veins. The management of primary varicose veins is evolving. Recovery time, cost, recurrence rate, and cosmesis are critical determinants. Classic ""high ligation"" and ankle-to-groin stripping is expensive, results in a long convalescence, and may produce unacceptable scarring and possible permanent nerve injury. This report describes the technique of stab evulsion phlebectomy performed in an outpatient setting. Under loco-regional anesthesia, and after high ligation, existing tributary and trunk varicosities are evulsed with specially designed hooks. The multiple stab incisions, 1.5- to 3-mm long, are closed with adhesive strips. Fifty-six patients, with 69 involved limbs, have been operated on during the past 9 months. Postoperative pain and complications were minimal. Convalescence was eliminated and all patients immediately resumed normal daily activities. Cosmesis was excellent. This technique is based on hemodynamically accurate principles. It effectively removes all varicosities, eliminates the proximal source of reflux, and disconnects potentially outflowing perforators, yet leaves in situ undamaged trunk veins, which may be used as potential vein grafts."
-What imaging features help distinguish between primary central nervous system lymphoma and toxoplasmosis in AIDS patients?,Primary central nervous system lymphoma versus toxoplasmosis in AIDS. The imaging studies of 16 patients with acquired immunodeficiency syndrome (AIDS) and proved primary central nervous system (CNS) lymphoma were reviewed. All studies included computed tomography (CT); six also included magnetic resonance (MR) imaging. A periventricular lesion was seen in 50% of patients. At least one such lesion exhibited subependymal spread or ventricular encasement in 38%. One-third of lesions in three of five patients who underwent nonenhanced CT were hyperattenuating. Five lesions were at least in part hypointense on T2-weighted MR images. The specificity of these findings was evaluated with a similar review of the imaging studies in 28 patients with AIDS and proved toxoplasmosis. Only 3% of lesions were periventricular. None exhibited subependymal spread or encasement. None were hyperattenuating on nonenhanced CT scans. Similar findings in other CNS lesions in AIDS patients could not be found in the literature. A focal enhancing mass with subependymal spread on CT or MR images and hyperattenuation at nonenhanced CT were the most reliable features in distinguishing between primary CNS lymphoma and toxoplasmosis in AIDS patients.
-What was the predictive accuracy of electrophysiologic localization for single and multiple accessory pathways in this study?,"Predictive accuracy of electrophysiologic localization of accessory pathways. Operative ablation of accessory pathways depends critically on preoperative localization when technical limitations preclude complete intraoperative mapping. To assess the accuracy of localization, 345 patients undergoing operative ablation were studied; 316 (91.6%) had a single accessory pathway and 29 (8.4%) had multiple accessory pathways. The electrophysiologic study was diagnostically complete and accurate in 294 patients (93%) with a single accessory pathway and 19 (61%) with multiple accessory pathways. A left lateral accessory pathway was most accurately localized with excellent sensitivity (99%) and positive predictive value (98.5%). Diagnostic errors occurred in 33 patients because of 1) incorrect localization (n = 16), 2) failure to detect a second pathway (n = 9), and 3) diagnosis of a second pathway not verified intraoperatively (n = 8). Multiple pathways were more prevalent in the group with errors (33.3% vs. 5.8%, p = 0.0001), as were unidirectional pathways (48.5% vs. 24.3%, p = 0.003). It is concluded that preoperative localization of accessory pathways is sufficiently accurate to allow intraoperative mapping to be brief and focused."
-What method is proposed for estimating the optimum ventricular catheter length when intraoperative ultrasound is not available?,Index for optimum ventricular catheter length. Technical note. The optimum length of a ventricular catheter to be placed in a particular patient may be difficult to determine when either intraoperative ultrasound is not available or considerable time has elapsed between the diagnostic computerized tomography scan and the operation. An index for estimating ventricular length based on the head circumference of the individual is described. This method was tested clinically and proved to be successful.
-What did the population-based study reveal about the influence of gender on multiple sclerosis susceptibility in sibling pairs?,"The influence of gender on the susceptibility to multiple sclerosis in sibships. A population-based study of pairs of relatives (siblings, second- and third-degree) concordant for multiple sclerosis did not show an excess of like-sexed pairs. In addition, data on human lymphocyte antigen typing for sibling pairs concordant for multiple sclerosis did not find an increase in haplotype sharing for like-sexed pairs. These data do not support the notion that sex-related factors influence multiple-sclerosis susceptibility in families."
-How did intermittent negative pressure ventilation (INPV) affect oxygen and carbon dioxide levels in COPD patients with severe hypercapnic respiratory failure?,"Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. With the aim of testing a method that allows increasing concentrations of oxygen to be administered to patients with severe hypoxemia and hypercapnia while avoiding the risk of increasing respiratory acidosis, we studied 17 male patients with advanced chronic obstructive pulmonary disease (COPD) and severe hypercapnic respiratory failure. During 6 h and on one day only, all patients were given intermittent negative pressure ventilation (INPV) together with oxygenation starting at a concentration of 24 percent and increasing to 30 percent. Using this procedure, it was possible to raise arterial PaO2 to safe levels (from 47.2 +/- 3 mm Hg to 61.5 +/- 6 mm Hg, p less than 0.001) without increasing hypercapnia, and a significant drop in PaCO2 levels (from 74.4 +/- 9 mm Hg to 65.6 +/- 12 mm Hg, p less than 0.005) was even observed. One hour after INPV ended, the mean values of PaO2, PaCO2, oxygen saturation, and pH were also significantly better than prestudy values. We conclude that INPV and oxygen therapy with increasing oxygen flow could constitute an alternative option to intubation and mechanical ventilation in cases of severe hypercapnic respiratory failure due to advanced COPD."
-What are the key findings regarding ventricular tachycardia in patients with sarcoidosis based on this study?,"Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin."
-How did the researchers detect DNA sequence polymorphisms in the retinoblastoma susceptibility locus?,"Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. The discovery of RFLPs and their utilization as genetic markers has revolutionized research in human molecular genetics. However, only a fraction of the DNA sequence polymorphisms in the human genome affect the length of a restriction fragment and hence result in an RFLP. Polymorphisms that are not detected as RFLPs are typically passed over in the screening process though they represent a potentially important source of informative genetic markers. We have used a rapid method for the detection of naturally occurring DNA sequence variations that is based on enzymatic amplification and direct sequencing of genomic DNA. This approach can detect essentially all useful sequence variations within the region screened. We demonstrate the feasibility of the technique by applying it to the human retinoblastoma susceptibility locus. We screened 3,712 bp of genomic DNA from each of nine individuals and found four DNA sequence polymorphisms. At least one of these DNA sequence polymorphisms was informative in each of three families with hereditary retinoblastoma that were not informative with any of the known RFLPs at this locus. We believe that direct sequencing is a reasonable alternative to other methods of screening for DNA sequence polymorphisms and that it represents a step forward for obtaining informative markers at well-characterized loci that have been minimally informative in the past."
-"What were the age-adjusted incidence rates of amyotrophic lateral sclerosis for males and females in Harris County, Texas, during the period 1985-1988?","Incidence and prevalence of amyotrophic lateral sclerosis in Harris County, Texas, 1985-1988. The incidence of amyotrophic lateral sclerosis was determined in Harris County, Texas, for the period 1985 through 1988. Amyotrophic lateral sclerosis cases were ascertained from four sources: area neurologists, hospitals, death certificates, and the Muscular Dystrophy Association. The age-adjusted incidences of 1.27 per 100,000 person-years in males and 1.03 per 100,000 person-years in females were lower than recent rates in the northern US, Canadian, and northern European studies but higher than rates in southern European studies. Comparisons with other recent incidence studies show less uniformity in occurrence of amyotrophic lateral sclerosis, in both the overall rates and in the age- and sex-specific patterns, than was suggested by mortality studies. The incidence of amyotrophic lateral sclerosis among blacks and whites was similar. Hispanic males had incidences similar to white males, although a deficit of female Hispanic cases was found in Harris County. The prevalence of amyotrophic lateral sclerosis peaked in the 65- to 74-year age group at 33 per 100,000 population among males and 19 per 100,000 population for females."
-What unique histological feature was observed in the liver of this peripheral T-cell lymphoma case?,"Extensive hepatic granulomas associated with peripheral T-cell lymphoma. A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver."
-What are the most practical and useful techniques for diagnosing perivalvular extension of infection in patients with infectious endocarditis?,"Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review."
-What is microvascular angina and how does it differ from traditional coronary artery disease?,"Microvascular angina. Cardiovascular investigations regarding pathophysiology and management. A significant minority of patients with chest pain who undergo cardiac catheterization are found to have angiographically normal coronary arteries. Over the past 25 years, several studies have shown that a subset have demonstrable abnormalities in coronary flow and cardiac function; however, only a minority of these patients have convincing evidence for myocardial ischemia during stress, and alternative mechanisms have been explored to explain the frequent and debilitating symptoms of pain experienced by the majority of these patients undergoing study. Abnormal visceral nociception appears to be a fundamental abnormality in this population, whether or not demonstrable abnormalities in coronary flow or cardiac function can be demonstrated."
-What is Bazex syndrome and what are its key characteristics?,"Bazex syndrome (acrokeratosis paraneoplastica). An analytic review. Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions."
-How do phalloidin and antamanide help mitigate the side effects of interleukin-2 (IL-2) in rats?,"Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide. Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak."
-What is telangiectatic osteosarcoma and how has its prognosis changed over time?,"Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy."
-How do the contractile responses to norepinephrine and caffeine differ in mesenteric arteries from normotensive and hypertensive rats?,"Agonist-sensitive calcium stores in arteries from steroid hypertensive rats. The present study characterizes cellular calcium stores that are sensitive to norepinephrine and caffeine in arteries from deoxycorticosterone acetate hypertensive rats. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. In calcium-free solution, phasic contractile responses to norepinephrine (5.9 x 10(-9) to 5.9 x 10(-6) M), but not caffeine (0.3-30 mM), were greater in hypertensive arteries. D-600, a calcium channel blocker, or removal of the endothelium did not alter phasic contractions to norepinephrine or caffeine. In contrast, contractions to both norepinephrine and caffeine were inhibited by ryanodine, a drug that depletes calcium from intracellular stores. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl N,N-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites."
-What were the key differences observed between patients with Hodgkin's disease above the diaphragm (ADHD) and below the diaphragm (BDHD) in this study?,"Stage I and II subdiaphragmatic Hodgkin's disease. From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease."
-How does high-resolution contact B-scan echographic imaging help in diagnosing and assessing anterior hyaloidal fibrovascular proliferation?,"Echographic diagnosis of anterior hyaloidal fibrovascular proliferation. High-resolution contact B-scan echographic imaging of the ciliary body and peripheral retina was performed on five eyes with anterior hyaloidal fibrovascular proliferation and media opacity by means of a wide (58 degrees) scanning arc. This technique determined the circumferential and anteroposterior extent of peripheral traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation, which correlated highly with findings at subsequent vitrectomy. Final visual acuity of 20/400 or better was achieved in the two eyes (50%) with more limited peripheral traction detachment. In the presence of media opacity, anterior echographic imaging may allow early detection of traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation and may be useful in characterizing the severity of this condition."
-How reliable is pulse oximetry in assessing collateral blood flow to the hand compared to Doppler ultrasound?,"Pulse oximetry compared with Doppler ultrasound for assessment of collateral blood flow to the hand. Ischaemic injury to the hand after arterial cannulation is a rare but well documented complication and routine testing of the adequacy of collateral circulation is widely advocated. The widespread availability of the pulse oximeter in the operating theatre. its applicability in circumstances where the patient is unable to cooperate, and its dependence on pulsatile blood flow suggest that this device could potentially be usefully applied to the assessment of collateral blood flow. The reliability of the pulse oximeter to detect the presence or absence of collateral circulation was prospectively compared to Doppler ultrasound in 109 hands from 64 adult patients. Nine hands demonstrated inadequate ulnar collateral flow, one hand demonstrated inadequate radial collateral flow and a persistent median artery was found in one hand. In all patients the results of pulse oximeter testing (probe placed on the thumb correlated precisely with the results obtained with the Doppler device (probe located over the lateral aspect of the superficial palmar arch). These results demonstrate pulse oximetry to be a reliable method of assessing collateral blood flow to the hand before arterial cannulation."
-What was the range of ionized calcium levels observed in patients with chronic lung disease?,"Ionized calcium in blood: studies on patients with pulmonary disease. A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01-1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults."
-"What were the key findings regarding macrophages, microglia, and HLA-DR antigens in the fetal and infant brain tissue samples?","Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain. Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA-DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection."
-What are the advantages of using mandibular reconstruction plates for jaw reconstruction?,"Immediate mandibular replacement using reconstruction plates. Mandibular reconstruction at the time of tumor resection remains a surgical dilemma. Primary reconstruction allows for immediate reconstitution of mandibular form and function. Various methods have been attempted, but none enjoys uniform success. With advances in the field of microvascular surgery have come numerous options in replacing these defects. These procedures, however, require special surgical teams and are associated with an increase in operative time as well as morbidity at the donor site. An alternative method involves the use of mandibular reconstruction plates to bridge the defect between segments. This review focuses on 19 patients whose jaws were reconstructed in this fashion. Although not free of complications, mandibular plate reconstruction offers the advantages of (1) lack of donor site morbidity, (2) expediency, (3) excellent mandibular contour, and (4) the ability to reconstruct the condyle when necessary. The technique, results, and complications associated with this procedure are discussed."
-What is the key advantage of the modified craniofacial approach described in the context for ethmoid and anterior skull base surgery?,"Modified approach for ethmoid and anterior skull base surgery. The use of combined craniofacial resection is well established for tumors of the ethmoid bone and the anterior aspect of the base of the skull. Mobilization of the medial fronto-orbital ridge improves the transbasal approach and can be performed with a monobloc bone flap. We describe an en bloc bifrontal craniotomy including the supraorbital ridges and the nasal bones. This provides a wider angle of approach to the anterior aspect of the base of the skull than any other method and avoids retraction of the frontal lobes. This type of bone flap procedure can be performed after a wide periosteal dissection in the coronal area of the scalp alone, without facial skin incision."
-What were the hemodynamic effects of a 24-hour milrinone infusion in patients with severe heart failure?,"Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition. The systemic and pulmonary arterial hemodynamics of 40 patients with severe congestive heart failure were determined during a 24-hour infusion of milrinone (0.5 micrograms/kg/min) after a loading dose of 50 micrograms/kg. A subgroup (n = 18) with severe cardiac pump dysfunction and three patients in cardiogenic shock were analyzed separately; their hemodynamic response was compared with that of the total group (n = 40). After 15 minutes of intravenous therapy with milrinone, the total group (n = 40) showed an increase of 65% in cardiac index; in the subgroup (n = 18) cardiac index increased by 94% after 15 minutes and by 106% after 30 minutes. Likewise, pulmonary capillary wedge pressure decreased after 30 minutes in both the total group (n = 40) and the subgroup (n = 18). The heart rate showed an overall tendency to decrease. The systolic blood pressure tended upward and remained statistically unchanged in the total group, whereas in the subgroup in which pressure was initially low, there was an increase in the systolic pressure after 1 hour and a further increase after 24 hours. Mean arterial pressure also rose in this subgroup. The early improvement in all measured hemodynamic parameters was sustained throughout the 24-hour infusion period. Development of tolerance was not observed, nor were any clinically symptomatic side effects or symptomatic arrhythmias. Thus intravenous milrinone is a safe medication for the rapid and prolonged improvement in hemodynamics, specifically in patients with severely restricted cardiac pumping function."
-How do different antihypertensive agents impact serum lipid profiles?,"Antihypertensive therapy: taking lipids into consideration. Several antihypertensive agents have been found to influence serum lipid profiles. Thiazide diuretics increase total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and slightly reduce high-density lipoprotein (HDL) cholesterol. Most beta-blockers substantially increase triglycerides and lower HDL cholesterol. Angiotensin-converting enzyme inhibitors, calcium channel antagonists, alpha- and beta-blockers, and beta-blockers with intrinsic sympathomimetic activity are lipid neutral. alpha 1-Antagonists (e.g., terazosin and prazosin) lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improve total cholesterol/HDL ratios. Observational epidemiologic studies indicate that the lipid effects of antihypertensive agents are large enough to account for substantial differences in the predicted incidence of coronary heart disease. Combination therapy with the alpha 1-antagonist terazosin plus either thiazides or beta-blockers also ameliorates the adverse lipid effects of these agents used alone. A reasonable approach to managing the lipid problems often associated with hypertension is to advise a cholesterol-lowering, low-sodium diet and weight reduction and to select drugs that alone or in combination do not adversely affect lipid profiles."
-What is the dissociation index (DI) and how does it help in assessing brainstem maturation in infants with cyanosis during feeding?,"Phasic sleep components in infants with cyanosis during feeding. Although brainstem immaturity has been postulated as one of the pathogenesis underlying cyanosis during feeding (CDF), there has been no widely accepted physiologic parameter that reflects brainstem function. We recently proposed that the dissociation index (DI), one of the phasic sleep parameters, is a reliable and quantitative sleep parameter for assessing brainstem maturation during early infancy. In the present study, we evaluated brainstem impairment in infants with CDF using phasic sleep components. Polysomnographies were obtained for 12 infants with CDF who were equally divided into 2 groups: one had or subsequently experienced apparent life-threatening events or sudden infant death syndrome (ALTE-SIDS group) and the other did not (CDF group). Rapid eye movement density and the number of gross movements (body movements, including the trunk, lasting greater than or equal to 2 sec) in the patients were identical to those in the controls. In the CDF group, the decrease of the average DI value from the controls was significantly less than the decrease in the ALTE-SIDS group. CDF may be a mild expression of brainstem immaturity. DI appears to be useful when evaluating infants with cyanosis during feeding."
-What was the surgical success rate for patients with and without asthma in this study of intranasal ethmoidectomy?,"The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present."
-Does chronic triamterene therapy lead to folate deficiency in humans?,"Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency. The diuretic drug triamterene has previously been shown to be a competitive inhibitor of folate absorption in the rat intestine (J Lab Clin Med 1986;108:272-6). We therefore investigated whether human subjects who are taking the drug on a long-term basis are at increased risk of folate deficiency. In each of two free-living populations, a study was performed to compare the folate status of triamterene users with those not taking the drug. The first population consisted of 272 elderly individuals not living in institutions who were participants in a nutrition status survey and who were taking a variety of antihypertensive medications; 32 of these individuals were daily users of triamterene. The hemoglobin concentration, red blood cell (RBC) count, and mean corpuscular volume (MCV) values were not significantly different between the triamterene users and nonusers. The female triamterene users had a slightly higher serum folate level than the female nonusers (p less than 0.04); a similar pattern was observed among the men, although the difference was not statistically significant. The second population consisted of 27 individuals attending a hypertension clinic; 18 subjects were taking 50 to 150 mg of triamterene per day and nine were taking antihypertensive drugs other than triamterene. The hemoglobin concentration, RBC count, MCV, serum folate values, and RBC folate values were found to not differ significantly between the triamterene users and the hypertensive controls (p greater than 0.05). These data suggest that chronic triamterene administration in individuals not living in institutions, at the doses examined in this study, is not associated with indications of folate deficiency."
-What is the relationship between left atrial myxoma and pulmonary haemosiderosis in the given medical case?,Pulmonary haemosiderosis associated with left atrial myxoma. A patient with features suggesting pulmonary haemosiderosis was found to have a myxoma. The pulmonary lesion cleared after excision of the tumour.
-How effective was hematoporphyrin derivative (HPD) in identifying early colonic cancer in rats?,"Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative. Laser excitation of hematoporphyrin derivatives (HPD) localizing in tumors of the tracheobronchial tree and bladder is useful in the identification and treatment of those tumors. A comparable utility for HPD in the endoscopic localization of colonic tumors may be possible. In this study the ability of HPD to identify 1,2 dimethylhydrazine (DMH) induced colon cancer in rats is evaluated. A total of 111 rats were studied with HPD. Sixty-nine rats received weekly injections of DMH (20 mg/kg) and 42 received injections of the vehicle alone. Twenty-four hours after the intravenous injection of 5 mg/kg of HPD, 18 DMH-induced tumors were identified by visual fluorescence using excitation by either a blue light (390-436 nm) or an argon laser (488 and 514 nm). This represented 100% of the visually or microscopically detected tumors. Seventy-five fluorescent areas were noted that did not contain evidence of cancer. The majority (63) of false positive areas contained lymphoid follicles. All but 2 false positive areas (73/75, 97%, p less than .001) were seen in DMH-treated animals, suggesting that they were an artifact of DMH treatment. HPD fluorescence did not identify microscopic dysplasia. We conclude that HPD fluorescence is an effective method of identifying early colonic cancer and may have a potential clinical role in patients at high risk for colorectal cancer."
-Does preoperative and postoperative anticoagulant medication improve the short-term outcomes of lower-limb arterial thromboembolectomy?,"Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study. The value of short-term anticoagulant treatment in improving the early outcome in patients operated on for acute lower-limb ischemia has been debated and so far unproven. In this prospective randomized multi-center study, 188 such patients were randomized on admission, either to preoperative and postoperative anticoagulant medication (AC group, n = 94) or no anticoagulant treatment during the first month after surgery (O group, n = 94). Background factors were evenly distributed in the two groups, and 89% of the cases were considered as embolic. Analysis on an intention-to-treat basis showed no differences in outcome after 30 days. Good results, survivors who had amputation, and patients who died in the two groups are given respectively: AC group, 61%, 9%, 30%; O group, 65%, 11%, 24%. The results were similar in the two treatment groups also if only patients with a cardiac source of embolism were analyzed. Local bleeding complications were more common in the AC group (17% vs 2%, p less than 0.01). It is concluded that preoperative and early postoperative anticoagulant medication should not be routinely administered since such treatment is unlikely to improve the short-term results of lower-limb arterial thromboembolectomy while bleeding complications increase. The possible value of late (beyond 1 month) long-term anticoagulant treatment remains to be studied."
-How does intraperitoneal contrast material improve the detection of peritoneal metastases compared to standard CT examinations?,"Intraperitoneal contrast material improves the CT detection of peritoneal metastases. The preoperative detection of peritoneal metastases from gynecologic malignancies is difficult; in particular, CT often fails to detect peritoneal implants. This study was designed to determine if the administration of intraperitoneal iodinated contrast media would increase the CT detection of such peritoneal metastases. Prospectively, both standard and intraperitoneal contrast-enhanced CT studies of the abdomen and pelvis were performed in 16 patients with suspected gynecologic tumors. All patients then underwent operative staging, with the location and number of metastases documented. The intraperitoneal enhanced CT studies were more sensitive in the detection of peritoneal metastases than standard CT examinations. Whereas routine CT detected peritoneal metastases in seven (64%) of 11 patients with surgically proved implants, the intraperitoneal enhanced CT studies detected peritoneal metastases in all 11 patients. Depending on the specific intraperitoneal compartments involved, the sensitivity of intraperitoneal enhanced CT in the detection of peritoneal metastases was two- to fourfold greater than that of standard CT examinations. Our results suggest that intraperitoneal enhanced CT is superior to standard CT in the detection of peritoneal metastases."
-What was the restenosis rate for patients with unstable angina pectoris compared to those with stable angina pectoris after percutaneous transluminal coronary angioplasty (PTCA)?,"Higher recurrence rate after coronary angioplasty in unstable angina pectoris. PURPOSE: Recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA) is a significant problem, requiring repeat dilation in about one-third of all treated patients. Various clinical and procedure-related predictors have been proposed. Between 1983 and 1987, 257 patients underwent 322 procedures, where 380 stenoses were attempted. Indications were: stable angina pectoris 73%, unstable angina pectoris 22%, other indication 5%. The primary success rate was defined as a less than 50% remaining postprocedure stenosis. FINDINGS: Repeat angiograms were done for 88% of the initially successful cases, either six months after PTCA or if there was a clinical recurrence. Restenosis was defined as a recurrence of a more than 50% diameter stenosis. The restenosis rate was 33% and was significantly higher (p less than 0.05) for unstable (46%) than for stable angina pectoris (29%). There was a nonsignificant tendency to a higher restenosis rate in the left anterior descending artery than in the other coronary vessels. IMPLICATIONS: The increased restenosis rate seen after PTCA for unstable angina pectoris could be caused by a higher activity in systems affecting the proliferative processes in the smooth muscle cells of the arterial wall, which is thought to form the pathophysiologic basis for restenosis after PTCA."
-How did the nutritional status of patients with left ventricular assist device (LVAD) support change from implantation to cardiac transplantation?,"Nutritional assessment of patients with extended left ventricular assist device support. The nutritional status of nine patients with end-stage heart disease who were supported by a left ventricular assist device (LVAD) for more than 30 days while awaiting cardiac transplantation was evaluated. Nutritional status was indicated by the following scale: 0-2, adequate nourishment; 3-5, moderate malnourishment; greater than 5, severe malnourishment. This scale was based on serial assessments of albumin, transferrin, total lymphocyte count, percentage of ideal body weight, midarm circumference, triceps skinfold, and arm muscle circumference. Each variable was compared with established standards before implantation and before transplantation times and assessed 1 point if less than the normal value and 0 points if within the normal range. At the time of LVAD implantation, 5 patients had a score of 0-2, 3 patients had a score of 3-5, and 1 patient had a score greater than 5. At the time of cardiac transplantation, 7 patients had a score of 0-2, 2 patients had a score of 3-5, and no patients had a score greater than 5. The patients who were able to meet at least 50% of their daily caloric and protein requirements by oral intake alone were noted. At LVAD implantation, only 2 patients (22%) met this requirement; however, 6 patients (67%) met this requirement at the time of cardiac transplantation. All 9 patients underwent cardiac transplantation, and 8 survived. Thus, it appears that extended LVAD support and maintenance of hemodynamic stability allow patients to regain the desire and ability to achieve adequate nutritional status, which may considerably reduce their perioperative transplant risks."
-What rare combination of vascular conditions was observed in the patient described in the context?,"Congenital arteriovenous communications and the development of two types of leaking retinal macroaneurysms. We treated a patient with a rare combination of congenital arteriovenous communications and the development of leaking macroaneurysms of different types. Initially, leaking macroaneurysms developed in the shunt area of the arteriovenous communication; later, a preexistent fusiform macroaneurysm in the afferent arteriole of the congenital communication started leaking. Because exudates and fluid from the leaking macroaneurysms reached the fovea, laser treatment was performed to obliterate the macroaneurysms. We assume that after obliteration of the macroaneurysms with laser in the shunt area, the increase of hydrostatic pressure on the thin wall of the fusiform aneurysm of the afferent artery led to its leaking. We saw no signs of vascular occlusion after laser treatment."
-What is post-traumatic syringomyelia and how can it develop after a spinal fracture?,"Post-traumatic syringomyelia following uncomplicated spinal fracture. Two cases of post-traumatic syringomyelia presenting 10 and 41 years after spinal injuries that had caused lumbar vertebral fractures but no lasting neurological deficits are reported. In both patients the caudal end of the syrinx cavities, as shown by MRI, corresponded to the level of the previous vertebral fractures. Patients presenting with post-traumatic syringomyelia after uncomplicated spinal fracture are very rare, and the significance of the past history of spinal trauma may be overlooked."
-How effective was epidermal growth factor in treating chronic wounds in this study?,"Stimulation of healing of chronic wounds by epidermal growth factor. We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing."
-What were the cognitive outcomes for elderly patients with major depression after receiving tricyclic antidepressants or electroconvulsive therapy (ECT)?,"Cognitive outcome following tricyclic and electroconvulsive treatment of major depression in the elderly. OBJECTIVE: This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. METHOD: Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months. RESULTS: Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified. CONCLUSIONS: The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population."
-What were the main findings of the study comparing different anesthetic regimens in pediatric strabismus surgery?,"Effect of propofol on the incidence of postoperative vomiting after strabismus surgery in pediatric outpatients. Vomiting is a common problem after strabismus surgery in pediatric outpatients. We compared the effects of propofol with and without N2O and droperidol to the effects of a conventional regimen consisting of halothane-N2O-droperidol on the recovery characteristics and the incidence of postoperative emesis after strabismus surgery in 120 ASA physical status 1 or 2 children. After induction of anesthesia with halothane-N2O, patients were randomly assigned to one of four groups. Group A (control) received halothane, 66% N2O, and droperidol 75 micrograms.kg-1; group B, propofol 2 mg.kg-1 bolus followed by infusion of 160 microgram.kg-1.min-1; group C, propofol (as in group B) and 66% N2O; and group D, propofol (as in group B), 66% N2O (as in group C), and droperidol 75 micrograms.kg-1. Patients in group B had more episodes of intraoperative oculocardiac reflex responses than patients in group A, but had shorter times to extubation, oral intake, ambulation, and discharge, as well as a lower incidence of postoperative emesis (P less than 0.05). The addition of N2O to the propofol anesthetic regimen (group C) was associated with an increased incidence of emesis (P less than 0.05), whereas the addition of droperidol to the propofol-N2O regimen (group D) did not affect the incidence of emesis compared to the other three groups. We conclude that maintenance of anesthesia with a total intravenous regimen using propofol results in a more rapid recovery and less postoperative emesis than with a halothane-N2O-droperidol regimen."
-What surgical technique was used to address a persistent filtration bleb leak?,Donor scleral graft patching for persistent filtration bleb leak. We report effective and efficient sealing of a persistent leak in a cystic filtration bleb by applying a full-thickness donor scleral patch.
-What is the significance of finding occult submucosal duodenal-wall microgastrinomas in patients with Zollinger-Ellison syndrome?,"Zollinger-Ellison syndrome. A new look at regression of gastrinomas. Of 44 patients with the Zollinger-Ellison syndrome treated at our institution, nine appeared to have undergone ""regression"" of their gastrinomas. Six of the nine patients had sporadic gastrinomas and became permanently eugastrinemic following excision of nodal metastases and total gastrectomy (n = 4), antrectomy (n = 1), or pancreatoduodenectomy (n = 1) (mean survival, 13 years). The other three patients had Zollinger-Ellison syndrome as part of the multiple endocrine adenopathy type 1 syndrome and became temporarily eugastrinemic after total gastrectomy (mean survival, 11 years). Occult submucosal duodenal-wall microgastrinomas (mean size, 3.0 mm) were found to have been serendipitously excised in four patients. Long-term follow-up of these nine patients, as well as of six other patients described in the literature, demonstrates that excision of occult duodenal-wall gastrinomas provides a plausible explanation for the phenomenon of apparent regression of primary gastrinomas and the eugastrinemia that may follow total gastrectomy."
-How do neonates respond hormonally and metabolically to operative stress?,"Hormonal and metabolic response to operative stress in the neonate. It is evident from this review that newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with a suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin."
-What was the main finding of the study regarding neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities?,"Continuation of normal neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities. Detailed serial observations of behaviour were made in four singleton fetuses who were very small for dates and who had persistently absent umbilical artery end diastolic velocities for 2 to 9 weeks duration. All were born preterm for deteriorating maternal disease, and in two there were additional fetal indications for delivery. Behavioural comparison with 45 low risk singleton fetuses, at comparable gestations, revealed no significant differences in the development of behavioural cycles, the proportion of time spent in quiet cycles, or the amount of fetal breathing. None of the fetuses developed an abnormal heart rate pattern. We conclude that prenatal neurobehavioural development may continue apparently unimpaired in the presence of absent umbilical artery end-diastolic velocity of several weeks duration. Long term data of infant outcome are necessary before the clinical significance of this can be assessed."
-What are the potential complications of untreated abdominal aortic thrombosis?,"Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function."
-What were the most common neuro-ophthalmologic signs observed in AIDS patients in this study?,"Neuro-ophthalmologic signs of AIDS: 50 patients. In 50 hospitalized patients with acquired immunodeficiency syndrome, signs of central eye movement limitation (28 cases) were most common. Peripheral eye movement limitations (18), abnormalities of vision (18), and abnormal spontaneous eye movements (15) occurred with about equal frequency. Meningitis (17), usually due to lymphoma (8) or Cryptococcus (8), was the usual cause of peripheral nervous system involvement, while toxoplasmosis (18) was more common than lymphoma (4) or presumed viral causes (8) in producing CNS dysfunction. The midbrain and pretectal (8) were affected about as often as the pontine tegmentum (9), but rostral brainstem lesions appeared to be the result of toxoplasmosis (4) or lymphoma (3), whereas a viral etiology was the presumed cause of most caudal stem involvement."
-What specific changes in medullary catecholaminergic neurons were observed in Parkinson's disease brains compared to normal human brains?,"Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation."
-What was the main objective of the study comparing ivermectin and diethylcarbamazine (DEC) in patients with bancroftian filariasis?,"Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitologic observations. We compared the efficacy of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) for the control of microfilaremia in 60 patients with bancroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but in some cases, transient clearance of microfilaremia was observed in both treatment groups. At one year, recurrent microfilaremia was present in seven patients treated with ivermectin and in five treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremic. Side effects with both treatments were common, but mild. Febrile reactions were more frequent in the ivermectin group; localized reactions consistent with a flare-up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis."
-Does using a drain after cholecystectomy improve patient outcomes?,"Cholecystectomy is safer without drainage: the results of a prospective, randomized clinical trial. Drainage after cholecystectomy remains routine despite the lack of scientific supportive data. Numerous clinical studies in the past have attempted to address this controversy but have failed to resolve the issue for different reasons. These include retrospective design, inclusion of only selected cases, and randomization before surgery. In this study 479 patients undergoing cholecystectomy were randomly allocated to a drainage group (a high-pressure suction drain in Morison's pouch for 48 hours) or a nondrainage group. Randomization was performed at the time of peritoneal closure. All patients undergoing cholecystectomy, both elective and urgent, were included and the operations were performed by all grades of surgeons. There were two deaths from cardiopulmonary causes, both in the drainage group. No patient required reoperation in either group. The incidence of both wound infections (15 vs 5; p less than 0.05) and chest infections (56 vs 19, p less than 0.02) was significantly higher in the drainage group. Three hundred fifty-six patients underwent abdominal ultrasonography 72 hours after surgery. The number of subhepatic fluid collections thus detected was significantly higher in the patients who received a drain (17 vs 6, p less than 0.05). None of these collections was clinically significant. The postoperative hospital stay was longer in the patients with drains (10.3 vs 9.1 days), but this difference failed to reach statistical significance. We conclude from this study that the use of a drain after cholecystectomy serves no useful purpose and is potentially harmful. This practice should be abandoned."
-How can striae of Retzius in dental enamel help in identifying an individual in forensic anthropology?,"Individualization and enamel histology: a case report in forensic anthropology. The cranium of a native Indian child about six years old was found in 1979 near Taseko River, British Columbia, Canada. While the remains matched the report of a child missing for eight years in terms of race, age at death, locale, and elapsed time since death, the cranium and dentition were basically unidentifiable because of the claimed lack of medical or dental history. There was no dental work, and the parents were unknown or dead. We report the presence, in the dental enamel of the primary and secondary dentition, of stress markers, termed striae of Retzius, whose locations correspond well with anecdotal reports and recently discovered medical records which describe the timing of specific episodes of stress. The enhanced probability of personal identification from dental histological stress markers is evaluated."
-What medication was used to manage hypotension during the perioperative period for a patient with idiopathic orthostatic hypotension undergoing coronary artery bypass grafting?,"Idiopathic orthostatic hypotension, midodrine, and anaesthesia. A patient with idiopathic orthostatic hypotension receiving chronic oral midodrine therapy required anaesthesia for coronary artery bypass grafting. A perioperative infusion of phenylephrine was substituted for midodrine, an alpha-2 agonist, enabling hypotension resulting from low systemic vascular resistance to be controlled easily. Anticipated adrenergic receptor denervation hypersensitivity was noted. The only significant perioperative problem was one episode of syncope from orthostatic hypotension during the reambulation period."
-"What medical condition did the patient initially present with, and how was it resolved?","Hemidystonia due to a contralateral parieto-occipital metastasis: disappearance after removal of the mass lesion. A patient presented with left-sided hemidystonia. CT revealed a contralateral parieto-occipital mass lesion compressing the basal ganglia, which were spared by the mass. After microsurgical resection of the tumor, which was verified histologically as a metastasis of a large-cell anaplastic carcinoma, the movement disorder dissolved completely."
-What was the primary finding of this study regarding bradycardia in children with leukemia after sepsis?,"Postsepsis bradycardia in children with leukemia. OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta-adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated."
-What potential complication can occur to the pancreas during extracorporeal shock wave lithotripsy (ESWL) for renal calculus fragmentation?,"Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed."
-What was the purpose of the study on recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers?,"The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination."
-What association was found between HLA-DR1 and the development of multiple basal cell carcinomas in southern Australia?,"Multiple basal cell carcinomas and HLA frequencies in southern Australia. An association between HLA-DR1 and the development of multiple basal cell carcinomas was detected in southern Australia. A reduction in HLA-DR4 was found in patients with basal cell carcinoma compared with a local control group. The relative risk for HLA-DR1 was 2.1, which was lower than that for persons in farther countries from the equator."
-What is a coronary arteriovenous fistula and how rare is it?,Successful operation on a coronary arteriovenous fistula in a 74 year old woman. Coronary arteriovenous fistulas are rare and are usually diagnosed in children or young adults. Most are believed to be congenital. A right coronary arteriovenous fistula was first diagnosed in a patient of 74. Despite her age the fistula was successfully operated on and her symptoms were relieved.
-"What were the effects of different interferons (alpha, beta, and gamma) on human melanoma cell lines in terms of proliferation, differentiation, and cell surface markers?","Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells."
-What diagnostic technique was used to identify cor triatriatum and pulmonary venous stenosis in this adult case?,Cor triatriatum with isolated pulmonary venous stenosis in an adult: diagnosis with transesophageal two-dimensional echocardiography. The diagnosis of cor triatriatum in an adult was made from routine two-dimensional transthoracic echocardiography. The findings of aliasing and turbulence in the roof of the left atrium suggested pulmonary venous stenosis. A transesophageal echocardiogram defined both the hemodynamic features of nonobstructing cor triatriatum and the presence of isolated pulmonary venous stenosis. The clinical use of transesophageal echocardiography with color flow Doppler in the elucidation of complex anatomic substrate is demonstrated.
-What percentage of mastoid surgeries in children were performed for chronic otomastoiditis in this study?,"Mastoid surgery in childhood. The presenting features and operative findings in 105 patients aged 16 years or less undergoing mastoid surgery are reviewed. In 94% surgery was for chronic otomastoiditis, usually acquired, and associated with cholesteatoma in 64%. Post-operative otorrhoea persisted beyond 6 months in 44% and contralateral disease required some form of surgical procedure in 20%. Post-operative hearing thresholds were improved or unchanged in the majority of patients, most of whom underwent cortical or modified radical mastoidectomy. An improvement in the therapeutic results of mastoid surgery in childhood is clearly necessary, but requires a greater understanding of the aetiology of chronic middle ear disease."
-How does Doppler echocardiography help in monitoring cardiac transplant recipients compared to traditional cardiac biopsy?,"Doppler echocardiography for rejection surveillance in the cardiac allograft recipient. Echocardiography is noninvasive, allows real-time visualization of the heart, and can be performed serially without harmful biologic effects. It is also relatively inexpensive compared with other diagnostic modalities used for cardiac transplant rejection surveillance, such as cardiac biopsy, computed tomography, and magnetic resonance imaging. It is free of the potential complications associated with cardiac biopsy, such as accidental disruption of cardiac valves or chordae tendineae, ventricular septal perforation, introduction of bacteria, and the difficulty of obtaining adequate sampling for effective diagnosis as a result of formation of scar tissue. Unlike biopsy, echocardiography does not cause the patient anxiety and discomfort or use many physician and instrument or laboratory resources. Because the results of echocardiography are available within minutes compared with the hours usually needed for biopsy results, it allows prompt decisions regarding patient clinical care and treatment. In our work to date, echocardiography has not replaced the cardiac biopsy in surveillance of rejection in the cardiac transplant patient, but rather has become a useful adjunct to it. When echocardiographic findings indicate changes characteristic of rejection, biopsies are performed earlier, leading to earlier diagnosis and treatment. Furthermore, when echocardiographic findings are stable and negative for rejection, the number of routine cardiac biopsies performed can be reduced. This article discusses the use of echocardiography in surveillance of the cardiac transplant patient and the ability of echocardiography to augment the biopsy and clinical regimens in assessing cardiac allograft rejection."
-How do different alpha 1-adrenergic receptor blockers affect the incidence of abnormal automaticity in ischemic Purkinje fibers?,"Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype. BACKGROUND. Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101. METHODS AND RESULTS. In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment. CONCLUSIONS. Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment."
-What complications did the 12-year-old girl develop after receiving chemotherapy for osteogenic sarcoma?,"Secondary myelodysplastic syndrome complicating therapy for osteogenic sarcoma. A 12-year-old girl with nonmetastatic osteogenic sarcoma received treatment with doxorubicin, methotrexate, cisplatin, cyclophosphamide, bleomycin, and dactinomycin. She developed unexplained persistent pancytopenia after completion of chemotherapy. Twenty-three months after the initial diagnosis of osteosarcoma an evaluation revealed a bone marrow pattern consistent with the diagnosis of refractory anemia with excess blasts, and karyotype analysis showed characteristic findings of therapy-related myelodysplasia (loss of chromosomes 5 and 7, as well as 12p and 17p deletions). Bone marrow transplantation from an human leukocyte antigen (HLA)-compatible sibling donor was performed 26 months after the diagnosis of the primary malignancy. Although it is unproven that the alkylating agents administered to this patient were responsible for the myelodysplastic syndrome, careful follow-up of osteosarcoma patients who receive alkylating agents is warranted."
-What was the most common gastrointestinal complication in patients who underwent cardiopulmonary bypass surgery?,"Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group."
-How does the pH level affect gastrin secretion from antral G-cells?,"Much ado about gastrin [editorial; comment] The regulation of gastrin secretion from antral G-cells is of major importance in the physiologic control of acid secretion. Gastrin secretion is highly dependent upon gastric intraluminal pH and is inhibited significantly by a pH of less than 3.0. Acute gastric alkalinization greater than pH 6.0 with antisecretory agents such as H2-receptor antagonists or H+/K+ ATPase inhibitors has little impact on fasting serum gastrin levels but promotes an enhanced sustained rise in meal-stimulated gastrin release. Courses of standard therapy with both H2-antagonists and H+/K+ inhibitors cause a significant rise in 24 h integrated plasma gastrin levels that is inversely correlated to the 24-h integrated gastric acidity. The rise in fasting or integrated plasma gastrin levels observed in patients treated with H2-antagonists is small and of unclear clinical significance. Therapy with antisecretory agents leads to earlier ulcer relapse than with other agents. A variety of factors have been proposed to explain the earlier ulcer relapse rate, including secondary hypergastrinemia with rebound acid hypersecretion after discontinuation of the drug. Secondary hypergastrinemia may also lead to tolerance to prolonged courses of H2-antagonists therapy with a decrease in acid inhibition. This may contribute to break-through ulcer recurrence during maintenance H2-antagonist therapy. However, the relative importance of hypergastrinemia and tolerance to H2-antagonists compared with other factors such as baseline gastric acid secretion, smoking status, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori status is difficult to assess."
-What was the purpose of using Indium-111-leukocyte imaging in conjunction with 99mTc-iminodiacetic derivative (IDA) scintigraphy for detecting acute cholecystitis?,"Indium-111-leukocyte imaging in acute cholecystitis. Eleven patients with suspected acute cholecystitis underwent sequential 99mTc-iminodiacetic derivative (IDA) and 111In-white blood cell (WBC) imaging to determine if 111In-WBCs accumulate within an acutely inflamed hemorrhagic gallbladder wall and, thus, could be employed as a reasonable alternative to 99mTc-IDA scintigraphy in detecting acute cholecystitis. Seven patients had surgically confirmed acute cholecystitis. Of these cases, five had a true-positive 99mTc-IDA and 111In-WBC, one an indeterminate 111In-WBC and true-positive 99mTc-IDA, and one a true-positive 111In-WBC and false-negative 99mTc-IDA scan. The remaining four patients did not have acute cholecystitis. All visualized their gallbladder within 1 hr after 99mTc-IDA administration and none had 111In-WBC gallbladder wall uptake. Both 111In-WBC and 99mTc-IDA scintigraphy accurately detected acute cholecystitis: hepatobiliary scintigraphy demonstrated a cystic duct obstruction and 111In-WBC imaging detected the inflammatory infiltrate within the gallbladder wall. The sensitivity and specificity of each was 86% and 100%, respectively."
-What was the overall response rate in the study of recurrent and/or metastatic head and neck squamous cell carcinoma treated with cisplatin-based chemotherapy?,"Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy. One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What was the main objective of the study on visual evoked potentials in migraine patients?,"Visual evoked potentials and background EEG activity in migraine. To investigate whether quantification of the background EEG during a visual evoked potential (VEP) study is of value for the diagnosis of migraine we studied 8 unmedicated migraineurs between attacks, and 10 age-matched controls. Three paradigms were used: the first two concerned pattern-reversal VEPs with different analysis times (500 and 1500 ms), and in the third paradigm the pattern did not reverse. Power spectra were calculated for individual responses, and the delta, theta, alpha and beta areas of the averaged spectra were noted as indicators of background reactivity. Alpha and beta powers were consistently but not significantly higher in the migraine group. The difference was too small to be of value as a diagnostic test. Alpha power was (not significantly) lower in the presence of photic stimulation than in its absence. As this was the case in both groups photic stimulation does not explain the higher alpha powers in the migraine group. We conclude that EEG background activity during the VEP does not distinguish reliably between migraineurs and controls."
-How does interferon-gamma affect the bone marrow response to lipopolysaccharide after hemorrhagic shock?,"Interferon-gamma reverses bone marrow inhibition following hemorrhagic shock. Hemorrhagic shock has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide. Interferon-gamma has been shown to improve the immune response following experimental shock and injury; however, its effect on myelopoiesis is controversial. This study was performed to determine whether treatment with interferon-gamma will improve the bone marrow response to lipopolysaccharide after hemorrhagic shock. Rats subjected to either shock or a sham procedure were allocated into three groups: (1) control rats received no further treatment; (2) lipopolysaccharide-treated rats received saline for 3 days and then were challenged with lipopolysaccharide to stimulate myelopoiesis; and (3) interferon-treated rats received interferon-gamma (7500 U subcutaneously 1 hour after shock and then every day for 3 days) and lipopolysaccharide as in group 2. Serum colony-stimulating factor levels were measured 6 hours and bone marrow white blood cell count and granulocyte-macrophage colony-forming units (CFU-GM) were measured 24 hours following lipopolysaccharide administration. In sham-treated rats, lipopolysaccharide increased CFU-GM 77% compared with controls. In contrast, treatment with lipopolysaccharide decreased CFU-GM 43% following shock. Treatment with interferon-gamma increased CFU-GM in all animals and reversed the decline in CFU-GM seen in shocked lipopolysaccharide-treated animals. Serum colony-stimulating factor levels were unaffected by either shock or interferon-gamma administration. These data demonstrate that interferon-gamma exerts a stimulatory effect on bone marrow following shock and restores the myelopoietic response to lipopolysaccharide."
-What methods were used to study the proliferative activity of neuroendocrine tumours in this research?,"Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations. The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment."
-What were the survival rates for different groups of patients undergoing hepatic resection for hepatocellular carcinoma?,"Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period. During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively."
-How did tamoxifen therapy affect the incidence of contralateral breast cancer in postmenopausal breast cancer patients during the randomized trial?,"Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer."
-What are the key differences between B-cell and T-cell types of clear-cell immunoblastic lymphoma (IBLC) in terms of morphologic and clinical characteristics?,"Immunoblastic lymphoma with abundant clear cytoplasm. A comparative study of B- and T-cell types. The morphologic, phenotypic, molecular genetic, and clinical features of 34 cases of clear-cell immunoblastic lymphoma (IBLC) are described. Sixteen cases were of B-cell type (IBLC-B) and 18 cases were of T-cell type (IBLC-T). There were no significant differences in the morphologic characteristics of the neoplastic cells in the two types, although IBLC-B was less likely to be polymorphic than IBLC-T. Interfollicular proliferation, a higher mitotic rate, infiltration by eosinophils, and an increase in capillary-sized blood vessels were also features of IBLC-T, whereas necrosis and fibrosis were more extensive in IBLC-B. Patients with IBLC-B were predominantly female, whereas those with IBLC-T were predominantly male. The mean age was 62 years for those with IBLC-B and 46 years for those with IBLC-T. Patients with IBLC-B usually had lower-stage disease, but there was no significant difference in survival rate between those with IBLC-B and those with IBLC-T. Although most cases of IBLC have been considered to be of peripheral T-cell origin, the authors conclude that IBLC-B is more common than previously considered and that clear-cell morphologic characteristics are not a reliable indicator of T-cell type."
-What was the estimated reduction in death rate and recurrence rate for patients treated with levamisole in this melanoma study?,"Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guerin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma."
-How do the intrarenal hemodynamic parameters differ between the stenotic and contralateral kidneys in patients with renovascular hypertension?,"Glomerular hypertension in renovascular hypertensive patients. Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Forty patients with essential hypertension and 40 patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for effective renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as afferent arteriolar resistance (RA), efferent arteriolar resistance (RE) and glomerular hydrostatic pressure (PG) in each kidney. Normal values of intrarenal hemodynamic parameters were obtained in 24 normotensive subjects without ureteral catheterization, assuming each kidney had the half function of both kidneys. Systemic mean arterial pressure did not differ between essential and renovascular hypertension (141 +/- 3 vs. 148 +/- 3 mm Hg). Effective renal plasma flow and glomerular filtration rates were decreased in the stenotic kidney of RVH (98 +/- 8, 24 +/- 2 ml/min/m2), while increased in the contralateral kidney (195 +/- 11, 48 +/- 2), compared with the right kidney of essential hypertension (162 +/- 8, 33 +/- 1). Although effective renal plasma flow rate was not different from normal (191 +/- 8), glomerular filtration rate was significantly higher in the contralateral kidney of RVH than in normal (38 +/- 1). RA was elevated due to the stenotic lesion in the stenotic kidney (28,500 +/- 1,900 dyns.sec.cm-5), while the elevation in the contralateral kidney (10,800 +/- 600) was less than in the right kidney of essential hypertension (14,900 +/- 1,200). RE (5,800 +/- 300) in both kidneys of RVH was higher than in the right kidney of essential hypertension (4,500 +/- 200)."
-What is the significance of recognizing graft-vs-host disease-like histology in small intestinal biopsy specimens from patients with common variable immunodeficiency?,Small intestinal lesion resembling graft-vs-host disease. A case report in immunodeficiency and review of the literature. We report graft-vs-host disease-like histology in a small intestinal biopsy specimen that was obtained from a patient with common variable immunodeficiency and related T-cell defect. We include findings from immunohistochemical studies and follow-up information. Review of the literature yielded only a small number of histologically documented cases of this lesion without previous bone marrow transplantation. Awareness of this clinicopathologic entity is important in the interpretation of gastrointestinal biopsy specimens.
-What was the maximum tolerated dose of CPT-11 in this Phase I study of non-small-cell lung cancer treatment?,"Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance."
-How did the number of preoperative chemotherapy courses affect tumor necrosis and surgical outcomes in patients with osteosarcoma?,"Increased survival, limb preservation, and prognostic factors for osteosarcoma. Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery."
-What is a mesenchymoma of the chest wall and how rare is it in children?,"Mesenchymoma of the chest wall in children. Benign chest wall mesenchymoma in children is an extremely rare disease. Only 20 patients have been reported in the world literature. We report a chest wall mesenchymoma in a 2-year-old boy who was admitted to the hospital after a routine chest roentgenogram showed a mass in the right upper chest wall. The patient was asymptomatic. Clinical examination was negative, but chest roentgenograms and computed tomography showed a mass in the right upper chest wall involving the third rib. A 2 x 2 x 1.5-cm tumor was excised totally with partial resection of the third rib. The histology of the lesion corresponded to a mesenchymoma (hamartoma) of the chest wall. Our patient has been followed up for 8 years without recurrence."
-What was the primary treatment approach for chiasmal and hypothalamic gliomas in infants and children during the study period?,"Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease."
-What is the significance of the prolonged postischemic ventricular dilatation observed in the 99mTc MIBI scan?,"Transient prolonged postischemic ventricular dilatation documented by 99mTc MIBI scan. We describe two cases of prolonged postischemic ventricular dilatation during myocardial scintigraphy with 99mTc MIBI, the new perfusion tracer that has only negligible redistribution. Ventricular dilatation, caused by true chamber dilatation and/or subendocardial ischemia, was still present over two hours after the induced ischemic episode, suggesting a prolonged duration of such a commonly believed fleeting scintigraphic finding."
-What was the main purpose of the clinical study involving lidoflazine in cardiac arrest survivors?,"A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial II Study Group BACKGROUND. Abnormalities of cellular calcium homeostasis have been implicated in the pathophysiology of postischemic encephalopathy. Calcium-entry-blocking drugs inhibit the influx of calcium into cells and have been shown to mitigate postischemic encephalopathy in animal models. METHODS. Five hundred twenty patients with cardiac arrest who remained comatose after the restoration of spontaneous circulation were randomly assigned to receive three doses of lidoflazine, an experimental calcium-entry blocker, or a placebo and were followed for six months. Four patients were lost to follow-up. Treated patients received an intravenous loading dose (1 mg per kilogram of body weight) of lidoflazine and two subsequent doses (0.25 mg per kilogram) 8 and 16 hours after resuscitation. The investigators were blinded to treatment assignment. RESULTS. There was no statistically significant difference between the lidoflazine group (n = 259) and the placebo group (n = 257) in the proportion of patients who died during the six-month follow-up (82 vs. 83 percent), who survived with good cerebral recovery (15 vs. 13 percent), or who survived with severe neurologic deficit (1.2 vs. 1.9 percent). Analysis of the best level of recovery achieved at any time during follow-up also did not show a difference between the treatment groups: 24 percent of those given lidoflazine and 23 percent of those given placebo recovered good cerebral function (normal or only moderately disabled cerebral performance) at some time. CONCLUSIONS. The administration of lidoflazine after cardiac arrest was not found to be beneficial. Our data do not support the routine use of this calcium-entry-blocking drug in comatose survivors of cardiac arrest."
-What is an ileal neobladder and what makes it an optimal bladder substitution technique?,"The ileal neobladder. The ileal neobladder in many respects approximates the theoretically ideal continent urinary diversion. The technique, while more technically demanding than the performance of the standard ileal loop diversion, is not difficult, particularly for surgeons used to performing radical retropubic prostatectomies. The ileal neobladder appears to approximate most closely the optimal bladder substitution. Although currently feasible only in males, future considerations could conceivably involve urologists working with their colleagues in gynecology and colorectal surgery to extend the benefits of bladder substitution using the ileal neobladder to selected patients having cystectomy for associated gynecologic or colorectal malignancies."
-What was the surgical success rate for patients with and without asthma in this study of intranasal ethmoidectomy?,"The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present."
-What conservative treatment method was used to manage vesicovaginal fistulas in the described cases?,Conservative treatment of vesicovaginal fistulas by bladder drainage alone. We describe 4 cases of conservative management of vesicovaginal fistulas occurring as a complication of abdominal and vaginal hysterectomy. In all cases treatment involved simple bladder drainage for periods ranging from 19 to 54 days. At follow-up all patients remained dry. Such spontaneous closure of vesicovaginal fistulas following adequate bladder drainage has not been previously reported.
-How did early captopril administration affect infarct expansion and left ventricular segment length in patients with acute myocardial infarction?,"Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04)."
-How can AIDS prevention programs help in controlling the spread of hepatitis B virus in sub-Saharan Africa?,"How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa For developing countries the cost-benefit of vaccination in the control of hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that, compared with south-east Asia, infection occurs later in childhood and spread is horizontal rather than vertical, investigation of the method of spread of HBV may result in a means of control other than by vaccination. In the meantime, because of the overlap in the means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking advantage of existing AIDS prevention programmes to educate people about how to avoid both HBV and HIV infections."
-What are the key characteristics of pulmonary angiitis and granulomatosis syndromes in terms of clinical presentation and radiologic features?,"Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions."
-How does core temperature affect splanchnic sympathetic nerve activity in rats during environmental heating?,"Splanchnic sympathetic nerve activity and circulating catecholamines in the hyperthermic rat. The mechanisms responsible for the initial rise in splanchnic vascular resistance with environmental heating are controversial, and those responsible for the subsequent fall in splanchnic resistance in the severely hyperthermic animal are unknown. Thus we examined the effect of environmental heating on plasma catecholamine concentration, splanchnic sympathetic nerve activity (SNA), and select blood chemistries. In one study, 25 male Sprague-Dawley rats (270-300 g) were assigned to one of five groups on the basis of their core temperature (Tc, 37, 39, 41, 43, or 44 degrees C) at death. Heart rate (HR), mean arterial pressure (MAP), and Tc were monitored during heat stress under alpha-chloralose anesthesia (12.5 mg.ml-1.h-1). At each predetermined Tc, an aortic blood sample was drawn and analyzed for mean plasma concentration of norepinephrine (NE), epinephrine (E), Na+, K+, and lactate. From 41 to 43 degrees C, NE and E rose significantly, and the animals became hyperkalemic and lactacidemic. In a separate study, we quantitated SNA from the greater splanchnic nerve during heat exposure of artificially respired animals anesthetized with pentobarbital sodium (50 mg/kg). MAP, splanchnic SNA, and Tc were recorded. Tc was elevated from 37.0 +/- 0.12 to 41.3 +/- 0.18 degrees C in 70 min by increase of ambient temperature to 38 degrees C in an environmental chamber. Splanchnic SNA was 54 +/- 8 spikes/s at a Tc of 37 degrees C and increased significantly as Tc exceeded 39 degrees C (P less than 0.05)."
-How does clonidine affect blood pressure and hemodynamic responses differently in normal subjects compared to tetraplegic patients?,"Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action. BACKGROUND. Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated. METHODS AND RESULTS. The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors. CONCLUSIONS. Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension."
-What were the treatment methods used for prostatic cancer in the study involving 63 patients?,"Morbidity of modified pelvic lymphadenectomy and radiotherapy for prostatic cancer. The records of 63 patients treated by pelvic lymphadenectomy and radiotherapy at the University of Tennessee, Memphis, Baptist Memorial Hospital of Memphis, and the Memphis Veterans Affairs Hospital were reviewed. Of those patients, 45 received external beam radiation therapy to the prostate while 16 were treated by Iodine-125 implantation. Two patients had only staging lymphadenectomy. The incidence of postoperative and late complications were analyzed."
-How did the application of a smooth Teflon clip to the inferior vena cava affect the incidence of pulmonary embolism in patients undergoing radical cystectomy?,"Application of smooth Teflon clip to inferior vena cava during radical cystectomy to prevent postoperative pulmonary embolism. Between 1976-1986, a smooth Teflon clip was applied to the inferior vena cava of 56 patients who underwent radical cystectomy for bladder cancer. The purpose of the clip is to narrow the lumen of the inferior vena cava so that large emboli will be trapped and thus prevented from reaching the lungs. These 56 patients were compared with a group of 26 historical controls who underwent radical cystectomy without application of such a clip between 1967-1976. One patient (1.8%) whose vena cava was clipped had a pulmonary embolus which was fatal. Four (15.4%) of the 26 control patients had postoperative pulmonary emboli, the embolic event being fatal in 3 (11.5%). Application of the smooth Teflon clip to the inferior vena cava significantly lessens the incidence of pulmonary embolism following radical cystectomy."
-Who was Paul Broca and what significant medical procedure did he perform in 1871?,"Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization."
-What makes coronary restenosis a significant challenge in interventional cardiology?,"Coronary restenosis: what have we learned from angiography? Coronary restenosis remains a major problem for interventional cardiology not only by virtue of its frequency, but also because of the current inability to prevent it. Symptomatic status and non-invasive evaluation have been used to study restenosis, but both lack specificity and sensitivity, particularly in patients with multivessel disease. Angiography remains the reference standard. Several arbitrary definitions have been used, some related to visual estimates of coronary stenosis and others to quantitative angiographic techniques. In another approach, linear modeling is used to assess minimal luminal diameter of lesions on restudy. Although angiographic studies have been essential in the study of restenosis, questions concerning the underlying mechanism and pathophysiology remain. The development of animal models that closely resemble human restenosis should allow evaluation of pathophysiologic mechanisms and development of new strategies to prevent the problem."
-What are the main sources of mortality data for shigellosis in developing countries?,"Mortality due to shigellosis: community and hospital data. Almost all fatal cases of shigellosis occur in developing countries, and data on mortality are generally compiled from three sources: investigations of epidemics caused by Shigella dysenteriae type 1, surveillance of endemic diarrheal disease, and reports from hospitals. Attack rates during epidemics of dysentery due to infection with S. dysenteriae type 1 have ranged from 1% to 33%, and case-fatality rates have ranged from 1% to 7%. In Matlab, a rural district in Bangladesh, most diarrhea-related deaths and approximately 25% of all deaths among children 1 through 4 years of age are attributable to dysentery. In 1984, an epidemic of dysentery was associated with a 42% increase in the death rate in that age group. At the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, the fatality rate for 970 inpatients with shigellosis was 11% in 1988, with most deaths occurring among malnourished children who were infected with Shigella flexneri. Control of mortality from shigellosis will require prevention of epidemic S. dysenteriae type 1 disease and endemic S. flexneri infections in children who live in countries with a high prevalence of malnutrition."
-How does diclofenac affect the healing of gastroduodenal mucosal lesions according to the study?,"Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions."
-What is auriculotemporal syndrome (ATS) and how does it relate to temporomandibular joint (TMJ) surgery?,"Auriculotemporal syndrome following the preauricular approach to temporomandibular joint surgery. Forty-seven joints in 28 patients were examined 4 months to 10 years after temporomandibular joint (TMJ) surgery via a modified preauricular approach. Many patients had undergone multiple procedures. None of the patients had any subjective or objective evidence of auriculotemporal syndrome (ATS), although patients in previous studies with more extensive incisions have demonstrated ATS. It was concluded that ATS is an unlikely complication following TMJ surgery. A small incision without an oblique superior extension may further reduce the risk."
-How does left ventricular hypertrophy (LVH) impact cardiovascular health and what role do calcium channel blockers play in managing this condition?,"Left ventricular hypertrophy: impact of calcium channel blocker therapy. Left ventricular hypertrophy (LVH) of the concentric type is the classic cardiac adaptation to sustained arterial hypertension. Data from the Framingham cohort have shown that patients with LVH have a severalfold higher risk of sudden death, acute myocardial infarction, and other cardiovascular morbidity than those with normal hearts. Common sequelae of LVH are ventricular ectopy, impaired ventricular contractility, myocardial ischemia, and decreased left ventricular filling. The benefits of antihypertensive therapy should not be limited to lowering arterial pressure, but should extend to preventing or reducing target organ damage. A variety of antihypertensive agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, antiadrenergic drugs, and, to a lesser extent, beta blockers, have been shown to reduce LVH and to improve left ventricular filling. We have shown that calcium channel blockers diminish ventricular ectopy in parallel with the reduction of LVH, whereas antihypertensive therapy with diuretics neither reduced LVH nor suppressed ventricular ectopy, although it lowered arterial pressure to a similar extent. Whether or not these cardiac changes with antihypertensive therapies will improve cardiovascular morbidity and mortality in patients with LVH remains to be documented."
-What was the unusual finding in this patient's case that led to a pathological confirmation during nephrectomy?,"Intrarenal pancreatic cyst. A case report of intrarenal true cyst of the pancreas is presented. The patient presented with flank pain. Her diabetes and hypertension were well-controlled. The cause of the pain was presumed to be a cystic renal mass, which proved to be of pancreatic origin only after the pathologic confirmation from the nephrectomy specimen."
-How has the understanding and diagnosis of preeclampsia changed over time according to the given context?,"Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased."
-What unique medical technique was used to manage a through-and-through knife injury of the aortic arch in this case report?,"Artificially induced ventricular fibrillation in the management of through-and-through penetrating wounds of the aortic arch: a case report. Case report of a 28-year-old woman in whom a through-and-through knife injury of the aortic arch is presented. The hemorrhage could not be brought under control by conventional means and was handled by artificially induced temporary electric fibrillation of the heart, direct suture, and immediate defibrillation. The patient made an uneventful recovery."
-How does profound cerebral hypothermia (Ttm less than 10 degrees C) compare with deep hypothermia (15 degrees C) in terms of neurologic outcomes after circulatory arrest in dogs?,"Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery. Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia."
-How does the location of the sample volume affect the transmitral filling measurements in pulsed Doppler echocardiography?,"Dependency of the pulsed Doppler-derived transmitral filling profile on the sampling site. In previous reports that evaluated pulsed Doppler transmitral filling, the sampling site has varied; we examined the effect of the sample volume location on Doppler measurements. Studied were 97 patients: 58 with normal echocardiograms, 20 with mitral regurgitation, and 19 with miscellaneous cardiac diseases. Transmitral filling was recorded at the mitral anulus and at the left atrial and left ventricular (LV) sides of the mitral tips. As the sample volume was moved from the mitral anulus to the LV side, the peak velocity and time-velocity integral of early diastole increased (40.6 +/- 13.8 versus 59.0 +/- 19.0 cm/sec, 5.26 +/- 1.65 versus 8.35 +/- 2.37 cm; p less than 0.001) as did those of late diastole (48.7 +/- 11.5 versus 57.5 +/- 17.0 cm/sec, 3.48 +/- 0.97 versus 4.59 +/- 1.39 cm; p less than 0.001). The late-to-early diastolic peak velocity and time-velocity integral ratios and the late-to-total diastolic time-velocity integral ratio decreased (1.33 +/- 0.51 versus 1.06 +/- 0.41, 0.71 +/- 0.24 versus 0.58 +/- 0.19, 0.40 +/- 0.09 versus 0.36 +/- 0.08; p less than 0.001). The dependency of these indices on the sampling site was in the same degree in all three groups. However, the peak filling rate normalized to mitral stroke volume (4.71 +/- 1.43 versus 4.63 +/- 1.32 l/sec; p = NS) was not influenced by the sample volume location; thus this parameter may be more reliable for assessing LV filling."
-Is anticoagulation completely contraindicated in hemorrhagic cardioembolic stroke?,"Hemorrhagic cardioembolic stroke: is anticoagulation absolutely contraindicated? Hemorrhagic cerebral embolism should not be considered an absolute contraindication to immediate low-dose systemic anticoagulation. Low levels of anticoagulation may give some protection from recurrent embolism while minimizing the risks of intracranial bleeding. Until further studies are available, these decisions must be made on a case-by-case basis, supported by limited scientific information."
-What are the key advantages of laparoscopic cholecystectomy compared to conventional cholecystectomy?,"Laparoscopic cholecystectomy: 111 consecutive cases. Laparoscopic cholecystectomy removes the gallbladder through three or four puncture wounds in the abdominal wall. The technique reduces the recuperative time to full activity, from as long as 4 wk to as little as 3 days, compared with conventional cholecystectomy. We herein present our initial experience with this procedure. In this series of 111 laparoscopic cholecystectomies, there were no mortalities and only one morbidity. Thirty-nine patients (35%) had a history of prior abdominal surgery. Fourteen underwent laparoscopic lysis of adhesions. Intraoperative cholangiograms were performed in 24 patients (21%), demonstrating choledocholithiasis in three. Two of the three patients underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP); in the other, laparoscopic common bile duct exploration was performed. In each case, the common bile duct (CBD) was completely cleared of stones. Incidental laparoscopic appendectomy was also performed in three patients. The average time for completion of laparoscopic cholecystectomy in cases of chronic cholecystitis was 40 min. If the gallbladder was acutely inflamed, the procedure took a mean of 126 min. This series had a higher percentage of patients (19%) with acute cholecystitis then previously reported; therefore, the 2% conversion rate in this series emphasizes the broad applicability of the technique. The average length of stay in the hospital was 1.4 days, and patients returned to work in about 7 days."
-How did infection and malnutrition affect liver glutathione and cytochrome P450 levels in the experimental rat study?,"Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition. OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients."
-"What is the significance of the ""Metsovo lung"" phenomenon in Greece?","Metsovo lung outside Metsovo. Endemic pleural calcifications in the ophiolite belts of Greece. Endemic PCs and high incidence of malignant mesothelioma from household use of asbestos have been reported in Metsovo in northwestern Greece (""Metsovo lung""). In the present study, we present similar findings in six more areas of Greece. Like Metsovo, all these areas are located within ophiolite belts. Like Metsovo, material similar to ""Metsovo whitewash"" has been used for various domestic uses. Asbestos fibers (chrysotile, antigorite and tremolite) were found in three of the six areas. Also, in two, MPM has been diagnosed. These findings suggest that ""Metsovo lung"" occurs in several areas of Greece and has similar etiology and epidemiology."
-How does the radionuclide technique (VEST) help in detecting silent myocardial ischemia during balloon angioplasty?,"Validation of continuous radionuclide left ventricular functioning monitoring in detecting silent myocardial ischemia during balloon angioplasty of the left anterior descending coronary artery. Silent myocardial ischemia has been inferred from transient ST-segment depression during continuous electrocardiographic monitoring. Recently, continuous ambulatory monitoring of left ventricular (LV) function using a radionuclide technique (VEST) has demonstrated episodes of significant silent LV dysfunction in the absence of electrocardiographic changes. To validate the demonstration of silent LV dysfunction with this technique, 12 men were studied during percutaneous transluminal coronary angioplasty. A total of 18 left anterior descending coronary artery balloon inflations were performed. Balloon inflations at 8 +/- 2 atm (4 to 10 atm) lasted 70 +/- 16 seconds. Seventeen of 18 inflations were associated with a decrease in LV ejection fraction greater than 0.10. Mean LV ejection fraction decreased from 0.53 +/- 0.08 to 0.28 +/- 0.11 (p less than 0.0001). In contrast, there was pain in only 10 inflations and ST-segment changes in 7. LV dysfunction was associated with a minimal increase in end-diastolic volume (4 +/- 3%, p less than 0.003), and a major increase in relative end-systolic volume (69 +/- 43%, p less than 0.001). These data suggest that continuous monitoring of LV function with the VEST can sensitively detect silent ischemic decreases in LV function occurring during angioplasty, and provide further validation of the use of this technique for detecting silent myocardial ischemia."
-What is the relationship between primary sclerosing cholangitis and bone mineral density?,"The metabolic bone disease of primary sclerosing cholangitis. The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis."
-How do propofol and methohexital differ in their effects on left ventricular performance and hemodynamic parameters?,"Left ventricular performance during propofol or methohexital anesthesia: isotopic and invasive cardiac monitoring. Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect."
-How does the orientation of a lipid-water interface affect the chemical shift artifact in magnetic resonance imaging?,"Chemical shift artifact: dependence on shape and orientation of the lipid-water interface. On magnetic resonance images, chemical shift artifact (CSA) can be seen at a planar lipid-water interface oriented within the plane of the phase-encoding and section-select directions (ie, perpendicular to the frequency-encoding direction). Phantoms and a clinical case were used to demonstrate that when a lipid-water interface is curvilinear (eg, spherical) or planar but not oriented along the section-select direction, CSA may be absent or diminished. This effect can be seen at interfaces of normal structures (kidneys, bladder) as well as at interfaces with pathologic lesions such as lipid-containing dermoids. Not only is this effect dependent on section thickness, field of view, matrix size, and receiver bandwidth, but it is also strongly dependent on the orientation of the interface with respect to the section-select direction. Knowledge of the factors that can alter CSA is important since it is used to distinguish lipid-containing from nonlipid-containing structures of similar signal intensities."
-How does exercise echocardiography compare to electrocardiography as a screening test for coronary artery disease?,"Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography. We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease."
-How can nutrition therapy potentially help in managing immune dysfunction in critically ill patients?,Potential of parenteral and enteral nutrition in inflammation and immune dysfunction: a new challenge for dietitians [published erratum appears in J Am Diet Assoc 1991 Aug;91(8):913] Advances in the understanding of the interrelationship between immunology and nutrition indicate that immune dysfunction in critically ill patients is linked with nutrient deficiency and abnormal acute-phase response to illness. Immune dysfunction requires special nutrition therapy and metabolic support; immunoregulation by nutrition manipulation may lead to specific immunotherapies for defined groups of patients. The success of dietary strategies must be measured not only by metabolic indexes but also by effects on immune function. The health profession must combat immune dysfunction and inflammation for the sick and frail patients under its care.
-What were the main risk factors for cerebrovascular events in patients with acute myocardial infarction according to the GISSI trial?,"Cerebrovascular events after myocardial infarction: analysis of the GISSI trial. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). OBJECTIVES--To describe the epidemiology of cerebrovascular events in patients given or not given fibrinolytic treatment and to assess the prognostic implications and risk factors. DESIGN--Case series derived from the GISSI randomised trial. SETTING--176 coronary care units in Italy giving various levels of care. PATIENTS--5860 patients with acute myocardial infarction treated with 1.5 million units of intravenous streptokinase and 5852 patients not given fibrinolytic treatment. MAIN OUTCOME MEASURES--Cerebrovascular event, sex, age, blood pressure, history of previous infarct, site of infarction, and Killip class. RESULTS--99 of 11,712 patients (0.84%) had a cerebrovascular event. Older age, worse Killip class, and anterior location of infarction seemed to be risk factors for cerebrovascular events (40/3201 aged 65-75 v 42/7295 aged less than 65, odds ratio 2.18; 9/437 class 3 v 55/8277 class 1, 1.81; and 57/4878 anterior v 24/4013 posterior, 1.96). No significant difference was found in the rate of cerebrovascular events between patients treated with streptokinase and controls (45/5852 (0.92%) streptokinase v 54/5860 (0.77) control). More patients in the streptokinase group than in the control group had cerebrovascular events (especially haemorrhagic strokes) on day 0-1 after randomisation (27 streptokinase v 7, control), although this was balanced by late events in control patients (54 streptokinase v 45 control at one year). The mortality of patients who had a cerebrovascular event was higher than that of those who did not (47% (47/99) v 11.6% (1350/11,613]. CONCLUSIONS--Although the incidence of cerebrovascular events complicating myocardial infarction was low, they increased morbidity and mortality. Treatment with streptokinase did not significantly alter the incidence, but age and poor haemodynamic state were associated with an increased risk."
-"What surgical approach was used for treating orbital floor and rim fractures in this study, and what were its advantages?","Treatment of 813 zygoma-lateral orbital complex fractures. New aspects. A 10-year experience with surgical treatment of 813 zygomalateral orbital complex fractures is reviewed. Regardless of the type or severity of the fracture pattern, concomitant fractures of the orbital floor and rim were approached exclusively through the transconjunctival approach without a lateral canthotomy. The advantages of this approach compared with the subciliary access are the avoidance of a visible scar and markedly reduced incidence of postoperative lower eyelid complications such as ectropion and edema. Implants of lyophilized dura or cartilage and autogenous bone were used to reconstruct orbital floor defects. Malar asymmetry is a frequent complication of zygoma fractures resulting from inadequate three-dimensional reduction. Methods for accurate reduction and stabilization, indications for closed and open reduction, and management of the fractured infraorbital rim are emphasized. The indications for miniplates vs wire ligatures for the infraorbital rim are discussed. Long-term follow up and evaluation of the results with regard to the fracture pattern, complications, maxillary sinus dysfunction, and facial and orbital symmetry are presented."
-What was the key finding regarding lymphocyte response to group A haemolytic streptococcal antigens in patients with chronic plaque psoriasis?,"Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis. The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed."
-What is the prevalence of celiac or superior mesenteric artery stenoses among male veterans evaluated for peripheral vascular disease?,"Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients."
-What medical treatments were used for lichen sclerosus and squamous hyperplasia in this clinical study?,"Lichen sclerosus and squamous hyperplasia of the vulva. A clinical study of medical treatment. One hundred thirty-eight cases of nonneoplastic epithelial disorders of the vulva treated with medical therapy from 1984 to 1988 were evaluated at the University of Florence, Florence, Italy. The 67 cases of lichen sclerosus were treated with testosterone propionate or progesterone ointment for 32 weeks. The 31 cases of squamous hyperplasia were treated with corticosteroid ointment for 16 weeks. The 40 patients with lichen sclerosus associated with squamous hyperplasia were treated with corticosteroid ointment for 12 weeks and then with testosterone propionate ointment for another 20. To evaluate the efficacy of the treatments, the patients were examined before and after therapy. The evaluation took into account the symptoms and gross appearance of the lesions, which were given a score of 1-3. Considering all the cases evaluated, a total regression of symptoms occurred in 82 patients (59.4%), while a partial regression occurred in 37 (26.8%). Furthermore, there was a total regression of gross changes in 68 cases (49.3%) and a partial one in 43 (31.1%). The best results were obtained with squamous hyperplasia, which lichen sclerosus, alone or associated with squamous hyperplasia, yielded less successful results."
-What were the key findings of the study on the Duhamel operation for treating idiopathic megarectum and megacolon?,"Results of the Duhamel operation in the treatment of idiopathic megarectum and megacolon. The results of the Duhamel operation in patients with idiopathic megarectum and megacolon have been reviewed. Twenty patients (14 males, six females) underwent the Duhamel operation over a 17-year period for this condition. The mean age at operation was 25 years; the mean age of onset of constipation was 3 years; and the mean follow-up period was 4.5 years. All the resected colons were of enlarged diameter. There was agreement between the preoperative radiographs and the operative specimens with regard to which parts of the rectum and colon were dilated. Subjective feelings of well-being were generally improved by surgery, as was bowel frequency in ten patients. Soiling, straining, abdominal pain and distension were, however, common after operation. Early complications were also common and five patients required further surgery for constipation. The Duhamel operation for megarectum and megacolon is characterized by an improved sense of well-being and improved bowel frequency, but it is associated with the persistence of many symptoms and further surgery is often required."
-What are the key clinical considerations when managing cocaine-induced thrombocytopenia and hypertension during early pregnancy?,"Acute transient thrombocytopenia associated with cocaine abuse in pregnancy. A case is described of cocaine-induced severe transient thrombocytopenia associated with a hypertensive crisis at 21 weeks' gestation. Liver function tests and coagulation studies were all within normal ranges. Blood pressure was controlled with hydralazine. This clinical presentation, similar to severe preeclampsia, should be considered in the differential diagnosis of acute hypertension and low platelet count, especially in early gestations when preeclampsia is relatively rare. Unlike severe preeclampsia, for which active intervention and delivery are usually selected, cocaine-related hypertension-thrombocytopenia, especially in very premature gestations, may warrant conservative management."
-What treatment was found effective for adult patients with severe abdominal complications of Henoch-Schonlein purpura?,"Successful treatment of adult Henoch-Schonlein purpura with factor XIII concentrate. We report the cases of three adult patients with severe abdominal complications of Henoch-Schonlein purpura who had low activity of factor XIII during the acute phase of the disease. In all three cases, abdominal symptoms and purpura immediately responded to heat-treated, placenta-derived factor XIII concentrate. No adverse effects were experienced. Factor XIII concentrate replacement should be considered as the initial treatment for severe abdominal symptoms in adult Henoch-Schonlein purpura associated with a decreased level of factor XIII activity."
-What percentage of patients in the study experienced a decrease in arterial oxygen saturation levels during colonoscopy?,"An evaluation of multiple clinical variables for hypoxia during colonoscopy. One hundred consecutive patients undergoing routine colonoscopy were evaluated for changes in arterial oxygen saturation levels. All of the patients were monitored with the Nellcor N-200 pulse oximeter (Nellcor Incorporated) by finger probe and received supplemental oxygen when SaO2 levels decreased below 90 per cent. Forty patients demonstrated a decrease in SaO2 to less than 90 per cent after intravenous sedation but prior to colonoscopy, 14 patients demonstrated a decrease in SaO2 to less than 90 per cent during colonoscopy, and 46 patients maintained SaO2 levels greater than 90 per cent at all times. No statistical differences were found when these three groups were compared for age, body surface area, drug dosage, smoking history and a history of pre-existing hypertension, diabetes, arrhythmias, angina or myocardial infarction and pulmonary disease. These data indicate that all patients undergoing colonoscopy should be placed on supplemental oxygen. We further recommend continuous cardiac and pulse oximetry monitoring when available."
-What unusual cause of pneumoperitoneum was revealed in this case report?,"Recurrent pneumoperitoneum following vaginal insufflation. The authors report a case of a 24-year-old nulligravida woman who presented to the hospital with complaints of severe abdominal pain and radiographic evidence of pneumoperitoneum. She had two prior nondiagnostic laparotomies for similar complaints and radiographic findings. After a careful sexual history was taken the patient revealed that she had sexual intercourse preceding every similar episode including this one, during which her partner forcefully blew air into her vagina. Pneumoperitoneum associated with vaginal insufflation has been previously reported in two multigravida patients with and without anatomic abnormalities. When pneumoperitoneum is present in the absence of gastrointestinal symptoms or trauma, a meticulous sexual history should be made to avoid unnecessary laparotomies."
-What were the key findings of the study regarding the performance of the new radiopaque balloon-expandable coil stent in pigs?,"Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs. BACKGROUND. Intracoronary stents may be effective when used as ""bail-out"" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited."
-What unique characteristics were found in the promoter region of the human platelet-derived growth factor A-chain gene?,"Promoter region of the human platelet-derived growth factor A-chain gene. The platelet-derived growth factor (PDGF) A- and B-chain genes are widely expressed in mammalian tissues and their homodimeric gene products appear to regulate the autocrine growth of both normal and transformed cells. In this study, we analyzed the 5' flanking sequences of the human PDGF A-chain gene to seek elements important to regulating its transcription. The promoter region was exceptionally G + C-rich and contained a ""TATA box"" but no ""CAAT box."" The transcription start site was identified 845 base pairs 5' to the translation initiation site by S1 nuclease mapping and by primer extension. Both in vitro transcription and transient expression of the chloramphenicol acetyltransferase gene linked to the PDGF A-chain 5' flanking sequences established that the putative promoter region was active, and RNase H mapping established that the three characteristic mRNAs (1.9, 2.3, and 2.8 kilobases) used the same transcription start site, which was used in normal endothelial cells and in two human tumor cell lines that express high levels of A-chain transcripts. The results established an exceptionally G + C-rich promoter region and a single transcription start site active for each of the three mRNAs of the PDGF A-chain gene. DNA sites of potential importance in mediating the activation of the PDGF A-chain gene in normal cells and in transformed cell lines expressing high levels of PDGF A chain were identified."
-"What was the primary objective of the multicenter, prospective trial involving the Nd:YAG laser in treating endometriosis and pelvic adhesions?","Operative laparoscopy with the Nd:YAG laser in the treatment of endometriosis and pelvic adhesions. A multicenter, prospective trial was initiated to test the effectiveness and safety of the Nd:YAG laser equipped with artificial sapphire contact tips for the laparoscopic treatment of pelvic pain. Ninety-three women were enrolled in the study, 37 with endometriosis alone, 47 with endometriosis complicated by pelvic adhesions, and 9 women with adhesions alone. In over 90% of adhesions and 96% of endometriotic implants the Nd:YAG laser could be delivered to the site and be used to restore normal anatomy. The exception was deep bowel involvement with endometriosis, which was not treated. The majority of women had marked reduction or resolution of their symptoms for up to 12 months postoperatively. We conclude that the use of the Nd:YAG laser is an appropriate method to laparoscopically treat pelvic pain resulting from endometriosis or pelvic adhesions."
-What challenges do physicians face when treating patients who have used designer drugs?,"'Designer drugs'. Treating the damage caused by basement chemists. Use of ""designer drugs"" has created a new dilemma for physicians. Generally, it is possible to recognize symptoms and signs of intoxication that fit a specific class of substances, such as amphetamine-like effects for the phenylethylamines and opioid effects for the fentanyl analogues. Designer compounds have crossed these boundaries, and toxicology laboratories cannot readily identify them. For now, physicians must rely on clinical presentation and treat accordingly."
-What percentage of patients with high-energy midface fractures experienced orbital dislocations in the study?,"High-energy orbital dislocations: the possibility of traumatic hypertelorbitism. In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness."
-How does the combination of hemorrhage and intracranial hypertension affect thromboxane A2 production in the brain?,"Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2. BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock."
-How do oxygen-derived free radicals impact myocardial injury during coronary microvascular embolization?,"Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization BACKGROUND. Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization."
-What percentage of heart failure patients die suddenly before reaching New York Heart Association class IV symptoms?,"Genesis of arrhythmias in the failing heart and therapeutic implications. Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life."
-How did the perceived beliefs of others and attitudes impact regimen compliance among myocardial infarction patients two years after the intervention?,"Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens."
-What was the overall response rate of the high-dose cisplatin with dacarbazine and tamoxifen treatment in patients with metastatic melanoma?,"High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine."
-What are the key diagnostic modalities used for accurately classifying subtypes of lymphoma and leukemia?,"Cytologic diagnosis of leukemia and lymphoma. Values and limitations. The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented."
-How does left ventricular mass relate to symptoms and cardiac function in childhood dilated cardiomyopathy?,"Left ventricular mass in childhood dilated cardiomyopathy: a possible predictor for selection of patients for cardiac transplantation. To determine the relationship of left ventricular hypertrophy (as assessed by mass) to symptoms and cardiac function in chronic childhood dilated cardiomyopathy, 17 long-term survivors (12 asymptomatic, 5 symptomatic) were studied at a median follow-up of 6.25 years (1.25 to 16.8 years). Left ventricular mass, dimension, wall stress, and contractility (relationship between velocity of circumferential fiber shortening and end-systolic wall stress) were assessed by echocardiography. These data were compared to measurements at the onset of disease. At follow-up, mass decreased significantly from the onset in the asymptomatic patients but remained elevated in the symptomatic patients (101 +/- 35 gm/m2 to 54 +/- 12 gm/m2, p = 0.001; 122 +/- 55 gm/m2 to 198 +/- 115 gm/m2, p = 0.23, respectively). Shortening fraction and contractility were both significantly lower in the symptomatic group compared with the asymptomatic group at follow-up (shortening fraction = 21 +/- 7% vs 29 +/- 5%, p = 0.02; contractility = -0.24 +/- 0.14 circ/sec vs -0.05 +/- 0.11 circ/sec, p = 0.01). Follow-up wall stress was slightly higher in symptomatic patients compared with asymptomatic patients. Three symptomatic patients had progressive hypertrophy and either died or required transplantation. Higher left ventricular mass is associated with the presence of symptoms, depressed contractility, and slightly higher wall stress. Persistence or progression of hypertrophy may be a poor prognostic sign in survivors of childhood dilated cardiomyopathy. Measurement of mass may be useful to indicate the necessity for closer follow-up to select patients for cardiac transplantation before hemodynamic decompensation."
-How do immune complexes modulate granuloma formation in patients with chronic schistosomiasis?,"Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins."
-How did the patient's Cushing's disease potentially contribute to the development of cutaneous alternariosis?,"Cushing's disease and cutaneous alternariosis. Alternaria species are common plant pathogens, but a rare cause of human infection. We present a patient with cutaneous alternariosis that revealed a relapse of an old case of Cushing's disease. Immunosuppression following the excessive glucocorticoid production seemed to contribute to the development of dermatosis. We also present a review of the literature on the association of Cushing's disease and cutaneous alternariosis. Our case is unique because the ketoconazole therapy that we used was successful in the treatment of both diseases."
-What surgical technique was used to successfully treat the esophagocutaneous fistula in this case report?,"Esophagocutaneous fistula after anterior cervical spine surgery and successful treatment using a sternocleidomastoid muscle flap. A case report. An esophagocutaneous fistula following anterior cervical fusion is rare. A 61-year-old man had cervical myelopathy because of ossification of the posterior longitudinal ligament of the cervical spine. Anterior decompression of the cervical spine and anterior fusion with strut bone grafting were performed. A second anterior fusion was done because the graft was dislodged after the patient fell out of bed one month after surgery. An esophagocutaneous fistula occurred three months after the second anterior surgery. One of the causes of this esophagocutaneous fistula was considered to be a pressure necrosis of the esophagus because of to projection of the bone graft. Conservative treatment, which consisted of wound drainage and intravenous administration of antibiotics, was tried but was unsuccessful. A good result was achieved by cancellous bone grafting, closure of the esophageal fistula, and transposition of a sternocleidomastoid muscle flap to the interspace between the esophagus and the cervical spine."
-How does diazepam binding inhibitor (DBI) affect mitochondrial steroidogenesis in Y-1 adrenocortical and MA-10 Leydig cell lines?,"Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. A recognition site for benzodiazepines structurally different from that linked to various gamma-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide diazepam binding inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-1 adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17-50)] and octadecaneuropeptide [DBI-(33-50)]. When DBI purified from rat brain was added to mitochondria prepared from Y-1 and MA-10 cell lines, it increased the rates of pregnenolone formation in a dose-related manner. In both cell lines, maximal stimulation (3-fold) of mitochondrial steroidogenesis was obtained with 0.33 microM DBI, with an EC50 of approximately 0.1 microM. However, DBI concentrations higher than 1 microM caused a smaller increase in pregnenolone formation. Flunitrazepam, a benzodiazepine that binds with high nanomolar affinity to MBR, was recently shown to act as an antagonist of ACTH and LH/hCG-induced steroidogenesis and was found in the present studies to inhibit DBI-stimulated mitochondrial steroidogenesis. During the incubation with mitochondria, DBI was partially processed to different peptide fragments, including octadecaneuropeptide and TTN. To determine whether DBI processing products influence mitochondrial steroid biosynthesis, several DBI fragments and other peptides structurally unrelated to DBI were tested. Among these, only TTN stimulated mitochondrial steroid synthesis in a dose-dependent manner similar to DBI."
-What are the advantages of centrally acting sympatholytic agents in managing hypertension?,"Use of centrally acting sympatholytic agents in the management of hypertension. Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction."
-What was the main finding of the Medical Research Council Vitamin Study regarding the prevention of neural tube defects?,"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid."
-What are the key findings of the study regarding the distribution of neurofilament protein epitopes in cortical Lewy bodies?,"Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (Mr) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport."
-How can sexually transmitted diseases impact the reproductive health of women and their offspring?,"Preventing fetal damage from sexually transmitted diseases. The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death. An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially. Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well. Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections. Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections."
-What are the two main groups of drugs used in migraine therapy?,"Pharmacology of antimigraine drugs. The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT1-like receptors, beta-adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT1-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine."
-What are the most practical and useful techniques for diagnosing perivalvular extension of infection in patients with infectious endocarditis?,"Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review."
-What are the primary aims of treatment for patients with heart failure?,"Assessing drugs for the treatment of heart failure. The aims of treatment in patients with heart failure, as with any other condition, are to relieve symptoms and prolong life. A secondary objective is to do so at the lowest possible economic cost. When treatment of the cause of heart failure is possible--which usually means some form of surgery, but could include treatment of a primary disease, such as thyrotoxicosis--then this is obviously the treatment of choice. In patients for whom there is no such definitive treatment, a wide and increasing variety of drugs are available. When new antifailure drugs are to be developed there are therefore two problems: first, to ensure that they are more effective than placebo treatment, and second, to compare them with existing drugs. Both of these tests can present ethical difficulties, for it is unreasonable to withhold established effective treatment in order to conduct a placebo-controlled trial, and when drugs are being compared, it is unlikely that any new medication will be dramatically superior to an old one. The more effective the treatments already available, the harder it becomes to evaluate a new drug."
-How quickly do motor units diminish in muscles affected by amyotrophic lateral sclerosis (ALS) during the first year of disease progression?,"The extent and time course of motoneuron involvement in amyotrophic lateral sclerosis. The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction."
-How does prolonged hypoxia affect prostacyclin production and adenylate cyclase activity in rat pulmonary arteries?,"Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat. Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta-adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia."
-How was the treadmill score calculated in this study of outpatients with suspected coronary artery disease?,"Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease BACKGROUND. The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS. We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS. Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS. The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment."
-How did iodine-131-3F8 radioimmunoscintigraphy compare to other diagnostic methods in detecting neuroblastoma sites?,"Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection."
-How does the number of metastatic lymph nodes affect the 5-year survival rate in patients with gastric cancer?,"Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer. To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer."
-How does the biopsychosocial model fall short in understanding the role of culture in the experience of illness?,"Culture, illness, and the biopsychosocial model. Family medicine has appropriated the biopsychosocial model as a conceptualization of the systemic interrelationships among the biological, the psychological, and the social in health and illness. For all its strengths, it is questionable whether this model adequately depicts the centrality of culture to the human experience of illness. Culture (as meaning system) is not an optional factor that only sometimes influences health and illness; it is prerequisite for all meaningful human experience, including that of being ill. A more adequate model of the relationship between culture and illness would demonstrate the preeminence of culture in the experience of illness among all people, not just members of ""exotic"" cultures; would view healers as well as patients as dwellers in culture; would incorporate the role of culture as meaning system in linking body, mind, and world; and would promote the significance of the cultural context as a resource for research and therapy."
-How did the levels of von Willebrand factor (vWF) and factor VIII (FVIII) change in renal transplant recipients during the first 4 months after transplantation?,"von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients. In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment."
-What are the key clinical manifestations of liver involvement in Alpers disease?,"Liver involvement in Alpers disease. Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction."
-How does ischemia affect the density and regeneration of nerve fibers?,"Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration."
-How do endogenous free radical scavengers impact gastric ulcer formation in the experimental rat model?,"The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model. The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation."
-What was the overall hospital mortality rate in the urokinase and heparin groups after 16 days in this study of acute myocardial infarction patients?,"Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar."
-What language-related difficulties were observed in patients with progressive supranuclear palsy?,"Language functions in progressive supranuclear palsy. Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy."
-How does the growth cycle of malaria parasites in erythrocytes contribute to the periodic nature of malaria fever?,"Periodic and chaotic host-parasite interactions in human malaria. It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite."
-How did hypotensive epidural anaesthesia impact the quality of cement-bone interface in total hip arthroplasty?,"Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. We selected 20 matched pairs of patients who had had total hip arthroplasty by the same surgeon using the same cemented technique. Matching was by age, sex, height, weight and diagnosis. One of each pair had received hypotensive epidural anaesthesia, with less than 300 ml blood loss: the other had normotensive general anaesthesia with more than 500 ml of blood loss. Early postoperative radiographs were evaluated independently by three blinded observers, using a scoring criteria which assessed the quality of the cement-bone interface. The results showed that patients who had received epidural anaesthesia had significantly better radiographic scores (p less than 0.02). Our findings suggest that hypotensive anaesthesia facilitates penetration of cement into bone."
-What echocardiographic measurements were found to be risk factors for perioperative death in infants with isolated aortic valve stenosis?,"Echocardiographic estimation of critical left ventricular size in infants with isolated aortic valve stenosis. With the current trend to performing surgical valvotomy for infantile aortic stenosis without cardiac catheterization, there is a need to develop echocardiographic criteria for adequacy of left ventricular size. The echocardiograms and catheterization data of all 25 infants less than 3 months of age undergoing aortic valvotomy for isolated aortic valve stenosis from September 1980 through July 1990 were reviewed. Significant differences (p less than 0.05) between the survivors and nonsurvivors were noted for age at operation (30 +/- 28 vs. 3 +/- 1.5 days), mitral valve diameter (10.1 +/- 1.7 vs. 7.7 +/- 1.5 mm), left ventricular end-diastolic dimension (18.4 +/- 6.4 vs. 11.4 +/- 3 mm), left atrial dimensions (15.3 +/- 3.8 vs. 10 +/- 2.4 mm), left ventricular cross-sectional area on the parasternal long-axis echocardiogram (4 +/- 1.9 vs. 2 +/- 1.9 cm2) and angiographically determined left ventricular end-diastolic volume (43 +/- 23 vs. 11 +/- 5 ml/m2). There was no difference with respect to patient weight, body surface area, aortic root dimension or left ventricular ejection fraction. Left ventricular cross-sectional area less than 2 cm2 as measured on the parasternal long-axis echocardiogram was found in 5 of 7 nonsurvivors and 0 of 12 survivors, making this a risk factor for perioperative death (p less than 0.05). Left ventricular end-diastolic dimension less than 13 mm was found in 5 of 6 nonsurvivors and 2 of 17 survivors, making this another risk factor for early mortality (p less than 0.05)."
-What medical condition did the 27-year-old man with osteogenesis imperfecta develop after sustaining a femoral fracture?,Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.
-What were the acute hemodynamic effects of intravenous nicardipine in patients with a healed myocardial infarction?,"Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure. Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation."
-What is bioelectric impedance analysis and how was it used in this study of cirrhotic patients?,"Bioelectric impedance analysis: experience with male patients with cirrhosis. Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of ""compartmentalized"" fluid in the abdomen."
-How did the MR receptor imaging with asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide differ in normal liver tissue versus hepatocellular carcinoma (HCC) tissue?,"Experimental hepatocellular carcinoma: MR receptor imaging. Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules."
-What were the key findings of the study regarding the effects of dexamethasone in treating bacterial meningitis in infants and children?,"The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. BACKGROUND. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San Jose, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis."
-How does collateral circulation impact left ventricular function in patients with total occlusion of the left anterior descending coronary artery?,"Evolution of myocardial ischemia and left ventricular function in patients with angina pectoris without myocardial infarction and total occlusion of the left anterior descending coronary artery and collaterals from other coronary arteries. Repeated episodes of myocardial ischemia might lead to progressive impairment of left ventricular (LV) function. This radionuclide study assessed myocardial ischemia and LV function several years after documented coronary occlusion without myocardial infarction. Over 5 years, 24 consecutive patients, who underwent cardiac catheterization for angina pectoris without myocardial infarction, had isolated total occlusion of the left anterior descending coronary artery with well-developed collateral vessels. Five patients were successfully treated by coronary bypass grafting and 3 by coronary angioplasty. Among the 16 medically treated patients, 1 was lost to follow-up and 1 died (extracardiac death). The mean (+/- standard deviation) follow-up (14 patients) was 48 +/- 15 months. At follow-up, 8 patients still had clinical chest pain, 11 received antianginal therapy, 4 patients had no stress ischemia and the other 10 had greater than or equal to 1 sign of stress ischemia. All patients had a normal LV ejection fraction at rest (mean 60 +/- 3%; range 55 to 65%). Collateral circulation preserves LV function at the time of occlusion and, in some cases, prevents the development of myocardial ischemia; in patients with persisting myocardial ischemia after well-collateralized coronary occlusion, LV function is not impaired at long-term follow-up."
-What was the median survival time for melanoma patients with metastases to two or more lymph node areas?,"The prognosis of melanoma patients with metastases to two or more lymph node areas. The prognosis of melanoma patients who present with metastatic involvement of two or more noncontiguous lymph node regions before the detection of extranodal metastases has not been previously reported. We identified 21 patients with metastatic melanoma in at least two nodal basins in a review of 175 patients with melanoma undergoing lymphadenectomy at the National Cancer Institute. The median survival time of these patients was 46 months, with 55%, 27%, and 17% of the patients alive 2, 5, and 10 years, respectively, after the second lymphadenectomy. Because the prognosis of melanoma patients with metastases to two or more regional nodal areas appears equivalent to that of patients with metastatic involvement of only one regional node site, lymphadenectomy of the involved groups should be performed with therapeutically curative intent."
-What is the Currarino triad and what are its key characteristics in the described family?,"Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality."
-What was the effect of leuprolide acetate depot treatment on uterine volume in women with leiomyomata uteri?,"Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms."
-How does the presence of bile affect bacterial growth and clearance in Escherichia coli peritonitis?,"Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis. The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis."
-What are the main side effects observed in the low-dose recombinant interferon-gamma study?,"Recombinant interferon-gamma (rIFN-gamma) in dermatology. This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients."
-What is the Currarino triad and what are its key characteristics in the described family?,"Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality."
-What multimodality treatment approach was used for patients with malignant pleural mesothelioma in this study?,"Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma. Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach."
-What are the three distinct cell types observed in the adamantinoid basal cell carcinoma during the ultrastructural study?,"Adamantinoid basal cell carcinoma. An ultrastructural study. We describe an adamantinoid basal cell carcinoma that has developed in the mucocutaneous border of the upper lip. An ultrastructural study disclosed three types of cells that were morphologically distinct in the tumor nest. Cells of the first type were basically the same as those of ordinary basal cell carcinoma. Cells of the second type showed varying degrees of cytoplasmic content loss in a worm-eaten pattern and seemed to consist of degenerating cells. Cells of the third type possessed a well-developed rough endoplasmic reticulum filled with medium electron-dense fine substance, which was also seen in the extracellular space. In relationship with the histochemical findings, and based on the histogenesis of adamantinoid basal cell carcinoma, we propose that subpopulations of tumor cells undergo spontaneous degeneration and that the spaces of such disappearing cells are refilled with products containing glycosaminoglycans secreted by another subpopulation of the tumor cells."
-What imaging techniques were used to diagnose choledochal cyst and biliary atresia in the neonates?,"Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management."
-How does the HBx gene of hepatitis B virus contribute to liver cancer development in transgenic mice?,"HBx gene of hepatitis B virus induces liver cancer in transgenic mice. The exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility of placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer."
-What is the significance of bacterial translocation in trauma patients according to the study?,"Bacterial translocation in trauma patients. Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients."
-What were the main objectives of the study on optical properties of myocardium?,"Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength. Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation."
-How does the presence or absence of an androgen receptor affect blood pressure in hybrid male rats?,"Androgen receptor and the testes influence hypertension in a hybrid rat model. The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males."
-What was the primary aim of the study investigating total parenteral nutrition in patients with head and neck cancers?,"Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers. Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration."
-What is the importance of obtaining a comprehensive patient history during preoperative evaluation of a cardiac patient undergoing non-cardiac surgery?,"Preoperative evaluation of the cardiac patient for noncardiac surgery. In summary, obtaining a comprehensive patient history is a critical part of the diagnostic and risk stratification process of the patient with cardiac disease undergoing non-cardiac surgery. Many of the factors associated with perioperative cardiac morbidity are treatable and early and aggressive management appears to have beneficial effects on morbidity and mortality rates."
-What is the rare medical condition described in this case report involving a plasmacytoma and superior vena cava syndrome?,"Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described."
-What is the rare cause of left-sided portal hypertension described in this medical case report?,"Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature."
-How does the accumulation of PrPSc in different brain regions correlate with scrapie infectivity in Syrian hamsters?,"Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases."
-What is the rarity and pattern of association between squamous cell carcinoma of the upper aerodigestive tract and well-differentiated thyroid carcinomas?,"Squamous cell carcinoma of the upper aerodigestive tract associated with well-differentiated carcinoma of the thyroid gland. The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer."
-What are the key endogenous mediators involved in gastroprotection according to the review?,"Mechanisms of gastric mucosal injury and protection. This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy-dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed."
-What percentage of patients in the study had at least one preoperative risk factor?,"Comorbidities and perioperative complications among patients with surgically treated benign prostatic hyperplasia. We address the question of whether or not age and comorbidity are related to intra- and postoperative complications after a transurethral resection. The data are derived from a retrospective, population-based study conducted in Hagen, Germany, which included all patients with an initial prostatectomy for benign prostatic hyperplasia (N = 621) during the five-year period 1984-1988. Seventy-seven percent of the patients had at least one of the following preoperative risk factors: heart disease, hypertension, smoking, chronic obstructive lung disease, and diabetes. There was no intraoperative death. The risk of intraoperative circulatory complications was found to be related to age only for patients without a history of heart diseases or hypertension. The incidence of major complications was 3.1 percent and was significantly higher in the oldest age group. Three patients (0.54%) died postoperatively in the hospital. Infections were the most frequent postoperative complications. The relationship of age and overall postoperative complications was not statistically significant either for patients with (p = 0.121) or without any comorbidity (p = 0.651). Based on this study it seems reasonable to conclude that age is not a clinically relevant risk factor for perioperative complications in patients who have a transurethral resection for benign prostatic hyperplasia."
-"What is the purpose of using a free gastric mucosal flap with microvascular transfer in the reconstruction of malignant lesions in the oral cavity, base of tongue, and oropharynx?","Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered."
-What are the key clinical characteristics of the dominantly inherited mitochondrial myopathy described in this study?,"Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies. We studied a large family with a dominantly inherited mitochondrial myopathy characterized by progressive external ophthalmoplegia, dysphagia, cataract, lactic acidosis, exercise intolerance, and early death. Morphologic studies of muscle biopsies suggested mitochondrial heteroplasmy and revealed ragged-red fibers and decreased histochemical reactions for cytochrome c oxidase and succinate dehydrogenase. Biochemistry showed a partial defect of cytochrome c oxidase and a mild generalized reduction of other mitochondrial enzymes requiring mitochondrial DNA-encoded subunits. Southern blot analysis and PCR amplification showed mitochondrial DNA deletions in muscle of all affected members, but not in lymphocytes or fibroblasts, suggesting a tissue-specific distribution. Deletions were multiple and seemed to increase with time and to correlate with the severity of the disease."
-What correlation was found between periventricular lesions on MRI and the severity of white matter changes in elderly patients?,"Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Magnetic resonance imaging (MRI) was performed postmortem on the brains of 40 patients aged over 60 yrs who had died from causes other than brain disease. Periventricular lesions of increased signal intensity on T2-weighted images, graded as moderate or severe, were found in 10% of the patients in the age group between 60 and 69 yrs, and in 50% between 80 and 89 yrs. Macroscopic and microscopic whole-brain sections were studied in 19 brain specimens (8 with normal white matter, 4 with moderate lesions and 7 with severe lesions of the white matter on MRI). The presence or absence of periventricular lesions on MRI correlated well with the severity of demyelination and astrocytic gliosis. Demyelination was always associated with an increased ratio between wall thickness and external diameter of arterioles (up to 150 microns). A variable degree of axonal loss in Bodian-stained sections was present in the white matter of all brains with demyelination. Dilated perivascular spaces were found and studied morphometrically in 9 brain specimens; their presence correlated strongly with corrected brain weight, but incompletely with demyelination and arteriolosclerosis. Our findings suggest that arteriolosclerosis is the primary factor in the pathogenesis of diffuse white matter lesions in the elderly. This is soon followed by demyelination and loss of axons, and only later by dilatation of perivascular spaces."
-What are the key considerations in sphincter-sparing surgery for patients with ulcerative colitis or rectal tumors?,"Sphincter-sparing surgery. Since World War II, a variety of technical innovations have been introduced to preserve the anal sphincter in patients with chronic ulcerative colitis or tumors of the rectum. Studies of anorectal physiology have yielded guidelines for preserving continence and minimizing morbidity. For example, preservation of the anal rectal angle is essential; the rectal mucosa can be removed without impairing neural mechanisms; construction of a reservoir increases rectal compliance. Following these guidelines, surgeons have introduced new techniques and applications benefiting a larger and more varied patient population. Some technical problems remain, however, and patient selection criteria for restorative rectal surgery need to be refined."
-What was the mean time from symptom onset to diagnosis for patients with an identifiable syndrome in this study of adrenal tumors?,"Efficient management of adrenal tumors. A retrospective analysis was carried out on 121 patients with primary adrenal tumors operated on at 2 Vancouver hospitals between the years 1970 and 1990. The purpose of the study was to identify discriminating factors between the various diagnoses in order to minimize both the time and the cost of the investigative process. There were 57 cortical adenomas, 35 pheochromocytomas, 15 carcinomas, 8 cases of cortical hyperplasia, and 6 miscellaneous tumors. The mean time from the onset of symptoms to diagnosis of those patients presenting with an identifiable syndrome was 48.3 months. Those with a hypertensive syndrome presented significantly later than those with Cushing's syndrome (57.7 months versus 22.8 months, p less than 0.01). There was a significant delay in diagnosis in those patients with hypertension on the basis of an aldosteronoma as compared with those with hypertension secondary to a pheochromocytoma (75.4 months versus 36.1 months, p = 0.02). Cortical carcinomas were significantly larger than benign cortical tumors (12.7 cm versus 5.5 cm). No malignant neoplasm measured less than 5 cm in diameter. Diagnostic sensitivity for intravenous pyelogram (IVP) was 59%, for ultrasound 71%, for venography 50%, for meta-iodobenzylguanidine (MIGB) (pheochromocytoma only) 80%, and for angiography 70%. However, for those patients with adrenal carcinomas, angiography was positive in 100% of cases. Computed tomography (CT) was the most sensitive localizing investigation with a sensitivity of 98%. While other localizing techniques were less sensitive than CT, they may still play a useful role in selected situations. Factors causing delay in diagnosis and the role of the various imaging modalities are discussed."
-What were the key findings of the Jamaican study regarding nutritional supplementation and growth in stunted children?,"Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study. The benefits of nutritional supplementation, with or without psychosocial stimulation, on the growth of stunted children were evaluated. Children aged 9-24 mo with lengths less than -2 SD of the National Center for Health Statistics references (n = 129) were randomly assigned to four groups: control, nutritional supplementation, stimulation, and both interventions. A fifth group with lengths greater than -1 SD was also enrolled. Length, weight, head and arm circumferences, and triceps and subscapular skinfold thicknesses were measured on enrollment and 6 and 12 mo later. Multiple-regression analysis was used to determine the effects of the interventions in which age, sex, initial status, initial dietary intake, and several socioeconomic variables were controlled for. Stimulation had no effect on growth and there was no interaction between the interventions. After 12 mo supplemented children had significantly increased length, weight, and head circumference (all P less than 0.01). The effects of supplementation were not cumulative but occurred in the first 6 mo."
-How is gastric cancer different during pregnancy compared to other periods of a woman's life?,"Gastric carcinoma presenting as an exacerbation of ulcers during pregnancy. A case report. Gastric cancer is unusual during pregnancy. Also, because of the physiologic changes that occur with pregnancy, it is rare to see a worsening of peptic ulcers during pregnancy. A patient with an exacerbation of peptic ulcers presented with gastric carcinoma during pregnancy."
-What are the key diagnostic and treatment strategies for stress fractures in athletes?,"Stress fractures in athletes. How to spot this underdiagnosed injury. Stress fractures are an increasingly common injury in competitive athletes, especially runners. Amenorrheic athletes are at particularly high risk. A radionuclide bone scan should be considered when the index of suspicion for stress fracture is high. Plain radiographs are of little use in establishing the diagnosis in the early stages of the injury. Early diagnosis and prompt institution of conservative therapy allow for a favorable outcome in most cases. Avoidance of or reduced participation in the inciting activity is important for pain control. Certain stress fractures, such as those involving the femoral neck, should be monitored closely and treated aggressively with internal fixation when conservative measures fail. Runners who have exercise-induced amenorrhea should be advised to decrease their training intensity to a level where menses resume. Cyclic therapy with conjugated estrogens and progesterone should also be considered, as should daily calcium supplementation."
-What were the main causes of death among patients treated with human pituitary growth hormone in this study?,"Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom OBJECTIVE--To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN--A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS--All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES--Death or development of neoplasia. RESULTS--110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS--Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review."
-What differences were observed in neutralizing antibody development among patients treated with different interferon-alpha preparations?,"Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1."
-What is the significance of Glial fibrillary acidic protein (GFAP) expression in pleomorphic adenomas and chordomas?,"Glial fibrillary acidic protein expression in pleomorphic adenoma, chordoma, and astrocytoma. A comparison of three antibodies. Glial fibrillary acidic protein (GFAP) is a major constituent of glial cytoplasmic intermediate filaments. Glial fibrillary acidic protein expression has been accepted as a marker of astroglial differentiation or origin. However, GFAP expression has been demonstrated in a variety of normal and neoplastic tissues outside the central nervous system, including pleomorphic adenomas, chordomas, bone, and cartilage. It has been postulated that coexpression of GFAP and vimentin in neoplastic myoepithelial cells in pleomorphic adenomas reflects early chondroid differentiation. Glial fibrillary acidic protein expression in chondromyxoid and chordoid tumors was studied in formaldehyde solution-fixed, paraffin-embedded sections of 20 pleomorphic adenomas and 10 chordomas by the immunoperoxidase method with the use of commercially available monoclonal (n = 2) and polyclonal (n = 1) antibodies. All pleomorphic adenomas and chordomas demonstrated expression of GFAP with the use of the polyclonal antibody (Biomeda Corp [Foster City, Calif]). Variable expression of GFAP was present in 90% (18/20) and 70% (14/20) of pleomorphic adenomas, and in 20% (2/10) and 0% of chordomas, with the use of the two monoclonal preparations (Dakopatts [Glostrup, Denmark] and BioGenex Laboratories [San Ramon, Calif]), respectively. Normal brain tissue and eight astrocytomas were used as ""controls"" to compare staining intensity and quality between the polyclonal and monoclonal anti-GFAP antibodies. Glial fibrillary acidic protein positivity with the polyclonal antibody was more intense than that with either monoclonal antibody despite similar (congruent) distributions of tumor cell types that were stained in control brain and astrocytoma tissues. The GFAP polyclonal antibody was more frequently immunoreactive than the monoclonal antibodies, particularly in cells that exhibited chondroid differentiation. These findings may have practical application in surgical pathology."
-What was the primary purpose of the study on endovascular stents in congenital heart disease?,"Use of endovascular stents in congenital heart disease. BACKGROUND. Balloon expandable intravascular stents have been used to support vessel walls in coronary and peripheral arteries in adults. The purpose of this study was to examine the efficacy and safety of these stents in the treatment of congenital heart disease. METHODS AND RESULTS. Forty-five stents were placed in 30 patients, who were 0.2-30.2 years old (weight, 3.5-76 kg). Patients with areas of stenosis that were difficult to approach surgically were chosen. Stents were mounted over balloons and placed by standard catheterization techniques. Twenty-three patients had branch pulmonary artery stenosis. Thirty-six stents were placed successfully and had reduced pressure gradients from 50.6 +/- 24 to 15.9 +/- 13.4 mm Hg. Five patients had stents placed after atrial surgery: three in obstructed Fontan repairs, one at the superior vena cava-right atrial junction after sinus venous defect repair, and one at the site of a Glenn shunt. Atrial stents reduced pressure gradients from 9.8 +/- 8.2 to 2.0 +/- 2.6 mm Hg. One patient had a stent placed in the descending aorta after coarctation dilation, and the pressure gradient was reduced from 50 to 25 mm Hg. One patient had pulmonary vein dilation with stent placement. Two stents migrated at the time of placement; one required surgical removal, and one was anchored in place by balloon dilation. One patient died within 24 hours of catheterization because of thrombus obstruction of the Fontan repair. Nine patients have undergone recatheterization. All stented vessels have remained at the same caliber as at original stent placement. CONCLUSIONS. We conclude that balloon expandable stents are useful in selected postoperative stenoses in congenital heart disease."
-What potential complication can tissue plasminogen activator (t-PA) cause during treatment of acute myocardial infarction?,"Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable."
-What percentage of patients with clinical stage A1 and A2 prostate cancer were found to have no cancer during radical prostatectomy?,"Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome. Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice."
-What is the overall mortality rate for patients with group B streptococcal endocarditis of the tricuspid valve?,"Group B streptococcal endocarditis of tricuspid valve. We report three cases of group B streptococcal endocarditis of the tricuspid valve. Two patients were intravenous drug abusers. In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve. Half of the patients were intravenous drug abusers. Four of the other patients had underlying conditions. All patients were treated with a penicillin with or without an aminoglycoside. Three patients underwent tricuspid valve surgery. The overall mortality was 20 percent. Both patients who died received medical therapy only."
-What diagnostic technique ultimately revealed the presence of a myocardial abscess in this case of aortic valve endocarditis?,"Coronary artery narrowing due to extrinsic compression by myocardial abscess. A case of aortic valve endocarditis complicated by perivalvular abscess extending into myocardium is presented. Echocardiography and aortography failed to detect the abscess, but coronary angiography revealed its presence by extrinsic compression of left anterior descending and diagonal arteries. Morphological features of this rare cause for coronary narrowing are described."
-What preoperative evaluations are recommended for diagnosing urethral diverticulum and stress incontinence in female patients?,"Surgical treatment of concomitant urethral diverticulum and stress incontinence. Urinary incontinence is frequently associated with a urethral diverticulum in female patients. Preoperative evaluation including a thorough history and physical examination, voiding cystourethrogram, urethroscopy, and urodynamic studies can diagnose both the urethral diverticulum and any concomitant bladder-urethral dysfunction. Preoperative recognition of stress urinary incontinence or patients at risk for this problem postoperatively permits effective treatment with concomitant transvaginal bladder neck suspension and urethral diverticulectomy."
-What surgical technique was used to treat chronic infected hip arthroplasty wounds in this study?,"Treatment of chronic infected hip arthroplasty wounds by radical debridement and obliteration with pedicled and free muscle flaps. Nine patients with extensive wounds of the hip joint due to chronic infection following total hip arthroplasty or internal fixation of fractures of the femoral head and neck have been treated by serial radical debridements to remove infected bone, contaminated remnants of bone cement, and the surrounding fibrotic soft tissues. The resultant deep cavity extending down to the acetabulum has then been obliterated with either pedicled muscle flaps or free muscle flaps. Subcutaneous or transpelvic transposition of rectus abdominis muscle flaps is preferred for smaller defects, but only the free latissimus dorsi muscle flap provides sufficient volume of tissue to obliterate the more extensive hip defects. Systemic antibiotics have been continued only for a short-term course of 14 days postoperatively. There has been no recurrence of infection, with follow-up ranging between 6 months and 3 1/4 years. One patient has undergone reimplantation of a second custom hip prosthesis into the vascularized bed of a free latissimus dorsi muscle flap."
-What technique was used to treat large bony defects after cystectomy in this study?,A modified technique for obliteration of large bony defects after cystectomy. Thirteen cysts treated by enucleation followed by collapsing an osteoperiosteal flap to eliminate dead space are presented. Four of the cysts were dentigerous and nine were radicular. The bony defects ranged in size from 3 to 7 cm in greatest dimension. Healing by primary intention occurred in all cases. This method has been found to be successful in the obliteration of large bony defects after cystectomy.
-"What were the antibody response levels for pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens in infants aged 3 to 8 months and children aged 24 to 30 months after the fourth vaccine dose?","A comparative trial of the reactogenicity and immunogenicity of Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids. Outcome in 3- to 8-month-old infants, 9- to 23-month-old infants and children, and 24- to 30-month-old children. The reactogenicity and immunogenicity of the Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids were compared in 139 infants aged 3 to 8 months, 60 infants and children aged 9 to 23 months, and 99 children aged 24 to 30 months. Good antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens occurred in all age groups after both the third and fourth doses. After the fourth (booster) dose, the mean antibody values in initially seronegative infants vaccinated at 3 to 8 months of age were as follows: anti-PT, 67.8 enzyme-linked immunosorbent assay units (EU) per milliliter; anti-FHA, 149.5 EU/mL; the agglutinin titer was 125.6. The values in initially seronegative children vaccinated at 24 to 30 months of age were as follows: anti-PT, 92.9 EU/mL; anti-FHA, 251.7 EU/mL; the agglutinin titer was 275.8. Reactions following immunization were minimal. Except for drowsiness after the first dose in infants, there were no clinically significant differences in reactions between infants and older children. The findings in this study coupled with the recent demonstration of efficacy of this vaccine in 2-year-old children supports the recent Japanese recommendation to lower the age of immunization with acellular pertussis vaccine combined with tetanus and diphtheria toxoids to 3 months."
-What is a ganglioglioma and how can it cause hemifacial spasm in an infant?,"Hemifacial spasm in an infant due to fourth ventricular ganglioglioma. Case report. The case of an infant is reported in which hemifacial spasm due to a ganglioglioma of the fourth ventricle was relieved by surgery. Previously described causes of hemifacial spasm are summarized, and the relevance of this case to theories on the pathogenesis of the condition is discussed."
-What was the key finding regarding the relationship between spinal cord ischemia duration and neurologic outcomes in the rabbit study?,"The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia."
-What were the long-term surgical outcomes for patients who underwent lateral cranial base surgery between 1970 and 1987?,"Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis."
-How does gastric intramucosal pH relate to mortality rates in critically ill patients?,"Gastric mucosal pH as a prognostic index of mortality in critically ill patients. OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU."
-What percentage of patients showed allelic loss at the retinoblastoma (RB) locus in their ovarian tumor tissues?,"Allele loss at the retinoblastoma locus in human ovarian cancer. To gain a broad spectrum on allelic loss of specific loci in ovarian tumors, we initially examined DNA from 23 pairs of ovarian tumors and matched peripheral blood lymphocyte samples from the same patients, using 27 polymorphic DNA markers distributed on 13 chromosomes. Significant high frequency of allelic deletion (22%-44%) at chromosome 13 loci (D13S31, D13S32, D13S33, and D13S34) at bands q12-q34 was observed in tumor tissues. These results led us to investigate the loss of heterozygosity at the retinoblastoma (RB) locus in ovarian tumors, because the RB gene is a tumor-suppressor gene located at 13q14. Analysis of the variable number of tandem repeat sequence polymorphism in intron 20 in the RB gene revealed that 6 (30%) of 20 patients with informative samples showed allelic loss at the RB locus in their tumor tissues. This loss, of relatively high frequency, suggests that the RB gene, or a closely linked gene, seems to be involved in the development of ovarian cancer."
-What were the most frequently reported prodromal symptoms in soldiers who experienced exertional sudden death?,"Exertional sudden death in soldiers. To address the problem of a significant rise in the incidence of exertional sudden death worldwide, the medical records and necropsy reports of all deaths that occurred in the Israel Defence Forces (IDF) during 1974-1986 were scrutinized. Twenty male soldiers, aged 18-29 yr, died suddenly and unexpectedly within 24 h of strenuous exercise. Necropsy results, available for 90% of the subjects, included underlying cardiac disease in 50% and noncardiac causes of death in 33.3%; the cause of death was unidentifiable in 16.7% of the subjects. Prodromal symptoms in 70% of the subjects are presented as a main focus of this investigation. The most frequently reported symptom was exertional or nonexertional syncope in 40% of the subjects. Chest pain, acute gastrointestinal symptoms, or febrile disease were reported in 30% of the cases. The findings of this research suggest that syncope is a major antecedent symptom of exertional sudden death. An attack of syncope in young conditioned individuals should be followed by thorough medical surveillance, and strenuous exercise should be avoided until this procedure is completed. Sports and military officials have the obligation to promote awareness that strenuous exercise should not be performed in the presence of acute gastrointestinal symptoms or febrile illness."
-How does early chronic administration of clonidine affect portal pressure and mesenteric-systemic shunts in portal vein-stenosed rats?,"Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats. The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day-1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats."
-What was the primary hypothesis tested in this study regarding atrial natriuretic factor in cerebrospinal fluid?,"Cerebrospinal fluid atrial natriuretic factor in intracranial disease. We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury."
-"How did exercise-induced myocardial ischemia affect the peak E and A velocities and E/A velocity ratio in the>>
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-Human question:","Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference)."
-What are the long-term pathologic consequences of CNS treatment for childhood cancer?,"Long-term consequences of CNS treatment for childhood cancer, Part I: Pathologic consequences and potential for oncogenesis. The pathologic changes associated with the treatment of cancer of the nervous system are reviewed. Computed tomographic, magnetic resonance imaging, and positron emission tomographic findings of these abnormalities are described, followed by discussion of the known histopathologic features. For the most part, pathologic effects are primary vascular and/or demyelinating. We review each of these effects at all levels of the neural axis. This review concludes with a discussion of the risk of developing second malignancies. Although this complication is infrequent, the likelihood that survivors of childhood cancer will develop a second malignancy is 10 times that of age-matched controls. This phenomenon in part relates to genetic predisposition, environmental factors, and host susceptibility. These qualifications not withstanding, most studies implicate central nervous system radiation with and without chemotherapy as the primary etiology for second malignancies."
-"What clinical and laboratory features characterize the ""lymphoma syndrome"" in childhood acute lymphoblastic leukemia?","Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the ""lymphoma syndrome"" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL."
-How effective was the 2-mm choledochoscope in exploring small bile ducts and the pancreatic duct during intraoperative procedures?,"Intraoperative use of a 2-mm choledochoscope for the exploration of small bile ducts and the pancreatic duct. Intraoperative visualization of the biliary and pancreatic ducts can be difficult in a nondilated system. Very small extra- and intrahepatic bile ducts occasionally require visualization but do not admit the traditional 6.5-mm intraoperative flexible choledochoscope. We have prospectively examined the use of a 2-mm choledochoscope for the intraoperative evaluation of the biliary and pancreatic ducts in 36 patients. In 27 patients, the choledochoscope was advanced through the cystic duct stump for examination of the common bile duct following cholangiography. The scope was successfully passed into the cystic duct stump and into the common bile duct in 76 per cent of patients. Inability to pass the scope through the cystic duct was usually due to acute angulation of the cystic duct/common duct junction. In an additional five patients, intraoperative cholangiography revealed a filling defect in a very small duct. A choledochotomy was made and the 2-mm choledochoscope was used to exclude the presence of stones in a small bile duct. In four patients the choledochoscope was used during a Puestow procedure to visualize and help extract stones in the tail and head of the gland. No complications occurred in these patients due to the use of the choledochoscope. We conclude that the 2-mm choledochoscope aids in internal visualization of small intra- and extrahepatic bile ducts and the pancreatic duct. It may be useful as an adjunct to cholangiography in determining the nature of filling defects."
-What is hemifacial spasm and how was it diagnosed in this case report?,AAEM case report #21: hemifacial spasm: preoperative diagnosis and intraoperative management. A 75-year-old man developed progressive involuntary hemifacial spasm. Electrophysiologic evidence of abnormal cross-transmission between neurons of the facial nerve was demonstrated. Electrodiagnostic studies were used to confirm the diagnosis preoperatively and determine the adequacy of vascular decompression of the facial nerve intraoperatively.
-What gene rearrangement and deletion mechanisms are involved in the generation of human IgE-secreting cells?,"Generation and cloning of stable human IgE-secreting cells that have rearranged the C epsilon gene. Although the secretion of Ig isotypes other than IgM is generally accompanied by a DNA rearrangement that deletes C mu (and the other IgCH genes located between VDJ and the expressed CH gene), a system has recently been described that generates a high frequency of IgE-secreting cells that have failed to delete IgCH genes or to rearrange their C epsilon genes. These cells, derived from EBV-transformed human PBMC, secrete IgM and IgD as well as IgE. To determine whether the absence of C epsilon rearrangement and CH gene deletion is a general phenomenon for human IgE-secreting cells, we have characterized IgE-secreting cells that are generated by culturing purified human B cells with EBV plus IL-4 in the presence of irradiated human PBMC. In contrast to the earlier observation, we have not been able to detect any cells that demonstrate cytoplasmic staining for IgE and concurrently stain for a second Ig isotype. Stable IgE-secreting cell lines and clones produced by this method have rearranged one of their C epsilon genes and have deleted both C mu genes. These observations demonstrate that the generation of human IgE-secreting cells can involve the same gene rearrangement and deletional mechanisms that lead to the generation of cells that secrete other isotypes."
-What diagnostic method was used to evaluate lower-extremity vascular grafts in this study?,"Lower-extremity vascular grafts placed for peripheral vascular disease: prospective evaluation with duplex Doppler sonography. Eighty-five men with 92 vascular grafts placed for peripheral vascular disease of the lower extremity underwent a total of 264 examinations with duplex Doppler over a 2.5-year period. In 64 patients who underwent more than one examination, the total follow-up encompassed 740 months. In 220 native femoral arteries (96.0%) the peak systolic velocity (PSV) was higher than that in the graft. Arteriovenous shunting was associated with a normal PSV and a markedly elevated diastolic component at spectral analysis. Focal fluid collections were common initially near the graft and usually disappeared uneventfully. An average PSV of 32 cm/sec or less was always associated with impending occlusion. The sensitivity of an average PSV of 40 cm/sec or less to indicate impending graft occlusion by the next visit was only 33%; the specificity, 94%. At initial examination, stenoses were associated with high PSV focally in the graft or low PSV with absent diastolic flow."
-How do migraine sufferers describe their family environment differently compared to headache-free controls?,"The role of family structure, functioning, and pain modeling in headache. In an initial attempt to examine relationships between family functioning and chronic headache disorders, the present study examined: a) family structure characteristics, b) family functioning, and c) family pain modeling. Subjects completed an assessment battery consisting of several measures of family functioning. Analyses showed that migraine sufferers (N = 42) as compared to headache-free controls (N = 59) were more likely to describe their families as emphasizing clear organization, structure, rules, and overall control, but less likely to encourage emotional expression. No differences were found between tension headache subjects (N = 43) and headache-free controls. While only an initial exploration of the importance of family characteristics in chronic headache, these results suggest that there are important differences in headache subjects' (particularly migraine) reports of family environment and functioning."
-What are the five key managerial challenges identified for ensuring effective delivery of cancer services through strategic alliances?,"Community cancer programs as strategic alliances: challenges and guidelines for action. This paper assesses the utility of strategic alliances as a way of expanding and improving the quality of cancer care provided in communities with limited access to major treatment centres. Alliances provide an organizational model for future community-based cancer programs by accommodating a growing need for interdependence among organizations and providers while permitting substantial independence and autonomy. Five managerial challenges to ensuring effective and efficient delivery of cancer services are identified: to secure mutually reinforcing exchanges between and within all levels of cancer care, to develop protocols and programs relevant to the unique characteristics of patients and providers, to provide treatment and cancer control services, to involve interdisciplinary teams of providers at all levels of care and to achieve quality assurance, improvement and evaluation. In addition, the paper includes a set of guidelines to facilitate the implementation of community cancer programs as strategic alliances: reaffirm the role of community oncologists, primary care physicians and nurses as partners in the program; define the structure and culture necessary for commitment rather than simply compliance; redefine the role of management; establish data-monitoring systems; modify reward systems; and set realistic time frames and expectations."
-What were the most common CT findings in patients after liver transplantation?,"Abdominal CT findings after liver transplantation in 66 patients. CT scanning is used frequently to assess the condition of patients after liver transplantation. The CT records of 174 adult patients who underwent liver transplantation were studied retrospectively to determine the number and timing of CT studies as well as the frequency and significance of the findings. One-hundred seventy CT scans were obtained in 66 (38%) of the 174 patients, with a mean of 2.6 scans/patient. The interval between transplantation and scanning was 1 day to 24 months; in 59 (89%) of 66 patients, the first CT scan was obtained within 30 days. The acute indications for CT scanning were fever or leukocytosis in 54 (92%) of 59 patients and abnormal liver function tests in five (8%) of 59 patients. CT scans obtained more than 30 days after transplantation were repeat scans in all but seven patients. Indications in this latter group were the same as for the acute group, plus evaluation of hepatic neoplasia in three patients. CT findings included periportal low attenuation in 41 (62%) of 66 patients; ascites in 25 (38%); splenomegaly in 19 (29%); loculated intraperitoneal noninfected fluid collections in 13 (20%); intrahepatic, splenic, pancreatic, or perihepatic abscesses in seven (11%); hepatic infarction in six (9%); splenic infarction in three (4%); and hepatic calcification in two (3%). Other major abnormalities included inferior vena caval thrombosis (one patient), pseudoaneurysm of the hepatic artery with rupture (one patient), and recurrent hepatocellular carcinoma (one patient). CT scanning after liver transplantation is used predominantly in the acute setting to evaluate for liver infarction or intraabdominal abscess. In this setting, CT showed these abnormalities, in addition to tumor recurrence or vascular abnormalities, in 15 (23%) of 66 patients."
-What were the key differences in outcomes between patients who received prosthetic valves and those who received human allografts during emergency aortic valve replacement for infective endocarditis?,"Comparison of allografts and prosthetic valves when used for emergency aortic valve replacement for active infective endocarditis. Aortic valve replacement (AVR) using allografts is an established method of treating aortic valve disease. It is uncertain, however, whether the increased technical demands of allograft AVR can be justified in emergency operations. This study reports 15 patients treated between 1987 and 1990 for acute bacterial or fungal endocarditis involving the aortic valve. Patients underwent emergency AVR because of severe congestive failure, overwhelming sepsis or cerebral emboli. Eight patients received prosthetic valves (group I: 4 mechanical, 4 porcine) and 7 received human allografts (group II: 5 aortic and 2 pulmonary). The groups were comparable in age (group I, 55 years; group II, 51 years), intravenous drug abuse (group I, 1; group II, 3), and previous AVR (group I, 3; group II, 2). One group I and 4 group II patients had septal abscesses. Additional procedures in group I included mitral valve replacement (2), tricuspid valve replacement (1) and aortic root replacement (1). Additional procedures in group II were mitral valve repair (1), root replacement (1), atrial septal defect closure (1) and aortocoronary bypass (1). Mean bypass times (group I, 189 minutes; group II, 204 minutes) and cross-clamp times (group I; 108 minutes; group II, 121 minutes) were similar. Operative deaths occurred in 4 of 8 group I and 1 of 7 group II patients. All surviving patients have been successfully followed (group I, 28 months; group II, 18 months). No group I patient has required reoperation. One group II patients required reoperation for recurrent infection affecting the allograft, and another group II patient died 10 months postoperatively from noncardiac causes."
-What did the review of 200 consecutive patient case notes reveal about the necessity of specialist opinion in hearing aid prescription?,Hearing aid prescribing: is the specialist opinion necessary? A restructuring of the service for provision of hearing aids has been proposed by the Royal National Institute for the Deaf. This is based on the assumption that very few patients referred for hearing aids have significant ear disease and it is not necessary for them to see an ENT specialist. The case notes of 200 consecutive patients referred to the Hearing Aid clinic were reviewed. In only half of these would a hearing aid have been prescribed without a specialist opinion. The remainder either did not need a hearing aid or required further investigation and surgical or medical treatment. In addition there was significant evidence of lack of expertise amongst General Practitioners in recognizing ear disorders. It is imperative that any patient requiring a hearing aid be seen by someone experienced in otology rather than be dealt with by the General Practitioner alone.
-How does the expression of P-glycoprotein change in bladder cancer patients before and after chemotherapy treatment?,"Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications. We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy."
-How does sucralfate potentially enhance healing in the experimental pig ulcer model?,"Administration of sucralfate prolongs survival of animals with experimental peptic ulceration. Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation."
-How did the variability among surgeons impact postoperative outcomes and survival rates for patients undergoing colorectal cancer surgery?,"Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival. OBJECTIVE--To assess the differences among surgeons in postoperative complications, postoperative mortality, and survival in patients undergoing surgery for colorectal cancer. DESIGN--Prospective study of patients with colorectal cancer managed by one of 13 consultant surgeons, none of whom had a special interest in colorectal surgery. SETTING--Royal Infirmary, Glasgow. PATIENTS--645 sequential patients with colorectal cancer presenting over the six years from 1974 to 1979. MAIN OUTCOME MEASURES--Postoperative complications, postoperative mortality (within 30 days), and survival (up to 10 years); predictive factors for postoperative mortality and survival; and relative hazard rate ratios for individual surgeons. RESULTS--The proportion of patients undergoing apparently curative resection varied among surgeons from 40% to 76%; overall postoperative mortality varied from 8% to 30%. After curative resection postoperative mortality varied from 0% to 20%, local recurrence from 0% to 21%, and the rate of anastomotic leak from 0% to 25%. Survival at 10 years in patients who underwent curative resection varied from 20% to 63%, two year survival in those who underwent palliative resection varied from 7% to 32%, and median survival in those who underwent palliative diversion varied from one to eight months. The hazard rate ratios among individual surgeons, taking into account the identified risk factors, varied from 0.56 to 2.03, from 0.17 to 1.92, and from 0.57 to 1.50 for curative resection, palliative resection, and palliative diversion, respectively. CONCLUSION--There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery were undertaken by surgeons with a special interest in colorectal surgery or surgical oncology."
-"What rare complication of diagnostic cardiac angiography is discussed in this context, and how was it successfully managed?",Coronary occlusion following diagnostic angiography: salvage by intracoronary stenting. Catheter-induced coronary artery dissection and occlusion is a rare but serious complication of diagnostic cardiac angiography. This report describes the successful management of this complication with an intracoronary stent after prolonged balloon inflations and intracoronary thrombolytic therapy were unsuccessful.
-How do serum aluminum levels change during and after plasmapheresis treatment?,"Trace elements and plasmapheresis. The relationship between serum aluminum (Al), zinc (Zn), copper (Cu), and iron (Fe) and plasmapheresis (PP) treatment was examined. Three patients with rheumatoid arthritis, six with myasthenia gravis, and 6 with multiple sclerosis were studied. Serum Al, Zn, Cu, and Fe were measured before and after PP. Plasma was separated by first filtration; a second filtration separated the plasma components. Three liters of plasma were treated in each PP session. With each PP treatment, total protein (TP) removed was 20 +/- 5% and serum albumin removed was +/- 6%. Serum Al rose significantly (p less than 0.01 from 1.1 +/- 0.2 micrograms/dl pre-PP to 2.8 +/- 0.4 micrograms/dl post-PP. Serum Zn, Cu, and Fe decreased significantly (p less than 0.01) from 86.2 +/- 7.4 micrograms/dl, 126 +/- 18 micrograms/dl, and 108 +/- 14 micrograms/dl pre-PP to 58.4 +/- 10.2 micrograms/dl, 104 +/- 6 micrograms/dl, and 82 +/- 16 micrograms/dl post-PP, respectively. Two days after the end of the six-month PP treatment, serum Al levels rose significantly (p less than 0.01), from 1.1 +/- 0.2 micrograms/dl to 3.6 +/- 0.8 micrograms/dl. However, serum TP, serum albumin, and serum Zn, Cu, and Fe did not change significantly. It thus appears essential in PP treated patients, to remove Al from the blood to protect against aluminum intoxication."
-"What were the key findings comparing surgical and percutaneous placement of Greenfield filters in terms of safety, efficacy, and cost?","Analysis of the transition to percutaneous placement of Greenfield filters. To establish whether a transition from surgical to percutaneous placement of Greenfield filters was justified, a review of the safety, efficacy, and cost-effectiveness of the two approaches was conducted. Between 1984 and 1989, 168 filters were placed in 169 patients, 48 surgically and 120 percutaneously. Placement was successful in 45 (94%) of the 48 surgical patients and 120 (99%) of the 121 percutaneous patients. Filter misplacement occurred in three (6%) surgical patients and no percutaneous patients. Clinically evident femoral vein thrombosis occurred in only four (5%) of the percutaneous patients, while inferior vena cava thrombosis occurred in three (3%) of the percutaneous patients. One pulmonary embolus occurred after percutaneous filter placement and resulted in death. The cost of percutaneous placement was 58% that of surgical placement. A retrospective review of the experience in our patient population indicates that safety, cost, and ease of insertion make the percutaneous approach the procedure of choice for Greenfield filter placement."
-What medical condition did the 32-year-old woman develop 20 years after receiving 198Au synoviorthesis for juvenile rheumatoid arthritis?,"Chronic myeloid leukemia in a woman with Still's disease treated with 198Au synoviorthesis. A 32-year-old woman presented with chronic myeloid leukemia 20 years after 2 198Au synoviortheses to her knees for severe juvenile rheumatoid arthritis. She progressed to blast phase of her disease and died from complications of therapy. The literature on rheumatoid arthritis, its therapy, radioisotopes and leukemia is reviewed."
-What is K-edge energy digital subtraction arthrography (KEDSA) and how does it improve the detection of hip prosthesis loosening?,"K-edge digital subtraction arthrography of the painful hip prosthesis: a feasibility study. K-edge energy subtraction radiography is a method for detecting the presence of iodinated contrast material by subtracting two digital radiographs produced by X-ray beams with energies above and below the iodine K edge. We performed a feasibility study on the application of K-edge energy digital subtraction arthrography (KEDSA) to painful hip prostheses. During arthrography, loosening of the prosthesis is implied if contrast material is seen dissecting around the prosthesis, an often difficult detection task because of adjacent prosthesis metal or cement. In conventional arthrography a preliminary mask image is thus used from which films obtained after injection of iodinated contrast material are subtracted. Movement by the patient during this process may preclude subsequent subtraction. With KEDSA, since multiple image pairs may be obtained after the injection of contrast material, the problem of patient motion is virtually eliminated. A conventional X-ray tube operating between 55 and 65 kVp was alternately filtered by iodine and cerium filters to produce the KEDSA images. The apparatus was capable of producing a subtracted image within 3 sec. The technique was applied to phantoms and to six patients immediately after hip arthrography that had been positive for prosthesis loosening. Although of lower spatial resolution, the KEDSA images were, in all cases, positive for loosening in a pattern consistent with the conventional arthrographic images. KEDSA was shown to be successful in detecting extraarticular contrast material. During a single study, subtraction in various imaging planes as well as postexercise subtraction imaging can be accomplished-techniques not heretofore possible in routine subtraction arthrography."
-What were the key findings regarding the sensitivity of 12-lead electrocardiogram versus limb-lead monitoring in detecting ischemia during percutaneous transluminal coronary angioplasty?,"Twelve-lead electrocardiographic evaluation of ischemia during percutaneous transluminal coronary angioplasty and its correlation with acute reocclusion. The sensitivity of the surface 12-lead electrocardiogram and that of standard (limb-lead) monitoring for the detection of ischemia during percutaneous transluminal coronary angioplasty were compared in 115 patients. The purpose was to identify the electrocardiographic leads that provide the most sensitive indicators of coronary ischemia during percutaneous transaluminal coronary angioplasty and to evaluate the ""ischemic fingerprint"" that is obtained with 12-lead electrocardiogram during balloon inflation as a predictor of abrupt reocclusion after successful percutaneous transaluminal coronary angioplasty procedures. During balloon inflations of 30 seconds, ischemia was detected in 61 of 145 vessels (42%) by limb-lead monitoring alone versus 130 of 145 vessels (90%) by 12-lead electrocardiography (p less than or equal to 0.001). In the nine patients (7.8%) who experienced abrupt reocclusion within 24 hours, the electrocardiogram during chest pain after percutaneous transaluminal coronary angioplasty was identical to that obtained during percutaneous transaluminal coronary angioplasty (""ischemic fingerprint""). None of the six patients who had chest pain after percutaneous transaluminal coronary angioplasty without evidence of abrupt reocclusion reproduced their ischemic fingerprint. The suggested optimal leads for monitoring ischemia are as follows: left anterior descending coronary artery, V2, and V3; circumflex artery, V2, and V3; and right coronary artery, III and aVF."
-What type of adenoma was found in the left lung of the 28-year-old woman during autopsy?,"Adenoma of type 2 pneumocytes with oncocytic features. An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly."
-What factors can increase the risk of vasovagal syncope during spinal anesthesia?,Vasovagal asystole during spinal anaesthesia. A patient in whom vasovagal asystole was induced by the performance of a spinal anaesthetic in the upright position is described. This illustrates the importance of routine monitoring of the electrocardiograph during regional anaesthesia. The risk of vasovagal syncope may be increased by the use of the sitting position and by the omission of anxiolytic premedication.
-How do motor initiation and execution differ between normal subjects and Parkinson's disease patients?,"Motor initiation versus execution in normal and Parkinson's disease subjects. We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way."
-What is sonoelasticity imaging and how does it potentially help in detecting neoplasms?,"Sonoelasticity imaging: results in in vitro tissue specimens. The authors present a method for imaging tissue stiffness (sonoelasticity) that has been developed and tested in a laboratory setting by using in vitro canine and human prostate glands. A low-frequency acoustic source was used to induce vibration in tissue under examination, and a color Doppler ultrasound (US) instrument was modified to detect vibration amplitude. The resulting image is a color ""map"" of tissue vibration superimposed on conventional gray-scale US images. Stiffer tissues vibrated less in response to audible sound, regardless of echogenicity. Normal human and canine prostate glands demonstrated a uniform vibration pattern. Four of four human prostatic adenocarcinomas and two stiff inclusions injected into canine prostate glands demonstrated a lack of vibration in comparison with normal surrounding tissue. The authors conclude that while further study is necessary, sonoelasticity imaging may enhance the detection of neoplasms by enabling their identification solely on the basis of stiffness."
-What were the key prognostic factors significantly associated with disease recurrence in clinical stage I endometrial adenocarcinoma according to the multivariate analysis?,"Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Two hundred sixty-four consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and August 1988 were followed prospectively and evaluated for disease recurrence for 8-112 months (mean 51.5). Thirty-three patients (12.5%) developed recurrence or died of disease. In univariate statistical analysis, prognostic factors significantly associated with disease recurrence were as follows: age (mean 68.6 years with versus 60.3 years without recurrence; P = .0001); histology (adenocarcinoma 8.8%, adenosquamous 35.7%, papillary 25%, clear-cell 57.1%; P less than .0001); tumor grade (grade 1, 7.7%, grade 2, 10.5%, grade 3, 36.1%; P less than .0001); depth of myometrial invasion (none 9.8%, less than one-half 7.4%, one-half or greater 29.6%; P = .0001); lymph node status (negative 8.3%, positive 47.6%; P less than .0001); non-nodal extrauterine disease spread (absent 11.0%, present 50%; P = .0003); peritoneal cytology (negative 9.4%, positive 26.3%; P = .004), and tumor size (2 cm or less 7%, greater than 2 cm 17.3%; P = .05). Cervical extension and uterine size had no significant effect on recurrence. Using multivariate analysis, grade 3 tumor (P = .002), advancing age (P = .004), lymph node metastasis (P = .006), and presence of extrauterine disease spread other than lymph node metastasis (P = .038) were the only variables significantly associated with disease recurrence or death. This study supports the new International Federation of Gynecology and Obstetrics surgical staging system for endometrial cancer."
-What percentage of patients developed aneurysms at the surgical repair site during childhood years after coarctation of the aorta repair?,"Preoperative and postoperative ""aneurysm"" associated with coarctation of the aorta. The reported incidence of aortic aneurysm after surgical repair or balloon angioplasty for aortic coarctation varies widely. To determine the incidence of aneurysm formation after surgery, preoperative and postoperative cineangiograms from 65 patients who underwent operation at age 1.5 +/- 3.4 years were examined. Repair included a prosthetic patch in 14 patients, end to end anastomosis in 28 and subclavian flap in 23. Aneurysm was documented by change in contour or irregularities in contour at the repair site or by abnormal dimensions at the repair site, defined by the ratio of the widest measurement at the repair site to the measurement of the aorta at the diaphragm. An aneurysmal bulge above the ductus diverticulum was identified in 14 (23%) of 60 patients preoperatively; the area showed no change 4.72 +/- 4.07 years after surgery. Significant changes at the repair site were seen in only three patients, all of whom had Dacron patch repair. One patient had a change in contour at the repair site, one had an abnormally high repair site to diaphragmatic aorta ratio and one had a progressive increase in this ratio. Thus, during childhood years, 3 (5%) of 65 patients were diagnosed as having aneurysm at the surgical repair site. In conclusion, 1) comparison with preoperative cineangiograms, especially for aneurysmal bulges above the ductus arteriosus, is essential before an aneurysm can be attributed to coarctation repair by any technique, and 2) aneurysm developed only in patients subjected to Dacron patch repair."
-What is unique about the lymphoma case described in this context?,"Ki-1-positive lymphoma developing 10 years after the diagnosis of hairy cell leukemia. The case is described of a 62-year-old man with a 10-year history of hairy cell leukemia (HCL) who subsequently had a large-cell anaplastic or so-called Ki-1-positive lymphoma. Immunocytochemical staining of the lymphomatous node revealed positivity for Ki-1 (CD30) and epithelial membrane antigen in the tumor cells, and flow cytometric analysis showed simultaneous expression of Leu M5 (CD11c) and Leu 14 (CD22). Although HCL has been reported to coexist with both Hodgkin's disease and non-Hodgkin's lymphoma, the authors believe this is the first case in which a Ki-1-positive lymphoma developed in a patient with HCL. The clinicopathologic and immunologic features of both entities are discussed, as is the association of HCL with other neoplasms."
-What is the weaning index (WI) and how is it calculated in this study?,"Evaluation of a new weaning index based on ventilatory endurance and the efficiency of gas exchange. We hypothesized that the ventilatory capacity needed to wean from mechanical ventilation (mv) depends on two variables: ventilatory endurance and the efficiency of gas exchange. We also hypothesized that these variables could be assessed from data readily available at the bedside, including tidal volume (VT) on mv and during spontaneous breathing (sb), ventilator peak inspiratory pressure (Ppk), and patient negative inspiratory pressure (NIP). Ventilatory endurance was evaluated using a modified pressure-time index: PTI = TI/Ttot x Pbreath/NIP, where Pbreath = Ppk x VTsb/VTmv. Defining VE40 as the minute ventilation needed to bring PaCO2 to 40 mm Hg, the efficiency of gas exchange was evaluated by calculating VE40/VTsb = (VE x PaCO2)mv/VTsb x 40. Because high levels of inspiratory effort might cause patients to reduce VTsb and thereby compromise CO2 elimination, we devised a weaning index (WI) that combines ventilatory endurance and the efficiency of gas exchange: WI = PTI x (VE40/VTsb). The study population comprised 38 patients with chronic obstructive pulmonary disease, adult respiratory distress syndrome, pneumonia, neuromuscular disease, and miscellaneous other conditions. They had been mechanically ventilated more than 3 days and were considered by clinical criteria to be ready for weaning. Of 46 weaning trials, 19 were successful, 2 were partially successful, and 25 failed. PTI and VE40/VTsb were higher in patients who failed (p less than 0.05), but neither variable alone had sufficient sensitivity or specificity to predict the outcome of weaning trials accurately."
-What percentage of postmenopausal women experienced persistent side effects from tamoxifen treatment in this study?,"Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance."
-What was the primary objective of the experimental in vivo model described in the study?,"Nephrotoxic potential of Bence Jones proteins BACKGROUND. The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. METHODS. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. RESULTS. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 mumol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 mumol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. CONCLUSIONS. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain-associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains."
-Does the level of axillary lymph node involvement independently predict survival in clinical stage I and II breast cancer patients?,"Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival. We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance."
-What is the purpose of the in situ venous valve construction technique described in the context?,"In situ venous valve construction. A technique of in situ deep venous valve construction based on vein wall intussusception is described. The technique has been used to construct a size-matched, autogenous valve in the femoral vein of the dog. Forty-one valves have been constructed. Immediately after construction, all 41 were patent at ascending phlebography and Harvey's test showed them to be competent. Descending phlebography demonstrated competence in 38 valves. Hydrostatic testing was performed on 27 valves in the vertical position at pressure gradients in the range 0.2-250 cmH2O. Of these, 24 valves were fully competent. Six valves were studied at intervals between 1 and 112 days after construction. All six were competent by Harvey's test and five were competent at descending phlebography. There was no evidence of thrombosis in any valve. This technique may be suitable for replacement of deep venous valves in patients with the calf pump failure syndrome caused by deep venous reflux."
-What was the relationship between the degree of coronary stenosis and mortality in patients who survived an anterior wall Q-wave acute myocardial infarction?,"Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05)."
-How many deaths and new cases of illness are estimated to occur annually in the United States due to occupational diseases?,"The recognition and control of occupational disease. Occupational diseases account each year in the United States for an estimated 50,000 to 70,000 deaths and 350,000 new cases of illness. Often, however, occupational diseases are not correctly diagnosed, because they mimic diseases due to other causes and because most physicians are not well trained in their recognition. Opportunities for prevention and treatment are therefore lost. The occupational history is the most effective means for proper diagnosis of occupational illness. It should routinely be obtained for every patient. A brief but systematic guide for obtaining an occupational history is presented in this report. Also, approaches are summarized for the recognition and diagnosis of such important occupational diseases as occupational cancer, asbestosis and other respiratory disorders, and occupational neuropsychologic disorders. The management and prevention of occupational diseases depend on reduction of hazardous exposures in the workplace and better education of workers, industrial managers, and physicians. This report outlines a program for the control of occupational disease based on (1) preventing exposures in the workplace, (2) premarket toxicity testing of new chemicals and technologies, and (3) astute clinical diagnosis."
-What was the main objective of the North American Symptomatic Carotid Endarterectomy Trial?,"Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators BACKGROUND. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS. Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery."
-How does insulin resistance potentially contribute to increased blood pressure through altered cation transport mechanisms?,"Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What percentage of superficial femoral artery stenoses did not progress after a mean follow-up interval of 37 months?,"The natural history of superficial femoral artery stenoses. Since the natural history of specific superficial femoral artery stenoses is not known, we examined progression rates of superficial femoral artery stenoses in 45 lower extremities found when arteriograms were obtained of 38 patients for symptomatic atherosclerotic disease in the opposite leg or abdomen. These initial superficial femoral artery arteriograms were compared with later arteriograms in 25 limbs, duplex scans in 27 limbs, and both modalities in 7 limbs. After a mean interval of 37 months, most superficial femoral artery stenoses (72%) did not progress. However, 12 superficial femoral artery stenoses progressed (28%; mean follow-up, 37 months, including 7 that occluded (17%). Superficial femoral artery stenoses progressed among patients who complained of symptom progression at a rate faster than that among asymptomatic patients (15.6%/year vs 3%/year; p = 0.006). Superficial femoral artery lesions also progressed more rapidly among patients whose contralateral superficial femoral artery was occluded (10%/year vs 1.6%/year; p = 0.04). By multivariate regression analysis, symptom progression and smoking history were predictive of superficial femoral artery stenosis progression. In the seven patients whose superficial femoral artery stenoses progressed to occlusion, the average rate of stenosis progression was 12%/year (maximum predicted rate, 30% per year by 95% confidence limit). These results indicate that superficial femoral artery stenoses usually progress with synchronous symptomatic deterioration. Other than symptom progression, only cumulative smoking history and contralateral superficial femoral artery occlusion could be associated with superficial femoral artery stenosis progression in this small series."
-What misconceptions about cancer were found among the socioeconomically disadvantaged patients in the study?,"Knowledge and beliefs about cancer in a socioeconomically disadvantaged population. Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors."
-What were the key differences in safety and tolerance between amphotericin B lipid complex (ABLC) and amphotericin B desoxycholate (AB) in the study?,"Comparative safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. Amphotericin B lipid complex (ABLC), a lipid complex formulation of amphotericin B, and amphotericin B desoxycholate (AB) were compared for safety, tolerance, and pharmacokinetics in two groups of eight healthy male volunteers. After a 1-mg test dose, study drug was infused at 0.1, 0.25, and 0.5 mg/kg; the 0.5-mg/kg dose was not given to subjects receiving AB. ABLC caused few acute adverse effects except for mild somnolence (drowsiness) in six volunteers. In addition, three of eight ABLC recipient had asymptomatic, transient serum transaminase elevations that resolved spontaneously. The AB recipients experienced more acute side effects, but only one had a mild shaking chill: three of eight also experienced sleepiness. No significant changes in vital signs, electrocardiogram, oximetry, pulmonary function, or clinical status were observed in either group. Due to its increased estimate volume of distribution and estimated clearance. ABLC yielded decreased amphotericin B levels and area under the serum concentration versus time curve relative to AB."
-How does continuous positive airway pressure (CPAP) affect ventilatory output and pulmonary resistance during different stages of non-rapid-eye-movement (NREM) sleep?,"Effects of sleep-induced increases in upper airway resistance on ventilation. To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone."
-What was the average functional rating of the hips before and after total hip arthroplasty in patients who had childhood sepsis?,"Total arthroplasty of the hip after childhood sepsis. Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood. The average age of the patients was 36.4 years (range 19 to 50). The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80). Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection. The mean functional rating of the hips was 58 points before operation and 90 at the final review. Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration. Acetabular allografts were required in 27 hips (60%). All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all."
-What are the key findings suggesting that the postsurgical hemorrhage resulted from venous thrombosis after AVM excision?,"Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report. A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM."
-How did the use of hyaluronidase affect cell recovery during intestinal perfusion?,"Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease. The recovery of cells arising from small intestinal mucosa alone was studied during continuous perfusion of a closed segment of jejunum. The perfusion technique minimised the contamination of the perfused segment with, for example, proteolytic enzymes from pancreas, allowing recovery of viable cells. The use of hyaluronidase in the perfusion fluid increased the recovery of cells fivefold, the median recovery being 8 x 10(6) cells. The cells were analysed with monoclonal antibodies and flow cytometry. Nearly all cells (98-99%) recovered during perfusion of healthy control subjects and patients with Crohn's disease were epithelial cells. The jejunal cells expressed HLA-DR in similar proportions--around 30%--in patients and control subjects. The ratio between CD4+ and CD8+ lymphocytes was similar (0.2) in control subjects and patients with inactive Crohn's disease but decreased (0.03) in patients with active Crohn's disease in the ileum."
-What is the potential outcome of untreated or late-treated candidal mediastinitis?,"Candidal mediastinitis after surgical repair of esophageal perforation. Candidal mediastinitis, like Boerhaave's syndrome, is uncommon, and both, if treated late or incompletely, frequently result in death. Early recognition and aggressive medical and surgical intervention are the best means to convalescence and cure in both conditions."
-How does the experimental model (open-chest vs. conscious dog) affect the assessment of postischemic myocardial stunning?,"Postischemic myocardial ""stunning"". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog. Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial ""stunning""). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically ""protective"" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What immune system abnormality was observed in the patient with primary sclerosing cholangitis?,"Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study. Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters."
-What is the key characteristic of the chondroblastomalike extraskeletal tumor found in the patient's right thumb?,Chondroblastomalike extraskeletal chondroma. An unusual extraskeletal tumor occurring in the right thumb of a 44-year-old man exhibited histologically a chondroblastomalike appearance. The tumor was characterized by dense proliferation of chondroblastic cells admixed with a few multinucleated giant cells of osteoclast type. The patient had no evidence of local recurrence or metastasis three-and-a-half years after a simple excision.
-How was bile peritonitis managed in this patient without resorting to exploratory laparotomy?,"Novel approach to iatrogenic bile peritonitis. Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice."
-What quantitative liver function tests were found to be significant predictors of survival in patients with cirrhosis?,"Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification."
-What factors were found to be associated with increased elastic recoil after percutaneous transluminal coronary angioplasty?,"Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study. The immediate result of percutaneous transluminal coronary angioplasty is influenced by both plastic and elastic changes of the vessel wall. To evaluate the amount of elastic recoil after coronary balloon angioplasty, the minimal luminal cross-sectional area of the largest balloon used at highest inflation pressure was compared with the minimal luminal vessel cross-sectional area directly after final balloon deflation in 607 lesions (526 patients). Elastic recoil was defined as the difference between balloon cross-sectional area and minimal luminal cross-sectional area of the dilated coronary segment immediately after balloon withdrawal. A videodensitometric analysis technique was used to avoid geometric assumptions on stenosis morphology directly after angioplasty. Mean balloon cross-sectional area was 5.3 +/- 1.6 mm2 and minimal luminal cross-sectional area after angioplasty was 2.8 +/- 1.4 mm2. Reference areas before and after angioplasty did not differ (6.0 +/- 2.6 and 6.2 +/- 2.6 mm2, respectively). Univariate analysis revealed that asymmetric lesions, lesions located in less angulated parts of the artery and lesions with a low plaque content showed more elastic recoil. Lesions located in distal parts of the coronary tree were also associated with more elastic recoil probably related to relative balloon oversizing in these distal lesions."
-What was the key finding regarding CD34 mRNA expression in the B-precursor acute lymphoblastic leukemia cell subpopulations?,"Differentiation in B-precursor acute lymphoblastic leukemia cell populations with CD34-positive subpopulations. B-precursor acute lymphoblastic leukemia bone marrow specimens that contained subpopulations of cells with immunophenotypes corresponding to early (CD34) and late (CD20) and (CD22) stages of normal B-cell differentiation were studied. Subpopulations of cells were isolated according to immunophenotype and then analyzed by both a clonogenic assay and molecular genetic methods. Clonal equivalence of the early and late immunophenotypic subpopulations was confirmed for each case by the demonstration of identical lg gene rearrangements. The in vitro colony-forming assay consistently showed a growth advantage for the CD34+ subpopulations over the CD34- subpopulations. CD34 mRNA was detected readily in these isolated precursor cells. When two specimens in which virtually all of the leukemia cells were CD34+ and CD34+CD20+ and CD34+CD22+ subpopulations were also present the CD34 mRNA was limited to the cells without the late-stage differentiation antigens on their surface. Furthermore, the c-myb mRNA was found only in the subpopulations that also contained CD34 mRNA. Our results show that a limited program of differentiation reminiscent of normal B-cell development may be present in this leukemia."
-What is the gender distribution observed in the study of global T wave inversion?,"Global T wave inversion. Because global T wave inversion has not been specifically characterized, 100 electrocardiograms (ECGs) with this pattern (frontal plane T vector -100 degrees to -170 degrees with precordial T inversion) were prospectively collected from approximately 30,000 consecutively interpreted ECGs and analyzed blindly. There was a striking female predominance (82 women vs. 18 men; p less than 0.0005) despite an essentially equal number of female and male hospital admissions. There was a single statistically significant ECG correlate: a more vertical QRS axis in women (+14.1 degrees +/- 45.3 degrees vs. -5.6 degrees +/- 31.3 degrees; p = 0.034). The T waves were basically symmetric (68%), the influence of this factor usually altering the characteristically asymmetric T wave inversions of right bundle branch block (4 of 5) and left ventricular hypertrophy (21 of 36). Asymmetry was mainly associated with digoxin therapy (21 of 32 patients taking digoxin; p less than or equal to 0.0005) and a corrected QT (QTc) interval (0.433 +/- 0.095) shorter than with symmetric T wave inversions (0.507 +/- 0.074; p less than or equal to 0.0005) though not reaching the degree of shortening expected for digitalization. Twenty-eight patients admitted for acute myocardial infarction and 23 for a central nervous system disorder accounted for the majority of patients with symmetric T wave inversion. Fifteen of 18 patients who had coronary angiography had some degree of coronary artery disease: 3 had angiographically normal coronary arteries."
-What was the suspected pathophysiologic mechanism causing the referred pain in this patient with a spinal cord tumor?,"Somato-somatic referred pain caused by suprasegmental spinal cord tumor. Tactile stimulation of a coin-sized area in a T-2 dermatome consistently triggered a lancinating pain in the ipsilateral C-8 dermatome in a 38-year-old woman. The SEP and an MRI led to a diagnosis of a tumor at the left cervico-medullary junction, much higher than the clinically suspected level. Surgical exploration revealed an exophytic glioma, and the pain was abolished postoperatively. Ephaptic transmission at the tumor site was suspected as a pathophysiologic mechanism."
-What medical condition developed in a 52-year-old man after an inferior wall myocardial infarction complicated by Dressler's syndrome?,Early constrictive pericarditis and anemia after Dressler's syndrome and inferior wall myocardial infarction. Early constrictive pericarditis and anaemia developed in a 52 year old man after he had an inferior wall myocardial infarction complicated by Dressler's syndrome. Total pericardiectomy at the time of coronary artery bypass surgery resulted in complete resolution of signs and symptoms.
-"How does sinorphan, an enkephalinase inhibitor, affect plasma atrial natriuretic factor (ANF) and sodium urinary excretion in cirrhotic patients with ascites?","Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites. We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites."
-What medical procedure was performed to treat the patient's aneurysm in this case report?,"Aneurysm of the distal anterior inferior cerebellar artery unrelated to the cerebellopontine angle: case report. This is a case report of an unusual aneurysm of the distal anterior inferior cerebellar artery. A 44-year-old woman had a severe frontal headache and vomiting of sudden onset. On the day after admission, the patient began to demonstrate nuchal rigidity and difficulty with upward gaze bilaterally. There were no complaints at this time suggestive of a syndrome of the cerebellopontine angle. A computed tomographic scan revealed an intraventricular hemorrhage of the 3rd and 4th ventricles; however, multiple attempts at four-vessel angiography were required before an aneurysm could be demonstrated. On the 28th hospital day, a suboccipital craniectomy using the retromastoid approach in the lateral position was performed. A saccular aneurysm with a surrounding hematoma in the distal anterior inferior cerebellar artery was found and clipped. The operative findings revealed that the aneurysm was unrelated to the cerebellopontine angle. After surgery, the patient had an uneventful recovery and complete resolution of symptoms."
-What was the standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared to the general population?,"Cancer incidence in Norwegian Seventh-Day Adventists 1961 to 1986. Is the cancer-life-style association overestimated? Standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared with the general population was not significantly different from unity (men 91, women 97). Persons converting late in life had a higher incidence than those converting at an earlier age. Respiratory cancers (standardized incidence ratio [SIR] 59, 95% CI = 36 to 91) and cancers with an unspecified site (SIR 53, 95% CI = 25 to 97) were rarer and cancer of the uterine corpus (SIR 164, 95% CI = 109 to 237) was more common in Seventh-Day Adventists before the age of 75 years. Inclusion of all registered Seventh-Day Adventists regardless of religious activity and the relatively low cancer incidence rates in the Norwegian population could contribute to the nonsignificant result with regard to total cancer. Main etiologic factors in cancer development in Norway should be sought in areas where Seventh-Day Adventists do not differ from the general population."
-At what postnatal ages did the rats show the highest incidence of epileptiform EEG activity during hypoxia?,"Epileptogenic effect of hypoxia in the immature rodent brain. The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia."
-What differences were observed in childhood cancer incidence and outcomes between Polynesian and non-Polynesian children in the study?,"Childhood cancer among the Polynesian population. From June 1981 through June 1989, 95 Polynesian children were seen for initial care of malignancy at the Princess Mary Hospital for Children (PMHC). The incidence of malignancy in the Polynesian populations served, the histology of the malignancies, and the outcome of therapy were reviewed and compared with 185 non-Polynesian (non-P) patients seen during the same period. Incidence figures for Polynesians and non-P were similar, but histologic patterns differed, showing an increased occurrence of leukemia, particularly nonlymphoblastic leukemia, an increased occurrence of bone tumors, and a decreased incidence of central nervous system tumors for Polynesians. Survival for Polynesian children with acute lymphoblastic leukemia was worse than for non-P. Survival in all other disease categories was similar."
-What factors were associated with major or minor hemorrhagic events during thrombolytic therapy for acute myocardial infarction?,"Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. OBJECTIVES: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. DESIGN: A multicenter, randomized, controlled trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). INTERVENTIONS: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. MEASUREMENTS: Patients were monitored for hemorrhagic events during hospitalization. MAIN RESULTS: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. CONCLUSIONS: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy."
-How does mifepristone potentially help in treating unresectable meningiomas?,"Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors. The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (greater than or equal to 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective improvement (improved extraocular muscle function or relief from headache). The side effects of long-term mifepristone therapy have been mild. Fatigue was noted in 11 of the 14 patients. Other side effects included hot flashes in five patients, gynecomastia in three, partial alopecia in two, and cessation of menses in two. Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma."
-What is a transscleral leiomyoma and how did it manifest in the 31-year-old woman described in the context?,"Transscleral leiomyoma. A bluish-pink epibulbar lesion, which slowly enlarged over a period of 5 years, developed in a 31-year-old woman. The lesion initially resembled a staphyloma, based on the very thinned overlying sclera, but subsequent evaluation suggested that it was a solid mass. At the time of surgical removal, the mass appeared to have originated in the supraciliary region and to have eroded outward through the sclera. Histopathologically, the mass proved to be a leiomyoma. The authors propose theoretic possibilities to explain the location of this rare type of ocular smooth muscle tumor."
-How effective is electromyographic monitoring in detecting facial nerve injuries caused by carbon dioxide lasers during surgical procedures?,"Detection of intraoperative laser injury to the facial nerve by electromyographic monitoring of facial muscles. Injury to the facial nerve is a significant risk during resection of cerebellopontine angle tumors. To minimize the risk of facial nerve injury, intraoperative electromyographic monitoring of facial musculature is frequently used. However, the reliability of such monitoring systems for detection of thermal nerve injury resulting from the use of carbon dioxide lasers has not been systematically evaluated. We determined the sensitivity of a computerized electromyographic monitor for detection of laser facial nerve injury in an anesthetized rat model. The mandibular and buccal branches of the facial nerve were isolated in 12 rats. A carbon dioxide laser was used to create controlled sites of thermal injury to both nerves over a 3-hour period. When a laser injury was created distal to previous injury sites, electromyographic discharge was noted in 72% to 82% of injuries. Laser injury proximal to previous injury sites was detected with 33% efficiency. These detection rates did not change significantly over a 3-hour period. This preliminary data suggests that electromyographic monitoring of facial musculature allows detection of facial nerve injury caused by carbon dioxide lasers."
-"What were the key differences in acute coronary lesions among patients with unstable angina, sudden coronary death, and acute myocardial infarction?","Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. The frequency and type of acute lesions in the four major (right, left main, left anterior descending, left circumflex) epicardial coronary arteries were examined at necropsy in 14 patients with unstable angina pectoris, 21 patients with sudden coronary death and 32 patients with a fatal first acute myocardial infarction. None of the 67 patients had a grossly visible left ventricular scar (healed myocardial infarct) and only the group with acute myocardial infarction had left ventricular myocardial necrosis. Although the frequency of intraluminal thrombus was similar in patients with unstable angina (29%) and sudden death (29%) and significantly lower than in those with acute infarction (69%) (p = 0.02), the thrombus in the patients with unstable angina and sudden death consisted almost entirely of platelets and was nonocclusive, whereas the thrombus in the group with acute infarction consisted almost entirely of fibrin and was occlusive. The frequency of plaque rupture was insignificantly different in the groups with unstable angina (36%) and sudden death (19%), and was significantly lower than in the group with acute infarction (75%) (p = 0.02). The frequency of plaque hemorrhage was insignificantly different in the groups with unstable angina (64%) and sudden death (38%) and was significantly lower than in the group with acute infarction (90%) (p = 0.04)."
-What imaging features are characteristic of adrenal hemangioma on magnetic resonance imaging?,"Adrenal hemangioma: an unusual adrenal mass delineated with magnetic resonance imaging. Adrenal hemangioma should be included in the differential diagnosis of any large calcified adrenal mass. We report to our knowledge the eighth surgically removed lesion and describe its appearance on magnetic resonance imaging. This imaging includes features seen in hemangiomas elsewhere, in particular a heterogeneous mass with enhancing peripheral high intensity foci on T1 images."
-What modifications were made to the standard aortography technique to improve visualization of lower limb arteries?,"A modified technique of pre-operative aortography to demonstrate the complete arterial tree of the lower limb. One hundred consecutive aortograms were studied to establish the efficacy of conventional arteriography in demonstrating distal vessels and the pedal arch. The standard technique was modified by using a long injection time, a large volume of contrast material (iopamidol 370), prolonged filming and multiple exposures of the feet. On the basis of these examinations each limb was classified as having aorto-iliac disease (18 limbs), superficial femoral disease (103 limbs), combined segment disease (28 limbs) or generalised disease (51 limbs). Calf and ankle arteries were seen in 196 of the 200 limbs (98%). Patency of the pedal arch was established in 184 (92%). Fourteen percent of the group of patients with combined segment disease did not have their pedal arch visualised and this group contained most of the examination failures. This modified method of aortography can demonstrate the entire arterial tree from the aorta to the foot in 92% of limbs with symptomatic chronic atherosclerotic disease. This allows the majority of peripheral vascular reconstructions to be planned and performed without the need for intra-operative arteriography."
-What is the recommended treatment for cerebral air embolism and how effective is it when administered late?,"Hyperbaric treatment of cerebral air embolism sustained during an open-heart surgical procedure A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment."
-What were the key findings of the study regarding the growth of human basal cell carcinomas transplanted to beige-nude mice?,"Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJ/bgJ nu/nu (beige-nude) mice. The purpose of this study was to measure growth parameters of transplanted basal cell carcinoma (BCC) to beige-nude mice during a 4-month observation time. Forty male beige-nude mice were transplanted with human BCC with our reported subcutaneous implantation technique. Initial volume and wet weight were determined for each tumor. The tumors were measured every 2 weeks by calipers with a final volume determined at 120 days, at which time the tumors were harvested, weighed, and processed for routine histology. Thirty-two tumor sites were positive for persistent tumor at harvest. Tumor volumes declined by an average of 51% and average tumor weight by 33%. There were increased numbers of mast cells surrounding the BCC tumor lobules. These results indicate that BCC can survive for 120 days in the beige-nude mouse."
-Does carbon dioxide laser treatment disperse human papillomavirus deoxyribonucleic acid during genital infection procedures?,"Carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields. The possibility of dispersing viral deoxyribonucleic acid during carbon dioxide laser treatment of human papillomavirus-containing genital infections has been investigated with a commercially available dot blot hybridization technique. The viral ribonucleic acid probes were specific for groups of human papillomavirus types 6/11, 16/18, and 31/33/35. Laser energy was delivered by continuous-wave mode and the plume of smoke was evacuated by a vacuum suction system. Samples were taken with Dacron swabs from lesional tissues of 43 patients as well as from the treated areas and from the 5 cm surrounding normal skin before and after laser vaporization. Human papillomavirus deoxyribonucleic acid was identified in swabs from 34 of 43 (79%) lesional tissues and 7 of 43 (16%) treatment fields. Although a trend for higher human papillomavirus deoxyribonucleic acid positivity in laser margins after therapy (7/43, 16%) than before (4/43, 9%) was observed, the rates were not statistically significant. It is concluded that carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields and the adjacent normal epithelium. Viral contamination of treated areas may be reduced by positioning the fume evacuator within 1 cm of the field of laser vaporization and cleaning the treated areas and surrounding tissue after therapy."
-What is Bouveret's syndrome and how does it typically manifest?,"Bouveret's syndrome: an unusual twist on the classic cause. Bouveret's syndrome is a duodenal obstruction caused by a gallstone, manifested mostly as a gastric outlet obstruction. We have reported an instance of Bouveret's syndrome caused by two separate stones, either of which could independently have caused the obstruction. It is imperative to be sure that the obstruction is relieved before terminating the operative procedure."
-What is the primary medical intervention discussed for managing retroperitoneal hemorrhage from renal angiomyolipoma in a patient with polycystic kidney disease?,"Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited."
-What is the primary purpose of the study on CGS 16949A (fadrozole hydrochloride) in postmenopausal women with metastatic breast cancer?,"Specificity of low dose fadrozole hydrochloride (CGS 16949A) as an aromatase inhibitor. CGS 16949A (fadrozole hydrochloride), a potent cytochrome P450-mediated steroidogenesis inhibitor, blocks aromatase at low doses, but other biosynthetic steps at higher concentrations. Recent studies demonstrated inhibition of C11-hydroxylase, corticosterone methyloxidase-II, and deoxycorticosterone to corticosterone conversion with this agent at some-what higher concentrations than those required for blockade of aromatase. Based upon phase I studies, we postulated that relatively selective inhibition of aromatase might be possible if sufficiently low doses of CGS 16949A were used. A phase II study in 54 postmenopausal women with metastatic breast cancer examined the effects of low dose CGS 16949A on estrogen, mineralocorticoid, and glucocorticoid secretion. Two dose schedules and two dose levels were chosen based upon our prior dose escalation protocol study. Plasma estrone, estradiol, and estrone sulfate as well as urinary estrone and estradiol fell equally with 1.8-4 mg CGS 16949A given either on a twice daily or three times daily dose schedule. Isotopic kinetic studies demonstrated an 84% decrease in the rate of conversion of androstenedione to estrone to 0.40 +/- 0.07% (patients receiving 1.8-4 mg CGS 16949A daily). With these three regimens, basal levels of aldosterone and cortisol did not change significantly over a 12-week period of observation. Clinical examination, plasma electrolytes, and urinary sodium/potassium ratios suggested no biological evidence of mineralo-corticoid deficiency. ACTH-stimulated cortisol concentrations, however, were blunted at each dose level compared to pretreatment values. Nonetheless, peak responses exceeded 550 nmol/L, or a basal to peak difference of 190 nmol/L or greater, in 97% of instances. This probably reflected inhibition of C11-hydroxylase, since basal and ACTH-stimulated levels of 11-deoxycortisol were increased in response to CGS 16949A. Androstenedione and 17 alpha-hydroxyprogesterone also exhibited an upward trend in response to drug treatment. ACTH-stimulated aldosterone levels were blunted to a greater extent than those of cortisol, probably as a reflection of corticosterone methyloxidase type II blockade. Overall, the results suggest that CGS 16949A, at doses of 1.8-2 mg daily, blocks aromatase effectively and does not produce clinically important inhibition of cortisol or aldosterone biosynthesis. Thus, this agent can probably be used safely without glucocorticoid or mineralocorticoid supplementation."
-What are the different histologic patterns of isolated neurofibromas of the conjunctiva observed in the study?,"Isolated neurofibromas of the conjunctiva. We studied four histologically verified cases of isolated neurofibromas of the conjunctiva. The histologic pattern was diffuse in two patients, plexiform in one patient, and solitary in one patient. Simple excision was curative in all cases. We emphasize the importance of distinguishing neuromas (which may be associated with multiple endocrine neoplasia) from neurofibromas."
-What is a double anal canal and how can it develop as a complication of chronic constipation?,"Double anal canal: complication of rectal fecalith. Fecaliths and stercoraceous ulcerations are well-known complications of chronic constipation. The authors present the case of a double anal canal in an elderly man. This anorectal fistula (complex anal fistula) developed as a complication of an impacted rectal fecalith with resultant stercoraceous ulceration. Eventually, a persistent epithelialized canal developed and was demonstrated at double-contrast barium enema examination. The patient remained continent at all times."
-What percentage of patients with closed-head injury were discharged in a vegetative state according to the Traumatic Coma Data Bank Report?,"Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report. To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state."
-What were the key findings regarding the prognosis of B-cell and T-cell diffuse large-cell lymphomas in this Stanford study?,"Similar outcome of treatment of B-cell and T-cell diffuse large-cell lymphomas: the Stanford experience. Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone."
-"What type of cancer was successfully treated in this case report, and how long did the patient survive after the surgical intervention?","Long survival after excision of a primary malignant melanoma of the oesophagus. A woman who had a large primary malignant melanoma of the oesophagus, with evidence of submucosal invasion and several local metastases, underwent resection two years after the onset of retrosternal pain and has survived for 12 years with no recurrence."
-What were the main findings of the study regarding the use of beta-adrenergic-antagonist drugs in preventing gastrointestinal bleeding in patients with cirrhosis and esophageal varices?,"Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. BACKGROUND. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS. After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity."
-What were the key findings from the renal biopsy in the patient with Donohue syndrome?,"Glomerulopathy in patient with Donohue syndrome (leprechaunism). OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen."
-How does endolymphatic pressure differ between normal and hydropic ears in guinea pigs?,"The measurement and manipulation of intralabyrinthine pressure in experimental endolymphatic hydrops. Three to four months after unilateral surgical ablation of the endolymphatic duct and sac, endolymphatic and perilymphatic pressures were measured in both the normal and hydropic ears of 11 guinea pigs. In normal ears, endolymphatic pressure always approximated perilymphatic pressure. Endolymphatic pressure exceeded perilymphatic pressure in all ears with hydrops, except one in which these pressures were equal. The effect of postural inversion on inner ear pressures were studied in both normal and hydropic inner ears. Normal ears showed endolymphatic and perilymphatic pressure to rise equally during this maneuver. In hydropic ears, the difference between endolymphatic and perilymphatic pressure was notably reduced from measurements obtained in the prone position. This study indicates that an alteration in pressure regulation within the inner ear may be important in the pathogenesis and manifestation of experimental endolymphatic hydrops in the guinea pig. Physiologic mechanisms and clinical implications of these results are described."
-What was the cumulative success rate of custom-made distal femoral prostheses at five and seven years?,"Prosthetic replacement of the distal femur for primary bone tumours. Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery."
-What are the key neurological features observed in patients with endemic cretinism across different types of the syndrome?,"The neurology of endemic cretinism. A study of two endemias. Endemic cretinism is the most severe manifestation of dietary iodine deficiency. Two forms of the syndrome are traditionally described: neurological and myxoedematous. Although this classification highlights the important neurological sequelae of the disorder it implies that myxoedematous cretins have an alternative mechanism. Further, the nature of the neurological deficit associated with both types of endemic cretinism has received scant attention in recent times considering that it remains a common disorder in many parts of the world. The nature and extent of the neurological deficit found in endemic cretinism was investigated in 104 cretins from a predominantly myxoedematous endemia in western China and in 35 cretins from central Java, Indonesia, a predominantly neurological endemia. We found a similar pattern of neurological involvement in nearly all cretins from both endemias, regardless of type (myxoedematous or neurological), and of current thyroid function. Hallmarks of the neurological features included mental retardation, pyramidal signs in a proximal distribution and extrapyramidal signs. Many patients exhibited a characteristic gait. This probably reflected pyramidal and extrapyramidal dysfunction, although joint laxity and deformity were important contributing factors. Other frequently encountered clinical features were squint, deafness, and primitive reflexes. Cerebral computerized tomography (CT) revealed basal ganglia calcification in 15 of 50 subjects. The presence of basal ganglia calcification was confined to cretins with severe hypothyroidism. Otherwise, cerebral CT scanning demonstrated only minor abnormalities which did not contribute to the localization of the clinical deficits. We conclude that the same neurological disorder is present in both types of endemic cretinism reflecting a diffuse insult to the developing fetal nervous system. These clinical findings support the concept of maternal and fetal hypothyroxinaemia, arising from severe iodine deficiency, as the primary pathophysiological event in endemic cretinism. Differences between the two types of cretinism may be explained by continuing postnatal thyroid hormone deficiency in the myxoedematous type, which results in impaired growth, skeletal retardation and sexual immaturity."
-What rare complication did the patient experience following a middle and lower lobectomy?,"Pulmonary vein thrombosis following bilobectomy. Acute thrombosis of the pulmonary vein following lobectomy or bilobectomy is a rare complication with no standard guideline for diagnosis or management. In this report, we present a case of right upper lobe vein thrombosis following a middle and lower lobectomy. Diagnosis was confirmed by ventilation-perfusion lung scan, pulmonary angiogram, and bronchoscopy. The patient was treated conservatively with no further complications and had a partial recovery of the circulation to the right upper lobe. A review of the literature is also presented along with the experimental data demonstrating the mechanisms of recovery."
-What percentage of women with atypical squamous cells on Papanicolaou smears were found to be positive for HPV DNA in the study?,"Atypical squamous cells. A case-series study of the association between papanicolaou smear results and human papillomavirus DNA genotype. Thirty women with ""atypical"" squamous cells but not cervical intraepithelial neoplasia (CIN) on their Papanicolaou smears were tested for the presence of human papillomavirus (HPV) with the Southern blot hybridization technique. The Papanicolaou smears were reviewed for the presence of atypical squamous cells according to Patten's criteria. Comparison groups consisted of 30 patients with normal, 29 patients with CIN I and 24 patients with CIN II Papanicolaou smears. Ten of the 30 women (33%) with atypical cells on Papanicolaou smears were positive for HPV DNA as compared to 17% with normal and 59% with CIN I or II Papanicolaou smears. HPV 16 was present in 70-80% of the HPV DNA-positive patients in each Papanicolaou smear group. Concurrent CIN was also identified on colposcopically directed biopsies in 27% of the patients with squamous atypia. Patients with atypical squamous cells on Papanicolaou smears had coexisting HPV infection and CIN in about one-third of the cases. Colposcopy and further follow-up are recommended for such patients."
-How does the injury current affect the excitability of normal tissue during acute regional myocardial ischemia?,"Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. During acute regional myocardial ischemia, a ""current of injury"" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the ""ischemic"" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia."
-How does intraoperative facial nerve monitoring with electrical stimulation (IFNMES) help predict facial nerve function during acoustic tumor removal?,"Intraoperative facial nerve monitoring: prognostic aspects during acoustic tumor removal. Intraoperative facial nerve monitoring with electrical stimulation (IFNMES) has become an integral part of acoustic tumor surgery. We reviewed the records of fifty-six patients who underwent translabyrinthine acoustic tumor removal with IFNMES. There was excellent correlation between intraoperative facial nerve activity and immediate postoperative facial nerve function (24 hours after surgery and at hospital discharge). Our data would suggest that patients who exhibit less than 500 microvolts of ongoing EMG activity during surgery, and who yield at least a 500-microvolt contraction when stimulated with 0.05 milliamps at the brainstem after tumor removal, can expect an excellent immediate facial nerve result (grade I or II)."
-What is the typical treatment approach for diskitis in children according to the study?,"Diskitis in children. Thirty-six patients diagnosed with diskitis from 1978 to 1988 and followed for an average of 29.2 months were reviewed. The study included 23 boys and 13 girls with an average age of 5.3 years. The initial symptoms varied, but distinct clinical patterns emerged and were identifiable in different age groups. Both the leukocyte count and sedimentation rate were elevated. Routine roentgenograms were positive for intervertebral disk space narrowing in 82% of cases, technetium bone scans positive in 72%, and magnetic resonance imaging positive in all recent cases. Treatment consisted of bed rest for all patients, plaster casts for 50%, antibiotics for 40%, and traction for 23%. Regardless of the treatment combination, the course of the disease in most children is benign. At the completion of the study, all patients were asymptomatic including three children who had recurrences. In spite of being asymptomatic, 74% had persistent roentgenographic changes. The administration of antibiotics appears to be appropriate when indicated, i.e., failure to respond to immobilization. Disk space aspiration or biopsy should be reserved for those cases that are refractory to immobilization and antibiotics."
-How does external leg counterpressure affect cardiovascular parameters in simulated mild hypovolemia?,"The autotransfusion effect of external leg counterpressure in simulated mild hypovolemia. We examined the cardiovascular response of external leg counterpressure in healthy volunteers at 100 mm Hg compression pressure. To stimulate mild hypovolemia, measurements were made with the subjects in a 60 degrees head-up tilt position. Left ventricular end-diastolic volume (LVEDV) and cardiac output (CO) were calculated from two-dimensional echocardiography. Flow through the inferior vena cava (IVC) below the origin of the hepatic veins was determined by the Doppler ultrasound technique. The application of counterpressure significantly increased LVEDV, CO, and arterial blood pressure over that seen with tilting without the device. These responses were accompanied by a small but significant increase in IVC flow. We therefore concluded that external leg counterpressure transferred blood to the central circulation by compression of the venous capacitance vessels (an autotransfusion effect) in mild hypovolemia, but such an effect may not benefit patients in a hypovolemic shock state because of the small amount of translocated blood."
-How do cardiovascular reflexes differ between Parkinson's disease patients and healthy subjects in this study?,"Cardiovascular reflexes and autonomic dysfunction in Parkinson's disease. Cardiovascular reflexes were analysed in a group of 20 patients suffering from Parkinson's disease and in 12 age-matched healthy subjects, in order to ascertain the incidence and degree of autonomic dysfunction. The following were measured: heart rate variation during normal breathing, postural change (30/15 ratio) and during the Valsalva manoeuvre: blood pressure variation after standing. These measurements were taken at least 12 h after therapy had been withdrawn and were repeated after therapy had been resumed. Significant changes in the different heart rate variation indices were found in the parkinsonian patients which correlated with the duration and severity of the extrapyramidal symptomatology. After standing the patients showed a significant drop in blood pressure, when compared respectively with their base values and with the response in controls. Anticholinergic drugs had no significant effect on the heart rate variation indices, whereas antiparkinsonian therapy seems to have contributed to the drop in blood pressure after standing."
-What are the potential clinical manifestations of dysfibrinogenemia during pregnancy?,"Dysfibrinogenemia associated with thrombosis and third-trimester fetal loss. A case report. Dysfibrinogenemias are rare genetic disorders that are clinically silent, cause a mild bleeding tendency or have thromboembolic manifestations. During pregnancy they often cause hemorrhage and first-trimester abortions. A patient with a severe thrombotic tendency during pregnancy had a third-trimester fetal loss."
-What were the comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction?,"Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study. BACKGROUND. Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS. One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS. The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications."
-What method was used to assess DNA profiles in the oral exfoliative cytologic study?,"Detection of field change in oral cancer using oral exfoliative cytologic study. Four smears were taken from the normal buccal mucosa of 55 oral cancer patients and 76 cancer-free patients. In each case, two were stained by the Papanicolaou method and two underwent Feulgen hydrolysis. Quantitative assessment of nuclear area (NA) and cytoplasmic area (CA) of the Papanicolaou smears was undertaken using a semiautomatic image analysis system. DNA profiles were assessed from the Feulgen smears using a Vickers M85 microdensitometer (Vickers Instruments, York, England) and were found to be diploid for all patients. Results were then analyzed with respect to those patients who took alcohol, tobacco, combination of alcohol and tobacco, and those who took neither. A significant reduction in CA for the oral cancer group (P equals 0.001) but no change in NA (P equals 0.74) was observed. A detailed analysis of alcohol and tobacco habits could identify no significant role for these two factors, in the reduction in cytoplasmic area. Such field change may prove to be of value in predicting the development of second malignant tumors."
-What percentage of respondents in the Norwegian population study believed penicillin to be effective against viral infections?,"Fever: knowledge, perception and attitudes. Results from a Norwegian population study. To investigate the layman's knowledge, perception and attitudes regarding normal body temperature, fever, infections and the effect of penicillin on virus infections a representative sample of the Norwegian population (619 women and 592 men over the age of 15) was interviewed in 1988 as part of a monthly national opinion poll. One-third thought body temperatures up to 40.5 degrees C to be life-threatening, but the results do not justify the application of the term 'fever phobia' as described in other studies based on non-representative samples. More respondents were afraid of viral infections (48%) than bacterial infections (9%), which may be due to the media focus upon the HIV/AIDS epidemic. Thirty-five per cent believed penicillin to be effective against virus infections. Educational programmes on fever should also include information about virus infections and their treatment."
-How does fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) help in assessing the response to cancer therapy?,"Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects."
-What rare medical condition is described in this case report involving the cauda equina?,Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis.
-How does compression-ischaemia nerve block differently affect warm sensation and heat-induced pain in human volunteers?,"Differential effect of compression-ischaemia block on warm sensation and heat-induced pain. The effect of compression-ischaemia nerve block on psychophysical thresholds for warm sensation and heat-induced pain was studied on 19 normal human volunteers. Although those two sensory submodalities should be predicted to block simultaneously, based on the fact that both are served by unmyelinated primary afferents, it was actually found that warm sensation was much more vulnerable to compression-ischaemia than heat-induced pain. This is interpreted as resulting from different summation requirements for each of the two sensory modalities; sensation of warmth depends on spatial summation to a larger extent than heat-induced pain. Such differential vulnerability is in line with recent clinical studies reporting deterioration of warm sensation associated with preservation of heat pain in peripheral nerve disorders caused by diabetes, ageing and other neuropathic processes."
-What challenges are associated with detecting and treating acoustic schwannomas in children?,"Acoustic schwannomas in children. The clinical presentation and treatment of three cases of acoustic schwannoma occurring in children are described. All the tumors were detected late, when they had attained a large size and were extremely vascular. The use of preoperative tumor embolization as an adjunct to surgical excision is discussed."
-What characteristic of Doppler ultrasound helps differentiate between bland thrombus and tumor thrombus in the main portal vein?,Hepatofugal arterial signal in the main portal vein: an indicator of intravascular tumor spread. Five patients with thrombosis of the main portal vein underwent Doppler ultrasound (US). Three of these patients had confirmed hepatocellular carcinoma. Doppler US allowed differentiation between bland thrombus and tumor thrombus in two of the three patients. Tumor thrombus of the main portal vein was characterized at US by an intraportal arterial waveform in a hepatofugal direction.
-How can forensic experts differentiate between hydrocephalic calf and human calvariae?,"Differentiation of hydrocephalic calf and human calvariae. Occasionally, partial calvariae of hydrocephalic calves are found in forensic contexts and mistakenly identified as human. Such specimens can be properly identified through immunological assessment of associated soft tissue, microscopic analysis of associated hair, and morphological comparison with documented museum specimens. Morphological comparison should focus on the form of the occiput, supraorbital grooves, and bulbous vault and presence of coronal processes."
-What are the key risk factors for infusion-related phlebitis in peripheral intravenous catheters?,"Risk factors for infusion-related phlebitis with small peripheral venous catheters. A randomized controlled trial. OBJECTIVE: To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters. DESIGN: A randomized trial of two catheter materials, with consideration of 21 potential risk factors. SETTING: A university hospital. PATIENTS: Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter. INTERVENTIONS: House officers or ward nurses inserted the catheters, and each insertion was randomized to a catheter made of tetrafluoroethylene-hexafluoropropylene (FEP-Teflon) or a novel polyetherurethane without leachable additives (PEU-Vialon). MEASUREMENTS: Research nurses scored insertion sites each day for inflammation and cultured catheters at removal. RESULTS: The Kaplan-Meier risk for phlebitis exceeded 50% by day 4 after catheterization. intravenous antibiotics (relative risk, 2.00), female sex (relative risk, 1.88), prolonged (greater than 48 hours) catheterization (relative risk, 1.79), and catheter material (PEU-Vialon: FEP-Teflon) (relative risk, 0.73) strongly predicted phlebitis in a Cox proportional hazards model (each, P less than 0.003). The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection (relative risk, 6.19), phlebitis with a previous catheter (relative risk, 1.54), and anatomic site (hand: forearm, relative risk, 0.71; wrist:forearm, relative risk, 0.60). The low incidence of local catheter-related infection was comparable with the two catheter materials (5.4% [95% CI, 3.8% to 7.6%] and 6.9% [CI, 4.9% to 9.6%]); none of the 1054 catheters prospectively studied caused bacteremia. CONCLUSIONS: Multiple factors, including the infusate and the duration of cannulation, contribute to the development of infusion-related phlebitis. The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon, and PEU-Vialon can permit longer cannulation with less risk for phlebitis. The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy."
-What medical condition was the surgical depilation primarily used to treat in this study?,"Surgical depilation for the treatment of pseudofolliculitis or local hirsutism of the face: experience in the first 40 patients. Forty patients underwent surgical depilation for pseudofolliculitis barbae or local hirsutism of the face during a 15-year period. The operative method and its results and pitfalls are discussed. Although it is not the treatment of choice, this operation is very useful when other therapy has not been successful. This seems especially true in male-to-female transsexuals."
-How do the muscle characteristics of Himalayan Sherpas differ from sedentary lowlanders and Caucasian climbers?,"Muscle structure and performance capacity of Himalayan Sherpas. The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg(-1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross-sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density."
-What was the purpose of the study on isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis?,"Test-retest reliability of isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis. The purpose of this study was to evaluate and compare the test-retest reliability of isokinetic torque measurements in the involved and uninvolved knee musculature of 20 subjects with spastic hemiparesis. An isokinetic dynamometer was used to measure maximal voluntary knee extension and flexion at 60 degrees and 120 degrees/s. Peak torque (PT) and average peak torque (APT) data were collected from five repetitions on two separate occasions. Average peak torque was defined as the mean of the PT values obtained during each of the five repetitions. Spasticity was measured in the involved knee musculature prior to isokinetic testing using the Ashworth Scale. Pearson Product-Moment Correlation Coefficients and intraclass correlation coefficients (ICCs) were high (greater than or equal to .90) for both knees for PT and APT at both angular velocities. No clinically meaningful differences were found between the Pearson correlation coefficients and the ICCs of the involved versus the uninvolved knee for any testing conditions. We concluded that isokinetic evaluation of torque, as measured by PT and APT in subjects with spastic hemiparesis, can yield reliable results in both extremities."
-What is the purpose of the thrombogenic microballoon developed in this research?,"Thrombogenic microballoon for cerebral aneurysms, arteriovenous malformations, and carotid cavernous fistula occlusion. Preliminary technical note. A thrombogenic microballoon was developed to overcome the problems of cerebral aneurysm rupture during microballoon inflation and incomplete aneurysm obliteration by microballoons with subsequent fatal rupture. These complications occur in about 35% of reported series with current microballoon embolization techniques. The wall of the new thrombogenic microballoon allows 80% aneurysm occlusion by inflation, thus avoiding mechanical rupture, and at the same time it produces a blood clot in the space remaining between the microballoon and the aneurysm wall. This clot undergoes fibrosis with firm adherence of the microballoon to the aneurysm wall. Experimental evidence is presented to support these conclusions. This thrombogenic microballoon system is also applicable to carotid-cavernous fistulas and arteriovenous malformations."
-What surgical technique was developed to safely perform resternotomy in patients with valved conduits adherent to the sternum?,"Resternotomy in patients with valved conduits adherent to the sternum. Twenty-two patients with valved conduits adherent to the sternum underwent resternotomy. Mean age was 10 +/- 6 years, and mean conduit age was 4 +/- 4 years. Diagnoses were D-transposition (7), truncus arteriosus (7), univentricular heart (6), Taussig-Bing anomaly (1), and corrected transposition (1). The majority of patients (68%) had reoperation for outgrown or degenerated conduits. In 17 patients, the sternum was opened with a chisel. Two of these patients sustained conduit neointimal collapse from manipulation, and 3 had conduit tear requiring immediate cardiopulmonary bypass through the femoral vessels. In the last 5 patients, the sternum was opened above and below the conduit, and the inner table was chiseled and left attached to the conduit avoiding injury and undue conduit manipulation. Cardiopulmonary bypass and operation were carried out uneventfully. We believe that the recent technique described provides a safe alternative approach to valved conduits adherent to the sternum."
-How did the QRS vector changes correlate with infarct size and left ventricular ejection fraction in patients treated with recombinant tissue-type plasminogen activator (rt-PA)?,"Dynamic QRS-complex and ST-segment monitoring in acute myocardial infarction during recombinant tissue-type plasminogen activator therapy. The TEAHAT Study Group. Changes of the QRS complex are the electrocardiographic expression of irreversible injury of the myocardium. In humans, the process of infarction occurs over several hours. A more rapid development of QRS changes has been reported in patients treated with thrombolytic agents. Patients with strongly suspected acute myocardial infarction (AMI) included in a placebo-controlled trial of 100 mg of recombinant tissue-type plasminogen activator (rt-PA) were monitored for 24 hours with continuous, on-line vectorcardiography. The magnitude of the QRS vector changes correlated with infarct size estimated by the maximal value of lactate dehydrogenase-1 (r = 0.69, p less than 0.001) as well as with left ventricular ejection fraction 30 days after randomization (r = 0.49, p less than 0.001). Treatment with intravenous rt-PA limited total QRS vector change but the QRS vector changes observed occurred more rapidly and reached a plateau 131 minutes earlier in patients treated with rt-PA than in those receiving placebo (p less than 0.01). A certain pattern of highly variable ST vector magnitude was identified and was associated with higher maximal lactate dehydrogenase-1 values (23 +/- 13 vs 14 +/- 10 mu kat/liter, p less than 0.001) and a tendency to higher 1-year mortality (24 vs 9%, p = 0.08) than in patients without this pattern. In patients with this pattern, rt-PA did not affect maximal lactate dehydrogenase-1, time to maximal creatine kinase and final magnitude of QRS vector change."
-How do pulse pressure patterns in hypertensive pregnant women relate to birth weight and gestational age?,"Peripheral pulse pressure patterns in pregnancy hypertension. Maternal heart rate and pulse pressure patterns were examined in 30 hypertensive pregnant women using noninvasive methodology described previously. ""Narrow"" and ""wide"" pulse patterns were identified. Narrow cutaneous pulse pressure patterns, which are thought to be caused by vasoconstriction, were associated with lower birth weight infants (1870 +/- 983 versus 3225 +/- 838 g; P less than .001) and earlier deliveries (34.2 +/- 5.2 versus 37.9 +/- 2.8 weeks; P less than .05). The data suggest that these adjunctive maternal cardiovascular-system evaluation techniques may be useful in identifying patients at risk of adverse perinatal outcome by detecting vasospasm of the peripheral microcirculation."
-What techniques were used to detect right-to-left vascular shunting in patients with stroke or neurologic defects?,"Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound. Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization."
-What was the purpose of the study on intrathecal fibrinolytic therapy in patients with aneurysmal subarachnoid hemorrhage?,"Effect of intrathecal fibrinolytic therapy on clot lysis and vasospasm in patients with aneurysmal subarachnoid hemorrhage. A prospective series of 30 patients with a single, angiographically verified aneurysmal subarachnoid hemorrhage (SAH) was studied for the effect of intrathecal thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) on outcome, angiographic vasospasm, and computerized tomography (CT) findings after surgery. The patients included fulfilled the following criteria: operation was performed by Day 3 after the hemorrhage, CT showed only blood in the basal cisterns, and the patient had a single aneurysm or multiple aneurysms that could be treated surgically at the same operation. The patients were divided into groups of 10, with patients receiving 3, 10, or 13 mg of rt-PA in a single intracisternal injection at the end of the operation. There were no differences between the treatment groups in overall outcome. One patient from the 3-mg rt-PA group developed a postoperative intracerebral hemorrhage, and one patient from the 10-mg rt-PA group had a postoperative epidural hematoma. There was one death in the 13-mg rt-PA group that was caused by inclusion of a segment of pericallosal artery in the clip. In all treatment groups a reduction was observed in the amount of blood seen on the postoperative CT scans compared to the preoperative CT scans. The reduction in SAH grade between the 10-mg and 13-mg rt-PA groups was significant (p less than 0.05). The difference in the severity of angiographic vasospasm between the 3-mg and 13-mg rt-PA groups was also significant (p less than 0.05)."
-What were the 4-year actuarial local control and disease-free survival rates for patients undergoing resection in this study of retroperitoneal soft tissue sarcoma?,"Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma. From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance."
-How did the patient develop a meningioma 30 years after receiving a Torkildsen shunt and irradiation treatment?,"Meningioma: the role of a foreign body and irradiation in tumor formation. A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented."
-How did the researchers use PET and radiolabeled microspheres to measure critically ischemic myocardial tissue during acute coronary occlusion?,"Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET. Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography."
-What happened to the patient's auditory evoked potentials after the acoustic neurinoma excision surgery?,"Progressive deterioration of auditory evoked potentials after excision of an acoustic neurinoma: case report. The authors report the case of a 17-year-old girl who underwent excision of bilateral neurinomas of the cerebellopontine angle. Although her auditory evoked potentials were well maintained during the operation, they deteriorated gradually and progressively for the following 2 months. This seemed to reflect degeneration of the cochlear nerve fibers initiated by operative manipulation in the cerebellopontine angle in a patient who had no hearing when she awoke from surgery."
-What is diffuse pulmonary hemorrhage and what are its key clinical manifestations?,"Diffuse pulmonary hemorrhage. Diffuse pulmonary hemorrhage is a syndrome consisting of hemoptysis, anemia, and air-space consolidation. The radiologic appearance is non-specific. Pulmonary hemorrhage may be due to a number of different causes. The differential diagnosis and the diagnostic approach are different in the immunologically intact host as compared with the immunocompromised host. This article reviews the main diagnostic considerations in diffuse pulmonary hemorrhage."
-What are the key characteristics of gonococcal endocarditis during pregnancy based on the case report?,"Gonococcal endocarditis complicating pregnancy: a case report and literature review. The incidence of gonorrhea has decreased substantially in the past decade. Disseminated gonorrhea is more common in women than in men, although gonococcal endocarditis is more common in men. Disseminated gonorrhea is most commonly described in women during menses or pregnancy. Only two cases of gonococcal endocarditis during pregnancy have been reported in the literature since 1942. We report a patient who experienced sudden hemodynamic decompensation at 30 weeks' gestation, resulting in fetal death. Aortic valve replacement was performed, but extensive involvement of the aortic root made complete eradication of infection impossible and eventually resulted in maternal death."
-How do the biomechanical properties of the ankle joint differ between hemiparetic stroke patients and normal subjects?,"Biomechanical changes at the ankle joint after stroke. The resistance of the relaxed ankle to slow displacement over the joint movement range was measured on both sides of a group of hemiparetic stroke patients, in whom spasticity had been established for at least one year and who showed no clinical signs of contractures. The ankle joints of the age-matched normal subjects were flexible over most of the movement range, showing dramatically increasing stiffness only when the foot was dorsiflexed beyond 70 degrees, with a neutral range between 90-100 degrees, and a less dramatic increase in stiffness during plantarflexion. Hemiparetic patients showed identical curves to the normal subjects on the ""healthy"" side, ipsilateral to the causative cerebral lesion, but were significantly stiffer in dorsiflexion on the contralateral side, without change in the minimum stiffness range or during plantarflexion. Therefore significant changes in passive biomechanical properties occur at the affected ankle of hemiparetic subjects, predominantly as the result of a loss of compliance in the Achilles tendon, although an increase in the passive stiffness of the triceps surae may also occur. The contribution of these changes to the locomotor disability of hemiparetic patients is discussed."
-How did the medical team use auditory brainstem responses to help map electrodes in a child with cochlear ossification?,"Multichannel cochlear implant and electrically evoked auditory brainstem responses in a child with labyrinthitis ossificans. Ossification of the cochlea following meningitis presents a surgical challenge. Electrode mapping, especially in the young child, is difficult given the uncertainty of electrode contact with viable neural elements. This paper reviews surgical technique and the use of auditory brainstem responses to map the electrodes. A 4-year-old child deafened by meningitis at age 20 months had bilateral cochlear ossification by computed tomography. At surgery, a canal wall-down mastoidectomy and closure of the ear canal were performed. A trough around the modiolus was drilled, and the electrode array was placed in it. Post-operatively, the patient gave aversive or no responses to electrode stimulation. To assess electrode function, auditory brainstem responses to individual electrode activation were obtained under general anesthesia. Functioning electrodes could thus be selected for mapping. The patient now responds well to sound."
-What is the significance of left ventricular diastolic collapse in the context of regional cardiac tamponade?,"Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade. BACKGROUND. Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. METHODS AND RESULTS. We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. CONCLUSIONS. We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients."
-What was the effect of balloon dilation on the diameter of stenotic Blalock-Taussig shunts in patients with cyanotic heart disease?,"Percutaneous transluminal balloon angioplasty of stenotic standard Blalock-Taussig shunts: effect on choice of initial palliation in cyanotic congenital heart disease. To date, attempted balloon dilation of stenotic standard Blalock-Taussig shunts has been largely disappointing. It has been suggested that this may be due to the use of balloons of insufficient diameter. Balloon dilation of stenotic Blalock-Taussig shunts was attempted with use of relatively large balloons in five patients (11 to 67 months old) with cyanotic heart disease who were becoming progressively cyanotic and polycythemic (hemoglobin 17.9 +/- 1.1 g/dl) because of discrete shunt stenosis at the site of pulmonary anastomosis. Balloon diameters selected were equal to or within 1 mm of the unobstructed proximal shunt diameter. Before balloon dilation the diameter at the site of the stenosis was 2.8 +/- 0.8 mm (range 1.7 to 4); after balloon dilation it was 5.7 +/- 1.1 mm (range 4.5 to 7.5). The diameter increased in all patients (range 2.0 to 3.5 mm); the mean increase was 2.8 +/- 0.2 mm (p less than 0.005). Expressed as a percent, the increase in diameter at the stenosis ranged from 80% to 182.4% (mean 108.2 +/- 16.8%). Before balloon dilation the systemic oxygen saturation was 72.8 +/- 9.2% (range 55% to 80%) and after balloon dilation it was 83.6 +/- 2.9% (range 80% to 87%). A satisfactory increase (range 6% to 25%) in blood oxygen saturation was seen in all patients; the mean increase was 10.8 +/- 3.2% (p less than 0.01). At follow-up, the oxygen saturation by pulse oximetry was 85.8 +/- 2.9% (mean 5.8 +/- 1.7 months after balloon dilation) and the hemoglobin was 15.6 +/- 1.9 g/dl (mean 6.6 +/- 1.5 months after balloon dilation)."
-How do limited access to healthcare and cultural barriers impact neurological care for minority populations in the United States?,"Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies."
-What was the most frequent recognized abnormality in the study of cerebral infarction among young patients?,"Cerebral infarction in young people. A study of 148 patients with early cerebral angiography. The aetiology of strokes was studied in a hospital based series of patients aged up to 40 years with precise clinical and radiological criteria. One hundred and forty five patients (75 males and 73 females) aged five to 40 years with cerebral ischaemia were evaluated. Aetiology was heterogeneous and could be classified into seven groups. Cerebral arteriograms were performed in all cases and indicated the aetiological diagnosis in most patients. Embolism was the most frequent recognised abnormality (38.4%). There were no complications of arteriography. Arterial dissections discovered by arteriography were the cause of the stroke in 10.1% of the patients. Atherosclerosis was diagnosed in 32 cases and was the commonest cause (21.6%). In one fifth of cases no cause was found. Contraceptive drugs were considered as potential cause of ischaemic stroke in 11.5%, cardiac diseases in 12.8% and haematological disorders in 8.1%. Other potential causes included migraine, inflammatory diseases, pregnancy and lacunas. Follow up in 126 cases showed that many patients had good functional recovery."
-What were the predominant indications for knee arthrodesis using an intramedullary nail in this study?,"Arthrodesis of the knee with an intramedullary nail. The cases of twenty patients who had an arthrodesis in which an intramedullary nail was used for stabilization were reviewed at an average follow-up of six years. The predominant indications were infection after total knee arthroplasty and post-traumatic pain and instability. Other indications included aseptic loosening of the components of a total knee arthroplasty, reconstruction after resection of a giant-cell tumor, non-union of a fracture of the distal part of the femur or the proximal part of the tibia, and failed external-compression arthrodesis. Success was achieved in seventeen patients (85 per cent), and functional stability immediately postoperatively was gained in all twenty. Of the three patients in whom the arthrodesis failed, all had sustained an intraoperative fracture, and infection eventually developed. Of the twelve nails that were secured to the greater trochanter with a loop of stainless-steel wire, none showed evidence of proximal migration. Of the eight nails that were not thus secured, two migrated proximally, necessitating removal of the nail. Two drawbacks to this operation are the long duration and the large amount of blood that is lost. The major advantage is that a high percentage of patients have progression to a stable fusion despite serious problems. Furthermore, all but seven patients (including the six who had a tumor or who had sustained an intraoperative fracture) were able to bear full weight by the second postoperative week. Only a few patients needed an external support for walking."
-How do thromboxane A2 and serotonin contribute to platelet-mediated obstruction in coronary artery stenosis?,"Role of thromboxane and serotonin as mediators in the development of spontaneous alterations in coronary blood flow and neointimal proliferation in canine models with chronic coronary artery stenoses and endothelial injury. Platelet-mediated obstruction of stenotic and endothelium-injured coronary arteries may be important in the abrupt progression from chronic stable to unstable coronary heart disease syndromes in patients. Transcardiac accumulation of thromboxane A2 and serotonin has been demonstrated in patients as chronic stable angina is converted to unstable angina. In this study in anesthetized open chest dogs with coronary artery stenosis and endothelial injury, thromboxane A2 and serotonin were shown to be important mediators of intermittent coronary obstruction caused by platelet aggregation and dynamic vasoconstriction. Furthermore, thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists, singly and together, provided substantial protection against repetitive platelet aggregation and dislodgment in canine models with coronary artery stenosis and endothelial injury even when systemic catecholamine concentrations were markedly elevated. These same observations apply in chronically instrumented, awake, unsedated dogs with coronary artery stenosis and endothelial injury in which recurrent platelet attachment and dislodgment cause cyclic flow alterations that may be prevented by thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists. Chronically instrumented dogs with coronary stenosis and endothelial injury in which recurrent platelet attachment and dislodgment occurred also developed neointimal proliferation of varying severity within 10 days to 3 weeks; the morphologic appearance of the neointimal proliferation was identical to that found in patients who develop restenosis after coronary angioplasty."
-How does a leucine to isoleucine substitution in the retroviral envelope surface glycoprotein affect the lytic properties of the Friend murine leukemia virus?,"Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain."
-What is mesonephric rest hyperplasia and how can it be misdiagnosed?,"Mesonephric rest hyperplasia. A potential diagnostic pitfall. A case of mesonephric rest hyperplasia, an incidental finding in the hysterectomy specimen of a 48-year-old woman, was initially misdiagnosed as a well-differentiated cervical adenocarcinoma. We highlight the histologic, histochemical, and immunohistochemical features of this potential diagnostic pitfall and review the relevant literature."
-What are the potential disadvantages of the subclavian flap aortoplasty procedure in treating coarctation?,"Coarctation: do we need to resect ductal tissue? A review of the literature as well as a retrospective review of 100 neonates undergoing operation for coarctation at Children's Hospital in Boston between 1972 and 1984 has not established clear superiority for either resection and end-to-end anastomosis or subclavian flap aortoplasty with respect to risk of recurrent coarctation. However, there is histological evidence that the juxtaductal coarctation shelf is composed of smooth muscle of ductal origin, which subsequently fibroses. This abnormal tissue may be at risk for late aneurysm development, particularly if balloon dilatation angioplasty is required. The fact that this abnormal tissue is not removed by the subclavian flap procedure is one of the inherent disadvantages of that procedure. Other disadvantages include the need to sacrifice the left subclavian artery and the fact that, unlike resection and end-to-end anastomosis, the subclavian flap procedure does not lend itself to augmentation of the hypoplastic distal aortic arch. Furthermore, occasionally a secondary coarctation membrane is present within the distal aortic arch, and though it is readily detected during the resection procedure, it can be missed with the subclavian flap procedure. Based on these considerations rather than on a demonstrated superiority of either procedure, my colleagues and I currently prefer resection and end-to-end anastomosis over subclavian flap aortoplasty."
-What variations were observed in the classical activation pattern during atrial flutter entrainment in the canine sterile pericarditis model?,"Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo. BACKGROUND. Recently, we used a custom designed ""jacket"" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels. METHODS AND RESULTS. In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a ""classical"" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry. CONCLUSIONS. The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the ""figure-eight"" reentrant circuit."
-What was the primary aim of the study on nasal calcitonin in treating post-traumatic algodystrophy?,"The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration. For this reason, we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post-traumatic algodystrophy in a prospective randomized double-blind study. We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment. There was, however, a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover. Possible reasons for this lack of clinical and skeletal effect are discussed."
-What is the primary diagnostic procedure for identifying blunt traumatic bladder rupture according to this study?,"Blunt traumatic bladder rupture: the role of retrograde cystogram. STUDY OBJECTIVE: We evaluated the importance of microscopic and gross hematuria and the role of retrograde cystography and computed tomography (CT) in the diagnosis of blunt traumatic bladder rupture. DESIGN: All cases at a Level I trauma center between January 1, 1986, and March 31, 1989, were reviewed retrospectively. SETTING: Level I trauma center, university hospital. TYPE OF PARTICIPANTS: All patients with acute blunt abdominal trauma admitted to this Level I trauma center. INTERVENTIONS: The patients' charts were reviewed with emphasis on mode of diagnosis, treatment, and outcome. MEASUREMENTS AND MAIN RESULTS: Twenty-one patients had bladder rupture. All 21 had hematuria with more than 50 RBCs/high-power field, 17 gross and four microscopic. Twenty patients underwent retrograde cystography, which accurately identified bladder rupture, and one was found at laparotomy for other injuries. Seven patients had CT of the abdomen and pelvis, which failed to demonstrate bladder rupture. There were no associated urethral injuries in any of the patients with bladder rupture. CONCLUSION: Significant (more than 50 RBCs/high-power field) hematuria is the principal indication for evaluation for blunt bladder injury, and retrograde cystography is the diagnostic procedure of choice. CT is neither sensitive nor specific enough as primary diagnostic modality."
-What novel mutation was discovered in the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis patients?,"A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients. Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G----T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration."
-What are the main advantages of bopindolol in treating hypertension?,"Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension. Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism)."
-What were the key findings of the NHLBI PTCA Registry comparing outcomes of percutaneous transluminal coronary angioplasty in patients with stable versus unstable angina pectoris?,"Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: a report of the 1985-1986 NHLBI PTCA Registry. In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985-May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p less than 0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p less than 0.001). Incidence of major patient complications (p less than 0.01) and of emergency coronary bypass surgery (p less than 0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979-1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single- and multi-vessel coronary disease."
-What was the purpose of comparing laser-assisted thrombolysis (LAT) with enzymatic thrombolysis (ET) in the experimental treatment of thrombotic vascular occlusion?,"Experimental treatment of thrombotic vascular occlusion. The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01)."
-What is the Pena-Shokeir phenotype and what are its key pathological characteristics in an infant born to a cocaine-using mother?,"Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage."
-What percentage of patients in the study experienced otolaryngic complications during cancer chemotherapy?,"The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed."
-What percentage of patients with stage D2 prostate cancer showed elevated plasma chromogranin-A levels in the study?,"Elevated plasma chromogranin-A concentrations in prostatic carcinoma. Chromogranin-A is considered a sensitive immunohistochemical tissue marker in neuroendocrine prostatic carcinoma. We report that the plasma chromogranin-A level was elevated in 48% of 25 patients with stage D2 prostate cancer, and suggest that this marker can be used to monitor the clinical course of these patients."
-What is the recommended surgical procedure for treating thoracic myelopathy caused by ossification of the ligamentum flavum (OLF)?,"Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment. The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force."
-What is the significance of a negative exercise thallium test in patients with critical residual stenosis after thrombolysis for acute myocardial infarction?,"Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction. BACKGROUND. After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia. METHODS AND RESULTS. The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1-16.3). CONCLUSIONS. The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance."
-How does the genetically engineered toxin DAB486IL-2 specifically target and kill leukemic cells?,"Therapeutic effects of genetically engineered toxin (DAB486IL-2) in patient with chronic lymphocytic leukaemia. In DAB486IL-2 the receptor-binding domain of native diphtheria toxin is replaced by human IL-2 sequences. This recombinant fusion protein is selectively cytotoxic for cells bearing high-affinity IL-2 receptors--eg, leukaemic cells. A patient with chronic lymphocytic leukaemia who did not respond to gamma interferon and conventional antileukaemic drugs has responded to DAB486IL-2."
-What was the prevalence of autoantibodies in different pregnancy conditions according to the study?,"The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment."
-What is the proposed relationship between autonomic dysreflexia and atrial fibrillation in patients with high-level spinal cord injury?,"Atrial fibrillation associated with autonomic dysreflexia in patients with tetraplegia. Atrial fibrillation is an arrhythmia characterized by disorganized atrial depolarizations and an irregular ventricular response. Most patients with atrial fibrillation have underlying cardiac pathology. This paper presents the cases of three patients with high-level spinal cord injury and symptoms of autonomic dysreflexia who developed atrial fibrillation without any cardiac or metabolic disease that would predispose them to this. The paper proposes that autonomic dysreflexia might predispose a patient to atrial fibrillation by altering the pattern of repolarization of the atria, making the heart susceptible to a reentrant type of arrhythmia. High-level spinal cord injured patients may be at increased risk for the development of atrial fibrillation, an arrhythmia which, if left untreated, can increase the incidence of an embolic cerebrovascular accident that could further impair the patient's functional status."
-What techniques were used to extend the exposure of the distal internal carotid artery in the anatomic dissection study?,"Selection of the approach to the distal internal carotid artery from the second cervical vertebra to the base of the skull. Although several approaches for exposure of distal internal carotid artery lesions have been reported, the precise anatomic levels for which each of these maneuvers are most appropriate have not been well described. Since these techniques may require preoperative preparation, it is useful to determine in advance how much exposure will be needed and to select the most suitable and effective technique. We used anatomic dissection in 12 human cadaver specimens (24 carotid bifurcations) to define the limits of distal internal carotid artery exposure by several commonly advocated methods. The standard anterior approach along the sternocleidomastoid muscle allowed exposure of the internal carotid artery to the level of the upper one third of the second cervical vertebra. The upper limit of this exposure was extended to the middle of the first cervical vertebra by division of the posterior belly of the digastric muscle. Anterior subluxation of the mandible increased the distal exposure of the internal carotid artery to the superior border of the first cervical vertebra. Styloidectomy in combination with the preceding maneuvers extended the exposure an additional 0.5 cm cephalad. Lateral mandibulotomy did not significantly extend exposure beyond that obtained with mandibular subluxation and styloidectomy. Exposure of the internal carotid artery in the 1 cm immediately below the base of the skull required a posterior approach with mastoidectomy."
-How does cardioversion with multiple shocks potentially impact the diagnosis of myocardial infarction?,"Time course of creatine kinase release after termination of sustained ventricular dysrhythmias. Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern."
-What is the significance of the mitral valvuloplasty performed 5 years after the repair of a sinus venosus atrial septal defect?,"Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty."
-What was the attitude of Danish anaesthetic departments towards using lumbar regional anaesthesia in patients receiving prophylactic anticoagulant therapy?,"Lumbar regional anaesthesia and prophylactic anticoagulant therapy. Is the combination safe? A survey has been carried out in all Danish anaesthetic departments (n = 80) regarding the attitude towards the use of epidural/spinal lumbar analgesia in patients who were receiving prophylactic anticoagulant therapy for the prevention of thromboembolism. About 60% of the departments used the techniques in patients receiving low-dose heparin and no side effects had been experienced. Spinal and epidural anaesthesia were in general regarded as being contraindicated in patients fully anticoagulated with vitamin K antagonists. In the world literature, the attitude towards the combination is conflicting. No randomised trial has been performed and complications are almost entirely confined to patients fully anticoagulated with vitamin K antagonists. Only one case of an epidural haematoma has been recorded when subcutaneous low-dose heparin was used as thromboprophylaxis."
-What adverse reactions did patients experience when receiving subcutaneous methadone for cancer-related pain?,"Local toxicity with subcutaneous methadone. Experience of two centers. We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone."
-How does calcification affect the mechanical response of rabbit arteries during balloon dilation?,"Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation. BACKGROUND. Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term ""hardening of the arteries."" METHODS AND RESULTS. To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients. CONCLUSIONS. It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial ""hardening"" associated with atherosclerosis."
-Does the timing of aneurysm surgery after subarachnoid hemorrhage affect the development of delayed cerebral ischemia?,"Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia. A consecutive series of 145 patients with acute aneurysmal subarachnoid hemorrhage (SAH) were operated on within 7 days of SAH and were prospectively evaluated over a 4-year period to determine if the timing of aneurysm surgery influenced the development of delayed cerebral ischemia. All patients were managed with a standardized policy of urgent surgical clipping and treatment with aggressive prophylactic postoperative volume expansion. Patients with delayed ischemic symptoms were additionally treated with induced hypertension. Forty-nine patients underwent surgery on Day 0 or 1 (Group 1) post-SAH, 60 patients on Day 2 or 3 (Group 2), and 36 patients on Days 4 through 7 (Group 3). Postoperative delayed cerebral ischemia developed in 16% of (Group 1) patients, in 22% of Group 2 patients, and in 28% of Group 3 patients. Cerebral infarction resulting from delayed cerebral ischemia developed in only 4% of Group 1 patients, 10% of Group 2 patients, and 11% of Group 3 patients. A bad clinical outcome as a result of delayed cerebral ischemia occurred in one Group 1 patient (2%), two Group 2 patients (3%), and one Group 3 patient (3%). Preoperative grade was not significantly correlated with the incidence or severity of delayed cerebral ischemia at any time interval except that patients in modified Hunt and Hess Grade I or II who underwent surgery on Day 0 or 1 after SAH had no strokes or bad outcomes from delayed cerebral ischemia. This study demonstrates that there is no rationale for delaying aneurysm surgery based on the time interval between SAH and patient evaluation."
-What is the potential benefit of L-carnitine treatment for patients with ornithine transcarbamylase deficiency?,"Carnitine deficiency associated with ornithine transcarbamylase deficiency. An infant with X-linked recessive ornithine transcarbamylase deficiency is described who also had severe deficiency of plasma and liver carnitine during normoammonemic periods. Treatment with L-carnitine (100 mg/kg/day) for 12 months decreased the frequency of hospitalizations for hyperammonemia, although it did not alter his neurologic status. This report demonstrates that persistent carnitine deficiency may be present in patients with ornithine transcarbamylase deficiency even when plasma ammonia is normal. Carnitine evaluation and supplementation may be important in the treatment of patients with this metabolic disorder."
-How do primary dysfunctions in neural control of arterial pressure potentially contribute to the development of hypertension?,"Do primary dysfunctions in neural control of arterial pressure contribute to hypertension? This article is a summary of the physiological and clinical evidence that links the cause of essential hypertension to the brain. We stress the potential importance of a biochemical disturbance in the central role of angiotensin II in the regulation of arterial pressure. While the evidence is compelling, we acknowledge the need for further complete studies on this timely subject."
-"What is the relationship between oral contraceptive use, liver cell adenoma, and the potential progression to hepatocellular carcinoma?","Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation. From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine-needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as ""hepatocellular carcinoma"" and 9 as ""consistent with liver cell adenoma."" The cytologic diagnoses were confirmed in the follow-up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma."
-What were the ovarian ablation failure rates for breast cancer patients above 40 years old in the two different radiation dose schedules?,Ovarian ablation failures by radiation: a comparison of two dose schedules. Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.
-"What similarities were found in olfactory dysfunction among Alzheimer's disease, Parkinson's disease, and the parkinsonism-dementia complex of Guam?","Olfactory dysfunction in three neurodegenerative diseases. Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate."
-What is the predominant method for evaluating nonpalpable breast lesions detected by mammography?,"Mammographic guidewire localization of nonpalpable breast lesions. Guidewire-directed biopsy is the predominant method of evaluating nonpalpable breast lesions detected by mammography. It is an accurate and safe procedure for obtaining a histologic evaluation of abnormal tissue, leading to early diagnosis and improved survival rates. This report reviews 526 needle localizations and biopsies of nonpalpable breast lesions performed in two community hospitals over a 39-month period and compares early results with those achieved in the last 13 months of the study. This review indicates that as experience in using this modality increased, the cancer detection rate increased and the percentage of invasive cancers decreased. The percentage of cancers detected in the final 13 months of the study (19%, Group II) was higher than in the first 26 months of the study (13%, Group I). Although microcalcifications were found in 24 per cent of the mammograms leading to a diagnosis of cancer, they did not prove to be a reliable indicator of malignancy in this study."
-"What was the mean incidence rate of Parkinson's disease per year in the Local Health Service of Ferrara, Italy, between 1967 and 1987?","Parkinson's disease in Ferrara, Italy, 1967 through 1987. Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type."
-What was the outcome of transhepatic electrohydraulic lithotripsy in the 50 patients studied?,"Common bile duct and intrahepatic stones: results of transhepatic electrohydraulic lithotripsy in 50 patients. Percutaneous, transhepatic, intracorporeal, electrohydraulic shock wave lithotripsy was performed in 50 patients after failure of endoscopic treatment (n = 43) or directly in patients with a strictured hepaticojejunostomy (n = 7). Twenty-seven patients had common bile duct stones; 23, intrahepatic stones. Three steps were used: A transhepatic bilicutaneous fistula was created, a wide communication between the bile duct and the gut was established, and contact shock wave lithotripsy was performed under endoscopic guidance. Afterward, 46 patients were free of stones. In four patients with diffuse intrahepatic lithiasis, only 75% of stones could be cleared. Severe complications, seen in 11 patients (hemobilia necessitating transfusion [n = 6], bile duct perforation resulting in cholangitis [n = 3], acute pulmonary edema [n = 1], and hemothorax [n = 1]), were fatal in four patients; all occurred early in the study. The authors modified their technique by dilating the biliary tract in two sessions 3 days apart, waiting 6 days for the tract to mature, and then introducing the cholangioscope directly through the skin, significantly reducing complications and mortality (P less than .005)."
-How does mucociliary clearance change in asthmatic patients during and after an acute exacerbation?,"Changes in mucociliary clearance during acute exacerbations of asthma. Previous studies have suggested that mucociliary clearance (MC) is impaired in asthmatic subjects. If so, impaired clearance may be an important factor in acute exacerbation. We proposed that if MC plays a significant role in acute illness, MC should be impaired during the exacerbation but improve after recovery. To test this hypothesis, five asthmatic patients with attacks requiring hospitalization underwent measurement of MC using radiolabeled aerosol and a gamma camera. They were studied on the second or third day after admission with repeat measurements after discharge. Spirometry was performed before all studies. After an equilibrium xenon scan (133Xe), which defined lung borders and measured regional volume, radiolabeled saline particles containing technetium-labeled (99mTC) sulfur colloid were deposited and used to label airway mucus. Deposition patterns were matched by regulating particle distribution and breathing pattern. MC was then measured as percentage retention of radioactivity at 10-min intervals for 2 h. When hospitalized, 96.0 +/- 2.06% (SEM) of the initial radioactivity was retained in the lung after 2 h, indicating little clearance of mucus from the lung. In fact, no significant changes were detected when activity at 120 min was compared with measurements at 10 min (99.2 +/- 0.22%, NS). After discharge clearance was markedly enhanced. That is, retention of lung activity was significantly lower at all time intervals from 10 min onward, with only 70.9 +/- 3.86% retained at 120 min (p = 0.008). During an asthmatic attack warranting hospital admission, MC is significantly impaired, with marked improvement following recovery."
-How do changes in circulating pancreatic enzymes and protease inhibitors relate to the development of ERCP-induced pancreatitis?,"The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors. The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis."
-How does hypoxia affect glucose transport in skeletal muscle?,"Stimulation of glucose transport in skeletal muscle by hypoxia. Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia."
-What is tegmental dehiscence and what are its potential clinical manifestations?,"Tegmental dehiscence and brain herniation into the middle ear cleft. The tegmen tympani may occasionally be breached by herniation of the temporal lobe with or without dural cover. The clinical presentation may be obvious with CSF otorrhoea but less so with apparent middle ear effusion, CSF rhinnorrhoea, conductive hearing loss, recurrent meningitis or intracranial sepsis. Diagnosis requires suspicion of the condition, which may be aided by radiological imaging. Surgical repair is to be recommended: various techniques are available but bone enveloped by fascia placed by subtemporal approach is preferred. The features of this problem are highlighted by four cases."
-What are the key clinical and biochemical characteristics of the 32-year-old patient with chronic GM1 gangliosidosis?,"A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies. Clinical and biochemical studies are reported on a 32-year-old man with GM1 gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM1 ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM1 ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM1 ganglioside beta-galactosidase activity was only 10% of normal. These findings suggest that impaired GM1 ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM1 gangliosidosis."
-What treatment was used to manage the patient's intractable axial dystonia after spinal instrumentation for scoliosis?,"Intrathecal baclofen for intractable axial dystonia. Following spinal instrumentation for scoliosis, a patient developed intractable axial dystonia refractory to conservative medical management. We describe the successful treatment of this dystonia with a continuous infusion of intrathecal baclofen and the subsequent long-term management."
-What is the primary goal of treatment for metastatic breast cancer?,"The treatment of metastatic breast cancer. While metastatic breast cancer is not curable, it is treatable. Its treatment is associated with a relatively high rate of success, and patients are able to maintain a good quality of life for periods ranging from a few months to several years. This knowledge should encourage both the patient and the oncologist to maintain treatment as long as potentially effective therapeutic methods are available. Progress is ongoing both in the development of new forms of treatment and in new ways of using and combining already existing therapeutic modalities. There is still no established ""best"" or ""only"" first treatment of metastatic breast cancer. When secondary and later treatment is to be undertaken, the task of selecting the most appropriate treatment becomes even more complex. It is only through controlled clinical trials that useful therapeutic guidelines will develop. Treatment is a joint endeavor involving both the physician and the patient. Communication must remain open. In the final stages of the illness, treatment should be directed toward the relief of distressing symptoms and anxiety."
-What unusual presentation of cryptococcal infection was observed in the HIV-positive patient described in this case report?,Cryptococcal pleural effusion preceding cryptococcal meningitis in AIDS. The authors report a case in which a small cryptococcal pleural effusion preceded the development of severe cryptococcal meningitis in an HIV-positive patient. The appearance of an isolated transient pleural effusion is a very unusual presentation for AIDS-related complications. The authors suggest that cryptococcal infection be considered in this setting.
-What is the estimated number of premature deaths in the United States in 1985 attributed to smoking-related diseases?,"Smoking-attributable mortality and years of potential life lost--United States, 1988. Smoking is a leading cause of diseases associated with premature mortality in the United States; in 1985, these diseases accounted for an estimated 390,000 premature deaths. In this report, mortality data and estimates of smoking prevalence for 1988 are used to calculate smoking-attributable mortality (SAM), years of potential life lost (YPLL), and age-adjusted SAM and YPLL rates for the United States. Calculations were performed using Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC II) software, which includes relative risk estimates for 22 adult (i.e., greater than or equal to 35 years of age) smoking-related diseases and relative risk estimates for four perinatal (i.e., less than 1 year of age) conditions. Age-, sex-, and race-specific mortality data for 1988 were obtained from CDC's National Center for Health Statistics. Data on burn deaths caused by cigarettes were obtained from the Federal Emergency Management Agency. The estimated number of deaths among nonsmokers from lung cancer attributable to passive smoking was obtained from a report of the National Academy of Sciences. Age-, sex-, and race-specific current and former smoking prevalence rates in 1988 for adults aged greater than or equal to 35 years and for women aged 18-44 years were estimated by linear extrapolation using National Health Interview Survey data for 1974-1987."
-What are the questionable cancer treatment practices found in Tijuana and other Mexican border clinics?,"Questionable cancer practices in Tijuana and other Mexican border clinics. Tijuana, Mexico, has become a refuge for cancer patients who have been convinced that they may be cured of their terminal illness by unconventional, unproved, and disproved methods offered in the border clinics. About a dozen United States promoters have joined with Mexican colleagues to offer a variety of treatments. Some patients are diagnosed using standard methods prior to arrival at the clinics, but many healthy individuals are misdiagnosed as having cancer or ""precancer"" and are then treated there. Others are told they have been cured or are improving even though they still have active disease. The modalities and regimens used are often referred to as ""metabolic therapy"" and, for the most part, are either not based on sound scientific principles or have been shown in controlled clinical trials to be useless or even dangerous. A basic metabolic regimen consists of three phases: detoxification with fasting and bowel cleansing, strengthening the immune system with numerous ""supplements,"" and attacking cancer with ""natural and non-toxic"" chemicals. Popular treatments include injections of hydrogen peroxide, large quantities of pressed liver and carrot juice, coffee enemas, infusions of Laetrile mixed with massive doses of vitamins and dimethylsulfoxide (DMSO), special diets, and a host of other pseudoscientific regimens. Unfortunately, no evidence exists that any of these modalities is more effective than no treatment at all. Patients traveling to the Mexican border clinics for metabolic therapy are subjecting themselves to costly and hazardous regimens, especially if they forgo responsible medical care in the process. The American Cancer Society, therefore, strongly urges individuals with cancer not to seek treatment with metabolic therapies in the Mexican border clinics."
-What did the study reveal about Ki-67 reactivity and proliferative activity in different histological subtypes of breast carcinoma?,"Ki-67 staining in histological subtypes of breast carcinoma and fine needle aspiration smears. Thirty four cases of invasive breast carcinoma were analysed for heterogeneity of Ki-67 reactivity in a tumour, and proliferative activity in various histological subtypes was compared. The growth factions determined in areas of central and peripheral tumour were the same. Mucinous and lobular carcinoma showed lower Ki-67 activity than ductal carcinomas. When ductal carcinomas were subdivided according to their dominant growth pattern, the carcinomas with a solid or comedo growth pattern showed the highest proliferative activity. These results largely confirm data from previous cell kinetic studies on the incorporation of radioactively labelled thymidine. A correlation between the growth fraction determined by Ki-67 in fine needle aspiration smears and cryostat sections of corresponding tumours was shown, implying that the immunostaining of cytological smears gives a reliable impression of the growth fraction of a tumour and may therefore be used in prospective studies."
-What was the healing rate of transmetatarsal amputations in different patient groups based on revascularization?,"Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized."
-What medical specialties are involved in investigating the relationship between esophageal motility disorders and unexplained chest pain?,"The relationship between esophageal motility disorders and microvascular angina. Patients with unexplained chest pain have caused investigators in cardiology, gastroenterology, and psychiatry to find abnormalities with overlap among the three specialties. This article reviews the data concerning the potential interrelation of chest pain of cardiac or esophageal origin."
-What are the key challenges and uncertainties associated with using deep brain stimulation for pain control in humans?,"Deep brain stimulation: a review of basic research and clinical studies. Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control."
-How did A-LAK cells demonstrate their ability to establish contact with metastatic melanoma cells in this murine model?,"Establishment of cell-to-cell contact by adoptively transferred adherent lymphokine-activated killer cells with metastatic murine melanoma cells. A murine model of pulmonary B16 melanoma was used to study the infiltration into metastases of lymphokine-activated killer (LAK) cells and adherent lymphokine-activated killer (A-LAK) cells and, specifically, to study whether A-LAK cells are able to leave the tumor microcirculation and establish cell-to-cell contact with malignant cells. Fluorescence microscopy demonstrated that A-LAK cells accumulated in metastases twice as efficiently as LAK cells during interleukin-2 stimulation. Electron microscopy of pulmonary metastases 16 hours after administration of 2.5 x 10(7) A-LAK cells revealed A-LAK cells, identified by the presence of typical two-compartment granules, in direct contact with melanoma cells. This finding was confirmed by using A-LAK cells prelabeled with polycationized ferritin. In conclusion, our observations demonstrate unambiguously the ability of adoptively transferred A-LAK cells to establish contact with extravascular metastatic melanoma cells."
-How did the cardiovascular responses of hypertensive and nonhypertensive patients differ during social interactions in the coronary care unit?,"A comparison of hypertensive and nonhypertensive coronary care patients' cardiovascular responses to visitors. Patients with and without hypertension in a coronary care unit (n = 24) were compared with respect to cardiovascular responses to both a family visit and an interview by an investigator. Variables for each of the four cardiovascular indicators (systolic blood pressure, diastolic blood pressure, heart rate, and premature ventricular contractions) included the value before, the highest value during, the lowest value during, and the value after each social interaction condition. The highest group means for systolic blood pressure and heart rate were significantly higher for patients with hypertension than for patients without hypertension under both the interview and visit conditions. Differences in cardiovascular responses were not significantly greater for family visits than for interviews for patients with hypertension compared with those without hypertension. Thus, although hypertensive patients had greater cardiovascular reactivity to both social interaction conditions than nonhypertensive patients in the coronary care unit, family visits were no more physiologically stressful than a comparative interaction condition."
-What was the primary objective of the study involving surgical manipulation of primate cerebral arteries in established vasospasm?,"Surgical manipulation of primate cerebral arteries in established vasospasm. It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported. Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (greater than 40% reduction in vessel caliber compared to baseline, p less than 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation."
-"What was the frequency of pulmonary embolism at autopsy during the 1980s in the surgical department of Malmo, Sweden?","Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. A retrospective analysis was undertaken of all surgical patients in Malmo, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy. The analysis included a comparison with the earlier analysed and reported time period from 1951 to 1980. A continued high frequency of pulmonary embolism at autopsy was seen during the 1980s (20.3 per cent of deaths, 31.7 per cent of autopsies). Of the 391 autopsy-verified pulmonary emboli found between 1981 and 1988, 113 (28.9 per cent) were considered fatal, 104 (26.6 per cent) contributed to death and 174 (44.5 per cent) were incidental. Few patients had symptomatic deep vein thrombosis or pulmonary embolism before death. The overall frequency of major pulmonary embolism in surgical patients remained unchanged (0.3 per cent). The frequency of major postoperative pulmonary embolism showed an increase during the 1950s and 1960s (maximum 0.4 per cent) but a decrease in the last 5-year period of the 1970s (0.3 per cent), which has earlier been reported upon. This decrease continued during the 1980s (0.2 per cent) (P less than 0.05). An increase was found in the number of patients operated on who had autopsy-proven pulmonary embolism and who received thromboprophylaxis. Pulmonary embolism continues to be a major cause of death in surgical patients; however, postoperative major pulmonary embolism has shown a reduction in the last 15-year period."
-How does acetylcysteine improve hemodynamics and oxygen transport in patients with fulminant hepatic failure?,"Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. BACKGROUND. When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. METHODS. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. RESULTS. In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn.sec.cm-5 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. CONCLUSIONS. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen."
-"What are the two major pathological alterations observed in the mutant rats zitter, tremor, and spontaneously epileptic rat (SER)?","CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER. The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER."
-What were the most prevalent pathogens identified in the pneumonia cases among Filipino children in this study?,"Etiology of infection and morphologic changes in the lungs of Filipino children who die of pneumonia. Histopathologic studies and isolation of virus and bacteria in culture were carried out for 71 children less than 5 years of age with fatal pneumonia. A potential microbial etiology was identified for 61 children (86%): bacteria for 19 (27%), virus for 16 (23%), and virus plus bacteria for 26 (37%). Staphylococcus was the most prevalent pathogen, alone or in combination with other organisms, followed by Pseudomonas aeruginosa. Viral infection may predispose to bacterial infection in some children. A correlation of clinical course, results of cultures, and morphologic changes revealed cofactors that may have contributed to a fatal outcome. Lung abscess, pericarditis, myocarditis, endocarditis, and meningitis were associated with bacterial infection. Many patients in this study had severe bronchopneumonia, with a high prevalence of complications such as abscess (62%), atelectasis (40%), pericarditis (28%), and empyema (7%). Such complications added to multiple infections, measles, and malnutrition contributed to the fatal outcome in these children."
-How sensitive is magnetic resonance imaging in detecting dysplastic lesions in temporal lobe epilepsy?,"Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations. Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical-white matter architectonic pattern in 2 patients with moderate cortical dysplasia. In the remaining 3 patients, magnetic resonance imaging findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the detection of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy."
-What were the five-year patency rates for femoro-femoral and ilio-femoral grafts in this study?,"Femoro-femoral or ilio-femoral bypass for unilateral inflow reconstruction? Femoro-femoral and ilio-femoral bypass are two popular options for unilateral inflow reconstruction. In order to evaluate these alternative approaches, the records of 70 consecutive patients who underwent either femoro-femoral (n = 50) or ilio-femoral (n = 22) grafts were retrospectively reviewed. There were 46 men and 24 women, ranging in age from 27 to 84 years (mean: 66 years). Operative mortality was 10% for all femoro-femoral procedures, including 50% for emergent, 14% for synchronous, and 0% for solitary procedures; mortality was 9% for all ilio-femoral grafts including 20% for synchronous and 6% for solitary procedures. Among the elective solitary procedures, there was no significant difference with respect to operative time, blood loss, fluid requirement, time until resuming an oral diet, or duration of postoperative course for the two procedures. Five-year patency was 93% for all ilio-femoral and 57% for all femoro-femoral grafts. Although femoro-femoral bypass has been the more popular option for unilateral inflow reconstruction in this and other institutions, these findings justify the more widespread use of ilio-femoral bypass."
-What is the function of the vasoactive intestinal peptide (VIP) receptor identified in this study?,"Cloning and expression of the human vasoactive intestinal peptide receptor. Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands."
-What is the rare cause of left-sided portal hypertension described in this medical case report?,"Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature."
-What were the age-adjusted incidence rates for squamous cell carcinoma and basal cell carcinoma in men and women in New Hampshire and Vermont?,"Incidence of nonmelanoma skin cancer in New Hampshire and Vermont. A survey of skin cancer occurrence between June 1979 and May 1980 among residents of New Hampshire and Vermont identified 277 cases of squamous cell carcinoma and 1761 cases of basal cell carcinoma. The age-adjusted incidence rates for squamous cell carcinoma (32 per 100,000 in men, 8 per 100,000 in women) and for basal cell carcinoma (159 per 100,000 in men, 87 per 100,000 in women) were similar to those reported in other populations in the northern United States. Skin cancer incidence was particularly high among men more than 70 years of age and a large proportion (greater than 30%) of patients 55 years or older had a history of at least one previous skin cancer."
-What are the key clinical features associated with T-cell ALL cases having the t(11;14) translocation?,"Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations."
-"How does the affinity of thyroxine-binding globulin differ between hepatocellular carcinoma patients, cirrhotic patients, and normal subjects?","Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease. To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma."
-What is the key difference between parenchymal and reticuloendothelial iron overload in the liver as revealed by MR imaging?,"Parenchymal versus reticuloendothelial iron overload in the liver: distinction with MR imaging Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial (RE) cells after blood transfusions or rhabdomyolysis. Magnetic resonance images of patients with decreased liver signal intensity on T2-weighted images at 1.5 T were blindly compared in an effort to distinguish these conditions. In each of five patients with hemochromatosis, the pancreas had low signal intensity, but splenic signal intensity was decreased in only one. In contrast, only three of the 16 patients with RE iron overload had low pancreatic signal intensity, while all of these patients either had low splenic signal intensity (n = 14) or previously underwent splenectomy (n = 2). Distinction among these causes of iron deposition is clinically important because parenchymal iron overload from hemochromatosis may produce significant tissue damage, while the RE iron of transfusions and rhabdomyolysis is of little clinical consequence."
-What was the 5-year survival rate for elderly patients with locoregional breast cancer treated with tamoxifen alone?,"Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy."
-What did the study reveal about blood pressure responses in black and white children during a stressful video game?,"Stability of ethnic differences in children's pressor responses during three annual examinations. In this study, 395 healthy children had blood pressure and heart rate measured both at rest and during a stressful video game. Identical measurement procedures were used for three annual examinations. Consistently, black children demonstrated significantly greater pressor responses than white children. In view of the greater prevalence of hypertension among black adults than white adults, these data suggest that blacks exhibit hemodynamic irregularities well before the onset or diagnosis of hypertension."
-How does baseline skin microcirculation differ between patients with primary Raynaud's phenomenon and control subjects?,"Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon. 1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group."
-What were the different management approaches used for various types of choledochal cysts in this study?,"Variation in management based on type of choledochal cyst. The management of 23 patients treated for choledochal cysts at the Oregon Health Sciences University between 1969 and 1990 is reviewed. The median age was 27 years, with a range from 1 month to 90 years. Seventy-eight percent of patients presented with abdominal pain, and 35% were jaundiced. Three patients presented with cholangitis, two with cyst rupture, and one with recurrent pancreatitis. Nine patients had had previous biliary surgery. The diagnosis was made in all patients with ultrasound and/or cholangiography. Fifteen patients (65%) had type I cysts, 2 had a type II cyst, 5 (22%) had type III cysts, and 1 had a type IV cyst. Stones were present in four (17%) cysts, and all excised cysts were benign. Seventeen patients with type I and II choledochal cysts had complete cyst excision and choledochoenterostomy. Four of five patients with type III cysts had endoscopic cyst incision and drainage, while the fifth patient had transduodenal cyst excision and sphincteroplasty. The patient with a type IV cyst had extrahepatic cyst excision and choledochojejunostomy. There were no operative deaths. Two postoperative complications occurred: cholangitis and a prolonged ileus. All patients had resolution of their pain and jaundice. Two patients had late cholangitis. Cyst excision and choledochojejunostomy are the treatment of choice for types I and II choledochal cysts. Extrahepatic cyst excision and choledochojejunostomy may be adequate treatment for type IV cysts. Endoscopic incision and drainage is appropriate for selected patients with type III cysts."
-How does the combination of tetracycline and corticosteroid affect the development of crystalline stromal opacities in rabbit corneas infected with Streptococcus mitis?,"Characterization of infectious crystalline keratitis caused by a human isolate of Streptococcus mitis. Streptococcus mitis isolated from a human with infectious crystalline keratitis was injected intrastromally into corneas of adult New Zealand white rabbits that were treated with tetracycline hydrochloride, methylprednisolone acetate, or a combination of tetracycline and methylprednisolone. Animals were followed up for up to 44 days; untreated corneas and those treated with tetracycline developed no disease or ""fluffy"" stromal infiltrates with overlying epithelial defects representing an abscess. Corneas treated with the combination of tetracycline and corticosteroid usually developed crystalline stromal opacities that on histopathologic examination were shown to be intrastromal aggregates of cocci. Transmission electron microscopy of crystalline lesions within 10 days of infection revealed typical cocci intermixed with a fibrillar material having periodicity characteristic of fibrinogen or fibrin, and immunoperoxidase staining for fibrinogen was positive. By 1 month, electron microscopy revealed aggregates of degenerated bacteria that were surrounded by cellular processes of activated keratocytes. Our studies demonstrate a model for crystalline keratitis in which organisms are seen to reside within the stroma for up to 44 days without an inflammatory response. Periocular corticosteroids appear to be necessary to create this model. It is possible that the organisms are isolated from the host response by fibrin or by keratocytes."
-What advantages does intraoperative transesophageal echocardiography (TEE) offer in assessing surgical repair of congenital heart defects in children?,"Application of intraoperative transesophageal echocardiography in infants and small children. Intraoperative echocardiography is gaining increasing acceptance in the assessment of the surgical repair of congenital heart defects. Because of its ideal imaging location, intraoperative transesophageal echocardiography (TEE) has been especially helpful in evaluating pulmonary venous return and the integrity of the left atrioventricular valve following mitral valvuloplasty, complete atrioventricular valve repair and correction of complex congenital heart disease. It has not been routinely used in infants and small children because of a prohibitively large probe size. We report the successful use of a recently developed ""pediatric"" TEE probe capable of Doppler and color flow imaging in two patients less than 7 years of age. No complications were encountered. Recommendations regarding optimal probe imaging positions in infants are provided."
-What are the key steps in treating patients who survive out-of-hospital cardiac arrest?,"Current treatment of patients surviving out-of-hospital cardiac arrest. Most out-of-hospital cardiac arrests result from the sudden onset of a sustained ventricular arrhythmia in the absence of a new myocardial infarction. Individuals who survive cardiac arrest are at high risk for recurrent arrhythmias and sudden unexpected death. To prevent recurrent cardiac arrest, effective treatment must be provided during hospitalization after the initial episode. Caring for the survivor of cardiac arrest requires a detailed clinical investigation to define the underlying cardiac anatomy and left ventricular function and to elucidate the mechanism and characteristics of the patient's arrhythmia. Appropriate antiarrhythmic therapy, such as drugs or a nonpharmacological intervention (eg, implantable cardioverter-defibrillator), is then selected based on these considerations. In addition, ischemia is treated aggressively with beta-adrenergic blocking agents and, when appropriate, with surgical coronary artery revascularization."
-What is the significance of Tissue Polypeptide Antigen (TPpA) in detecting central nervous system metastases in breast cancer patients?,"Tissue polypeptide antigen activity in cerebrospinal fluid: a marker of central nervous system metastases of breast cancer. Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition."
-How did the researchers investigate the roles of thrombin inhibition and platelet membrane glycoprotein IIb/IIIa in platelet deposition after balloon angioplasty?,"Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model. BACKGROUND. Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. METHODS AND RESULTS. In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. CONCLUSIONS. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters."
-What was the cause of subarachnoid hemorrhage in the seventy-one-year-old Japanese man?,"Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery."
-How does interleukin-4 (IL-4) affect the growth of Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) cells?,"Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL."
-How did aztreonam and cefotaxime compare in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients?,"Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients. Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population."
-"How do passive upright tilting, Valsalva maneuver, and respiration affect the atrial flutter cycle length?","Effects of posture, Valsalva maneuver and respiration on atrial flutter rate: an effect mediated through cardiac volume. The effects of passive upright tilting from 0 degrees to +60 degrees (n = 27), Valsalva maneuver (n = 16) and respiration (n = 10) on the rate of atrial flutter were studied in 27 patients. After tilting to +60 degrees, the atrial flutter cycle length shortened in all patients from 247.5 +/- 7 to 236.7 +/- 6.9 ms (range of shortening 1 to 21 ms, p less than 0.001). The Valsalva maneuver (strain of 40 mm Hg) shortened the flutter cycle length during the strain (phase 2) from 242.2 +/- 4.6 to 230.5 +/- 5 ms (range of shortening 2 to 19 ms, p less than 0.001). In 10 patients whose respiration was monitored, the flutter cycle length consistently prolonged during inspiration and shortened during expiration. Combined beta-adrenergic and muscarinic receptor blockade in six patients did not significantly alter the flutter cycle length at rest or the effects of the various maneuvers on the changes in flutter cycle length. This study revealed that the atrial flutter cycle length can be shortened by passive upright tilting, the strain phase of the Valsalva maneuver and expiration. Changes in flutter cycle length were independent of autonomic tone, implying that by decreasing cardiac volume, these maneuvers affect characteristics of the atrial flutter circuit, thereby producing dynamic changes in the rate of atrial flutter."
-What is neoplastic angioendotheliomatosis (NAE) and how did it manifest in the two described cases?,"Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months."
-How do DNA ploidy and cell proliferation index relate to survival rates in Stage B2 and C colorectal adenocarcinoma?,"DNA ploidy and cell kinetic measurements as predictors of recurrence and survival in stages B2 and C colorectal adenocarcinoma. DNA content and cell proliferation were measured by flow cytometry on paraffin-embedded Stage B2 or C colorectal adenocarcinomas from 694 patients enrolled in adjuvant trials conducted by the North Central Cancer Treatment Group. Patients with diploid tumors had a higher survival rate than those with nondiploid tumors (P less than 0.001). The proliferation index (the sum of the percent of cells in S-phase plus those in G2M phase) was also a strong prognostic factor (P less than 0.001). The ploidy and proliferation data were combined, and the patients in the favorable group (diploid and low proliferative index) had a 5-year survival of 74% compared with 54% for the unfavorable group (high proliferative index or nondiploid, P less than 0.001). This grouping was prognostic for survival in B2 (P less than 0.001), C (P = 0.013), colon (P less than 0.001), and rectal (P = 0.026) patient subsets. This study indicates that cell kinetic parameters are important and independent prognostic factors for Stages B2 and C colorectal cancer."
-What is poststenotic dilatation and how does it develop in arteries?,"Poststenotic dilatation. Partial narrowing of arteries produces poststenotic dilatation. This appears as a dilation of the vessel wall 1 to 3 centimeters distal to the area of a partial stenosis. When a stenotic band is placed in dogs, poststenotic dilatation develops rapidly, often within eight to ten days. Moderate stenoses that produce a bruit and thrill are effective in eliciting poststenotic dilatation, whereas very tight and very mild stenoses usually are ineffective. Thus, development of poststenotic dilatation requires the presence of flow disturbances sufficient to produce an audible bruit and a palpable thrill. Although the exact flow disturbance is uncertain, statis, increased lateral pressure, cavitation, abnormal shear stresses and turbulence all have been postulated to be the cause of poststenotic dilatation. Of these, experimental studies support abnormal shear stresses and turbulence as the most likely causes. Whatever the flow disturbance, it must make the wall vibrate to produce poststenotic dilatation. Vibrations are thought to produce alterations in wall elastin and possibly in vascular smooth muscle tone. This leads to dilatation of the vessel. If the dilatation is slight, removal of the stenosis may cause reversal of poststenotic dilatation with recovery beginning within hours of correction of the stenosis. If the dilated area is enlarged to twice normal diameter, it may exhibit permanent aneurysmal changes and, therefore, requires resections with reanastomosis. Arteries that are dilated to as little as one-third more than normal size may contain areas of ulceration with overlying thrombus. These vessels also may require resection with reanastomosis."
-How do running shoes and spikes affect pronation and torsion angles compared to running barefoot?,"The effects of shoes on the torsion and rearfoot motion in running. Excessive pronation is accepted as a good indicator for various running injuries. The least amount of pronation takes place when running barefoot. The latest investigations show that this is connected to a large torsional movement between forefoot and rearfoot which can be influenced by the shoe sole construction. The shoes which are in use among runners in track and field are basically of two types, running shoes (in general torsionally stiff) and spikes (torsionally flexible). The possibly varying effect of these shoes on the shoe/foot motion in running is not known. The purpose of this investigation was therefore to show whether the pronation angle and the torsion angle differ when running barefoot, with spikes, and with running shoes (forefoot touchdown, N = 9 left and right). A film analysis provided the angular movements of the lower leg, rearfoot, and forefoot as well as pronation and torsion in the frontal plane. The results show that at touchdown the torsional movements with both shoe types are quite different from those of running barefoot. With shoes, the torsion angle is reduced back to zero--with running shoes more than with spikes--and the pronation angle is increased beyond the barefoot values (P less than 0.01). In order to reduce the risk of injury, both shoe types should be improved--the running shoes with respect to torsion and the spikes with respect to pronation."
-What was the significance of blood group antigen immunoreactivity in the study of superficial esophageal carcinomas?,"Immunohistochemical studies of blood group-related antigens in human superficial esophageal carcinomas. A total of 63 surgically resected esophageal carcinomas (including 49 superficial esophageal carcinomas) and histologically normal tissue adjacent to the superficial carcinoma (nontumorous epithelium) were examined immunohistochemically for the blood group antigens (BGA) A, B, H, Lewisa, Lewisb, Lewisx, and Lewisy. Deletion of an expected A, B or H antigen occurred in 12 (24.5%) of the 49 superficial carcinomas and three (21.4%) of the 14 advanced carcinomas. Incompatible expression of an unexpected A or B antigens occurred in only one case (1.6%) in the carcinoma. In the clinicopathologic study, there was a significant correlation between immunoreactivity of Lewisa and depth of cancer invasion (chi-square test, P less than 0.05). In the superficial carcinoma, there were significant correlations between immunoreactivity of Lewisx and lymph node status (chi-square test, P less than 0.05), immunoreactivity of Lewisy and prognosis (Z test, P less than 0.05), and incompatible expression of Lewisb for tumor against nontumorous epithelium and histologic variation (chi-square test, P less than 0.01). The functional significance of alternations in BGA expression that may be associated with oncogenesis is not clear. However, immunohistochemical determination of BGA may be a more advantageous marker to predict the patient's clinical course in superficial esophageal carcinoma."
-What percentage of patients with extraadrenal retroperitoneal paragangliomas had hypertension in this study?,"Extraadrenal retroperitoneal paraganglioma: clinical, pathologic, and CT findings. Paragangliomas of the retroperitoneum arise from specialized neural crest cells distributed along the aorta in association with the sympathetic chain. In order to ascertain characteristic CT features of extraadrenal retroperitoneal paragangliomas to differentiate them from other retroperitoneal tumors, 31 discrete tumors and two cases of paragangliomatosis in 28 patients were reviewed retrospectively, and the CT features were correlated with clinical and pathologic findings. There were 16 men and 12 women. Average age was 37 years (range, 11-70 years). Twenty-four patients (86%) had hypertension. Of these, catecholamine levels were elevated in all 18 patients who had biochemical studies. Four patients (14%) had malignant paragangliomas. The discrete tumors were classified by location as suprarenal (26%), renal hilar (32%), or infrarenal (42%). Suprarenal paragangliomas could not be distinguished from the ipsilateral adrenal gland on CT. The average size of functional tumors was smaller (7.0 cm) than that of nonfunctional tumors (12.0 cm), but the sizes of the two groups overlapped. Smaller tumors were more likely to be homogeneous and have well-defined margins than were larger tumors. Our findings indicate that extraadrenal retroperitoneal paragangliomas are functionally active more often than previously reported and that they are readily detected by CT as soft-tissue masses closely associated with the entire length of the abdominal aorta. However, no CT feature was found that was unique for paraganglioma."
-What unique pattern of nystagmus was observed in a patient with posterior medullary haemorrhage?,"Upbeat and downbeat nystagmus occurring successively in a patient with posterior medullary haemorrhage. In a patient with posterior medullary haemorrhage, first upbeat and later downbeat nystagmus occurred in the primary position. The lesion was limited to the posterior and medial part of the medulla. Clinical and electro-oculographic examination first showed upbeat nystagmus in the primary position and upgaze, with downbeat nystagmus in downgaze. Two and a half months later, there was downbeat nystagmus in the primary position and downgaze and upbeat nystagmus in upgaze."
-How does gadolinium contrast enhance the detection and delineation of choroidal melanoma in magnetic resonance imaging?,"Magnetic resonance imaging of choroidal melanoma with and without gadolinium contrast enhancement. Choroidal melanoma is the most common intraocular tumor and is uniquely suited for evaluation by magnetic resonance imaging (MRI) because of the paramagnetic effect of the melanin molecule. The authors performed T1-, T2-, and proton-density-weighted MRI on 34 patients with choroidal melanoma. Nineteen patients received gadolinium contrast, T1-weighted images were superior in both detecting and delineating tumors, showing increased contrast-to-noise ratios over other images. Gadolinium contrast further increased this ratio. These images are presented as evidence that gadolinium-enhanced MRI is valuable in the evaluation of choroidal melanoma."
-"What were the main findings comparing standard external CPR, open-chest CPR, and cardiopulmonary bypass in this canine myocardial infarct model?","Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model. STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB."
-What was the purpose of the study on creatine kinase MB (CK-MB) time-activity curve in patients with acute myocardial infarction?,"Indices of reperfusion in patients with acute myocardial infarction using characteristics of the CK-MB time-activity curve. The purpose of this study was to identify indices of coronary artery reperfusion in patients treated with thrombolytic therapy for acute myocardial infarction (AMI) by means of characteristics from the serum creatine kinase (CK) isoenzyme MB time-activity curve. Frequent blood sampling as performed in three groups with a first AMI: 29 patients treated with intravenous thrombolytic therapy who had a patent infarct-related artery with normal flow (TIMI-3) at acute catheterization (reperfusion group); four patients with a persistently closed infarct-related artery (no reperfusion group); and 44 patients who did not receive any therapy aimed at coronary reperfusion (no thrombolytic therapy group). In the latter group we prospectively estimated that 25% would have spontaneous reperfusion. A physiologically based computer-calculated multi-compartment method was used to determine the characteristics of the serum CK-MB time-activity curve. In addition to demonstrating an earlier increase, a shorter time to peak of serum CK-MB and a lower estimated infarct size in the reperfusion group (p = 0.025 to 0.00001), the appearance rate constant (k1) and time from estimated initial increase to peak of CK-MB in the blood stream (tRP) were significantly different from those values in the no thrombolytic therapy group (p less than 00001). A cutoff level indicating reperfusion if k1 was greater than 0.185 or tRP was less than 16.5 hours demonstrated overlapping values between these two groups in only four patients (k1), two patients (tRP), and six patients with a combination."
-What makes interstitial ectopic pregnancies more dangerous compared to other tubal pregnancies?,Ruptured interstitial pregnancy presenting as an intrauterine pregnancy by ultrasound. Interstitial pregnancy is an uncommon subset of ectopic pregnancy in which the conceptum implants in the intrauterine portion of the fallopian tube. These pregnancies tend to progress further before rupture than do other tubal pregnancies and subsequently have greater propensity for massive intra-abdominal bleeding and maternal demise. Abdominal ultrasound can be deceptive in evaluating interstitial ectopic pregnancies. Transvaginal ultrasonography is more sensitive in the diagnosis of early ectopic pregnancy. Knowledge of the application and limitations of both transabdominal and transvaginal ultrasound will assist the emergency physician in the timely evaluation of this potentially lethal condition.
-How accurate is transrectal sonography in detecting neurovascular bundle invasion in prostate cancer patients?,"Carcinoma of the prostate: value of transrectal sonography in detecting extension into the neurovascular bundle. Detection of involvement of the neurovascular bundles (NVB) by tumor is important in deciding whether sexual function can be preserved in patients undergoing radical prostatectomy for prostatic cancer. The nerve branches innervating the corpora cavernosa have a rather constant association with the capsular arteries and veins of the prostate, forming the periprostatic neurovascular bundle, which can be identified intraoperatively and spared during radical surgery, thus preserving potency. We examined 160 patients with biopsy-proved clinical stage A or B adenocarcinoma with transrectal sonography before radical prostatectomy to determine how useful the procedure is for predicting tumor extension into the NVB. Correlation with pathologic serial sections was obtained in each patient. The sonograms depicted the NVB on both sides in 77 patients (50%), on the right side only in 13 (8%), and on the left side only in 36 patients (23%). In 29 patients (19%) neither neurovascular bundle could be identified on the sonograms. Ninety-one tumors in this series showed evidence of extraglandular spread pathologically, which was posterolateral or into the NVB in 70 tumors involving 82 hemispheres. Using transrectal sonography, we correctly identified invasion of the NVB in 54 cases and missed it in 28 cases. NVB invasion was predicted incorrectly with transrectal sonography in 51 cases; absence of involvement of the NVB was correctly predicted in 177 hemispheres. The sensitivity of sonography for predicting invasion of the NVB was 66%, with a specificity of 78% and an accuracy of 75%. Positive predictive values and negative predictive values were 51% and 86%, respectively. We conclude that transrectal sonography currently suffers from lack of sufficient spatial resolution to detect accurately invasion of the NVB."
-How does C4b-binding protein (C4bBP) affect the host response to Escherichia coli infection?,"C4b-binding protein exacerbates the host response to Escherichia coli. Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What factors were found to be associated with better functional recovery after traumatic transtentorial herniation?,"Functional recovery after traumatic transtentorial herniation. To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation."
-What is the association between L-tryptophan ingestion and eosinophilic fasciitis (EF) according to the study?,"Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Recently, a causative association has been made between the ingestion of levotryptophan (L-tryptophan) and the eosinophilia-myalgia syndrome (EMS), a new entity manifested by peripheral blood eosinophilia, myalgias, constitutional symptoms, and cutaneous edema with fibrosis. Contaminated levotryptophan preparations produced at a single manufacturing company between October 1988 and June 1989 have been implicated in all EMS cases. In this study, we analyzed retrospectively 49 patients with cutaneous fibrosis for a history of levotryptophan use. Levotryptophan ingestion prior to the onset of their disease was reported by 11 (65%) of 17 patients with eosinophilic fascilitis (EF), two (20%) of 10 patients with localized scleroderma, and none of 22 patients with systemic sclerosis. The onset of levotryptophan-associated cutaneous disease preceded the availability of contaminated levotryptophan preparations in seven (54%) of 13 patients. One patient with levotryptophan-associated generalized morphea also had lichen sclerosus et atrophicus and acanthosis nigricans, findings not previously reported in patients with EMS. In addition, we compared the clinical and laboratory features of levotryptophan-associated EF and idiopathic EF. Myalgias, muscle weakness, paresthesias, morpheaform plaques, cutaneous ulcers, and livedo reticularis were more common in patients with levotryptophan-associated EF. We conclude that levotryptophan-associated EF and localized scleroderma were present before the presumed date of contaminated levotryptophan availability. The clinical spectrum of cutaneous fibrosis associated with the ingestion of levotryptophan includes generalized morphea and EF, which are similar though not identical to their idiopathic counterparts."
-What percentage of subjects in the study had adenomas detected during screening colonoscopy?,"Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men. Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated."
-What was the average number of bypasses per patient in this direct coronary surgery without extracorporeal circulation?,"Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients Between May 1978 and March 1990, 700 patients were operated on with direct coronary surgery without extracorporeal circulation (ECC): 529 (76 percent) were male and 171 (24 percent) were female. The average age was 64 years (range, 35 to 86 years), 454 (65 percent) had unstable angina, 163 (23 percent) had stable angina, 51 (7 percent) had postmyocardial infarction angina, and 32 (5 percent) had acute myocardial infarction at the moment of the operation. In this series of patients, all branches of the coronary arteries were bypassed; the mammary artery was used in 40 percent of the cases, the average bypass per patient was 2.2 (range, 1 to 5), and 26 percent had associated disease of high risk to undergo ECC. The morbidity was 4 percent and the mortality for this series of patients was 1 percent; the probability of survival at seven years was 90 percent. This experience shows us that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated disease, in some cases of acute transmural infarction, and also for patients who need coronary angioplasty. Also, it can improve the relation cost/benefit in coronary surgery."
-What was the main finding of the study regarding the use of diazepam in emergency treatment of seizures in children?,"Diazepam and intubation in emergency treatment of seizures in children. STUDY OBJECTIVES: This study was undertaken to determine the incidence of endotracheal intubation after the use of diazepam compared with phenobarbital or phenytoin in emergency treatment of seizures in children. DESIGN: The records of all children (98) were reviewed in a case-control fashion. A logistic regression model was used to determine whether there was an association between diazepam administration and intubation, adjusting for all other covariates (age, weight, convulsion time before first anticonvulsant was given, response latency, diagnosis, and therapy). SETTING: All children were treated in an emergency department and then transported to a tertiary pediatric center by a pediatric transport team. TYPE OF PARTICIPANTS: All patients were children, with a median age of 2.7 years (range 0.17 to 15.3 years). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only the use of diazepam was found to be significantly associated with intubation after adjusting for all other covariates (adjusted odds ratio, 49.4; P less than .001). In the comparison of diazepam versus phenobarbital or phenytoin used as the first anticonvulsant, median response latency did not differ (27.0 vs 32.5 minutes, P greater than .83). CONCLUSION: A significant association was found between diazepam use and intubation. Response latency was not shorter when diazepam was used as the initial anticonvulsant compared with phenobarbital or phenytoin."
-What is the significance of a 'sentinel bleed' after pancreatoduodenectomy?,"Arterial hemorrhage after pancreatoduodenectomy. The 'sentinel bleed'. Experienced centers report reduced operative mortality after pancreatoduodenectomy for cancer, but significant complications continue to occur in as many as 25% of patients. Anastomotic disruption leads to sepsis in the pancreatic bed where major vascular structures have been exposed by regional lymphadenectomy, creating a setting for arterial erosion or ligature slough and massive hemorrhage. Dehiscence of the pancreatojejunostomy is a particular risk. We treated five patients with arterial hemorrhage after pancreatoduodenectomy, all of whom had had ""sentinel"" bleeding from the abdominal drains or gastrointestinal tract. Results of endoscopy were misleading in two patients. Three of five patients were saved by prompt recognition, early operation, and, in one instance, angiographic embolization. Sentinel bleeding after pancreatoduodenectomy indicates local sepsis and probable anastomotic dehiscence. Recognition of its significance and prompt response may prevent exsanguination."
-What was the purpose of the study on neurophysical signs assessment among patients with head injuries?,"Observer variation in assessing neurophysical signs among patients with head injuries. As an early phase in the development of a valid and reliable measure of the neurophysical sequelae after head injury, we carried out assessments of interrater agreement on representative items. The purpose of this study was to determine the degree of agreement among expert raters who independently measured neurophysical signs on patients undergoing physical rehabilitation after brain injury. Agreement was described using the index of crude agreement, expected agreement and Kappa. Therapists showed a high degree of agreement on those items forming part of a routine neurological assessment: prehension, coordination, voluntary movements and tendon reflexes. Crude agreement ranged from 77.8-100%. There was considerable discordance in assessing muscle tonus, equilibrium and protective reactions, spinal reflexes, tremor and dysmetria (crude agreement ranged from 49.7-97.9%). Although, the number of subjects was small, the information generated from this study will be useful in refining our instrument for the assessment of neurophysical signs."
-What are the potential complications of untreated abdominal aortic thrombosis?,"Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function."
-What method was used to screen four large families for potential genetic linkages related to hypertension?,"Use of the robust sib-pair method to screen for single-locus, multiple-locus, and pleiotropic effects: application to traits related to hypertension. Robust sib-pair linkage analysis can be used as a screening tool in the search for the potential involvement of single-loci, multiple-loci, and pleiotropic effects of single loci underlying phenotypic variation. Four large families were each ascertained through one adult white male with essential hypertension. The robust sib-pair method was used to screen these families for evidence of linkage between 39 quantitative traits related to hypertension and 25 genetic marker loci. All traits were analyzed on the untransformed, square-root and log-transformed scales. Among other findings, there is a suggestion of linkage between the 6-phosphogluconate dehydrogenase locus on chromosome 1p36 and mean fifth-phase diastolic blood pressure. There may also be linkage between the following markers and traits: the adenylate kinase-1 marker and/or the Lewis blood group marker and the traits height, weight, and biacromial breadth; the glyoxylase I marker and the traits upper-arm circumference and suprailiac skinfold thickness; the ABO blood group and adenylate kinase-1 markers on chromosome 9q34 and the third component of complement marker on chromosome 19p13 and dopamine-beta-hydroxylase; and the P1 blood group and the traits weight and 1-h postload serum glucose level."
-What was the method used to manage neuropathic cancer pain in patients who did not respond to conventional analgesics?,"Subcutaneous lidocaine for treatment of neuropathic cancer pain. Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient."
-What are the key differences in breast cancer characteristics based on age and mammographic presentation?,"Not all nonpalpable breast cancers are alike. Clinical and mammographic data of 1009 consecutive patients were correlated with histopathologic data of 1144 biopsy specimens of nonpalpable breast lesions to better define the presentation and biologic behavior of early breast cancer. Patients with malignant neoplasms (269 [24%] of 1144 specimens) were older (mean age, 62.1 years) than patients with benign lesions (mean age, 54.9 years). Furthermore, patients with invasive disease were older (mean age, 63.3 years) than patients with noninvasive disease (mean age, 58.5 years) with an overall increased risk of invasive cancer per year of 1.035. A 58% incidence of invasive cancer was detected for lesions characterized by calcifications, while the incidence of invasive cancer was 84% for isolated mass lesions (relative risk, 4.31 for masses). Isolated mammographic calcifications associated with cancer appeared in a younger population and were significantly associated with noninvasive ductal cancer. Breast cancer presenting as a mammographic mass appeared in an older group and was highly associated with the presence of invasive disease."
-What were the effects of different lipid emulsions on hepatic lipid content and liver histology in rats receiving total parenteral nutrition?,"Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats. The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups."
-What are the two N-methyl-D-aspartate (NMDA) antagonists tested in this study for their anticonvulsant properties?,"Anticonvulsant activity of two orally active competitive N-methyl-D-aspartate antagonists, CGP 37849 and CGP 39551, against sound-induced seizures in DBA/2 mice and photically induced myoclonus in Papio papio. Two novel N-methyl-D-aspartate (NMDA) antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid CPG 37849 and the corresponding 1-ethyl ester CGP 39551, were tested as anticonvulsants in DBA/2 mice and photosensitive Senegalese baboons, Papio papio. In DBA/2 mice, CGP 37849 is more potent than CGP 39551 when administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) (ED50 for suppression of clonic seizures at 60 min: i.c.v. 0.038 and 0.21 nmol; i.p. 3.40 and 19.1 mumol/kg, respectively). When administered orally in mice, the two compounds are approximately equipotent (ED50 CGP 37849, 35.2 mumol/kg; ED50 CGP 39551, 28.1 mumol/kg). The time course of action of CGP 39551 is exceptionally prolonged: 42 mumol/kg i.p. protects against clonic seizures for 48 h. Protection provided by other NMDA antagonists in mice is of much shorter duration: 2-amino-5-phosphono-pentanoic acid (AP5) 1 h, 2-amino-7-phosphono-heptanoic acid (AP7) 4 h, 2-amino-7-phosphono-heptanoic acid 1-ethyl ester 3 h, 4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) 2 h, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) 4 h, and CGP 37849 4 h. After oral administration of the drugs, the therapeutic index (TI = ratio of the ED50 values for rotorod performance and anticonvulsant protection) remains relatively constant at 5.9-7.2 for 3 h (CGP 37849) and 4.0-6.1 for 24 h (CGP 39551). After i.p. administration, the TI values are CGP 37849 at 1 h 2.4, and at 3 h 20.0, CGP 39551 at 1 h 2.3, at 3 h 7.1, and at 24 h 3.6. In baboons, acute administration of CGP 37849 at doses of 48-191 mumol/kg intravenously (i.v.) suppresses photically induced myoclonus for at least 285 min, with severe side effects at the highest dose tested. CGP 39551 at doses of 169-675 mumol/kg i.v. shows weak anticonvulsant activity only at the highest dose tested (accompanied by severe side effects). CGP 37849 at 48-96 mumol/kg orally (p.o.) fails to protect against photically induced myoclonus up to 4 h after administration, but 191 mumol/kg (40 mg/kg) p.o. produces complete suppression of seizures after 24 h. On the other hand, CGP 39551 at 169 mumol/kg (40 mg/kg) p.o. produces total suppression of seizure activity at 4 h with a longer duration of anticonvulsant action (2-3 days).(ABSTRACT TRUNCATED AT 400 WORDS)."
-What was the primary aim of the geriatric-anesthesiologic intervention program for elderly patients with femoral neck fractures?,"A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay."
-What are the limitations of routine testicular scanning in diagnosing acute scrotal conditions?,"Testicular scanning: evaluating the acute scrotum in the clinical setting. In a retrospective study of patients with acute scrotal pain presenting to the hospitals of Southern Illinois University School of Medicine from January 1982 until September 1987, determination was made of the appropriate use of testicular scan for definitive diagnosis. Though the testicular scan is a highly sensitive and specific examination in the identification of testicular torsion, we believe its routine use in clinical practice is limited. Appropriate utilization of the examination requires its use in high-risk groups with equivocal physical findings or in patients with unusual presentations of age, anatomy, or neurologic deficit. The scan if used for routine screening of the acute scrotum would result in needless delays and unjustifiable expense when it is mandatory that the treatment be immediate surgical exploration."
-"What distinguishes the ossifying jaw fibromas in this syndrome from the ""brown tumors"" of hyperparathyroidism?","Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the ""brown tumors"" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in ""brown tumors."" The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct."
-"What medical condition did the 83-year-old woman have, and what was the suspected origin of her tumor?",Carcinoma erysipeloides. We report an 83-year-old woman with carcinoma erysipeloides due to an occult carcinoma. Immunohistochemical study of skin biopsies showed reactivity to S-100 protein and human milk fat globule antigen indicating that the tumour originated in the breast.
-What was the purpose of performing intraoperative transesophageal echocardiography in patients with atrioventricular septal defect?,"Intraoperative transesophageal echocardiography of atrioventricular septal defect. To determine the accuracy and utility of single-plane transesophageal echocardiography in analyzing atrioventricular (AV) septal defect, intraoperative transesophageal echocardiography was performed before and after institution of cardiopulmonary bypass in 16 patients (age 24 days to 14 years, weight 3 to 47 kg). Prebypass transesophageal echocardiography (including two-dimensional echocardiography, Doppler color flow mapping and pulsed wave Doppler ultrasound) correctly diagnosed divided AV valve, common AV valve and unbalanced AV valve, as well as atrial or ventricular septal defect, or both, in all cases. It correctly analyzed AV valve regurgitation in all 10 patients with right and all 14 with left AV valve regurgitation and correctly analyzed 30 of 33 additional cardiac anomalies. Transesophageal echocardiography was able to detect the absence of normal pulmonary venous connections but failed to demonstrate all of the complex anomalous pulmonary venous connections in three patients with atrial isomerism. Postbypass transesophageal echocardiography documented the absence of a significant residual shunt in 11 of 11 patients undergoing corrective surgery and verified residual AV valve regurgitation in 7 of 9 patients with tricuspid regurgitation and 11 of 13 with mitral regurgitation. Transesophageal echocardiographic information that altered or refined the surgical treatment was obtained in 5 (31%) of 16 patients. Epicardial and transesophageal echocardiography results were concordant in all 13 patients in whom both were performed. Transesophageal echocardiography provides useful and accurate imaging of the important two-dimensional, pulsed wave Doppler ultrasound and Doppler color flow mapping features in AV septal defect."
-What is the significance of the patient's survival in this case of primary angiosarcoma of the brain?,Primary angiosarcoma of the brain. We have described a 32-year-old black woman who had a primary angiosarcoma of the right occipital lobe. All three previously reported cases have been fatal within 1 year. Our patient is doing well more than 3 1/2 years after surgery.
-How might abnormal liver enzyme metabolism potentially contribute to the development of Parkinson's disease?,"Abnormal liver enzyme-mediated metabolism in Parkinson's disease: a second look. If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies."
-What is the potential serious late complication of aortic bifurcation surgery discussed in this medical report?,"Bilateral ureteral obstruction following aortobifemoral bypass graft. In this report we present a case of bilateral ureteral obstruction, a potentially serious late complication of aortic bifurcation surgery. The incidence, aetiology, clinical presentation and treatment are discussed."
-What was the main finding of the study regarding bacterial colonization in necrotizing enterocolitis?,"Does patient age or intestinal pathology influence the bacteria found in cases of necrotizing enterocolitis? To evaluate the relationship between bacterial colonization in neonatal peritonitis and patient age or intestinal pathology, we retrospectively reviewed peritoneal culture results from 96 infants having surgery for necrotizing enterocolitis. Microorganisms recovered mirrored those usually found as fecal flora within the neonatal intensive care unit. These reflect, in turn, the abnormal colonization intrinsic to care in the intensive care nursery. Analysis revealed no significant correlation between the disease and either age of the infant or intestinal site of disease."
-What were the clinical findings in patients with obstruction of the infrarenal portion of the abdominal aorta?,"Obstruction of the infrarenal portion of the abdominal aorta: results of treatment with balloon angioplasty. Our experience in the treatment of stenoses of the infrarenal portion of the abdominal aorta with balloon angioplasty in 27 patients is reported. Clinical findings were lower limb claudication (all patients), impotence (eight patients), and blue-toe syndrome (two patients). The underlying disease was atherosclerosis in 24 patients and nonspecific aortoarteritis in three patients. Dilatation was successful in all patients. Embolic occlusions of the left common iliac artery (one patient) and left superficial femoral artery (one patient) were the only major complications. Claudication in the affected limb continued in the first patient; the second died when diagnostic angiography, performed 3 months after angioplasty, caused a severe atheroembolus. Of the other 25 patients, nine of the 10 followed up for 13-48 months and all seven followed up for 3-8 months were free of symptoms. Six of eight patients with sexual dysfunction had normal function after angioplasty. Seven patients still awaited follow-up and one was lost to follow-up. Our experience suggests that balloon angioplasty is an effective treatment of stenoses of the infrarenal portion of the abdominal aorta."
-What imaging technique was used to diagnose the pulmonary artery aneurysm in this case report?,Magnetic resonance imaging of pulmonary artery aneurysm. Pulmonary artery aneurysm is a rare condition. We have presented what we believe to be the first case in the English literature to be diagnosed by magnetic resonance imaging.
-Which two monoclonal anti-idiotope antibodies (Ab2) were able to induce specific anti-TAA-specific (Ab1') responses in rabbits?,"Analysis of anti-tumor antibodies in mice and rabbits induced by monoclonal anti-idiotope antibodies. Eight different mouse monoclonal anti-idiotope antibodies (mAb2) generated against a mouse monoclonal anti-human melanoma proteoglycan Ag (MPG) antibody (mAb1), MEM136, were tested for their ability to induce anti-MPG responses in mice and rabbits. All Ab2 were idiotypically cross-reactive and combining site-specific as demonstrated by competitive cross-inhibition studies and their ability to inhibit the binding of MEM136 to the melanoma cells, Colo38. However, only two Ab2, IM32 and IM06, were able to induce specific anti-TAA-specific (Ab1') responses in rabbits. When IM32 and IM06 were tested in allogeneic stains of mice for the induction of anti-MPG responses, only IM32 produced an Ab1' response. In mice, the Ab3 response induced by IM32 is idiotypically cross-reactive with its Ab1. Furthermore, the IM32-induced murine Ab3 and MEM136 recognized a similar MPG epitope on the melanoma cells because the Ab3 inhibited the binding of MEM136 to melanoma cells. The Ab3 induced by IM32 and IM06 in rabbits also recognized a similar epitope as the Ab1. In rabbits, the Ab3 response induced by IM32 and IM06 were idiotypically cross-reactive with each other. However, additional studies indicated that the majority of Ab3 induced by IM32 were IM32 Id-specific and lacked IM06 idiotopes. Further experimentation indicated that IM32-induced rabbit Ab3 were biologically active as demonstrated by the ability of the Ab3 to inhibit melanoma cell invasion in a Matrigel assay."
-What correlation was observed between large amplitude sensory action potentials and myelopathy in the study?,"Large amplitude sensory action potentials in myelopathy: an observation. Subjects with at least one sensory action potential (SAP) amplitude greater than 2 SD above the age-matched mean during standard nerve conduction tests were evaluated for evidence of spinal cord disease. From a total of 153 subjects, 16 had at least one large amplitude SAP and 12 of 16 (75%) had a documented myelopathy. While a mechanism has yet to be determined, this observation suggests that SAP amplitudes greater than 2 SD above normal may be correlated with clinical evidence of injury to the central nervous system."
-What was the primary symptom experienced by the patient with recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue?,"Recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue. Torsion of the adnexa is rare, and diagnosis is difficult because of the sparse clinical findings. I describe a patient with recurrent torsion of the right adnexa, involving a cystadenoma of aberrant ovarian tissue. Her only symptom was recurrent right-sided pelvic pain."
-What is the effectiveness of optic nerve sheath decompression in treating patients with acute and chronic papilledema?,"Treatment of pseudotumor cerebri by primary and secondary optic nerve sheath decompression. We performed optic nerve sheath decompression in 53 patients (101 eyes) with pseudotumor cerebri and visual loss. Sixty-nine eyes (85 patients) with acute papilledema uniformly had improved visual function after optic nerve sheath decompression. Of 32 eyes with chronic papilledema (18 patients), only ten had improved visual function after optic nerve sheath decompression. This difference was significant (P = .0001). Thirteen eyes required secondary or tertiary optic nerve sheath decompression after an initial successful result. Eleven of 13 eyes had improved visual function after repeat optic nerve sheath decompression. We believe that patients with acute papilledema and visual loss should be offered optic nerve sheath decompression, and if symptoms recur, repeat optic nerve sheath decompression is a safe and effective treatment option."
-What was the main finding of the randomized trial comparing ticarcillin and clavulanate with gentamicin and clindamycin in patients with complicated appendicitis?,"A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis. Secondary bacterial peritonitis is usually a polymicrobial infection of facultative gram-negative aerobic and anaerobic organisms. Treatment consists of operation and broad-spectrum antibiotic administration. The antibiotic treatment of choice in these infections has been the combination of gentamicin and clindamycin. However, this combination can have toxic side effects and necessitates frequent monitoring of serum levels. Beta-lactam antibiotics provide broad-spectrum coverage and low toxicity, but can be inactivated by species of bacteria producing beta-lactamase enzymes. Clavulanic acid is a potent inhibitor of beta-lactamases and has been shown to extend the efficacy of ticarcillin to bacteria producing these enzymes. This combination was compared with gentamicin and clindamycin in 99 consecutive patients with complicated appendicitis. Eradication of identified pathogens was greater in the ticarcillin and clavulanate group (98 per cent) than in the gentamicin and clindamycin group (92 per cent), even for the subgroup of organisms producing beta-lactamases (97 versus 90 per cent eradication). Complications and clinical response were not significantly different between the two treatment groups. Ticarcillin and clavulanic acid is a safe and effective alternative to gentamicin and clindamycin in the treatment of secondary bacterial peritonitis and offers advantages in dosing simplicity and freedom from ototoxic and nephrotoxic effects."
-What was the accuracy of fine needle aspiration cytologic procedures in diagnosing malignant mammary masses in this study?,"The accuracy of malignant diagnoses established by fine needle aspiration cytologic procedures of mammary masses. Fine needle aspiration cytologic studies are being used with increasing frequency to diagnose carcinoma of the breast. To determine whether or not a diagnosis of carcinoma established by cytologic examination is sufficiently accurate to proceed to treatment without tissue confirmation, we have examined our results in a series of 109 patients who had 111 aspiration cytologic procedures followed by open biopsy between January 1985 and June 1987. From this group, 39 specimens were read as malignant and 19 were read as suspicious. Thirty-eight of 39 specimens with positive readings were from lesions that proved to be malignant on subsequent open biopsy. Seventeen of 19 suspicious specimens were also from malignant lesions. Three of 17 specimens that were inadequate and nine of 36 negative specimens were from lesions that were later shown to be malignant. Our single false-positive result occurred on cells that had been air dried during preparation in the early months of experience with this technique at our institution. Re-evaluated later in our series, the same specimen was called suspicious rather than malignant. We conclude that a positive reading on fine needle aspiration is highly accurate. The positive predictive value should be 100 per cent, once experience is gained in preparing and interpreting the material. Open biopsy is necessary for inadequate, negative or suspicious specimens to exclude a malignant lesion if the clinical or mammographic findings are consistent with carcinoma."
-What is neurocutaneous melanosis and what are its key characteristics?,"Neurocutaneous melanosis: definition and review of the literature. Neurocutaneous melanosis is a rare congenital syndrome characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The syndrome is thought to represent an error in the morphogenesis of the embryonal neuroectoderm. We review 39 reported cases of neurocutaneous melanosis and propose revised criteria for diagnosis. Most patients with neurocutaneous melanosis presented in the first 2 years of life with neurologic manifestations of increased intracranial pressure, mass lesions, or spinal cord compression. Leptomeningeal melanoma was present in 62% of the cases, but even in the absence of melanoma, symptomatic neurocutaneous melanosis had an extremely poor prognosis. Useful diagnostic procedures include cerebrospinal fluid cytology and magnetic resonance imaging with gadolinium contrast. Patients may be aided by palliative measures such as shunt placement to reduce intracranial pressure. Dermatologists in their follow-up of patients with large or multiple congenital melanocytic nevi should be aware of this condition, to aid in prompt diagnosis and because the treatment of cutaneous lesions may be altered in the presence of symptomatic neurocutaneous melanosis."
-What is the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in treating pancreatic duct stones in patients with chronic calcifying pancreatitis?,"Extracorporeal shock wave lithotripsy of pancreatic duct stones. Chronic calcifying pancreatitis presents a major clinical problem, often requiring extensive surgery. Extracorporeal shock wave lithotripsy (ESWL) offers a new therapeutic option. We applied ESWL after endoscopic sphincterotomy of the pancreatic orifice in eight patients with impacted pancreatic duct stones. An electromagnetic lithotriptor (Siemens Lithostar, Erlangen, FRG) was used. Patients were treated in prone position under fluoroscopic control. A mean of 6,813 shock waves (range 1,500-10,000) was delivered in one or two sessions. Disintegration of stones was achieved in 6/8 patients, initial relief of pain in 7/8 patients, and total clearance of the pancreatic duct in 3/8 patients. One patient had an exacerbation of her pancreatitis one day after ESWL, which resolved rapidly with medical treatment. No other complications were observed. Four of five patients with fragmented stones had no abdominal complaints at follow-up (mean 17 months, range 3-27). Three patients in whom ESWL was not completely successful (two without and one with partial fragmentation) underwent an operation according to Puestow. Two of them still have abdominal complaints after surgery. From these data, we conclude that ESWL of pancreatic duct stones is a promising new alternative for surgery, when endoscopic stone extraction fails."
-What are the key characteristics of Superparamagnetic iron oxide (SPIO) particles in MR imaging of the liver and spleen?,"Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years. Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins."
-How does the polymerase chain reaction (PCR) method compare to viral isolation in detecting herpes simplex virus (HSV) in genital lesions?,"Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative."
-"What combination of immunosuppressive drugs did the authors use to treat serpiginous choroiditis, and how effective was the treatment?","Triple agent immunosuppression in serpiginous choroiditis. Serpiginous choroidopathy is a progressive choroidal inflammatory disorder that typically has a variable saltatory course. Response to steroids is uncertain. By using azathioprine, cyclosporine, and prednisone in combination, the authors have observed rapid remission of active disease in five patients. Remissions have been maintained for periods up to 18 months. Because of the synergistic effects of this combination, doses could rapidly be reduced to maintenance levels without reactivation. Disease in two patients recurred immediately after discontinuation of low-dose therapy but was arrested when therapy resumed. Triple agent immunosuppressive therapy is well tolerated and appears to be effective."
-How does hypertension affect the expression of platelet-derived growth factor (PDGF) receptors in rat aorta and heart?,"Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF alpha- and beta-receptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF beta-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF alpha-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF beta-receptor mRNA levels. Aortic PDGF beta-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF alpha-receptor steady-state mRNA levels were unchanged in DOCA-salt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF beta- and alpha-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF beta-receptor. They also indicate that tissue-specific expression of the genes of the PDGF ligand/receptor system are differentially regulated in hypertension."
-What is the purpose of subglottic laryngeal closure in patients with severe neurological disease?,"Subglottic laryngeal closure for aspiration. Aspiration may be life threatening, particularly in those patients with severe central neurological disease. From such a group of patients, several were identified who had severe laryngeal dysfunction and aspiration. The majority of patients in this subgroup existed in a neurologically vegetative state. In an attempt to reduce the degree of aspiration they experienced, the procedure of subglottic laryngeal closure was performed. Essentially, the operation is designed to isolate the tracheal airway from the incompetent larynx. The aim is to protect the lower airway from pharyngeal contamination. In all 5 patients there was a marked improvement in general and pulmonary health."
-What is the most effective and safest form of anesthesia for newborn circumcision according to the context?,"Pain in neonatal circumcision. Because newborn circumcision is a quick and safe surgical procedure, any method to relieve pain must be almost risk-free in order to be acceptable. General anesthesia and narcotic analgesia are not appropriate. Dorsal penile nerve block (DPNB) with lidocaine hydrochloride is probably the most effective and safest form of anesthesia for newborn circumcision currently available, but it can cause significant local and systemic reactions. Only a limited number of cases of DPNB have been reported and we feel that this procedure should be used cautiously until there is more published evidence of its safety. Alternative methods of pain relief including oral acetaminophen and topical anesthesia should also be studied. Of special interest is recent evidence that a sucrose-flavored pacifier is an effective analgesic during newborn circumcision."
-What are the key differences between pre-T and thymic acute lymphoblastic leukaemia (ALL) in terms of immunological features and clinical characteristics?,"Heterogeneity of T cell lymphoblastic leukaemias. Twenty eight out of 170 consecutive cases of acute lymphoblastic leukaemia (ALL) were examined. They were of T cell origin, with the following distribution: seven (28%) cases had pre-T or prothymic features; nine (36%) cases showed early thymocytic features, six (24%) had cortical features; and three (12%) had a ""mature"" phenotype. The remaining three cases could not be sub-classified. A striking finding was that pre-T ALL differed from intrathymic ALL not only in the absence of both E rosettes and intrathymic differentiation antigens, but also in the expression of two non-lineage specific antigens HLA-DR and CD10. Both antigens appear in the bone marrow from the very first stages of lymphoid differentiation, implying that the origin for pre-T ALL is bone marrow. A comparison of the clinical features of pre-T and thymic ALL showed that pre-T ALL disease showed a pattern more similar to non-T ALL disease: a lower incidence of mediastinal mass, absence of extrahaematopoietic disease, lower white cell counts and haemoglobin concentrations, and a higher incidence of bone pain. No obvious difference in response to treatment was apparent. The results show that T-ALL is not only a heterogeneous immunological group but also suggest that it may have different origins: bone marrow for pre-T ALL and the thymus for thymic ALL."
-What is the new provocative test described for chronic mesenteric ischemia?,"A new provocative test for chronic mesenteric ischemia. A new provocative test for chronic mesenteric ischemia is described, based upon the demonstration of a fall in the intramural pH of the small bowel after introduction of a test meal into the stomach. Intramural pH (pHI) is determined indirectly by tonometry, utilizing a tonometer passed per os. Postoperative assessment of revascularization procedures is also possible by the same technique. Application of the test in an 84-yr-old woman showed good correlation between a preoperative fall in jejunal intramural pH and abdominal pain, and the absence of a fall postoperatively after successful revascularization."
-How does the expression of the human HLA-B27 transgene affect susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination in different mouse haplotypes?,"Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination. Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse."
-What is the significance of ventricular arrhythmias in children with a structurally normal heart?,"Ventricular arrhythmias in children with an apparently normal heart. Ventricular ectopy occurs frequently in normal children. In the presence of a normal heart, these arrhythmias, including asymptomatic, nonsustained ventricular tachycardia, carry a benign prognosis and are not associated with sudden, unexpected death. However, complex ventricular arrhythmias frequently indicate the presence of underlying cardiac disease; patients with such arrhythmias must undergo an appropriately thorough evaluation before decisions regarding prognosis and the need for therapy can be made."
-What is the significance of detecting fetal seizure activity during ultrasound?,Does fetal seizure activity mean a poor outcome? A case report. Fetal seizure activity is very rare: only three cases have been reported. A case of fetal seizure activity was detected with ultrasound. Such activity can be associated with a poor outcome.
-How does the carbon-14-urea breath test help in quantifying Helicobacter pylori infection and assessing gastritis severity?,"Quantification of Helicobacter pylori infection in gastritis and ulcer disease using a simple and rapid carbon-14-urea breath test. Gastric urease was studied isotopically in 230 patients with biopsy-proven normal mucosa or chronic gastritis, including 59 patients with ulcer disease. Carbon-14-urea was given in 25 ml of water without substrate carrier or nutrient-dense meal, and breath samples were collected over a 60-min period. The amount of 14CO2 excreted at 10 min was independent of the rate of gastric emptying and was not quantitatively influenced by the buccal urease activity. The 10-min 14CO2 values discriminated well between Helicobacter pylori positive and negative patients (94% sensitivity, 89% specificity) and correlated with the number of organisms assessed by histology. The test was a good predictor of chronic gastritis (95% sensitivity and 96% specificity), and a quantitative relationship was observed between 14CO2 values and the severity and activity of the gastritis. In H. pylori positive patients, breath 14CO2 was found to be similar in patients with and without ulcer disease, suggesting that the number of bacteria is not a determining factor for the onset of ulceration."
-"How does the presence of HCV RNA in serum relate to the progression of non-A, non-B hepatitis?","A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. BACKGROUND. Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis. METHODS. We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 10 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a ""nested"" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome. RESULTS. HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease. CONCLUSIONS. During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease."
-What are the key symptoms and characteristics of acute narrow-angle glaucoma as described in this case report?,"Narrow-angle glaucoma presenting as acute, painless visual impairment. A 42-year-old woman presented with the acute onset of bilateral blurred vision that occurred immediately after bending over. She denied pain or any other associated symptoms. Markedly increased intraocular pressure readings were found. Treatment for acute narrow-angle glaucoma was initiated, and normal vision returned. This case represents an atypical presentation of acute narrow-angle glaucoma, a true ophthalmological emergency. The pathophysiology and treatment options of this disease process are summarized."
-What is the sensitivity of thallium-201 single-photon emission computed tomography during adenosine-induced coronary hyperemia for diagnosing coronary artery disease?,"Assessment of coronary artery disease using single-photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia. Thallium-201 myocardial imaging during dipyridamole-induced coronary hyperemia has been an accepted method for diagnosing coronary artery disease (CAD) and risk stratification. Adenosine is a powerful short-acting coronary vasodilator. Initial results of thallium imaging during adenosine infusion have been encouraging. In 132 patients with CAD and in 16 patients with normal coronary angiograms, adenosine was given intravenously at a dose of 0.14 mg/kg/min for 6 minutes and thallium-201 was injected at 3 minutes. The thallium images using single-photon emission computed tomography were abnormal in 47 of the 54 patients (87%) with 1-vessel, in 34 of 37 patients (92%) with 2-vessel and in 40 of 41 patients (98%) with 3-vessel CAD. The sensitivity was 92% in the 132 patients with CAD (95% confidence intervals, 86 to 96%). In patients with normal coronary angiograms, 14 of 16 patients had normal thallium images (specificity, 88%; 95% confidence intervals, 59 to 100%). The results were very similar when subgroups of patients were analyzed: those without prior myocardial infarction, elderly patients and women. The nature of the perfusion defects (fixed or reversible) was assessed in relation to whether the 4-hour delayed images were obtained with or without the reinjection technique. In patients who underwent conventional delayed imaging, there were more fixed perfusion defects than in patients with reinjection delayed imaging (16 vs 0%, p less than 0.0001). The adverse effects were mild, transient and well tolerated. Thus, adenosine thallium tomographic imaging provides a high degree of accuracy in the diagnosis of CAD. The use of the reinjection technique enhances the ability to detect reversible defects."
-What is the significance of the malignant schwannoma found in this xeroderma pigmentosum patient?,"Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D. A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum."
-How does adenosine affect pulmonary vascular resistance in patients with primary pulmonary hypertension?,"Adenosine as a vasodilator in primary pulmonary hypertension BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension."
-How did the study assess the reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses between two different echocardiography centers?,"Reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses: comparison between two echocardiography centers. Doppler echocardiography has been widely used as a noninvasive method to quantify valvular heart diseases. This study assessed the variability between 2 echocardiography centers concerning 2-dimensional and Doppler echocardiographic results in the quantification of mitral and aortic valve stenoses. Forty-two patients were studied by 2 different echocardiography centers in a blinded, independent fashion. In patients with aortic and mitral valve stenosis, mean and maximal flow velocities were measured. The aortic valve orifice area was calculated according to the continuity equation. Mitral valve orifice area was determined by direct planimetry and by pressure half-time. In patients with an aortic valve stenosis, a close relation between the 2 centers was found for the maximal and mean flow velocities (coefficient of correlation, r = 0.72 to 0.92; coefficient of variation, 3.7 to 7.7%). A close correlation and a small observer variability was found for the flow velocity ratio determined by flow velocities measured in the left ventricular outflow tract and over the stenotic valve (r = 0.88; coefficient of variation, 0.01 +/- 0.009). In contrast, there was a poor correlation between the diameter of the left ventricular outflow tract and the aortic orifice area (r = 0.36 and 0.59, respectively). In patients with a mitral valve stenosis, mean and maximal velocities were closely correlated (r = 0.85 and 0.77, respectively). Velocities were not found to be significantly different between the 2 centers. Variability between the 2 centers for the mitral valve orifice area was 9.8% (2-dimensional echocardiography) and 5.7% (pressure half-time)."
-How do the hypercarbic ventilatory responses (HCVR) of heart-lung transplant recipients compare to those of normal control subjects?,"Hypercarbic ventilatory responses of human heart-lung transplant recipients. To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition."
-What was the initial presentation of the 10-year-old boy that led to the discovery of his obstructive sleep apnea syndrome?,"Antral choanal polyp presenting as obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome (OSAS) in children is commonly caused by adenotonsillar hypertrophy. The diagnostic criteria of OSAS in children are not so well delineated as in adults. We report the first case of antral choanal polyp presenting as OSAS in a 10-year-old boy that initially presented to the child psychiatry service for behavior disturbance, enuresis, and daytime somnolence. Overnight electroencephalogram sleep study revealed events consistent with OSAS. Multiple inhalant allergies, chronic maxillary sinusitis, and obstructive adenoid hypertrophy were diagnosed by the allergy and otolaryngology services. The child was scheduled for adenoidectomy when his sleep apnea symptoms persisted following antimicrobial therapy. Examination under anesthesia revealed a normal adenoid bed and a large left antral choanal polyp. Polypectomy was performed as dictated by parental consent. Postoperatively treatment with an intranasal steroid was begun. However, polypoid nasal mucosa recurred in 2 months and a Caldwell-Luc procedure was performed. Subjective reports following surgery indicated improvement in daytime irritability, attention, and mood. A follow-up overnight electroencephalogram sleep study confirmed resolution of OSAS."
-What percentage of leukemic children in the study were persistently positive for anti-HCV antibodies?,"Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia."
-What is the significance of fatty infiltration in the liver for diagnosing medium chain acyl CoA dehydrogenase deficiency?,Fatty infiltration in the liver in medium chain acyl CoA dehydrogenase deficiency. Fatty infiltration of the liver at postmortem examination has been recommended as a criterion for selection of infants who have died suddenly and unexpectedly for further biochemical investigation for disorders of fatty acid oxidation. We describe a boy with medium chain acyl CoA dehydrogenase deficiency who died four months after diagnosis and in whom only minimal hepatic fatty infiltration was found.
-How does the DNA ploidy pattern relate to tumor cell aggregation and metastasis in poorly differentiated stomach adenocarcinoma?,"Nuclear DNA content, tumor cell aggregation, and metastatic events in patients with poorly differentiated adenocarcinoma of the stomach. Data on 100 patients who had undergone resection for poorly differentiated adenocarcinoma of the stomach with serosal invasion were examined to assess the prognostic significance of the DNA distribution pattern in relation to the histologic tumor cell aggregation pattern. DNA distribution patterns were classified into low and high ploidies and tumor cell aggregation patterns were classified into free-cell, small nest, and large nest types. The rates of high ploidy in the free-cell, small nest, and large nest types were 23.1%, 48.0%, and 66.7%, respectively, with a significant increase according to the degree of aggregation. The high ploidy group and large nest type had a higher incidence of lymphogenous and hematogenous metastasis than the low ploidy group and free-cell type, respectively. DNA ploidy had no prognostic value for the free-cell type of tumor, but differences in prognosis and the incidence of metastasis between the DNA ploidies were evident in the nest-forming type. Aneuploid tumors consisting of a poorly differentiated adenocarcinoma were those with nest formation, from the standpoint of histologic structure and metastatic behavior. The DNA analysis of poorly differentiated adenocarcinomas was of prognostic value, especially in the nest-forming type."
-What was the peak level of interferon-gamma detected in urine samples after intravesical BCG therapy?,"Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity."
-What is asymptomatic bacterascites and how does it differ from spontaneous bacterial peritonitis?,"Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required."
-What was the main objective of the study conducted by the National Heart Foundation of Australia Coronary Thrombolysis Group?,"A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group. BACKGROUND. This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS. A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS. We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function."
-What is the potential primary treatment for patients with detrusor sphincter dyssynergia and failed sphincterotomy according to the study?,"Permanent urethral stents for detrusor sphincter dyssynergia. A series of 22 patients, most of whom had spinal injuries with detrusor sphincter dyssynergia, have had Medinvent Wallstents placed across the distal mechanism. All but 8 patients had undergone outflow surgery and 11 had had repeated unsuccessful sphincterotomies. The proximal end of the stent was placed over the verumontanum unless fertility was contemplated, when it was placed immediately below the verumontanum. Fifteen patients achieved complete voiding after placement of the first stent; 3 developed bladder neck obstruction after stenting, but in 1 of these cases resolution occurred after bladder neck incision. The 3 patients with artificial urinary sphincters failed to improve after stenting. Use of the urethral stent for patients with detrusor sphincter dyssynergia and failed sphincterotomy is a major advance. It should probably be the primary treatment in selected cases. Its effect on fertility is currently under assessment."
-How does the Tax protein of HTLV-I contribute to cellular transformation through transcription factor pathways?,"Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation."
-What unusual complication occurred during the sinography of a pancreatic pseudocyst in the described case?,"Drainage of a pancreatic pseudocyst: an unusual complication. A 34-year-old white woman had external drainage of a pancreatic pseudocyst. During sinography, contrast medium filled perigastric varices, causing septic shock. From this experience, we believe that although sinograms are helpful, they should be preceded by prophylactic administration of antibiotics and that contrast material should be sterile. The drainage catheter should be removed as soon as possible."
-What was the most commonly affected test of lung function in patients with advanced liver disease?,"Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance."
-What were the key findings comparing hand-sewn and stapled anastomosis techniques in oesophageal surgeries?,"Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomoses. A total of 611 patients with carcinoma of the oesophagus or gastric cardia were operated on between July 1982 and December 1989. Resection was performed in 491 patients (one-stage, 483; two-stage, eight), bypass operation in 97, and 23 had exploration alone. The anastomoses of 580 patients with one-stage resection and bypass operations were evaluated. Hand-sewn anastomosis using a single layer of continuous absorbable monofilament suture was performed in 304 patients (221 resections and 83 bypasses). A stapled anastomosis was performed on 276 patients (262 resections and 14 bypasses). Following resection, there were 11 (5 per cent) anastomotic leaks in the hand-sewn group and ten (3.8 per cent) in the stapled anastomosis group (P = 0.69). Excluding anastomotic leaks, hospital mortality and anastomotic recurrence, stricture occurred in 18 of 172 hand-sewn anastomoses (10.5 per cent) and in 57 of 195 stapled anastomoses (29.2 per cent) (P less than 0.001). In patients who had bypass operations there were 12 anastomotic leaks, ten in the hand-sewn group (12.0 per cent) and two in the stapled anastomosis group (14.3 per cent). Only two of the discharged patients with bypass developed anastomotic strictures, a low incidence probably because of short survival. In addition, there were 245 subsidiary anastomoses made in the abdomen by the hand-sewn method as part of the reconstructive procedure, and there was one leak. The results of this non-randomized study suggest that hand-sewn anastomosis using a single layer continuous technique for the oesophagus is as safe as the use of circular staplers; hand-sewn anastomosis is less likely to become stenotic."
-What makes it important to distinguish between general fatigue and depression-related fatigue in cancer patients?,"Depression and chronic fatigue in cancer patients. Fatigue is a very common symptom among cancer patients. It is crucial to diagnose those patients for whom the fatigue is a symptom of depression, and to treat them appropriately. The key to providing complete and satisfying care is to identify and address the psychologic, social, and medical vulnerabilities of each cancer patient. No one is in a better position to accomplish that than the primary physician."
-What are the potential hepatic vascular lesions associated with azathioprine-induced liver disease?,"Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis. Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present."
-What was the purpose of the study on intradermal hepatitis B vaccine administration?,"The immunogenicity and safety of intradermal hepatitis B vaccine. BACKGROUND. One of the chief barriers to a greater use of hepatitis B vaccine is the high cost of the vaccine itself. A number of small research trials have shown that an adequate immune response can be induced at a much lower cost by administering one tenth of the vaccine using an intradermal technique. The purpose of this study was to ascertain whether these results could be replicated in a larger clinical trial. METHODS. Vaccine recipients included health care providers, police officers, and firefighters. Recipients were given 0.1 mL of plasma-derived hepatitis B vaccine intradermally on days 1, 30, and 180. Antibody response was measured on day 210, with seroconversion defined as a sample-to-negative (S/N) ratio of greater than or equal to 10. Any local and systemic side effects were documented. RESULTS. Six hundred sixteen individuals completed the vaccination series, and seroconversion occurred in 534 (86.7%). The rate of seroconversion in those younger than 40 years was 91.2% and in those 40 years and older was 75.1%. The mean S/N ratio was 154.9 (range 0 to 620) and decreased with increasing age (r = -.25, P = .0001). Side effects were largely limited to local reactions. CONCLUSIONS. The results support the use of the intradermal technique as a cost-effective alternative to the intramuscular route in individuals younger than 40 years. The intradermal technique may be used in older individuals if titers are obtained to assure seroconversion. Because of the restricted availability of the plasma-derived vaccine used in this study, similar trials with recombinant vaccine should be undertaken."
-What trends were observed in the occurrence of hemorrhoids in the United States and England based on the study's analysis?,"Temporal changes in the occurrence of hemorrhoids in the United States and England. Although numerous etiologic risk factors have been proposed, the pathogenesis of hemorrhoids remains unknown. The present investigation assesses the temporal distribution of hemorrhoids as depicted by physician visits, hospital discharges, and surgical procedures to provide further insight into potential etiologic risk factors. The analysis was based on five data sources: from the United States, the National Disease and Therapeutic Index (NDTI), the National Hospital Discharge Survey (NHDS), and the Commission on Professional Hospital Activities (CPHA); from England and Wales, the Morbidity Statistics from General Practice (MSGP) and the Hospital In-patient Enquiry (HIPE). Results demonstrated a consistent decline in all data sources from the United States. The decrease occurred in males and females similarly and was most striking in those aged 45-64 years. Physician visits and hospital discharges for hemorrhoids in England and Wales likewise declined although the decrease was not as dramatic. The consistency of the temporal distributions among the two countries, as well as among the different sources, suggests that the observed decline may, in fact, reflect an overall decrease in the occurrence of hemorrhoidal disease."
-What was the main finding of this study regarding kidney protection during aortoiliac surgery in renal transplant patients?,"Aortoiliac surgery in renal transplant patients. Fifteen patients who had undergone renal transplantation 3 months to 25 years earlier were operated on for treatment of complicated aortoiliac atherosclerosis; eight had aneurysms and seven had stenotic or obstructive lesions. Except for the first patient, operated on in 1973, in whom the kidney was protected by general hypothermia, no special measure was used to protect the kidneys. A transient increase in creatinemia occurred in 11 patients during the postoperative period, whereas creatinine values remained unchanged in the other four. All patients had regained renal function identical to the + preoperative state in less than 10 days; three of them had significant improvement as a result of correction of a lesion that was impairing renal blood flow. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided an adequate surgical technique is used. This technique avoids the complex methods employed in the majority of previously reported cases and appears to be a safe procedure."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-What was the purpose of screening the expression cDNA library from the human melanoma cell line A375 with sera from melanoma patients?,"Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution."
-What were the key differences between the standard approach and the integrated approach in treating chronic pelvic pain in this clinical trial?,"A randomized clinical trial to compare two different approaches in women with chronic pelvic pain. One hundred six patients with chronic pelvic pain were randomly allocated to one of two treatment groups. In the standard-approach group, organic causes of pelvic pain were excluded first and diagnostic laparoscopy was routinely performed. If no somatic cause could be found, attention was given to other causes such as psychological disturbances. In the second group an integrated approach was chosen. From the beginning equal attention was devoted to somatic, psychological, dietary, environmental, and physiotherapeutic factors. In this group, laparoscopy was not routinely performed. Both groups were similar with respect to clinical characteristics of the patients and the severity of their pain as assessed by various pain parameters. Postcoital pain was reported by 27% of the patients. Twenty percent of the patients had had negative sexual experiences such as childhood sexual abuse or rape. Evaluation of the pain 1 year after the institution of treatment revealed that the integrated approach improved pelvic pain significantly more often than the standard approach for three out of four pain parameters (P less than .01). Laparoscopy played no important role in the treatment of pelvic pain. It is concluded that equal attention to both organic and other causative factors from the beginning of therapy is more likely to result in a reduction of pelvic pain than is a standard approach."
-What is the definition of multivessel disease in the context of this study?,"Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infarction. Therefore to better define the short-term prognostic value of early coronary angiography, and specifically the prognostic significance of multivessel coronary artery disease, the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome. All patients received intravenous thrombolytic therapy (tissue plasminogen activator, urokinase, or both agents) and underwent cardiac catheterization within 90 minutes of the initiation of therapy. Multivessel disease, defined as the presence of greater than or equal to 75% luminal diameter stenosis in two or more major epicardial arteries, was documented in 236 patients. When compared with the group of patients without multivessel disease, this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain. Although the severity of the infarct zone dysfunction was similar in the two groups (-2.77 +/- 1.00 vs -2.50 +/- 1.09 SD/chord, p = NS), global left ventricular ejection fraction was lower in the group with multivessel disease (48.6 +/- 12.4% vs 51.8 +/- 10.6%, p less than 0.01). This was associated with a significant difference in the function of the noninfarct zone. Whereas this region was hyperkinetic in the group with minimal or single-vessel disease, it was hypocontractile or dyskinetic in those with multivessel disease (+0.66 +/- 1.53 vs -0.52 +/- 1.73 SD/chord, p = 0.0001)."
-How does magnetic resonance imaging (MRI) help in managing diabetic foot infections?,"Impact of magnetic resonance imaging on the management of diabetic foot infections. This combined retrospective/prospective study evaluated the value of magnetic resonance imaging (MRI) in 18 diabetic patients with apparent foot infections. The goal was to define the impact of MRI on directing the expedient and accurate surgical intervention so important in achieving optimal preservation of limb tissue and function. We found that MRI provides a rapid and reliable means of ""viewing"" the diabetic foot. Unsuspected or poorly localized abscess cavities can be pinpointed for thorough drainage with minimal exploration. An abscess can be differentiated from cellulitis or osteomyelitis. Moreover, persistent fever following drainage of a foot abscess can be reliably evaluated via MRI, obviating the need for empiric surgical reexploration. This exciting noninvasive imaging technique leads to the most accurate surgical drainage of foot abscesses and, at the same time, can prevent unnecessary surgical exploration of the tenuous diabetic foot."
-How do posttranscriptional mechanisms contribute to protein increase during renal compensatory growth?,"Regulation of gene expression in renal compensatory growth. Compensatory renal hypertrophy is characterized by an increase in cell protein content. There are a number of different cellular mechanisms by which such an increase could be mediated. The relative contributions of transcriptional and posttranscriptional regulation of gene expression to the increase in constitutively expressed cellular proteins were examined in mouse kidneys undergoing compensatory growth following unilateral nephrectomy (UNI-NX). Over the 14-day study period, total protein per kidney increased by up to 37%. Northern blot analysis of the expression of the mRNAs for a number of genes associated with cell growth indicated that there was no significant increase in steady-state levels of these selected genes in nephrectomized compared with sham-operated animals. In vitro assays to measure transcriptional regulation of the same set of genes in compensatory growth showed no increase in the rate of transcription. However, transcription of the 18S ribosomal RNA gene was increased 24 hours after nephrectomy. Immunoblots of two representative proteins showed that the concentration of these proteins in total kidney protein remained constant in the different experimental groups. Since total protein increased, the concentration of these proteins in the hypertrophied kidney must have increased. Taken together, these data suggest that posttranscriptional mechanisms may account for the increase in at least some constitutively expressed proteins in cells undergoing compensatory growth."
-How does hydralazine prevent nitroglycerin-induced hemodynamic tolerance in experimental heart failure?,"Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. BACKGROUND. Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS. Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS. The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin."
-How does clonidine affect vesical and somatic reflexes in patients with suprasacral spinal cord lesions?,"Clonidine inhibits vesico-sphincter reflexes in patients with chronic spinal lesions. When administered systemically to spinalized animals, clonidine, the prototypic alpha 2 adrenergic receptor agonist, purportedly acts at spinal sites to suppress motor responses related to painful peripheral and vesical stimulation and spasticity, and to improve vesicourethral coordination. Hence, the action of clonidine (400 micrograms in three divided doses in a 16-hour span) on spinal vesical and somatic reflexes was examined in five patients with suprasacral spinal cord lesions by assessing volume-induced micturition reflexes and limb motor discharges that occurred spontaneously or were elicited by noxious and nonnoxious cutaneous stimulation. Clonidine caused a significant reduction in (1) blood pressure, (2) amplitude of detrusor contraction, and (3) vesical external urethral sphincter dyssynergia. Limb motor electromyography discharges were not markedly attenuated, although spatiotemporal changes (eg, irradiation, after-discharges) were observed in some of the patients. The results are ascribed to binding to spinal cord alpha 2 adrenergic receptors located on segmental and intersegmental (propriospinal) interneurons, released from descending inhibition, with greater motor system specificity on striated sphincter innervation. Clonidine may be clinically effective in the treatment of hyperactive micturition reflexes in patients with chronic spinal lesions."
-How does caffeine affect postprandial blood pressure in elderly subjects?,"The effect of caffeine on postprandial hypotension in the elderly In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension."
-What challenges do urinary tract infections (UTIs) pose for young women and the healthcare community?,"Advances in the understanding and treatment of urinary tract infections in young women. Despite relative ease of management, the high rate of urinary tract infections (UTI) among young women presents substantial problems for the health care community. Although the majority of UTIs in young women are simple and uncomplicated, the rate of recurrence is substantial. Each treatment of UTI recurrence brings greater antibiotic resistance, requiring the use of broader spectrum and more expensive antibiotic therapy. Moreover, infection in patients with underlying urinary tract or systemic diseases can lead to serious medical and financial consequences. A better understanding of antibiotic resistance, particularly in regard to beta-lactamase-producing pathogens, has allowed us to develop more appropriate criteria for selecting antibiotics as well as the duration of therapy. The overall cost for treating UTIs in young women is a substantial health care expenditure, and requires an ongoing examination of new information concerning pathogenesis and available antibiotic therapies."
-What was the survival rate for infants undergoing staged repair of interrupted aortic arch and ventricular septal defect between 1979 and 1990?,"Staged repair of interrupted aortic arch and ventricular septal defect in infancy. Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants."
-How do CEA levels in peripheral and draining venous blood correlate with the risk of hematogenous metastasis in colorectal cancer patients?,"Colorectal cancer patients with high risk of hematogenous metastasis: correlation with CEA levels in peripheral and draining venous blood during the period of operation. Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood during the period of operation, and pre- and post-operatively detected hematogenous metastases were examined in 78 patients with colorectal cancer. The metastases were found in 28 patients (HM group), but not found in the other 50 patients (non-HM group). The mean values (43 and 198 ng/ml) and positive rates (61 and 96%) greater than 5 ng/ml of p- and d-CEA levels in the HM group were significantly higher than those (6 and 14 ng/ml, and 22 and 48%, respectively) in the non-HM group. The differences (mean 184 ng/ml and positive rate 49%) of d-CEA levels between both groups were more significant than those (39 ng/ml and 30%) of p-CEA levels. The mean value (155 ng/ml) and positive rate (82%) greater than 5 ng/ml of the gradient between d- and p-CEA levels (d-p CEA gradient) in the HM group were significantly higher than those (8 ng/ml and 34%) in the non-HM group. These results suggest that patients with a high risk of hematogenous metastases are more effectively checked by the determination of d-CEA levels and d-p CEA gradient than of p-CEA levels, and that they are patients with positive d-CEA and d-p CEA gradient levels."
-What are the key characteristics and management strategies for neurofibromatosis-2?,"Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described."
-How did endoscopic variceal sclerotherapy affect portal venous pressure gradient in cirrhotic patients?,"The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy."
-What improvements are suggested for emergency medical services in the United States to enhance patient care and response times?,"Role of emergency medical services. For thrombolytic therapy to be effective in the treatment of acute myocardial infarction, the patient must enter the health care center delivery system in an efficient manner. Some entry delays are due to patient decisions and interactions with others. In the United States, prehospital care is delivered by a variety of different systems, varying from public service types such as fire-department based to private types of service. These personnel vary in level of training from paramedics with a high level of training to Emergency Medical Technicians-Ambulance with basic training (first aid), even less in some areas. The training should be upgraded so that training as an emergency medical technician with the ability to defibrillate would be the minimum level for emergency ambulance personnel; wherever economically and logistically feasible, ambulance personnel should be paramedics. Although the 911 emergency telephone system exists in some areas, there is no centralized, universal system for access, causing confusion and delays in obtaining care in critical situations such as cardiac arrest. There is a need for a national emergency number--911--with the ability to identify the calling number and address. Since dispatchers have little medical dispatch training, needed instructions are not given to the caller, which can reduce the patient's chance of survival. Trained dispatchers are needed to dispatch resources efficiently and to offer assistance until trained rescuers arrive. Ambulances are inefficiently located in some areas of the United States, slowing response to the patient."
-What is effort thrombosis of the axillosubclavian vein and how is it typically treated?,"Effort thrombosis of the axillosubclavian vein: a disabling vascular disorder. In the natural history of this disorder, resumption of normal activity after a period of recuperation (following an episode of thrombosis) frequently leads to symptoms of upper extremity venous hypertension exacerbated by using the arms in the overhead position. This position can be demonstrated venographically to further occlude collateral vessels in thoracic outlet. A number of patients develop more extensive symptoms of neurogenic thoracic outlet syndrome. Anticoagulation may protect the collateral vessels and interrupt the period of active clot propagation resulting in a better functional result than would be expected from the natural history of the thrombotic event. In our experience, local Urokinase was the most effective means for reestablishing venous patency. With clot dissolution the underlying compression of the vein at the thoracic outlet can be demonstrated. Balloon angioplasty should not be undertaken in the acute setting nor prior to relieving the tendinous compression. The acute phlebitic process should resolve under the protection of Coumadin for three months. At that time it can be determined more effectively which patients require additional therapy. Removal of the first rib will decompress the axillosubclavian vein and the thoracic outlet collaterals permitting the vein to regain its normal configuration particularly in younger patients with more acute onset of compression. In those patients with more chronic compression the vein becomes stenotic. Improvement of the luminal configuration has been accomplished with transvenous balloon angioplasty without the necessity for venous reconstructive procedures in this series. Patients with Paget-Schroetter syndrome have a symptom complex which often reflects more extensive neurovascular compression at the thoracic outlet than that which might result from venous hypertension alone. Although thrombolytic therapy can restore patency of the axillosubclavian vein, first rib resection is necessary to relieve the external compression. This procedure was very effective in patients who had restoration of subclavian vein patency, and to a lesser degree in those with residual occlusion."
-Who was Paul Broca and what significant medical procedure did he perform in 1871?,"Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization."
-How was HLA class I antigen expression evaluated in patients with chronic hepatitis B?,"HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy."
-What method did researchers use to detect regional disparities in ventricular recovery in patients with long QT syndrome?,"Dispersion of ventricular repolarization in the long QT syndrome. To identify markers of dispersion of the ventricular repolarization in the idiopathic long QT syndrome, body surface potential maps were analyzed in 40 such patients (mean age +/- standard deviation 21 +/- 11 years) and in 30 healthy control subjects (mean age 24 +/- 7 years). In each subject, 117 chest leads were recorded and maps of the integral values of the QRST interval were calculated. A multipolar distribution of the values, a marker of gross electrical inequalities of repolarization, was found only in 4 patients. To detect minor regional disparities of ventricular recovery, all the ST-T waveforms were analyzed in each subject. The ST-T waves were represented by a discrete series of potential values. The ""similarity index"" was computed by applying a principal component analysis, which represents (in percent) to what extent 1 fundamental pattern of ST-T reproduces all the recorded waveforms. The mean value of the similarity index was significantly lower in patients with long QT syndrome than in control subjects (49 +/- 10 vs 77 +/- 8%, p less than 0.0001). A value less than 61% (corresponding to 2 standard deviations below the mean value for controls) was found in 35 of 40 patients and in only 1 control subject (sensitivity 87%, specificity 96%). Thus, the similarity index is a more sensitive marker than the multipolar distribution of QRST integral maps in revealing electrical disparities of the ventricular recovery times."
-What is spatial misregistration in MR imaging of the CNS and how does it occur?,"Spatial misregistration of vascular flow during MR imaging of the CNS: cause and clinical significance. Spatial misregistration of signal recovered from flowing spins within vascular structures is a common phenomenon seen in MR imaging of the CNS. The condition is displayed as a bright line or dot offset from the true anatomic location of the lumen of the imaged vessel. Its origin is the time delay between application of the phase- and frequency-encoding gradients used to locate spins within the plane of section. The principal condition necessary for the production of spatial misregistration is flow oblique to the axis of the phase-encoding gradient. Flow-related enhancement (entry slice phenomenon), even-echo rephasing, and gradient-moment nulling contribute to the production of the bright signal of spatial misregistration. Familiarity with the typical appearance of flow-dependent spatial misregistration permits confirmation of a vessel's patency; identification of the direction of flow; estimation of the velocity of flow; and differentiation of this flow artifact from atheromas, dissection, intraluminal clot, and artifacts such as chemical shift."
-How did the surgical management of invasive squamous cell carcinoma of the vulva change at Indiana University between 1974 and 1988?,"Trends in the operative management of invasive squamous carcinoma of the vulva at Indiana University, 1974 to 1988. From January 1974 to March 1988, 150 patients with primary invasive squamous cell carcinoma of the vulva underwent surgery at Indiana University. There has been a trend toward more conservative surgical management of this disease. To determine the impact of this trend on clinical outcome, cases were divided into three groups according to date of operation: group I, 1974 to 1978; group II, 1979 to 1983; and group III, 1984 to 1988. Overall, 80 patients had en bloc radical vulvectomy and groin dissection, 20 had modified radical vulvectomy and bilateral groin dissection through three separate incisions, and 36 had modified radical vulvectomy and unilateral superficial groin dissection. Fourteen patients had other operations. Forty-two patients (27.3%) had radiotherapy in addition to surgery. Among the three groups, there were no differences when mean age, International Federation of Gynecology and Obstetrics stage distribution (1988 system), mean lesion size, mean depth of invasion, or grade distribution were compared. A significant trend toward more conservative surgical therapy was observed. En bloc radical vulvectomy was performed in 77.4% of group I patients, 71.1% of group II patients, and 35.8% of group III patients (p less than 0.001). Mean days of hospitalization were also reduced significantly. Group I had a mean stay of 30 days, group II had a mean stay of 23 days, and group III had a mean stay of 11 days (p less than 0.001). Mean operative blood loss (group I, 754.8 ml; group II, 620.0 ml; group III, 393.6 ml; p = 0.03), mean units of blood transfused (group I, 1.4 units; group II, 1.3 units; group III, 0.4 units; p less than 0.01), and mean hours of operating time (group I, 3.7 hours; group II, 3.7 hours; group III, 3.2 hours; p = 0.02) were also reduced."
-What are the potential advantages and challenges of using a detubularised bowel segment in cystoplasty?,"Detubularisation in cystoplasty: clinical review. Cystoplasty using a detubularised bowel segment is preferable to using a tubularised length of intestine. This has been shown experimentally to result in a reduction in the contractility of the neobladder, although contractions are not completely abolished. Incontinence, especially nocturnal, may still be a problem. Assessment of renal function has shown a marked incidence of upper tract dysfunction despite detubularisation. All patients remain at risk of upper tract obstruction following cystoplasty. Because bowel contraction waves are brought on by distension, it may be possible either to postpone or to prevent the onset of contractions by avoiding an excessive build-up of bladder volume. Clean intermittent self-catheterisation is an efficient means of emptying the bladder, although sphincter rebalancing may also be required."
-How did extracorporeal shock-wave cholecystolithotripsy (ESWL) affect gallbladder contractility in the studied patients?,"Altered gallbladder contractility after extracorporeal shock-wave cholecystolithotripsy. Change in gallbladder contractility after biliary extracorporeal shock-wave lithotripsy (ESWL) may significantly influence the clearance of fragments after successful gallstone fragmentation. We assessed changes in gallbladder contractility in response to an oral fatty meal in 50 patients 1 month after biliary ESWL (all fragments were smaller than 3 mm) and also in a separate group of 10 patients 3 months after complete clearance of fragments. The prevalence of persistent lumen-obliterating contraction of the gallbladder after biliary ESWL also was analyzed in 325 patients. Gallbladder contractility remained unchanged in 30, increased in nine, and decreased in 11 of the 50 patients. The average reduction in the fasting gallbladder volume after lithotripsy was 28% (p less than .001). Gallbladder contractility remained unchanged 3 months after complete clearance of fragments in six of 10 patients studied separately. A decrease (n = 2) or increase (n = 2) in contractility was seen in the remaining patients. No significant difference occurred in the average ejection fraction of the gallbladder before lithotripsy and after complete clearance of the fragments. Thirty-four of the 325 patients who have so far undergone biliary ESWL had a completely contracted gallbladder with no lumen visible on sonography. The gallbladder returned to a relaxed state in half of these patients within 1-9 months. Thus, biliary ESWL did not significantly alter gallbladder contractility in 60% of patients. A significant reduction in the volume of the fasting gallbladder occurred after lithotripsy. Successful clearance of fragments did not improve the contractility of stonebearing gallbladders in the majority of patients."
-What modifications were made to the transcochlear approach to improve surgical exposure in the cerebellopontine angle region?,"The modified transcochlear approach to the cerebellopontine angle. We have modified the transcochlear approach to improve exposure of the anterior petrous apex, clivus, anterior cerebellopontine angle, and the prepontine region. These changes include resection of the external auditory canal, middle ear, glenoid fossa, and posterior zygomatic arch. This approach provides improved exposure of the petrous carotid artery, jugular bulb, and clivus. It offers the largest and most lateral access to the anterior cerebellopontine and prepontine region. The results of this approach in 11 patients are discussed."
-What were the key differences observed between radiofrequency and direct current catheter ablation in the experimental study on dogs?,"Comparison of catheter ablation using radiofrequency versus direct current energy: biophysical, electrophysiologic and pathologic observations. The effects of catheter ablation with radiofrequency versus direct current energy were compared in 18 dogs assigned to two groups (of 9 dogs each). Each dog underwent a single ablation at two sites in the left ventricle at energy levels of 100, 200 or 300 J delivered in unipolar configuration to six dogs each. A transient decrease in left ventricular systolic pressure (from 121.3 +/- 24.5 to 94.2 +/- 18.7 mm Hg, p less than 0.01) and wall motion abnormality were noted in dogs with direct current shock. The left ventricular ejection fraction decreased (from 50 +/- 2% to 34 +/- 3%, p less than 0.001) shortly after direct current ablation but improved 4 weeks later to 43 +/- 3%. There were no significant changes in left ventricular pressure, wall motion or ejection fraction in dogs in the radiofrequency ablation group. Sustained ventricular tachycardia (greater than or equal to 30 s) was seen immediately after direct current shock in all dogs, and one dog died of intractable ventricular fibrillation. A 24-h ambulatory electrocardiographic (ECG) monitor obtained immediately after the procedure showed multiple runs of ventricular tachycardia in all dogs exposed to direct current ablation but in only three dogs that underwent radiofrequency ablation. No differences were found in peak creatine kinase, complete blood count with smear and B-beta 15-42 fibrinopeptide levels. Pathologically, direct current-induced lesions were larger (mean length x width x depth 10.9 x 7.5 x 5.2 vs. 4.8 x 4.6 x 4.3 mm) and were poorly circumscribed with inhomogeneous margins of necrosis."
-What was the most significant factor affecting recurrence rate in patients with colorectal liver metastases according to the study?,"The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. An increased interest in surgical treatment of liver metastases from colorectal origin has evolved recently. However not all patients benefit from this approach, with early recurrence and death still being encountered. To evaluate clinical as well as perioperative factors that might significantly affect the outcome of patients with completely resected colorectal liver metastases, we examined 116 patients who underwent resection between September 1987 and August 1989. Median follow-up time was 13.2 months (0.6 to 31.4 months). The overall survival rate was 91% at 1 year and 75% at 2 years. Median survival was not reached. Median disease-free survival time was 11.5 months, with 49.4% and 21.2% of the patients being free of disease at 1 and 2 years, respectively. By univariate analysis, site of primary colorectal cancer, preoperative carcinoembryonic antigen (CEA) level, size of metastases, number of metastases, length of operation time, percentage mean arterial pressure, number of hypotensive episodes, duration of hypotensive episodes, and whole blood transfusion significantly affected recurrence rate following resection. However only site of primary tumor, CEA, number of metastases, and number of hypotensive episodes remained significant in the multivariate analysis. The most significant single factor that affected recurrence rate was the number of hypotensive episodes during the operative procedure. It is concluded that hypotensive episodes, even when well controlled, should be avoided during operation to maximize the chances of cure and prolong disease-free survival of patients with colorectal liver metastases."
-Why is acetaminophen hepatotoxicity often missed in chronic alcoholic patients?,"Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics. We encountered six alcoholic patients with severe acetaminophen hepatotoxicity during a 2-year period. All patients had marked elevations of aminotransferases and sometimes remarkably high prothrombin times at, or shortly after, presentation. In five of six cases the diagnosis was missed by the physicians initially caring for the patient. The apparent reasons for the missed diagnosis were insufficient history regarding the use of acetaminophen, an inappropriate reliance on blood acetaminophen levels, and lack of knowledge regarding typical aminotransferase elevations in alcoholic hepatitis vs acetaminophen toxicity. The initial clinical presentation of acetaminophen hepatotoxicity in chronic alcoholics is easily recognized clinically and is distinct from acetaminophen hepatotoxicity in suicide ingestions and from alcoholic hepatitis. Internists and other physicians should be aware of this entity and rely on the clinical picture and the history of acetaminophen use to confirm the diagnosis."
-What alternative explanation is proposed for the genesis of closed-lock symptoms in temporomandibular internal derangement?,"An alternative explanation for the genesis of closed-lock symptoms in the internal derangement process. Clinical and surgical data on 194 operated joints (135 patients) were used to substantiate a new concept challenging the presumed natural history of temporomandibular internal derangement (ID). A number of findings were incompatible with the traditional depiction of a progressive process based on gradual changes in disc position and shape. These findings were a lack or correlation between increasing age and the stages of the process; the percentage of patients in the third stage (closed lock) with limited opening (less than 25 mm) too severe to be caused solely by a nonreducible, displaced disc; the unexpectedly high incidence (greater than 50%) of normally shaped discs in the third stage of the process. A specific condition of severe and stubborn limited maximal mouth opening caused by total cessation of gliding, liable to occur at any age and unrelated to disc shape or position, which responds successfully to simple treatment by lavage and lysis, pressured injection, or arthrocentesis, was discerned. Lack of gliding was attributed to adherence of the disc to the fossa by a reversible effect such as a vacuum and/or decreased volume of synovial fluid of high viscosity. This condition was deemed worthy of an independent identity, dissociated from disc displacement, as a causative factor in the second and third stages of ID, and particularly as an aid to accurate diagnosis and treatment."
-What percentage of acoustic neurinomas in this study were confined to the intracanalicular area?,"Intracanalicular acoustic neurinomas. The cases of 16 patients with acoustic neurinomas confined to the intracanalicular area are presented. These represent 2.7% of the 600 patients with acoustic neurinomas consecutively operated upon at the Neurosurgical Clinic at Nordstadt Hospital during the last 8 years. The comparatively earlier onset of vestibular symptoms and signs was characteristic of this group and precipitated diagnosis. The diagnostic reliability of magnetic resonance imaging was at least equivalent to that of air computed tomographic cisternography. Complete tumor removal was accomplished via the suboccipital approach in all patients, with 100% preservation of facial nerve and facial function; the cochlear nerve was preserved anatomically in 100% of the patients and functionally in 57%. No recurrence has occurred during follow-up periods of up to 8 years in all 16 patients. A broad spectrum of the current literature is considered, and purely intracanalicular acoustic neurinomas are discussed with regard to clinical characteristics, diagnostic steps-including neuroradiological and neurophysiological approaches-and surgical treatment and results."
-What makes gall bladder perforation a challenging medical condition to diagnose early?,Acute gall bladder perforation--a dilemma in early diagnosis. Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls.
-What percentage of men were found to have a genital human papillomavirus infection among the sexual partners of women treated for genital condylomata acuminata?,"Genital human papillomavirus infection in men. Diagnosis and treatment with a laser and 5-fluorouracil. One hundred twenty-eight consecutive men, sexual partners (for more than six months) of women treated for genital condylomata acuminata, were evaluated with colposcopy to assess the percentage of infected men among the couples. Ninety-three (73%) of the men were found to have a genital human papillomavirus infection on colposcopically directed biopsies. All but one patient were treated with outpatient colposcopically guided laser vaporization under local anesthesia (one patient with extensive condylomata required general anesthesia). Two weeks after laser surgery, 5% 5-fluorouracil cream, used in the genital area, was initiated on a weekly basis for two months and every other week for two more months. Patients were followed in the clinic with colposcopy performed every eight weeks for six months to evaluate the regimen's results. Thirty-seven (40%) of the 93 men had ""clinically"" apparent genital HPV infection, and 56 (60%) of the 93 had ""subclinical"" disease (as determined with colposcopy). The majority of the patients (87 of 93, or 94%) responded to one laser treatment followed by 5-fluorouracil cream and had no visible lesions at six months. Colposcopic evaluation of the male partners of infected women and laser surgery followed by topical 5-fluorouracil therapy appear to be safe and effective in controlling genital HPV infection."
-How does 3DFT MR angiography compare to digital subtraction angiography in assessing carotid artery stenosis?,"3DFT MR angiography of the carotid bifurcation: potential and limitations as a screening examination. The authors compared the three-dimensional Fourier transform (3DFT) time-of-flight magnetic resonance (MR) angiograms in 38 patients initially studied with selective intraarterial digital subtraction angiography (DSA) for suspected arteriosclerotic disease of the carotid bifurcation. MR angiograms were successfully obtained in 65 of the 75 carotid arteries (87%) visualized with DSA. DSA and MR angiographic studies were assessed for percentage area stenosis by two independent observers on two occasions. Statistical tests indicated consistency in interpretation for each observer as well as between observers. No significant difference was found between the two modalities in ability to depict changes in percentage area stenosis. For the 32 right carotid arteries in the comparison, the median for the difference between MR angiography and intraarterial DSA was 1.83% (range, -22.38% to 55.60%); for the 33 visualized left carotid arteries, it was 0.00% (range, -20.55% to 49.95%). Receiver operating characteristic analysis indicated that technically adequate MR angiography may be a sensitive screening examination for stenoses."
-How did transoesophageal echocardiography help in diagnosing and managing patients with pericardial haemorrhage after cardiac surgery?,"Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography. After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention."
-What therapeutic intervention led to dramatic and rapid clinical improvement in the case of a 40-year-old woman with eosinophilia-myalgia syndrome and ascending polyneuropathy?,Plasmapheresis in a case of eosinophilia-myalgia syndrome with ascending polyneuropathy. Eosinophilia-myalgia syndrome complicated by ascending polyneuropathy in a 40-year-old woman is described. High-dose intravenous steroids had no beneficial effect on the clinical course. Dramatic and rapid clinical improvement occurred with the use of plasmapheresis. The use of this therapeutic modality should be considered in patients with a similar clinical presentation.
-What were the key findings regarding prosodic features in patients with Parkinson's disease in this study?,"The interpretation of dysprosody in patients with Parkinson's disease. Prosodic features in the speech production of 21 patients with idiopathic Parkinson's disease were tested. The appreciation of vocal and facial expression was also examined in the same patients. Significant intergroup differences were found in the prosody production tasks but, in contrast to previous results, not in the receptive tasks on the recognition and appreciation of prosody and of facial expression. The discrepancy between the production and recognition of prosodic features does not support the suggestion that dysprosody in Parkinson's disease is necessarily a disorder of processing emotional information that could be misinterpreted as a dysarthria."
-What was the purpose of the phase I/II trial involving recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following allogeneic bone marrow transplantation?,"Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical ""good risk"" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients."
-What were the presumed etiologies of rhabdomyolysis/myoglobinuria in the pediatric patients studied?,"Rhabdomyolysis in children: a 3-year retrospective study. The case reports of 4 pediatric patients illustrate the complex clinical scenarios in which childhood rhabdomyolysis/myoglobinuria occurs. Children ranged in age from 8-18 years. Presumed etiologies of rhabdomyolysis/myoglobinuria included Neisseria sepsis, exertion-related episodes, dialysis disequilibrium, and diabetic ketoacidosis. No child developed respiratory or renal failure. all children were discharged with normal muscle power, indicating the benign nature of this disease and the importance of aggressive management."
-What was the outcome of the Strecker stent treatment for renal artery stenosis in the study?,"Renal artery stenosis: preliminary results of treatment with the Strecker stent. Use of the Strecker flexible balloon-expandable tantalum stent for treatment of renal artery stenosis after failed angioplasty or transaortic thromboendarterectomy was evaluated in 10 patients (nine hypertensive, one normotensive). Left (n = 3) and right (n = 5) renal arteries were involved; renal artery stenosis in two patients had developed after kidney transplantation. Indications for stent placement were inadequate immediate postangioplasty response (n = 7), development of considerable restenosis after angioplasty (n = 1), and obstructing intimal flaps following transaortic endarterectomy (n = 2). Stent placement was technically successful (less than 20% residual stenosis) and patency was preserved in eight patients. Of the seven hypertensive patients with successful implantation, two were cured, three had improvement, and two had no change at latest follow-up evaluation (mean, 10.6 months; range, 6-12 months). The Strecker stent may be helpful in treating restenosis after failed revascularization procedures, although the precise indication, true safety, and long-term efficacy of stent placement in renal arteries will not be known until trials with more subjects and longer follow-up periods are completed."
-How can rest-injected thallium-201 imaging help assess the viability of severely asynergic myocardial regions?,"Rest-injected thallium-201 imaging for assessing viability of severe asynergic regions. To evaluate the utility of rest-injected 201Tl initial and delayed images for assessing the viability of severe asynergic regions, we studied 17 patients with apparently prior infarcted myocardium in combination with 99mTc ventriculography before and after revascularization. In 51 regions with severe asynergy, the percent 201Tl uptake was calculated as the ratio of counts on the segment with asynergy to the maximum counts on the normal segment. Eleven of 14 regions with resting 201Tl redistribution (Group 1) had improved wall motion after revascularization. However, 14 of 37 regions without redistribution also improved (Group 2). Twenty-three regions without redistribution or improved wall motion after revascularization (Group 3) had lower regional 201Tl uptake on their delayed images than those in Groups 1 and 2. Moreover, the initial regional uptake of Group 2 was higher than that of Group 3. These results suggest that redistribution on rest-injected 201Tl scans indicates reversibility of severely asynergic myocardium and that high 201Tl uptake in regions without redistribution may predict improvement in wall motion after revascularization. We conclude that 201Tl uptake may be useful as a marker of viability of severe asynergic regions before revascularization."
-What was the outcome of administering ursodeoxycholic acid to a patient with benign recurrent intrahepatic cholestasis?,"Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism. Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid."
-"How do perceptions of physical and emotional distress during infertility treatment differ among patients, nurses, and physicians?","Physical and emotional stress associated with components of the infertility investigation: perspectives of professionals and patients. OBJECTIVE: The present study examined patients', nurses', and physicians' perceptions of the physical and emotional difficulty of infertility treatment. DESIGN: A mail survey method was used. PATIENTS, PARTICIPANTS: Participants included 26 patients, 76 nurses, and 71 physicians from infertility clinics in the United States and Canada. MAIN OUTCOME MEASURES: A rating scale measured the physical and emotional difficulty level of 36 components from the infertility investigation. RESULTS: Nurses rated the emotional and physical distress of patients higher than did patients and physicians, whereas patients rated their distress higher than did physicians. Older nurses and physicians inferred lower levels of physical and emotional distress than did their younger counterparts. A greater breadth of experience with infertility treatments was associated with higher ratings of emotional distress by nurses and lower ratings by physicians. CONCLUSIONS: Patients, nurses, and physicians perceive infertility treatment from unique vantage points creating differences in perceptions that have implications for patient care. Factors including era of professional training, stage of life, and changes resulting from advancing technology are viewed as influencing health care professionals' perceptions of infertility distress."
-How do renal hemodynamics and renin-angiotensin-aldosterone system characteristics differ in normotensive subjects with different parental hypertension backgrounds?,"Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents. BACKGROUND AND METHODS. The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS. The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS. Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension."
-What is the prevalence of acute pulmonary embolism among pediatric patients awaiting heart transplantation in this study?,"Acute pulmonary embolism in pediatric patients awaiting heart transplantation. Acute pulmonary embolism with infarction can delay urgently needed heart transplantation and increase the postoperative pulmonary complications. Few data are available concerning pulmonary embolization in the pediatric patient with end-stage congestive heart failure. Sixty-two consecutive pediatric patients awaiting heart transplantation were monitored for evidence of acute pulmonary embolism. Acute pulmonary infarction was documented by ventilation-perfusion scan, pulmonary angiography or pathologic examination in six patients. The prevalence differed by diagnosis; 5 of 36 patients with dilated cardiomyopathy and 1 of 20 patients with congenital heart disease developed acute pulmonary embolism with infarction. No significant difference in age at the time of transplantation evaluation, duration of congestive heart failure, presence of cardiac arrhythmias or degree of cardiac dysfunction was seen between patients with and without pulmonary embolism. Two-dimensional echocardiography failed to detect the presence of an intracardiac thrombus in four of the six patients. Two patients who developed acute pulmonary infarction are alive after successful heart transplantation. The remaining four patients died within 6 weeks of initiation of anticoagulant therapy before transplantation could safely be performed. In summary, pediatric patients with end-stage congestive heart failure are at risk for acute pulmonary embolism. No specific clinical factor identified those patients who developed acute pulmonary infarction. Anticoagulant therapy is strongly recommended in the pediatric patient with poor ventricular function awaiting heart transplantation."
-What is the relationship between chronic viral hepatitis and hepatocellular carcinoma in the United States according to the study?,"The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Although hepatocellular carcinoma is a relatively uncommon tumor in the United States, it is quite common in sub-Saharan Africa and the Far East, where most cases are associated with infection with the hepatitis B virus. We have studied 99 American patients with hepatocellular carcinoma for evidence of hepatitis B or hepatitis C viral infection and compared these findings to those in a group of matched controls with other cancers. The two groups differed in proportion, with hepatitis B surface antigen in serum being significantly higher in patients with hepatocellular carcinoma (7% vs. 0%, p = 0.009). Antibody to hepatitis C virus was also found more frequently in patients with hepatocellular carcinoma (13% vs. 2%, p = 0.002). The relative risk for hepatocellular carcinoma in hepatitis B surface antigen-positive patients was calculated to be 17.3 and for antibody to hepatitis C virus to be 7.3. The attributable fraction of cases related to the hepatitis B surface antigen carrier state was 6.7% and for patients infected with the hepatitis C virus was 11.4%. Approximately three quarters of cases of hepatocellular carcinoma did not have evidence of either hepatitis C or hepatitis B virus infection. These findings provide strong evidence that hepatitis C virus infection is associated with the development of hepatocellular carcinoma, and in the United States may even play a more important role than the hepatitis B virus."
-What is compartment syndrome and how can it be caused by prolonged use of the lithotomy position during surgery?,"Compartment syndrome complicating prolonged use of the lithotomy position. Two patients with three postoperative calf compartment syndromes, which followed prolonged lithotomy positioning, will be presented. Potential physiologic mechanisms are described, and a review of current cases in literature are summated."
-What percentage of patients received a correct initial diagnosis from the general practitioners in the study?,"Chest pain: an evaluation of the initial diagnosis made by 25 Flemish general practitioners. Twenty-five general practitioners collected information on 318 contacts of patients with a new episode of chest pain, discomfort or tightness. A list of complaints, signs and symptoms were checked, together with the initial diagnosis, made by the GP immediately after the physical examination. The initial diagnosis was compared to a follow-up diagnosis. The gain in certainty was also compared. The GP made a correct initial diagnosis in 82% of patients. In 8% there was a clinically important difference, and seven of 17 episodes of oesophageal disease were missed. For their initial diagnosis, the GP scored 74% certain, 20% uncertain and no diagnosis in 6%. For the final diagnosis, these figures were 88%, 8% and 4%."
-What were the key differences in complications between nonionic (iopamidol) and ionic (diatrizoate) contrast media during percutaneous transluminal coronary angioplasty (PTCA) procedures?,"Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty. To evaluate the effect of contrast agents on percutaneous transluminal coronary angioplasty (PTCA) complications, 913 patients undergoing 1,058 separate PTCA procedures were prospectively randomized to receive either nonionic iopamidol (Isovue-370) [n = 507 PTCA procedures] or ionic contrast media, meglumine sodium diatrizoate (Renografin-76) [n = 551 PTCA procedures]. Angioplasty operators, technicians, nurses and patients were blinded to the agent used. All patients were pretreated with 0.6 mg of atropine sulfate intravenously before any contrast injections. Hypotension (mean arterial pressure less than 65 mm Hg associated with contrast injections) occurred during 8.5% of PTCA procedures in which the patients were receiving iopamidol and during 9.5% of the procedures in which the patients were given diatrizoate (difference not significant). Bradycardia (heart rate of less than 40 beats/min associated with contrast injections) developed during 5.7% of procedures when patients were given iopamidol and during 5.1% of procedures when patients were given diatrizoate (difference not significant). The need for additional atropine or temporary pacing during the procedure was similar for patients given iopamidol and diatrizoate. The overall incidence of ventricular tachycardia or fibrillation, or both, during the procedure occurred less frequently when iopamidol was used compared with diatrizoate (1 vs 2.5%, p = 0.045). These serious ventricular arrhythmias were attributable to contrast injections in 0.6% of the PTCA procedures when iopamidol was given and in 2.0% of the cases in which diatrizoate was the contrast agent (p = 0.09). Only 1 patient had an allergic reaction to the contrast agent, and this was in a patient who received iopamidol."
-How does monocrotaline treatment affect the vascular structure in rat lungs?,"Monocrotaline-induced angiogenesis. Differences in the bronchial and pulmonary vasculature. Vascular corrosion casting was used to search for angiogenesis in the blood vessels of the lungs of rats given monocrotaline. Animals treated with monocrotaline had new well-differentiated arteries and veins on their pleural surfaces. Animals not treated had no large vessel on their pleural surfaces. Animals receiving monocrotaline had capillaries around major arteries that were more dense, widened, and less tubular than normal. These capillaries occasionally occurred in sheets and had blind endings. The control animals had delicate, uniform, tubular capillaries. Alveolar capillaries in both groups showed no evidence of increase in size or number or change in shape. Light microscopy confirmed the finding of new vessels found with the casts. The finding of angiogenesis on the pleural surface and in the bronchovascular bundle, but not in the alveolar capillaries, suggests a basic difference in how these capillary beds respond to angiogenic stimuli. If alveolar capillaries are unable to undergo angiogenesis, concepts of lung development and tumor growth may be significantly altered. The lung may be a unique organ to study angiogenesis because of the different angiogenic potential of its two circulations. Study of these differences may lead to better understanding of inhibition of angiogenesis."
-What medical condition did the patient have that required pulmonary resection and distal pancreatectomy-splenectomy?,Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature. A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy.
-What potential side effect did the study observe in patients treated with valproate?,"Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate."
-What is the kissing balloon technique in coronary angioplasty?,The kissing balloon technique with two over-the-wire balloon catheters through a single 8-French guiding catheter. Some of the newer over-the-wire coronary angioplasty catheters have shaft sizes of 3.0 French (F) or less. The inner diameter of modern 8-F guiding catheters is large enough to accommodate two of such balloon catheters. We report a kissing balloon procedure with two over-the-wire catheters through a single 8-F guiding catheter.
-What is the purpose of autotransplantation of dispersed pancreatic islet tissue in patients with chronic pancreatitis?,"Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis. Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain."
-What was the main finding of the study comparing recombinant tissue-type plasminogen activator (rt-PA) plus heparin with heparin alone in patients with refractory unstable angina?,"Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris. Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina."
-What was the resectability rate and pathologic complete response rate in this Phase I trial of preoperative pelvic radiation therapy and combined leucovorin/5-fluorouracil for unresectable rectal cancer?,"Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer. Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable."
-What is the Siriraj stroke score and how does it help differentiate between supratentorial intracerebral haemorrhage and infarction?,"Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction. OBJECTIVES--To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN--13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING--Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS--Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS--The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION--The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke."
-How do WSP and WSR mice differ in their response to glucocorticoids during ethanol withdrawal?,"Differential modulation by the stress axis of ethanol withdrawal seizure expression in WSP and WSR mice. Withdrawal from both acute and chronic ethanol (EtOH) exposure is associated with increased neural excitability and increased activity of the hypothalamic-pituitary-adrenal axis. There is some evidence that glucocorticoids are necessary for EtOH withdrawal seizure expression. Lines of mice that were selected for severe (WSP) and minimal (WSR) EtOH withdrawal (as estimated from handling-induced convulsion scores) have been shown to differ in their stress response following an acute dose of EtOH. In this study we provide evidence that these lines of mice also differ in their sensitivity to the excitatory effects of glucocorticoids. EtOH withdrawal seizures of WSP mice were significantly increased by chronic and acute corticosterone treatment, whereas those of the WSR mice were unaffected. Neural excitability was decreased in the WSP mice when aminoglutethimide, a glucocorticoid synthesis blocker, was administered. Thus, it appears that genetic differences in EtOH withdrawal seizure severity may be due, in part, to differences in sensitivity to the excitatory effects of glucocorticoids."
-"What was the success rate of percutaneous cholecystostomy in treating patients with persistent, unexplained sepsis?","Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy. Because of the difficulty in diagnosing acute cholecystitis in critically ill patients with severe intercurrent illness by clinical and imaging methods or percutaneous aspiration of the gallbladder, a trial of percutaneous cholecystostomy was performed in 24 patients in the intensive-care unit with persistent, unexplained sepsis after a complete clinical, laboratory, and radiologic search showed no alternative source of infection. Persistent high fevers, despite antibiotic therapy, were present in all patients, with elevated WBC count in 18 patients, vague abdominal tenderness in 11, and septic shock requiring vasopressors in 15. Sonographically, all patients had distended, spherical gallbladders, six had gallstones, eight had wall thickening, three had pericholecystic fluid, and four had Murphy's sign. All patients were seen by a senior abdominal surgeon, who agreed to a trial of percutaneous cholecystostomy. Fourteen patients (58%) responded to percutaneous cholecystostomy, as evidenced by a decrease in WBC count, defervescence, and the ability to be weaned off vasopressors. Bile cultures were positive in four patients. Ten patients (42%) did not respond to percutaneous cholecystostomy; five eventually died of unrelated causes. A respiratory source of infection was eventually found in three of these 10 patients, with no proved source of infection in the remainder. No complications related to catheter insertion occurred in this group of patients. Bile leaks occurred in two patients when the percutaneous cholecystostomy catheter was removed, but without serious consequence. Our experience suggests that a lower threshold for performing percutaneous cholecystostomy in this difficult clinical subset of patients is worthwhile."
-What is the potential cause of hypoglycemia in patients with mesenchymal tumor-associated nonislet cell tumors?,"Impaired formation of the ternary insulin-like growth factor-binding protein complex in patients with hypoglycemia due to nonislet cell tumors. In some subjects with hypoglycemia associated with tumors of mesenchymal origin, high insulin-like growth factor-II (IGF-II) levels have been described in serum and in the tumors. Tumor IGF-II of 10-15 kDa circulates in a 60-kDa complex, in contrast to the ternary 150-kDa complex in which serum IGFs normally circulate together with the IGF-binding subunit (IGFBP-3) and the acid-labile subunit (alpha-subunit). This study examines the molecular distribution and complex-forming activity of the components of the ternary complex in the serum of subjects with mesenchymal tumor hypoglycemia. Total serum IGFBP-3 levels were 60% of normal in tumor patients and appeared at 60 kDa on gel chromatography, shifting after tumor removal to 150 kDa. Total alpha-subunit levels were 40% of normal in patients with tumors, increasing after tumor removal to 70% of normal and changing in elution profile from a peak typical of uncomplexed alpha-subunit to the normal broad peak representing both complexed and uncomplexed alpha-subunit. Although low by RIA, alpha-subunit activity in a ternary complex formation assay was normal, indicating that the ability of free alpha-subunit in the patients' circulation to combine with exogenous IGFBP-3 plus IGF-I was not impaired. In contrast, in an assay that tested the ability of IGF-IGFBP complexes in the patients' circulation to combine with pure alpha-subunit, complex formation activity was 75-85% below normal in preoperative sera, despite low normal IGFBP-3 levels. Therefore, the cause of hypoglycemia in these patients may be the inability of complexes between the abnormal tumor IGF-II and IGFBP-3 to be sequestered in the biologically inactive ternary complex."
-What is the incidence of portal vein thrombosis after distal splenorenal shunt in this study?,"The significance of portal vein thrombosis after distal splenorenal shunt. The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long-term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival."
-What is an iatrogenic epidermoid cyst and how can it occur in the parotid region following ear surgery?,Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed.
-What are the potential major complications associated with endoscopic sinus surgery?,"Fatal and other major complications of endoscopic sinus surgery. Endoscopic sinus surgery has become an acceptable technique for the treatment of chronic sinus disease. This report analyzes five complications which came to my attention. Two cases were orbital:1 bilateral blindness due to damage of the optic nerves, and 1 damage of medial rectus muscle. The other 3 cases were intracranial:two cribriform plate damage with frontal lobe injury and hematoma, and 1 damage of the anterior cerebral artery, resulting in death. This rather novel technique, especially when used by less-experienced surgeons, has major complications similar to what has been reported with the traditional intranasal sphenoethmoidectomy. Knowledge of anatomy, good training, and meticulous surgical technique are very important. Endoscopic sinus surgery in patients with extensive pathology should be used with caution, especially if general anesthesia is selected or if excessive bleeding occurs. It would be beneficial to otolaryngologists to have previous experience in the traditional technique before adopting endoscopic sinus surgery to their armamentarium. Even then, major complications may occur in the hands of very experienced surgeons. Early recognition and proper management of these complications are of utmost importance in order to minimize disability or prevent death."
-What percentage of brachial plexus blocks were incomplete in this study?,"Brachial plexus anesthesia for outpatient surgical procedures on an upper extremity We retrospectively reviewed 543 brachial plexus blocks performed on 526 outpatients. Most (98%) of the blocks were performed by means of the axillary approach. Various techniques were used, including paresthesia, transarterial fixation, nerve stimulation, or a combination of techniques; a high success rate was achieved with each of them. Only 7% of the blocks were incomplete and thus necessitated either general anesthesia or block supplementation with thiopental sodium and nitrous oxide. No persistent neurologic deficit was ascribed to the anesthetic technique. This review indicates that brachial plexus block, especially with use of the axillary approach, is a safe and effective option for outpatient surgical procedures on an upper extremity."
-What potential side effect did the study observe in patients treated with valproate?,"Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate."
-What was the effect of increasing doses of flecainide acetate on the occurrence of tachycardia in patients with paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation?,"Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group. The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2)."
-How did hydroxyzine affect histamine release and clinical symptoms in patients with chronic urticaria compared to terfenadine and placebo?,"Effects of H1-antihistamine drug regimen on histamine release by nonlesional skin mast cells of patients with chronic urticaria. Profiles of compound 48/80-induced histamine release (HR) from mast cells of uninvolved skin from patients with chronic urticaria (CU) and from a normal control (NC) group were compared, and the effects of anti-H1 medications were assessed versus placebo. Then, patients with CU (15) and NC subjects (10) were randomly assigned to take either hydroxyzine (100 mg/day), terfenadine (120 mg/day), or placebo for 28 days. The effects of such treatment on the clinical response and on the profile of compound 48/80-induced HR during a 4-hour period were analyzed. Treatment with hydroxyzine in patients with CU improved the clinical symptoms and modified the profile of HR; more histamine was recovered at 1 hour (p less than 0.05) and 2 hours (p less than 0.05), as compared with baseline. Terfenadine and placebo had no effect on the clinical response or on the profiles of HR. In the NC group, the amounts of histamine recovered at 1 hour after challenge with compound 48/80 were lower than amounts of the pretherapy values (p less than 0.01). It could be concluded that (1) the profile of HR in patients with CU is reproducible during a period of 28 days, (2) only hydroxyzine modifies both the clinical response and the profile of HR, and (3) anti-H1 compounds decrease the HR in the NC group."
-What treatment was used to resolve the intraventricular hematoma in this case report?,"Lysis of intraventricular hematoma with tissue plasminogen activator. Case report. A 42-year-old woman suffered a severe intracerebral and intraventricular hemorrhage from a ruptured anterior cerebral artery aneurysm. Evacuation of the frontal hematoma and clipping of the aneurysm was performed but the intraventricular blood clot persisted, causing ventricular dilatation and high intracranial pressure (ICP) 24 hours after surgery despite external ventricular drainage. Over this period of time the patient's clinical condition improved from Grade V to Grade IVb (World Federation of Neurological Surgeons classification). The intraventricular hematoma was lysed with a total of 8 mg recombinant tissue plasminogen activator injected directly into the ventricles on the 1st and 2nd postoperative days, resulting in rapid normalization of ventricular size and ICP. The patient has since made a substantial recovery and has been able to return home."
-How does botulinum toxin treatment affect the neurophysiological characteristics of patients with dystonic blepharospasm?,"Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm."
-What are the key diagnostic criteria for quadrilateral space syndrome according to the context?,"Quadrilateral space syndrome: diagnosis and operative decompression technique. We present a series of five patients with quadrilateral space syndrome. All patients had the diagnosis made on the basis of (1) tenderness over the quadrilateral space, (2) paresthesia over the lateral shoulder and upper posterior arm, and (3) deltoid weakness associated with decreased shoulder abduction. A history of trauma was present in each patient. The operative technique described utilizes a cosmetically acceptable incision and is without the need to divide the deltoid from its origin on the scapular spine. The technique minimizes postoperative bleeding and facilities rehabilitation. Arteriography of the posterior circumflex humeral artery was not found necessary to make the diagnosis of axillary nerve entrapment in the quadrilateral space."
-What were the observed effects of the TRH analogue (RX77368) on patients with motor neuron disease?,"Comparative efficacy and safety of intravenous and oral administration of a TRH analogue (RX77368) in motor neuron disease. Ten consecutive patients with motor neuron disease (MND) who had bulbar symptoms received one or two intravenous doses followed by increasing oral doses of a TRH analogue (RX77368). Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. The initial time course of improvement correlated with increasing plasma levels of the drug, but most clinical effects persisted when the levels decreased and became undetectable after 24 hours. The oral solution was tasteless and had no, or minimal, side effects."
-What is the purpose of the clinical trial involving Cronassial in patients with Chagas' disease?,"Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo."
-What were the two methods compared in this study for preventing bone reunion after midline craniectomy for sagittal suture synostosis?,"Midline craniectomy for sagittal suture synostosis: comparative efficacy of two barriers to calvarial reclosure. This report quantitatively compares long-term head remolding achieved by two methods for retarding bone reunion after midline craniectomy for sagittal suture synostosis. In one group of six children the adjacent bone edges were overlayed with 1.0-cm-wide U-channel silicone strips, and in the other group, composed of seven patients, a considerably larger extent of the adjacent cranium was covered with silicone sheets. Mean percent change in the cephalic indices of the former group 18 months postoperatively was 9.1% +/- S.D. = 6.7, and of the latter group 23.7% +/- S.D. = 6.0 (p congruent to 0.01). These results indicate that the use of large silicone sheets lead to a significantly greater normalization of cranial proportions."
-What are the potential consequences of prolonged hiccups that may require medical intervention?,"Hiccups (singultus): review and approach to management. Hiccups are a common, and fortunately usually transient, benign malady. Occasionally, however, hiccups fail to resolve spontaneously, resulting in patient fatigue and incapacitation and the need for the affected individual to seek medical care for resolution of the problem. The approach to the management of these patients consists of the identification and treatment of serious underlying causes of the episode as well as therapeutic interventions to achieve hiccup resolution."
-Where was corticotropin-releasing hormone (CRH) immunoreactivity found in the human placenta and fetal membranes during gestation?,"The localization and distribution of corticotropin-releasing hormone in the human placenta and fetal membranes throughout gestation. Using immunohistochemical techniques, we have determined the localization and distribution of CRH immunoreactivity (CRH-IR) in the human placenta, fetal membranes, decidua, and umbilical cord. Tissues were obtained at 6-8 weeks of pregnancy, at term, in association with premature birth, and from patients with pregnancy-induced hypertension or diabetes mellitus. A polyclonal antibody to the epithelial cell marker cytokeratin was used to identify trophoblast cells. CRH-IR was not detected in placenta or decidua at 6-8 weeks gestation. In tissues obtained after idiopathic premature delivery after 21 weeks gestation, positive CRH staining was found in placenta in syncytiotrophoblast and intermediate trophoblast, but not cytotrophoblast. CRH-IR was present in intermediate trophoblast cells that had invaded maternal blood vessels in decidua basalis. In the fetal membranes, CRH-IR was localized in the epithelium and subepithelial cells of amnion, in the trophoblast layer, in some cells of the reticular and cellular layers of chorion, and in some stromal cells and invasive trophoblast cells of decidua. CRH-IR was found in the amniotic epithelium of the umbilical cord and in the musculature of the umbilical vessels. This pattern of distribution of CRH-IR was found in tissues from 21 weeks gestation to term and postterm, and was similar in tissues examined from patients with pregnancy-induced hypertension and diabetes mellitus. These results show clearly that in placenta and membranes, CRH is localized primarily to syncytiotrophoblast and intermediate trophoblast, but not to cytotrophoblast cells. We suggest that the localization of CRH-IR is consistent with CRH affecting paracrine/autocrine interactions within the placenta, fetal membranes, and decidua that may be involved in the maturation of the fetal hypothalamic-pituitary-adrenal axis and in the stimulus and maintainance of labor."
-How does brain temperature affect the cerebral metabolic rate of oxygen consumption (CMRO2) in dogs during hypothermia?,"The relationship among canine brain temperature, metabolism, and function during hypothermia. Cerebral protection by hypothermia is commonly attributed to cerebral metabolic suppression. However, at temperatures below 28 degrees C, the relationship of temperature to cerebral metabolic rate of oxygen consumption (CMRO2) has not been well characterized. Accordingly, the relationship between brain temperature and CMRO2 was determined in eight dogs during cooling from 37 to 14 degrees C while the EEG was continuously monitored. Cardiopulmonary bypass was initiated and control measurements were made at 37 degrees C during anesthesia with nitrous oxide 50-60% inspired and morphine sulfate 2 mg.kg-1 intravenously (iv). Upon cooling to 27 degrees C, the nitrous oxide was discontinued and the morphine was antagonized with naloxone 2 mg iv. Measurements were repeated at 27, 22, 18, and 14 degrees C and in four dogs again at 37 degrees C after nitrous oxide 50-60% had been reestablished at 27 degrees C along with administration of morphine sulfate 2 mg.kg-1. For each temperature interval, the temperature coefficient (Q10) for CMRO2 was calculated (Q10 = CMRO2 at x degrees C divided by CMRO2 at [x - 10] degrees C). Between 37 and 27 degrees C the Q10 was 2.23, but between 27 and 14 degrees C the mean Q10 was doubled to 4.53. With rewarming to 37 degrees C, CBF and CMRO2 returned to control levels, and brain biopsies revealed a normal brain energy state. During cooling, the EEG developed burst suppression at or below 22 degrees C. With further cooling, the periods of suppression increased; however, burst activity continued in seven of eight dogs even at 14 degrees C."
-What was the most significant prognostic factor for local recurrence in breast cancer patients treated with conservative surgery and radiation therapy?,"Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data. Between 1962 and 1984, a total of 433 patients were treated at Yale-New Haven Hospital with conservative surgery and radiation therapy (CS + RT) to the intact breast. As of January 1990, with a minimum assessable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Of all clinical factors tested, young age was the most significant prognostic factor for local recurrence (P less than .03). In addition, patients with pathologically involved lymph nodes were noted to have a lower local recurrence rate than patients with pathologically negative axillae (P less than .05). These findings were especially notable given the fact that the node-positive group had a higher percentage of T2 tumors and a higher percentage of patients in the young age group. These paradoxical findings, however, may be explained by the fact that 88% of the node-positive patients underwent adjuvant systemic therapy in the form of either systemic chemotherapy or hormonal therapy, while only 8% of node-negative patients underwent any adjuvant systemic therapy. When analyzed as a function of adjuvant therapy, those patients receiving adjuvant therapy had a lower local recurrence rate than those patients not receiving adjuvant therapy (P less than .08). We conclude that adjuvant systemic therapy impacts on the ipsilateral breast recurrence rate in patients treated with CS + RT. The implications of this study in light of the widespread use of adjuvant systemic therapy are discussed."
-What are the primary pathophysiologic mechanisms believed to cause sciatica?,"Pathophysiology of sciatica. The exact pathophysiologic mechanisms behind sciatica are incompletely known; however, compression of spinal nerve roots is known to be correlated to both pain and neural dysfunction in a segmental distribution of that specific nerve root. Compression per se may impair the transport of nutrients to the nerve tissue in such a way that affects the nerve root function. There also might be a local affect on nerve roots or root sleeves by substances leaking from the degenerated intervertebral discs."
-What were the main indications for surgical management of extracranial vertebral artery occlusive disease in this study?,"Surgical management of extracranial vertebral artery occlusive disease. Thirty-seven consecutive patients underwent vertebral artery (VA) reconstruction over a 6 years period (1983-1989). Detailed neurologic, medical, and angiographic information was obtained for all patients. Indications for surgery were as follows: (1) stenosis of VA with symptoms of vertebrobasilar insufficiency; (2) very tight stenosis (greater than 75%) of the dominant VA with stenosis or occlusion of the contralateral VA; (3) very tight stenosis of VA with bilateral occlusion of the internal carotid artery (ICA); (4) very tight stenosis of VA with homolateral ICA lesion eligible for simultaneous repair; (5) very tight stenosis of VA and very tight stenosis of the homo or contralateral carotid siphon. There were 15 isolated vertebral lesions (group I), and 22 were VA lesions associated with lesions of the supraaortic trunks which were simultaneously treated (group II). The reconstructions of the first portion of the VA were 30 (12 of group I and 18 of group II) and reimplantation of the VA into the common carotid artery was the procedure of choice. There were 7 revascularizations of the third portion of the VA at C1-C2 level (3 of group I and 4 of group II): carotid-vertebral bypass, using an autogenous vein graft, was the procedure of choice. Three patients in group II died in the immediate postoperative period from myocardial infarction but no patient presented immediate postoperative neurologic deficits. All symptomatic patients but one were relieved of their symptoms in a median follow-up of 31 months. No postoperative complications were observed. Long-term results were satisfactory in all the 28 patients at their last follow-up visit."
-What did the study reveal about transesophageal echocardiography's sensitivity in detecting mitral regurgitation in St. Jude Medical mitral valve prostheses?,"Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis. Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component."
-What factors have contributed to the recent reductions in liver cirrhosis deaths in Western countries?,"Factors in recent reductions in liver cirrhosis deaths. Since the mid-1970s, there have been substantial declines in liver cirrhosis deaths in many Western countries following a long period of increases. There is variability in the pattern of changes observed: in a sample of 29 countries between 1974 and 1982-83, seven countries showed a significant linear decline, three revealed a curvilinear pattern, increases were observed in six and the rest (13) showed no notable changes. Although reductions in per capita consumption of alcohol may be a contributing factor, these reductions do not seem to account for all of the decreases in cirrhosis deaths that have been observed. Among other factors that might contribute, changes or increases in treatment for alcohol abuse and AA membership have been most strongly linked to these declines; changes in patterns of consumption, dietary habits, prevention efforts and reduced exposure to predisposing factors may also be involved. In view of the importance of these declines for the understanding and prevention of alcohol problems, further research on this issue, perhaps involving international collaborative studies, is needed."
-"What are the key ultrastructural differences observed between adenomyotic glandular epithelium, proliferative endometrium, and well-differentiated endometrial cancer?",Ultrastructural study of glandular epithelium in adenomyosis in comparison with those of proliferative endometrium and well-differentiated endometrial cancer. Adenomyotic glandular tissue from five patients underwent electron microscopic investigation to observe its ultrastructural characteristics. The adenomyotic epithelium was compared with that of proliferative normal epithelium (two patients) and well-differentiated endometrial adenocarcinoma (two patients). The results revealed that morphologically the adenomyotic glandular epithelium is somewhat less differentiated than proliferative endometrium and that its cytoplasmic organelles have some similarities with those of endometrial cancer. Whether these similarities predispose the adenomyotic glandular tissue to malignant degeneration remains to be elucidated.
-What advantages did the 48 by 48 element biplane transesophageal probe offer compared to single-plane probes?,"Initial clinical experience with a 48 by 48 element biplane transesophageal probe. Recent technologic advances in ultrasound have resulted in the capability of transesophageal echocardiographic imaging in both transverse and longitudinal planes. Previous biplane probes suffered from inferior images because of reduced scan elements. We evaluated the utility of a prototype 48 X 48 element biplane transesophageal probe in 23 consecutive patients. Examinations were well tolerated with no side effects. In comparison to the single transverse plane, imaging with the longitudinal plane gave superior information on prosthetic valve pathology, atrial septal abnormalities, and pathoanatomy of the ascending aorta and mitral valve. Complementary information was provided by the longitudinal plane in patients with endocarditis and vegetations and in mitral protheses. Images obtained with this 48 X 48 element biplane probe along with color and spectral Doppler information were not perceptibly inferior to those obtained by single-plane probes. In conclusion, biplane transesophageal echocardiography with a 48 X 48 element probe indicates a great potential for enhanced three-dimensional understanding of cardiac pathology and diagnostic yield in specific pathologies."
-What is Klippel-Trenaunay syndrome (KTS) and what are its primary clinical characteristics?,"Klippel-Trenaunay syndrome: the risks and benefits of vascular interventions. Our experience with Klippel-Trenaunay syndrome (KTS), a rare congenital malformation, has increased considerably in recent years and now includes 144 patients (65 male and 79 female patients). Hemangioma was present in 137 patients (95.1%), varicosity in 110 (76.4%), and hypertrophy of the soft tissues or bones in 134 (93.1%). In most patients (71.5%) the disease involved one lower extremity. Diagnostic workup included roentgenogram to document limb length discrepancy, noninvasive arterial and venous evaluation, contrast venography, and nuclear magnetic resonance imaging. Most patients did well without treatment or with elastic compression only. Surgical treatment for the vascular malformation in KTS is rarely needed and it continues to be controversial. To evaluate the risks and benefits of vascular interventions, we examined in detail the clinical histories of nine patients who in the last decade underwent operation for a vascular malformation of the lower extremity. In seven patients we removed varicose veins or resected hemangioma of the lower extremity. Although none was cured, all five who underwent resection of varicose veins and one of the two patients who underwent resection of a hemangioma improved. Two additional patients, however, who underwent resection of varicose veins in another institution had worsening of the symptoms. In one patient we performed deep venous reconstruction for atresia of the superficial femoral vein, using the contralateral saphenous vein. Such operation in KTS has not been reported previously. The patient has a patent graft with a competent valve and clinical improvement 6 months after the operation. Although patients with severe chronic venous insufficiency, disturbing cosmetic appearance, or complications of hemangioma may benefit from surgical treatment, detailed preoperative imaging of the extremity and pelvis with magnetic resonance imaging and contrast venography is needed to decrease complications. Rarely, reconstruction for atresia or hypoplasia of the deep veins may be needed."
-How does platelet function change in patients with symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage?,"Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage."
-What technique was used to minimize postoperative hypotony in Molteno glaucoma implant procedures?,"The use of releasable sutures in Molteno glaucoma implant procedures to reduce postoperative hypotony. We used releasable sutures to minimize immediate postoperative hypotony and flat anterior chamber in 19 cases of refractory glaucoma requiring insertion of a single-plate Molteno implant in a one-stage procedure. A slip knot using 7-0 nylon suture was fashioned around the Molteno tube under a lamellar scleral flap. In 18 of the 19 eyes, anterior chamber depth was normal immediately after surgery."
-What was the purpose of using tissue-type plasminogen activator (tPA) in this study on subarachnoid hemorrhage patients?,"Prevention of vasospasm by clot removal and intrathecal bolus injection of tissue-type plasminogen activator: preliminary report. In this study, we evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in cases with a diffuse severe subarachnoid hemorrhage. All 10 cases were graded Group 3 according to the classification of Fisher and associates, and the CT number (Hounsfield number) of the subarachnoid clot was over 75. After clipping the aneurysm and removing the clot, three cisternal drainage catheters were inserted into both sylvian cisterns and the prepontine cistern, and continuous ventricular drainage was performed routinely. Postoperatively, tPA (0.5 mg/2.5 ml) was infused as a bolus into both basal cisterns and the lateral ventricle twice daily for about 6 days. Angiography and cerebral blood flow studies using single photon emission computed tomography were performed on Day 4 or 5 and between Days 7 and 10 after onset of the hemorrhage. To date, there have been no cases that have shown angiographic vasospasm or delayed ischemic neurological deficits. This preliminary study indicates that the intrathecal bolus injection of tPA produces a marked effect on vasospasm."
-What were the two most important independent prognostic factors for survival in this study of vulvar carcinoma?,"Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study). Analysis of 588 patients with vulvar carcinoma delineated four risk groups by the proportional hazards model. Groin node status (laterality and number positive) and lesion diameter were the only two important independent prognostic factors. The 5-year relative survival rates were 98%, 87%, 75%, and 29% for the risk group categories of minimal (negative groin nodes and lesion diameter less than or equal to 2 cm), low (one positive groin node and lesion diameter less than or equal to 2 cm or negative groin nodes and fewer than two lesions less than or equal to 8 cm diameter), intermediate (negative groin nodes and lesion diameter greater than 8 cm diameter, one positive groin node and lesion diameter greater than 2 cm, or two unilaterally positive groin nodes and lesion diameter less than or equal to 8 cm), and high (three or more positive groin nodes or two bilaterally positive groin nodes), respectively. Applying the International Federation of Gynecology and Obstetrics staging (1988) to these data discriminated risk of death (caused by recurrent vulvar cancer); the 5-year rates were 98%, 85%, 74%, and 31% for stages I, II, III, and IV, respectively. However, within International Federation of Gynecology and Obstetrics stage III there were 47 low-, 95 intermediate-, and 28 high-risk patients with relative survivals of 95%, 74%, and 34%, respectively. Overall, this assessment validates current International Federation of Gynecology and Obstetrics vulvar carcinoma staging, but further refinements are warranted in stage III."
-What diagnostic technique was used to study regional cerebral blood flow in a patient with alternating hemiplegia?,"Ictal 99mTc-HMPAO SPECT in alternating hemiplegia. 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) was performed in a patient with alternating hemiplegia during 2 episodes of the disease. The regional cerebral blood flow patterns correlated with the clinical manifestations during both episodes. Hyperperfusion of the contralateral hemisphere was suggested by asymmetric 99mTc-HMPAO uptake, whereas symmetric 123I-N-isopropyl-p-iodoamphetamine uptake was detected during the interictal period. The results suggested that alternating hemiplegia in infants represents an atypical manifestation of epilepsy, despite the lack of paroxysmal electroencephalographic abnormalities during the episodes. 99mTc-HMPAO SPECT appears to be a useful method for detecting transient regional cerebral blood flow alterations during paroxysmal events because the tracer is rapidly available for emergencies and retains a fixed distribution for 5-8 hours, sufficient time to allow for SPECT acquisition."
-What are the distinctive clinical characteristics of native valve endocarditis caused by Staphylococcus epidermidis compared to endocarditis caused by other organisms?,"Native valve Staphylococcus epidermidis endocarditis: report of seven cases and review of the literature. This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermidis. The literature on endocarditis caused by S. epidermidis is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and skin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis."
-What was the maximum hypothermic preservation time for skeletal muscle in rat hindlimbs using Euro-Collins solution?,"Preservation of skeletal muscle in tissue transfers using rat hindlimbs. Replantation of major extremities after long periods of ischemia can lead to viable replants in many cases, but functional restoration is often poor owing to fibrosis of the muscle. In this study, maximum hypothermic time in tissue transfers containing skeletal muscle using hindlimbs of Lewis rats preserved in 4 degrees C Euro-Collins solution was investigated. After preserving midthigh amputated legs in this solution for 6, 9, and 12 hours, the legs were transplanted to other inbred rats using microsurgical technique, and 1 week later, gastrocnemii were obtained to analyze ATP, ADP, and AMP using high-performance liquid chromatography. The values were compared with those for healthy legs, nonischemic operated control legs, and legs preserved in the same manner for 6, 9, and 12 hours. Histologic and serologic examinations were conducted. ATP values of the 9-hour preservation group resumed those of the nonischemic operated control group, with the values of the 12-hour preservation group remaining at 61 percent. Histologically, focal necrosis, hyaline degeneration, and regeneration processes were the most characteristic manifestations in the muscles transplanted after cold ischemia of 12 hours. It was concluded that skeletal muscle could be preserved for 9 hours in 4 degrees C Euro-Collins solution."
-What is Henoch-Schonlein purpura and how does it affect children according to the surgical evaluation in this study?,"Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived."
-How did chronic hypoxia affect the cardiovascular parameters of spontaneously hypertensive rats in the study?,"Effects of atrial natriuretic factor in chronic hypoxic spontaneously hypertensive rats. The present study was designed first to investigate the pulmonary hypertensive effects of chronic hypoxia in spontaneously hypertensive rats and second to compare the cardiovascular effects of atrial natriuretic factor on rats exposed to hypoxia and on control rats kept at sea level. Catheters were placed in the femoral and pulmonary arteries for measurement of mean systemic arterial pressure and mean pulmonary arterial pressure. The cardiac output was measured by thermodilution method. It was found that 4 weeks of simulated 18,000-foot hypoxia led to polycythemia, right ventricular hypertrophy, and pulmonary hypertension, which resulted from an increased pulmonary vascular resistance. However, systemic arterial pressure was not significantly different between the two groups of rats. Atrial natriuretic factor administration decreased systemic arterial pressure and pulmonary arterial pressure to a lesser extent in the hypoxic group compared with the sea level control group. It is concluded that these animals showed an impaired response to atrial natriuretic factor after long-term exposure to hypoxia."
-How did the second cerebrovascular accident affect the patient's long-standing hyperpathia in the right upper extremity?,"Disappearance of thalamic pain after parietal subcortical stroke. A hypertensive man had a long standing history of contumacious hyperpathia in the right upper extremity, resistant to medical therapy, secondary to a lacunar infarct in the left thalamus. A second cerebrovascular accident caused a small lesion in the left corona radiata, interrupting the thalamoparietal interconnections, and terminated the pain instantly. Interruption of the subcortical parietal white matter may more effectively control pain than cortical lesions. A few surgeons have successfully treated rebellious chronic pain with stereotaxic operations in the corona radiata, resulting in lesions very similar to our patient's. This overlooked and nearly forgotten technique may still have value in treating selected cases."
-What percentage of unselected blood donors were found to have antibodies to hepatitis C virus in the United Kingdom study?,"Hepatitis C virus antibodies in subjects with and without liver disease in the United Kingdom. The prevalence of antibody to hepatitis C virus, evidence of previous or current infection with this agent of parenterally transmitted non-A, non-B hepatitis, was determined in 340 subjects residing in the United Kingdom. The antibody was detected in 3 per cent of unselected blood donors and in 60 per cent of patients with chronic post-transfusion non-A, non-B hepatitis. Evidence for infection was also found in 30 per cent of intravenous drug abusers, and in 75 per cent of haemophiliacs receiving commercial factor VIII concentrate. The infection is uncommon in renal units and amongst sexually promiscuous groups attending sexually-transmitted disease clinics. Although the seropositivity rate in primary biliary cirrhosis and chronic B and delta hepatitis was very low (0-2 per cent), in patients with autoimmune and alcoholic liver disease it was 14-16 per cent which, although lower than that quoted in studies from Spain and Italy, is considerably higher than would be expected by chance. The reason for the high incidence of non-A, non-B hepatitis in this latter group of patients is unclear."
-What medical interventions were used to control blood pressure in the patient with severe hypertension after renal artery injury?,"Severe hypertension with segmental renal infarction following surgical removal of a retroperitoneal malignant hemangiopericytoma: a case report. Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed."
-What were the predialysis atrial natriuretic peptide (ANP) levels in the three patient groups studied?,"Atrial natriuretic peptide in dialysis patients under various conditions of volume homeostasis. Atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were studied in 19 patients with end-stage renal disease (ESRD) under haemodialysis (HD). On the basis of clinical findings, patients were divided into three groups: group A, 6 patients, of mean age 41 +/- 15 years, without heart failure and in need of ultrafiltration (658 +/- 282 ml h-1); group B, 6 patients, of mean age 54 +/- 15 years, without heart failure under isovolaemic HD; group C, 7 patients, of mean age 60 +/- 3 years, with heart failure (NYHA III-IV) and in need of ultrafiltration (607 +/- 120 ml h-1). The highest predialysis ANP levels were found in group C (1534 +/- 471 pg ml-1) followed by group A (476 +/- 168 pg ml-1) and group B (236 +/- 138 pg ml-1) (normal range 62 +/- 27 pg ml-1). Systolic and diastolic blood pressure and heart rate did not correlate with ANP levels in either of the groups. However, iso-osmotic reduction of the body weight by ultrafiltration was correlated with decreasing ANP levels during HD (for groups A and C, r = 0.88 and 0.98, respectively). Isovolaemic HD did not alter ANP concentrations (group B). All patients received a volume bolus at the end of HD, and they responded with an instant increase in ANP concentration, which was most pronounced in patients with concomitant heart failure. PRA was not significantly correlated with ANP levels during HD. In conclusion, the results of this study indicate that there is a sensitive response of ANP levels to changes in body fluid status in ESRD."
-What were the key findings of the Early Treatment Diabetic Retinopathy Study (ETDRS) regarding aspirin treatment for diabetic retinopathy?,"Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Aspirin treatment did not alter the course of diabetic retinopathy in patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). In this randomized clinical trial supported by the National Eye Institute, 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy were assigned randomly to either aspirin (650 mg per day) or placebo. Aspirin did not prevent the development of high-risk proliferative retinopathy and did not reduce the risk of visual loss, nor did it increase the risk of vitreous hemorrhage. This was true both for eyes assigned randomly to deferral of photocoagulation and for eyes assigned randomly to early argon laser photocoagulation. The ETDRS results indicate that for patients with mild-to-severe non-proliferative or early proliferative diabetic retinopathy, it is likely that aspirin has no clinically important beneficial effects on the progression of retinopathy. The data also show that aspirin 650 mg per day had no clinically important harmful effects for diabetic patients with retinopathy. These findings suggest there are no ocular contraindications to aspirin when required for cardiovascular disease or other medical indications."
-What were the key findings of the Medical Research Council European trial comparing chorion villus sampling and amniocentesis for prenatal diagnosis?,"Medical Research Council European trial of chorion villus sampling. MRC working party on the evaluation of chorion villus sampling. First-trimester chorion villus sampling has the advantage over second-trimester amniocentesis of allowing earlier prenatal diagnosis of various genetic and cytogenetic disorders in the fetus (and therefore earlier termination in affected pregnancies) but the relative safety and diagnostic accuracy remain unclear. Between 1985 and 1989, 3248 women seeking prenatal diagnosis, principally because of their age, were recruited to an international, multicentre, randomised comparison of the safety and diagnostic accuracy of the two techniques--5% of women allocated chorion villus sampling and 8% of those allocated amniocentesis were not tested, usually because of spontaneous miscarriage. 6% and 2% were retested, in most because of sampling failure. The endpoint of a liveborn infant who survived was achieved by 86% of women allocated chorion villus sampling and 91% of those allocated amniocentesis; statistical analysis, after appropriate weighting for a centre's contribution, showed that the typical difference between the groups was 4.6% (95% confidence interval 1.6-7.5%; p less than 0.01). This difference reflected more spontaneous fetal deaths before 28 weeks' gestation (2.9% [0.6-5.3%]); more terminations of pregnancy for chromosomal anomalies (1.0% [0.0-2.1%]); and more neonatal deaths (0.3% [-0.1 to 0.7%]). The difference in neonatal deaths was due to a preponderance of very immature liveborn infants in the chorion villus sampling group, and this factor also explained that group's longer mean stay in hospital. More abnormal diagnoses followed chorion villus than amniotic fluid analyses (5.6% vs 3.9%). This difference was largely due to diagnoses of trisomy 18 and of (usually mosaic) abnormalities known to be confined to the placenta. 3 terminated pregnancies were false positives, 1 tested by chorion villus sampling and 2 by amniocentesis, and 2 other mosaic cases diagnosed by chorion villus sampling may have been false positives. There was 1 false-negative result in the chorion villus sampling group. The possibility of earlier exclusion or diagnosis of some fetal disorders afforded by first-trimester chorion villus sampling must be set against its clinical risks."
-What were the key findings of the Ontario Child Health Study regarding the psychosocial characteristics of parents with children who have chronic health problems?,"Children with chronic illness: family and parent demographic characteristics and psychosocial adjustment. This paper presents the results of an epidemiologic study that compares and contrasts psychosocial characteristics of parents and family units of children with chronic illness or physical disability (chronic health problems) with those of healthy children. Data were derived from the Ontario Child Health Study of 1869 randomly selected families, with 3294 children aged 4 to 16 years. In the absence of significant differences between parents and families of children with chronic illness alone and those with physical disability, these groups were combined for analysis, for which odds ratios (OR) or t tests were used. Significant positive findings included increased rates of parental treatment for ""nerves"" (mothers' OR = 2.1, fathers' OR = 1.9) and increased maternal negative affect scores (Bradburn Affect Balance Scale) (P less than .001) among parents of children with chronic health problems. Important negative findings (95% confidence interval of the OR included 1) included no increase in single-parent families (OR = 1.2), social isolation (OR = 1.0), or alcohol problems (OR = 1.2) among parents of children with chronic health problems. Categorically defined family dysfunction did not differ between the two groups (OR = 1.1). These data contrast with several clinic-based studies and suggest that, in a widely generalizable population survey, families of children with chronic health problems including physical disability do not suffer a marked excess of dysfunction, although some indicators of individual parent psychosocial problems were modestly elevated."
-What was the key finding regarding IL-4 and IL-2 mRNA levels in mice infected with Schistosoma mansoni?,"In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. Using Northern Blot analysis, the endogenous levels of IL-4 and IL-2 mRNA in the spleens, mesenteric lymph nodes, and granulomatous livers of male CBA/J mice in the acute phase of infection with Schistosoma mansoni have been quantified. High levels of IL-4 mRNA were detected in all three tissues from infected mice, whereas none was detected in tissues from normal, uninfected, age-matched mice. Isolation of the granulomas from the livers of infected mice and subsequent extraction of total RNA from these lesions resulted in a 70-fold enrichment of IL-4 message compared with the whole, unseparated granulomatous liver tissue. Hence, the predominant source of the IL-4 mRNA detected in livers from infected mice appears to be the schistosome egg-induced granulomas within these livers. In contrast, IL-2 mRNA was never detected in any of these tissues from either infected or normal mice. Control experiments were performed that ruled out the possibility that this inability to detect IL-2 mRNA was due to a difference in the efficacy of the IL-4 and IL-2 probes or due to a selective lability of IL-2 message. These data imply that IL-4-producing, Th2 lymphocytes are active in and possibly integral to the granulomatous, delayed-type hypersensitivity response characteristic of this infection, and directly challenges the current hypothesis that delayed-type hypersensitivity responses are exclusively mediated by Th1 lymphocytes."
-What cardiac disturbances were observed in patients receiving taxol during clinical trials?,"Cardiac disturbances during the administration of taxol. The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined."
-What was the cause of subarachnoid hemorrhage in the seventy-one-year-old Japanese man?,"Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery."
-What was the overall 5-year actuarial disease-free survival rate after salvage surgery for patients with carcinoma of the buccal mucosa?,"Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05)."
-What percentage of patients achieved complete thrombolysis based on the duration of their limb ischaemia symptoms?,"Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected."
-What were the key findings of the study comparing different ventilation methods during single-operator cardiopulmonary resuscitation in an ambulance?,"Single operator cardiopulmonary resuscitation in ambulances. Which ventilation device? Cardiopulmonary resuscitation en route to hospital is performed by a single-handed operator in many British ambulances. In this study, three emergency ventilation devices, and mouth-to-mouth breathing, were compared for effectiveness in unintubated patients. Seventeen paramedics used each method on a Laerdal manikin in a randomised order, under identical conditions. Three experienced cardiopulmonary resuscitation instructors repeated the tests in a moving ambulance. There were significant differences in minute volume (p less than 0.01) and number of effective chest compressions (p less than 0.05); mouth-to-mouth breathing produced the best overall results and the simplest device was a close second. The value of automatic ventilators for single-operator cardiopulmonary resuscitation in unintubated patients is questioned."
-What is the significance of the first reported case of HTLV-1 associated T cell lymphoma in South East Asia?,"HTLV-1 associated T cell lymphoma in South East Asia: case report and family study. Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives."
-What is the key finding in this case study regarding neutrophil function and protein abnormalities?,"An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins. A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs."
-What was the purpose of studying programmed ventricular stimulation at different time points after acute myocardial infarction?,"Usefulness of early versus late programmed ventricular stimulation in acute myocardial infarction. To determine the influence of timing on the prognostic value of programmed ventricular stimulation after acute myocardial infarction (AMI), 32 patients were studied on day 19 (early study) and again on day 36 (late study) after AMI using up to 3 extrastimuli. At the early study, sustained monomorphic ventricular tachycardia (VT) was induced in 12 patients (38%), sustained polymorphic VT in 8 (25%), nonsustained monomorphic VT in 1 (3%), nonsustained polymorphic VT in 1 (3%) and no inducible arrhythmia in 10 (31%). At the late study, sustained monomorphic VT, nonsustained monomorphic VT and nonsustained polymorphic VT were induced in 8 patients (25%) each, and no inducible arrhythmia in 8 (25%). Of the 12 patients who had inducible sustained monomorphic VT at the early study, 7 had noninducibility of sustained monomorphic VT at the late study. Of the 20 patients who had noninducibility of sustained monomorphic VT at the early study, 3 had inducible sustained monomorphic VT at the late study. During the follow-up period (mean +/- standard deviation 21 +/- 8 months), there were 2 sudden cardiac deaths and 3 occurrences of sustained VT. Univariate analysis revealed both inducibilities of sustained monomorphic VT at the early study (p = 0.045) and at the late study (p less than 0.001) to be predictive of sudden cardiac death or clinical occurrence of sustained VT. However, inducibility of sustained monomorphic VT at the late study had a higher sensitivity (100%), specificity (89%), positive predictive value (63%) and negative predictive value (100%) than at the early study (80, 70, 33 and 95%, respectively)."
-What is the difference between allochiria and allesthesia according to the original descriptions by Obersteiner and Stewart?,"Allochiria vs allesthesia. Is there a misperception? Allochiria is the mislocation of sensory stimuli to the corresponding opposite half of the body or space. Obersteiner (1882) introduced the term allochiria (Greek allos = other + chiria = hand), and more than 20 authors employed it in this context over the next 25 years. Stewart (1894) described a related phenomenon in which stimuli are displaced to a different point on the same extremity. He noted that the displacements were different than allochiria and coined the term allachaesthesia (ie, allesthesia) (Greek allache = elsewhere + aisthesis = perception). Despite this historical background, Jones (1907) redefined both terms in an attempt to increase diagnostic specificity and attributed allochiria to hysteria. Jones' reinterpretation does not appear to be justified historically, etymologically, or scientifically and has resulted in contradictory definitions of allochiria and allesthesia in present-day medical dictionaries and neurologic textbooks. We advocate a return to usage consistent with the original descriptions and word derivations."
-What was the purpose of the study on autologous fat injection in the canine larynx?,"Autologous fat injection for vocal cord medialization in the canine larynx. This study examined the use of autologous fat as an alternative to Teflon and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show mode-rate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation."
-What percentage of age-matched elderly subjects made omissions on at least one visuo-spatial neglect test?,"Performance of age-matched controls on a battery of visuo-spatial neglect tests. Examination of 47 independent elderly subjects, matched with a population of patients with acute stroke, found that 55% made at least one omission on a battery of neglect tests. Up to 43% made omissions on any one test. Increasing age and other evidence of cognitive impairment were associated with impaired performance on the battery. Omissions were attributed to an age-related decline in visuo-spatial function. Cut-off points are provided to distinguish between such age-related impairment and visuospatial neglect. The importance of age-matched control studies in developing tests of cognitive impairment in stroke research is highlighted."
-What unique characteristics were observed in the hepatoid adenocarcinoma of the renal pelvis in this case study?,"Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. A right renal pelvic mass in a 72-year-old man was resected. The histologic appearance of the tumor was a mixture of tubular adenocarcinoma cells and hepatoid neoplastic cells, and there was a resemblance to hepatoid adenocarcinoma. The intraoperative level of serum alpha-fetoprotein (AFP) was calculated to be 2246 ng/ml, and the postoperative level ranges from 183.6 to 285.6 ng/ml. Lectin binding assays showed that the serum AFP was the hepatic carcinoma type. In a hepatoid portion, an iron-negative, brown to green pigment was positive for bile. Alpha-fetoprotein was immunohistochemically evident in the neoplastic cells. In addition to the hepatic differentiation, the tumor had differentiated into intestinal absorptive or pancreatobiliary tract cells, as deduced from the frequent presence of spicular bodies, a unique light microscopic feature equivalent to microvilli with an actin core. The hepatoid adenocarcinoma is a distinct type of AFP-producing carcinoma present in the organs with epithelium of endodermal origin. Hepatoid adenocarcinoma in the renal pelvis may arise from a metaplasia of neoplastic mesonephric cells into endodermal cells."
-How did the study evaluate the effects of oral magnesium on premenstrual syndrome symptoms?,"Oral magnesium successfully relieves premenstrual mood changes. Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster ""pain"" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster ""negative affect."" In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes."
-What were the key findings regarding the long-term quality of life for childhood and adolescent CNS tumor survivors in this study?,"Quality of life in long-term survivors of CNS tumors of childhood and adolescence. Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or their proxies) who had CNS tumors diagnosed before the age of 20 between 1945 and 1974, survived at least 5 years, and reached 21 years of age. Survivors were 32 years old on average at follow-up. When compared with 479 matched siblings as controls. CNS tumor survivors were more likely to have died or to have become mentally incompetent sometime during the follow-up period. They were more likely to be at risk for such adverse outcomes as unemployment (odds ratio [OR], 10.8; 95% confidence interval [CI], 4.6 to 25.7], to have a health condition that affected their ability to work (OR, 5.9; CI, 3.7 to 9.4), to be unable to drive (OR, 28.8; CI, 6.9 to 119.9), or to describe their current health as poor (OR, 7.8; CI, 1.7 to 35.7). Unfavorable outcomes were more frequent in male survivors than in females, in those with supratentorial tumors compared with infratentorial ones, and in those who received radiation therapy. As clinicians consider improving therapies, they should anticipate late effects, such as those we observed, and attempt to target subgroups for interventions that may improve subsequent quality of life."
-What was the gender distribution of children who were victims of dog bites in the study?,"Dog bites in urban children. As a result of a perceived increase in pit bull injuries, all children who presented to The Children's Hospital of Philadelphia during 1989 for evaluation of dog bite injuries were prospectively studied. Epidemiologic information was collected from parents, either at the time of visit or by phone on the following day. A total of 168 children were enrolled; the mean age was 8 years. Males outnumbered females 1.5:1. Most (61%) injuries occurred in or around the home and involved dogs known to the patient (77%). Types of injuries included abrasions (33%), punctures (29%), and lacerations (38%). Thirteen bites had associated complications; nine developed infection. Twelve (7%) children required admission to the hospital. More than 12 different purebreeds or cross-breeds were identified as perpetrators, including German shepherds (n = 35), pit bulls (n = 33), rottweilers (n = 9), and Dobermans (n = 7). Most (54%) animals were contained (ie, leashed, fenced, in-house) at the time of injury. Fewer (46%) were provoked prior to biting. Significantly more pit bull injuries (94% vs 43%, P less than .001) were the consequence of unprovoked attacks and involved freely roaming animals (67% vs 41%, P less than .01). Children aged 5 or younger were more likely to provoke animals prior to injury than were older children (69% vs 36%, P less than .001). It is recommended that families with young children be the target of pet safety education and that measures be sought that would lead to early identification of a potentially dangerous dog and restrict ownership."
-What medical condition did the 29-year-old man develop that led to the management of megaduodenum through duodenoplasty and feeding jejunostomy?,"Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy. A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo-obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum."
-How did the fentanyl consumption differ between the epidural and intravenous groups in this postoperative pain management study?,"Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. A prospective, open, clinical trial is described in which 20 patients having upper abdominal surgery were randomly allocated to receive fentanyl for postoperative analgesia by patient-controlled demand analgesic computer by either the epidural or intravenous route. Hourly pain, sedation and nausea scores were very similar in the two groups during the first 24 hours after surgery. What few differences there were favoured the epidural group. There was a highly significant difference in fentanyl consumption between the two groups, with the intravenous group demanding consistently more than twice as much as the epidural group."
-What were the most common viral and bacterial pathogens causing lower respiratory infections in children in this tropical southern Indian study?,"Etiology of acute respiratory infections in children in tropical southern India. Nasopharyngeal secretions and throat-swab specimens from 809 children less than 6 years old with acute respiratory infection were examined by culture and indirect immunofluorescence for the presence of virus or viral antigen. Blood was cultured for the presence of bacteria in selected cases of lower respiratory infection (LRI); pleural fluid also was cultured in cases of empyema. Viruses were detected in 163 (49%) of 331 children with LRI. Respiratory syncytial virus (RSV) was the commonest agent isolated (106 children). Other viruses isolated included parainfluenza viruses (36 children), adenoviruses (12), and influenza viruses (five). Outbreaks of infection due to RSV occurred during August through October. Pneumonia was the commonest LRI encountered (178 children). Among children with pneumonia, viruses were detected in 65 (37%) of 178 children, and bacteria were isolated from 27 (18%) of the 147 children for whom blood cultures were done. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the common bacterial pathogens isolated. In cases of empyema and pyopneumothorax, S. aureus was the commonest organism isolated. There were 116 children with bronchiolitis, 83 (72%) of whom had viral infections; the majority of these children (81%) had RSV infection. Croup was uncommon (eight cases) and was caused mainly by parainfluenza viruses."
-What were the two treatment methods compared in this study for managing refractory ascites in patients with cirrhosis?,"Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. BACKGROUND. There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS. We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS. During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS. The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved."
-How does a fish oil-enriched diet affect the microcirculatory manifestations of ischemia-reperfusion injury in hamsters?,"Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters. Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the break-down of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesion-promoting leukotriene (LT) B4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB5, emphasizing the mediator role of LTB4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury."
-How does the external anal sphincter function differ between spinal cord injury patients and healthy volunteers?,"External anal sphincter function in spinal patients. Electromyographic and manometric study. Six patients with complete transection of the spinal cord and six healthy volunteers were examined by using anorectal manometry together with electromyographic (EMG) recording of the external anal sphincter composed of striated muscle. Anal pressure and EMG activity of the external anal sphincter were continuously recorded at rest and during gradual rectal distention (10, 20, 30, 40, and 50 ml) by means of an air-filled balloon eliciting a rectoanal inhibitory reflex (RAIR) at the upper part, and an inflation reflex (IR) at the lower part of the anal canal. All patients and controls had a RAIR for each rectal distention volume. A relationship between the duration of the RAIR and the rectal distention volume was present in controls only. In controls the IR was present for each rectal distention volume, whereas it was present in only one patient for a 40-ml volume. During the resting period, all controls showed continuous tonic EMG activity of the external anal sphincter, but after 30 minutes all the patients showed a decrease and ultimately in five cases a disappearance of the tonic EMG activity of the external anal sphincter. In spinal patients, the presence or absence of EMG activity of the external anal sphincter did not modify the anal canal pressure. These results indicate that: 1) the tonic EMG activity of the external anal sphincter seems to be under the control of supraspinal structures, because in spinal patients it disappears in the absence of sensitive inputs toward the spinal cord; 2) the absence of EMG activity at rest indicates that the external anal sphincter is not implicated in the RAIR disturbances observed in spinal patients; 3) the IR is not a spinal reflex but is under voluntary control, because it is not present in spinal humans; 4) in spinal humans the tonic EMG activity of the external anal sphincter does not play a role in the maintenance of the anal pressure at rest."
-How can the expression of ABO(H) antigens and beta-2 microglobulin help predict the response to intravesical BCG treatment in superficial transitional cell carcinoma of the bladder?,"ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin. The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone."
-How does allopurinol (ALLO) mitigate norepinephrine-induced cardiac damage in rabbits?,"Modulation of catecholamine cardiomyopathy by allopurinol. It has been suggested that cardiac injury by catecholamines may be the result of coronary constriction leading to ischemic damage. Allopurinol (ALLO) has been shown to reduce the extent of myocardial necrosis in various systems. Hence the possibility that ALLO might limit norepinephrine (NE) injury was tested. Rabbit hearts were infused with NE (3 micrograms/min/kg) for 90 minutes, with or without ALLO (50 micrograms/min/kg). Control specimens infused with saline solution plus ALLO were also prepared. Hearts were excised 48 hours later and studied as isovolumic isolated heart preparations. Peak systolic pressure, coronary flow, and myocardial oxygen consumption were significantly reduced in the hearts infused with NE but not in the NE + ALLO hearts. Myocardial adenosine triphosphate and glycogen concentrations were 29% and 26% lower in the NE hearts compared with control hearts. These reductions were absent in the NE + ALLO group. Moreover, rates of creatine phosphokinase and lactic dehydrogenase release were sharply elevated in the NE hearts but not in those also given ALLO. These findings are consistent with the changes observed histologically. The amount of myocardial damage was less in the ALLO + NE group compared with the NE group (p less than 0.02). This appears to be the first report to demonstrate that ALLO reduces myocyte damage by NE. Possible mechanisms include decreased free radical production, scavenging of free radicals, and preservation of the adenine nucleotide pool. Because xanthine oxidase activity is absent in the rabbit, the latter two mechanisms are more likely explanations for the findings."
-What is autoerotic asphyxia and how can it lead to fatal consequences?,"A case of autoerotic asphyxia associated with multiplex paraphilia. During the past 20 years, the sensational aspects of autoerotic fatalities have captured the attention of medical examiners, psychiatrists, law enforcement agents, and the public, as well as the individuals themselves who engage in these dangerous practices. Reports of deaths related to sexual asphyxia have been presented numerous times at national and international meetings and have been the topic of discussion on television talk shows and in the press. Autoerotic fatalities and all the sexual curiosities related to these activities have prompted death scene investigators to publish case reports, and even textbooks, on the subject. The case presented herein is one of a multicomponent paraphilia in which self-asphyxiation (autoasphyxiophilia) led to a fatal autoerotic event."
-What was the unusual presentation of the child with a biopterin synthesis defect?,"Paroxysmal tremor and orofacial dyskinesia secondary to a biopterin synthesis defect. We report a child with a systemic biopterin synthesis defect due to an absence of 6-pyruvoyl-tetrahydropterin synthase who had an unusual presentation, with three episodes of coarse ""rubral-like"" tremor in arms and legs orofacial dyskinesia between the ages of 3 and 6 months. Response to levodopa therapy and CSF neurotransmitter metabolite concentrations before and after therapy suggests that his clinical syndrome resulted from a secondary dopamine deficiency."
-How do Quechua highlanders from the Andes demonstrate metabolic efficiency during exercise at high altitudes compared to lowlanders?,"Metabolic and work efficiencies during exercise in Andean natives. Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms."
-What changes in coronary diameter were observed 4 hours after percutaneous transluminal coronary angioplasty (PTCA)?,"Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course. BACKGROUND. To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA. METHODS AND RESULTS. All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments. CONCLUSIONS. Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA."
-What challenges did the study identify with laser cone biopsy specimens that could interfere with reliable histologic diagnosis?,"The histologic reliability of laser cone biopsy of the cervix. Laser conization of the cervix has been advocated as the technique of choice for the treatment of cervical intraepithelial neoplasia (CIN) in preference to ablative techniques, because it provides a specimen for histologic diagnosis while retaining the advantages of an outpatient procedure with minimal short- and long-term morbidity. To determine whether specimens so obtained are adequate for reliable histologic diagnosis, we reviewed 77 laser conizations performed for lesions confirmed to contain CIN in a colposcopically directed biopsy and satisfying the criteria for local ablation and scored the cones for the presence of epithelial denudation and laser coagulation artifact that interfered with the diagnosis of CIN or the assessment of the margins of excision. Thirty specimens (39%) were negative for CIN. Twenty-eight (36%) showed extensive epithelial denudation, ten (13%) contained coagulation artifact that made recognition of CIN extremely difficult or impossible, and in 11 (14%), assessment of margins was extremely difficult or impossible because of laser coagulation artifact. We conclude that these difficulties with the histologic interpretation of laser cone specimens make it an unsuitable excisional technique when reliable histologic diagnosis of cervical lesions is required."
-What did the study reveal about the relationship between alpha 1 antitrypsin phenotypes and alcoholic pancreatitis?,"Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis. Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis."
-What was the main objective of the study regarding ovarian hyperstimulation in patients treated with human menopausal gonadotropin?,"Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer. OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle."
-How do the plasma and saliva levels of PGI2 and TXA2 differ in classical migraine patients during an attack-free period?,"Plasma and saliva levels of PGI2 and TXA2 in the headache-free period of classical migraine patients. The effects of nicardipine. The levels of Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were assayed simultaneously (RIA) in the plasma and saliva of 9 patients suffering from classical migraine attacks. The assays were done during an attack-free period. In relation to the control group we observed a significant decrease in the plasma levels of PGI2 together with a sharp increase in TXA2 in saliva. When the patients were treated with nicardipine, a calcium antagonist, the TXA2 increase in saliva did not occur. These results suggest both a systemic and local effect in the classical migraine attacks. We explain and discuss our results by referring to the PGI2: TXA2 equilibrium system. Nicardipine action might be related to its ability to reduce the calcium entry into the cell induced by thromboxane."
-What type of rare neural tumor was observed within the mandibular bone in this case study?,"Unusual intramandibular neural tumor. Neural tumors within the jaw bones are exceptional. We present the histologic observation of a central mandibular tumor of neural origin. Immunohistochemistry confirmed the neural nature of the tumor, which had features of a schwannoma (neurilemmoma) together with ganglion cells as seen in ganglioneuroma. Moreover, the association with an intracranial tumor, possibly a meningioma, is emphasized."
-What percentage of reflux events were simultaneously detected by both scintigraphy and pH monitoring in patients with severe reflux esophagitis?,"Simultaneous esophageal pH monitoring and scintigraphy during the postprandial period in patients with severe reflux esophagitis. To compare reflux events detected by intraesophageal pH monitoring with that of scintigraphy, we simultaneously performed both techniques along with esophageal manometry in nine patients with severe reflux esophagitis. Two hundred eighteen reflux events were detected in the recumbent posture after a meal during a 40-min interval. Both techniques simultaneously detected only 23% of all reflux events. Scintigraphy alone detected 61% of all reflux events as opposed to 16% for pH monitoring. Of those reflux events diagnosed only by scintigraphy, more occurred while the intraesophageal pH was less than 4 (ie, during an acid-clearing interval) than while the intraesophageal pH was greater than 4 (ie, when intragastric contents were neutralized by the meal). Most reflux events occurred during periods of stable, but low LES pressure. While reflux events diagnosed by scintigraphy significantly decreased during the second of two 20-min postprandial intervals, those by pH monitoring tended to increase. That simultaneous scintigraphy and pH monitoring agreed on less than 1/3 of all reflux events not only underscores the fact that both techniques measured different physical components of the esophageal refluxate (ie, volume vs acid concentration, respectively), but also were influenced by different physiologic events such as the ingestion of a meal, gastric emptying, and esophageal acid clearance."
-"What approach do comprehensive multidisciplinary pain centers use to help patients with chronic, disabling pain?","Pain centers--organization and outcome. Pain treatment centers have evolved at a rapid rate, but they differ in their complexity and services provided. Patients, as well as primary care physicians, have difficulty in identifying the appropriate center for a specific problem. Guidelines for pain centers have recently been proposed by the International Association for the Study of Pain, along with an attempt at their accreditation. Outcome studies from pain centers have proliferated, with a wide range of treatment programs being reported. Comprehensive multidisciplinary pain centers using the rehabilitation medicine approach are effective in decreasing disability and increasing the productivity of patients with chronic, disabling pain."
-What differences were observed in motor fiber degeneration and conduction block between the extensor digitorum brevis (EDB) and anterior lateral (AL) compartment muscles in peroneal nerve palsies?,"Quantitation of axon loss and conduction block in peroneal nerve palsies. We compared conduction in motor fibers supplying the extensor digitorum brevis (EDB) and anterior lateral compartment (AL) muscles. The object was to determine whether there were any differences in the relative proportions of degenerated and blocked nerve fibers between the longer EDB and shorter AL fibers. In almost every case the percentage of motor fibers undergoing axonal degeneration was greatest in EDB fibers. Conversely, the percentage of conduction block was greatest in the AL motor fibers. As clinical recovery is dependent on AL muscles rather than EDB, electrophysiological study of the relative proportions of degenerated and blocked fibers in the former should provide a more reliable measure of outcome than similar studies of EDB. Conduction velocity distal to the fibular head was not slowed despite the large loss of EDB motor fibers. Evidence for selective involvement of the larger myelinated fibers is, therefore, lacking. The location of the major conduction abnormalities was in almost every case between the mid-fibular head and popliteal fossa."
-"How are depression, chronic fatigue, and chronic pain interconnected in terms of their psychological and neurobiological factors?","Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery."
-How do DNA methylation patterns change during embryonic development in mice?,"Demethylation of CpG islands in embryonic cells. DNA in differentiated somatic cells has a fixed pattern of methylation, which is faithfully copied after replication. By contrast, the methylation patterns of many tissue-specific and some housekeeping genes are altered during normal development. This modification of DNA methylation in the embryo has also been observed in transgenic mice and in transfection experiments. Here we report the fate in mice of an in vitro-methylated adenine phosphoribosyltransferase transgene. The entire 5' CpG island region became demethylated, whereas the 3' end of the gene remained modified and was even methylated de novo at additional sites. Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences. This suggests that gene sequences can be recognized in the early embryo and imprinted with the correct methylation pattern through a combination of demethylation and de novo methylation."
-What distinguishes Neisseria lactamica from Neisseria meningitidis in laboratory testing?,"Neisseria lactamica meningitis following skull trauma. A woman developed meningitis due to Neisseria lactamica in association with a cribriform plate fracture. Cerebrospinal fluid antigen tests for Neisseria meningitidis were negative. The patient recovered with intravenous penicillin therapy. N. lactamica can be rapidly distinguished from N. meningitidis by the hydrolysis of ONPG (o-nitrophenyl-beta-D-galactopyranoside). In contrast to N. meningitidis and Neisseria gonorrhoeae, N. lactamica lacks virulence properties. As 100% of N. lactamica strains are susceptible to penicillin and all three previously described patients with N. lactamica meningitis have recovered with penicillin treatment, the reason for distinguishing the organisms in this context is primarily to prevent unnecessary anxiety and prophylaxis among contacts."
-How might exclusion criteria in hypertension trials potentially impact the generalizability and statistical power of research findings?,"Potential impact of exclusion criteria on results of hypertension trials. Recent trials of antihypertensive therapy, including the Veterans Administration trials, the Hypertension Detection and Follow-up Program, the Multiple Risk Factor Intervention Trial, the Australian Mild Hypertension Trial, and the British Medical Research Council Trial, are reviewed with a particular emphasis on the criteria leading to the exclusion of potentially eligible participants. The observation of all-cause and cause-specific mortality rates in the group ultimately selected to participate in the trial is suggested as an index to the general applicability of trial results. Because end-point rates are fundamental for determining sample size, substantial reduction in these end-point rates by patient exclusion should be taken into account by the trial design. Some recent trials may have generated end-point-event rates so low that the power of the trial to detect reasonable treatment effects was substantially reduced. Future trials should attempt to take this important factor into account at the design stage."
-What is the association between adult polycystic kidney disease (APKD) and seminal vesicle cysts?,"Seminal vesicle cysts: association with adult polycystic kidney disease. Adult polycystic kidney disease (APKD) is associated with cyst formation in the kidney, liver, pancreas, esophagus, ovary, uterus, and brain. Four patients with APKD (aged 45-65 years) with computed tomographic evidence of seminal vesicle cysts are described. All seminal vesicles contained cystic masses with attenuation values of 0-30 HU. Seminal vesicle thickness was 3-4 cm (normal, 1.5 cm). High-attenuation walls separated the cysts, which were 3-35 mm in diameter. All patients had typical renal stigmata of APKD. None had cysts elsewhere, except one patient with hepatic cysts. Postmortem examination in one patient confirmed the seminal vesicle cysts as well as APKD. It is likely that a basement membrane defect allows cyst formation in multiple organs, presumably including the seminal vesicles. Because of the association of seminal vesicle cysts with ipsilateral urogenital anomalies, and because only 60% of patients with APKD have a relevant familial history, the kidneys of patients with cross-sectional imaging evidence of seminal vesicle cysts should also be studied."
-What treatment method was used to control bleeding from a penetrating atherosclerotic aortic ulcer in this case report?,"Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization. A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention."
-How does hypoxic exercise affect the levels of atrial natriuretic factor (ANF) and aldosterone in untrained men?,"Effect of hypoxic exercise on atrial natriuretic factor and aldosterone regulation. To evaluate the possible physiologic role of atrial natriuretic factor (ANF) in the observed dissociation of aldosterone secretion from the renin-angiotensin system during hypoxic exercise, 12 untrained men, ages 18 to 24, were studied on two separate days for 30 min during hypoxic (16% O2) and normoxic (room air) exercise on a bicycle ergometer. Workloads were adjusted to produce individual heart rates that remained within 70 to 75% of their previously measured maximum. Hemoglobin saturation decreased during hypoxia from 98 +/- 0.1% to 90 +/- 0.4% (P less than .01). Plasma aldosterone levels increased significantly (P less than .01) under both breathing conditions, yet were on average 36% lower during hypoxia than during normoxia (P less than .001). Plasma ANF levels increased during exercise under both conditions (P less than .01), yet levels were 45% greater during hypoxia than during normoxia (P less than .001). Plasma renin activity, adrenocorticotropic hormone, cortisol, potassium, and systolic blood pressure increased during exercise on both study days (P less than .01, compared to basal level), and showed no difference between normoxic and hypoxic conditions. Plasma pH was slightly higher during hypoxic exercise (P less than .05, compared to normoxia). We conclude that acute hypoxemia is a potent enhancing stimulus for ANF release during dynamic exercise and that ANF is probably a contributing factor in the dissociation of aldosterone secretion from the renin-angiotensin system under these conditions."
-How does technetium-HMPAO SPECT help in evaluating the effectiveness of carotid endarterectomy in patients with internal carotid artery stenosis?,"Use of technetium-HMPAO to demonstrate changes in cerebral blood flow reserve following carotid endarterectomy. Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy."
-What were the key findings regarding survival times between black and white patients with metastatic breast cancer in the Piedmont Oncology Association study?,"A comparison of treatment outcomes for black patients and white patients with metastatic breast cancer. The Piedmont Oncology Association experience. Prior studies have shown that black patients with breast cancer have poorer survival times compared with white patients even when adjusted for stage. Seventy-four black patients treated on six Piedmont Oncology Association (POA) protocols were compared with 74 randomly selected white patients treated with the same protocols to determine if race had any independent effect on response, time to progression, or survival time. Patients were evenly matched for pretreatment characteristics with the exception that white patients had a significantly higher percentage of bone metastases and significantly less skin involvement. Response rates and median time to progression were similar for black patients and white patients at 31% and 25%, and 9.3 and 9.1 months, respectively. Black patients had poorer survival times even when adjusting for covariables; median survival time was 14.3 months for black patients and 20.3 months for white patients (P less than 0.05). The reason for this survival difference in Stage IV patients is unclear, but is unlikely to be related to treatment. Additional research in this area will be necessary to resolve this issue."
-How does the type of muscle contraction (concentric vs eccentric) and exercise intensity affect exercise-induced muscle soreness?,"Exercise-induced muscle soreness after concentric and eccentric isokinetic contractions. The purpose of this two-part study was to determine whether the amount of exercise-induced muscle soreness differs between subjects who perform concentric and eccentric isokinetic contractions of their quadriceps femoris muscles. In experiment 1, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised at the same power level. In experiment 2, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised with maximal effort. Muscle soreness ratings, obtained by using a visual analogue scale, were taken immediately before exercise and at 24 and 48 hours postexercise. Changes in muscle soreness ratings between exercise groups from preexercise to postexercise periods were compared in both experiments, using a one-way between-subjects analysis of variance. There was no difference in the change in muscle soreness from preexercise to post-exercise periods between groups exercising at equal power levels. Subjects who exercised using eccentric contractions with maximal effort demonstrated greater increases in muscle soreness than those who performed concentric contractions. The results suggest that exercise intensity, rather than contraction type, may be the dependent factor in producing exercise-induced muscle soreness."
-How can ultrafast MR imaging help differentiate between liver hemangiomas and hepatic metastases?,"Differentiation between hemangiomas and metastases of the liver with ultrafast MR imaging: preliminary results with T2 calculations. We studied the efficacy of T2 measurements at high field strength in distinguishing between liver hemangiomas and hepatic metastases when an ultrafast (single-excitation) MR imaging technique is used. Fourteen patients with known liver tumors were imaged in a 2.0-T prototype ultrafast MR scanner with a spin-echo (infinite TR and TE of 30-340 msec) pulse sequence. Each image was obtained with a total data acquisition time of 20 msec. T2 calculations for hepatic metastases (n = 6) showed a mean of 79.3 +/- 13.5 msec, whereas hemangiomas (n = 8) showed a T2 of 139.8 +/- 18.8 msec (p less than .0001). T2 values of lesions had a smaller relative standard deviation than previously reported, and the range of T2 values of hemangiomas (119-181 msec) and metastases (68-103 msec) did not overlap. Our preliminary results suggest that T2 calculations with ultrafast MR imaging may be useful for differentiating hemangiomas from metastases. We hypothesize that T2 values obtained from ultrafast MR images are more reliable than those obtained from conventional MR images, primarily because of the elimination of T1 information and effects of motion on image signal intensity."
-What is the current status of thrombolytic treatment for patients with unstable angina according to the context?,"Thrombolysis in unstable angina: results of clinical studies. Ample evidence exists to support the major role of intracoronary thrombosis superimposed on a disrupted plaque in unstable angina. Consequently, thrombolytic treatment, already established to be highly beneficial in patients with acute myocardial infarction, might also be indicated in patients with unstable angina. The clinical response to thrombolytic treatment has been evaluated in several small-sized studies with inconsistent and somewhat deceiving results. Thus, the role of thrombolysis in the treatment of unstable angina is still controversial. Two ongoing large-scale, randomized, controlled trials, the Third Thrombolysis in Myocardial Infarction (TIMI III) in the United States testing recombinant tissue-type plasminogen activator and UNASEM in Europe testing anisoylated plasminogen-streptokinase activator complex will, it is hoped, solve the debate. At present, early thrombolysis might be considered for the treatment of the subset of patients with severe rest angina associated with transient ST-T ischemic changes."
-How does oximetry help in detecting sleep apnea syndrome (SAS) and quantifying apneic events?,"Does oximetry contribute to the detection of apneic events? Mathematical processing of the SaO2 signal. The purpose of this study was to assess the ability of continuous nocturnal oximetry to detect sleep apnea syndrome (SAS) and to recognize nonapneic oxyhemoglobin desaturations. Oxygen saturation oscillations, related to successive apneas in SAS or to apneic episodes in COPD or restrictive patients, were quantified using a new index: delta = 1/n sigma 1 n magnitude of delta(SaO2)/delta(t)(12-s intervals) Twenty-six patients (15 SAS, 8 COPD, and 3 restrictive patients) were included in a prospective study comparing nocturnal oximetry and polysomnography over 34 nights. In apneic patients, we found a strong correlation (r2 = 0.73, p less than 0.01) between time spent in apnea and the delta index. In COPD, the number of apneas was also correlated to the delta index (r2 = 0.92, p less than 0.01). A lower threshold for delta of 1.5 is accurate enough to detect apneas if initial SaO2 is greater than 93 percent. If initial SaO2 is greater than 93 percent, the delta threshold should be 0.8 (sensitivity 95 percent). Such a method could contribute to the accurate selection of patients for polysomnography."
-How did antibiotic treatment affect food intake and nutrient absorption in children with Shigella infection during the acute stage of the disease?,"Effect of antibiotics on food intake and absorption of nutrients for children with diarrhea due to Shigella. The effect of antibiotic therapy on intake of food and absorption of nutrients for 19 male children aged 1-5 years with suspected shigella infection was studied. The children were admitted to the hospital with acute diarrhea, high fever, abdominal pain, and greater than or equal to 25 red blood cells and white blood cells per high-power field in the stool. Microbiologic diagnosis was made within 48 hours of admission. On the basis of clinical and microbiologic criteria, children were classified as having mild or severe infection. Ten children with mild infection did not receive antibiotics, whereas nine children with severe infection were treated with ampicillin. After the children were rehydrated, a 72-hour balance study was carried out during the acute stage of infection with Shigella and was repeated 2 weeks after recovery. The levels of consumption of food and absorption of nutrients were estimated. During the acute stage of infection, such levels were higher for the children treated with antibiotics than for the untreated group. During the recovery phase, the levels of intake of food and absorption of nutrients were equal for both groups. Thus, children who are treated with appropriate antibiotics not only may recover from infection with Shigella more rapidly, but they also may be able to absorb nutrients more efficiently."
-How does bronchoscopy via the laryngeal mask provide advantages in assessing patients with malignant tracheal tumors and vocal cord paralysis?,Flexible bronchoscopy via the laryngeal mask: a new technique. Malignant tracheal tumours often cause airway obstruction and this may be aggravated by vocal cord paralysis due to invasion of the recurrent laryngeal nerve. Conventional endoscopic techniques performed under general anaesthesia do not give a simultaneous view of vocal cord function and the distal airways. The technique of bronchoscopy via the laryngeal mask allowed full assessment of the cause of stridor in a patient with a malignant tracheal tumour that was causing airways obstruction and vocal cord paralysis.
-What is the primary factor believed to be responsible for the development of diabetic retinopathy?,"On the pathogenesis of diabetic retinopathy. A 1990 update. Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane."
-What characteristic appearance did normal urethras demonstrate on T2-weighted MR images?,"Female urethra: MR imaging. The potential of magnetic resonance (MR) imaging in the evaluation of the female urethra was studied in 64 patients. Spin-echo T1- and T2-weighted images were obtained in all 64 patients, and contrast-enhanced T1-weighted images were also obtained in 27 patients. Urethral pathologic conditions, established with urethroscopy or histologic examination, or both, included urethral diverticula, inflammatory granuloma, and primary and metastatic neoplasms. On T2-weighted images, all normal urethras demonstrated a characteristic targetlike appearance with differentiation among the outer ring of low signal intensity, the middle zone of higher signal intensity, and the center of low signal intensity. After injection of gadopentetate dimeglumine, the targetlike appearance of the normal urethra was seen on the T1-weighted images. Urethral diverticula were detected with MR imaging in all nine patients with that diagnosis, and in each, MR imaging demonstrated urethral expansion, distortion of the zonal anatomy, and presence of fluid in the middle zone. Primary or metastatic urethral neoplasms were also detected with MR imaging in every patient with the diagnosis, but differentiation between benign and malignant disease was not possible. Local staging of primary or metastatic malignant disease was correct in eight of the 11 patients. In three patients, the inflammatory changes could not be differentiated from tumor invasion, resulting in overestimation of tumor extent."
-What is purpura fulminans and how is it related to meningococcemia in this case study?,"Purpura fulminans and adrenal hemorrhage due to group Y meningococcemia in an elderly woman. A 70-year-old previously healthy woman was admitted with a 1-day history of malaise, sore throat, nausea, vomiting, rigors, and confusion. She was found to be in septic shock with purpura fulminans and disseminated intravascular coagulation. She died within 36 hours of admission. Blood cultures grew Neisseria meningitidis group Y. Necropsy revealed evidence of shock and bilateral adrenal hemorrhage."
-What was the relationship between D-dimer plasma concentrations and intracardiac thrombus in patients with mitral stenosis?,"Intracardiac mobile thrombus and D-dimer fragment of fibrin in patients with mitral stenosis. OBJECTIVE--To investigate the relation between intracardiac thrombus and blood coagulability in patients with mitral stenosis. DESIGN--Prospective study. Cross sectional echocardiography and plasma concentrations of the D-dimer fragment of fibrin were used concurrently to detect intracardiac thrombus in patients with mitral stenosis. SETTING--Department of Medicine, National Cardiovascular Centre, Osaka, Japan. PATIENTS--63 patients with mitral stenosis. None of them had been receiving any anticoagulants or antiplatelet agents. MAIN OUTCOME MEASURES--Plasma concentrations of D-dimer in patients with a mobile intracardiac thrombus, those in patients with a non-mobile intracardiac thrombus, and those in patients without an intracardiac thrombus. RESULTS--A mobile intracardiac thrombus was found in 10 patients and a non-mobile thrombus in eight. The remaining 45 patients had no intracardiac thrombi. Plasma concentrations of D-dimer in the 10 patients with a mobile thrombus were all greater than 300 ng/ml (mean 983.3, 95% confidence interval 498.9 to 1467.7 ng/ml) and they were significantly higher than those in the patients with a non-mobile thrombus (226.2, 33.6 to 418.8 ng/ml) and the patients without an intracardiac thrombus (147.2, 110.4 to 184 ng/ml). CONCLUSIONS--A high plasma concentration of D-dimer seemed to reflect a hypercoagulable intracardiac state and may be a helpful indicator of the possible presence of mobile intracardiac thrombus in patients with mitral stenosis."
-What were the two treatment methods compared in this study for managing oesophageal achalasia?,Prospective clinical and manometric study comparing pneumatic dilatation and sublingual nifedipine in the treatment of oesophageal achalasia. A study was carried out in 30 patients affected by a mild or moderate degree of oesophageal achalasia to compare the clinical and manometric effects of sublingual nifedipine and pneumatic dilatation. Sixteen patients were dilated twice with Rider-Moeller dilators and 14 were treated with sublingual nifedipine 10-20 mg 30 minutes before meals. A manometric evaluation was performed before and six months after starting treatment. The clinical evaluation (according to Vantrappen's criteria) was performed every three months for a mean follow up of 21 months. In both groups of patients a significant (p less than 0.001) fall in lower oesophageal sphincter pressure was observed after treatment and excellent or good clinical results were observed in 75% of dilated patients and in 77% of patients treated with nifedipine. One patient could not tolerate nifedipine. No complications were observed after dilatation. It is concluded that longterm treatment with sublingual nifedipine and pneumatic dilatation are equally effective in the treatment of oesophageal achalasia of mild or moderate degree.
-How do p53 gene mutations potentially contribute to the development of lymphoid leukemias?,"Mutations of the p53 gene in lymphoid leukemia. p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase-polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias."
-How did the use of energy-weighted acquisition affect the quantitative analysis of SPECT thallium-201 images?,"Changes in quantitative SPECT thallium-201 results associated with the use of energy-weighted acquisition. The effect of utilizing energy-weighted acquisition on quantitative analysis of SPECT thallium-201 images was evaluated by simultaneously acquiring energy-weighted and windowed projection images in ten patients. The paired image sets were processed identically and evaluated by probability analysis of defect magnitude as indicated by a commercially available software analysis package. It was predicted that defect magnitude would increase as a result of improved image contrast. This was confirmed experimentally. One should be cautious in relying on strict quantitative criteria in cardiac studies with thallium-201, especially when major changes in the imaging system or technique are introduced."
-"What clinical and laboratory features characterize the ""lymphoma syndrome"" in childhood acute lymphoblastic leukemia?","Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the ""lymphoma syndrome"" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL."
-How does chronic xerostomia affect esophageal acid exposure and potential injury?,"Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency."
-How do insulin and glucagon contribute to liver recovery and cell proliferation in rats with acute hepatic failure?,"Insulin and glucagon therapy of acute hepatic failure. When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst of DNA synthesis reaches a maximum earlier than that seen in controls. Both hormones enhance the increment of hepatic putrescine essential for DNA synthesis through activation of ornithine decaroxylase and/or spermidine-N1-acetyltransferase. The enhancement of putrescine content by each hormone is additive. Putrescine supplementation promotes hepatic DNA synthesis after hepatectomy. Based on these data, we conclude that a combination of insulin and glucagon is effective in the therapy of acute hepatic failure in rats. The restoration of liver function as well as the stimulation of liver cell proliferation via putrescine production may contribute to this effect."
-What are the four common final pathways involved in understanding different types of obesity according to the MONA LISA hypothesis?,"Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis. The mechanisms underlying different types of obesity have been gradually clarified. Animal models with hypothalamic, genetic or dietary obesity have been examined with a feedback model. Four common final pathways are involved in this model. One of these final common pathways is the sympathetic nervous system. Most Obesities kNown Are Low In Sympathetic Activity states the MONA LISA Hypothesis. A second common pathway is the endocrine system involving adrenal glucocorticosteroids. The third common pathway is hyperphagia. Although not essential for most obesities, hyperphagia may be essential in animals with injury to the hypothalamic paraventricular nucleus. The final pathway is reduced physical activity. The tonic activity of these systems and their response to changes in the diet affect nutrient partitioning between fat and protein. This framework has been used to review genetic obesity, hypothalamic obesity and dietary obesity."
-"What was the main finding of the double-blind, placebo-controlled trial investigating topical PUVA treatment for persistent palmoplantar pustulosis?","A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis. The effect of topical PUVA was investigated in the treatment of patients with persistent palmoplantar pustulosis (PPP). In this double-blind, placebo-controlled trial of 27 patients with PPP there was an overall improvement of the hands and feet in both the active and placebo-treated areas and little difference between them."
-What was the operative mortality rate and 1-year actual survival rate in the Oregon Liver Transplantation Program during its initial two years?,"Initial two-year results of the Oregon Liver Transplantation Program. During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B."
-How do glomerular hypertrophy and sclerosis contribute to the progression of kidney disease?,"Evidence for a pathogenic linkage between glomerular hypertrophy and sclerosis. Primary renal disease of immunologic or nonimmunologic mechanisms induces loss of substantial nephron population. It is presumed that the initial loss of functioning nephrons causes alterations of function and metabolism in remnant nephrons, which per se are self-inflictive, leading to further loss of nephrons. The ultimate outcome of this vicious cycle is the end-stage kidney. The potential role of various pathophysiologic mechanisms has been explored. These studies have shown a tight link between glomerular hypertrophy and sclerosis. Analysis of individual glomeruli show a biphasic pattern of these two parameters. Early development of glomerular sclerosis takes place along with the hypertrophy of the glomerulus, and further advancement of sclerosis occurs with shrinkage in glomerular size. Thus, we propose that, after initial nephron loss, the remnant glomeruli are exposed to increased growth-promoting factors, which are self-inflictive in nature due to their capacity to produce excessive amounts of extracellular matrix in the mesangial area. When the excessive matrix obliterates the glomerular capillary lumen, a typical sclerotic lesion appears. This is a vicious and accelerating process, since sclerosis induces further reduction in the nephron population, thereby imposing greater influence of growth-promoting factors even on glomeruli that are initially resistant."
-What is endorectal sonography and what diseases can it be used to evaluate?,"Endorectal sonography in the evaluation of rectal and perirectal disease. Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases."
-How can quantitative motor performance tests help in early detection of Parkinson's disease?,"Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are ""at risk for"" Parkinson's disease and other related disorders."
-What was the average number of previous operations per joint in the study of elbow replacements for post-traumatic arthritis?,"Total replacement for post-traumatic arthritis of the elbow. Fifty-three of 55 consecutive elbow replacements for post-traumatic arthritis were followed for a minimum of two years (mean 6.3, range 2 to 14.4). The patients presented difficult management problems, having undergone an average of two previous operations per joint; 22 joints had suffered prior complications; 18 had less than 50 degrees of flexion and six were flail. One of three versions of the Coonrad prosthesis was employed in all. During the follow-up period, 10 patients underwent 14 revision procedures for aseptic loosening; 38 elbows are currently without progressive radiolucent lines. In two patients an elbow had to be resected, one for deep infection and the other for bone resorption following a foreign-body reaction to titanium. The current design of the Coonrad prosthesis offers a reliable option for the treatment of post-traumatic arthritis but should be used only in carefully selected patients over the age of 60 years."
-What were the key findings regarding treatment approaches for aortic graft infection in this study?,"Total excision and extra-anatomic bypass for aortic graft infection. Reports of high mortality and amputation rates following total excision and extra-anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared."
-"What type of cancer did the 77-year-old male develop in his gastric remnant, and how long after his initial gastric resection was it discovered?","Primary squamous cell carcinoma of a gastric remnant. A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting."
-How has the introduction of gadolinium-enhanced magnetic resonance imaging (MRI) impacted the diagnosis and treatment of acoustic neuromas?,"Acoustic neuroma: a cost-effective approach. A cost-effective approach to the diagnosis and treatment of acoustic neuromas continues to evolve as diagnostic methods improve. In the past 7 months, since gadolinium-enhanced magnetic resonance imaging (MRI) has become available in our practice, our screening and presurgical workup has changed. The purpose of this article is to outline the current philosophy of the senior authors in relation to acoustic neuroma management on the basis of 72 patients diagnosed from July 1988 to February 1989. With more sensitive diagnostic means, older less sensitive studies may be eliminated from the routine workup, thus maintaining cost-effectiveness while preserving the highest standard of patient care. The body of this article will review our current use of the many available diagnostic options and emphasize a cost-effective approach."
-What were the 4-year actuarial survival rates for patients who underwent aortic valve replacement with Omniscience and Omnicarbon valves?,"Aortic valve replacement with omniscience and omnicarbon valves. Clinical results achieved in 100 cases of aortic valve replacement with the Omniscience (O-S) valve during the period from 1980 to 1985 as well as 100 cases of aortic valve replacement with the Omnicarbon (O-C) valve during the period from 1985 to 1989 were studied. Concomitant surgical procedures including mitral valve replacement were performed in 63 patients in the O-S group and 67 patients in the O-C group. Cumulative follow-up in the two groups was carried out for a total of 559 and 273 patient-years, respectively. The overall 4-year actuarial survival rate was 82% +/- 3.8% in the O-S group and 89.5% +/- 3.2% in the O-C group, the corresponding rates for patients undergoing isolated aortic valve replacement being 82.9% +/- 4.2% in the O-S group and 91.9% +/- 3.5% in the O-C group. The overall 4-year actuarial event-free rate with respect to thromboembolic complications was 88.8% +/- 3.3% in the O-S group and 94.4% +/- 2.8% in the O-C group, as compared with the corresponding rates of 89.2% +/- 3.6% in the O-S group and 95.9% +/- 2.8% in the O-C group for patients undergoing isolated aortic valve replacement. The overall rate of valve-related complications, including thromboembolism, anticoagulant-related hemorrhage, perivalvular leak, infection, and structural failure, was 78.8% +/- 4.2% in the O-S group and 89.3% +/- 3.5% in the O-C group (p less than 0.05), and for isolated aortic valve replacement, 79.7% +/- 4.5% in the O-S group and 89.6% +/- 4.1% in the O-C group."
-What modifications were made to the titanium Greenfield filter to improve its performance compared to the original stainless steel version?,"Results of a multicenter study of the modified hook-titanium Greenfield filter. Initial efforts to modify the stainless steel Greenfield filter for percutaneous insertion led to development of a titanium Greenfield filter, which could be inserted by use of a 12F carrier. This device functioned well as a filter but had an unacceptable 30% rate of migration, tilting, and penetration. Therefore a titanium Greenfield filter with modified hooks was developed and has been tested in 186 patients at 10 institutions. Successful placement occurred in 181 (97%); placement of the remainder was precluded by unfavorable anatomy. A contraindication to anticoagulation was the most frequent indication for insertion (75%). All but two were inserted percutaneously, predominantly via the right femoral vein (70%). Initial incomplete opening was seen in four patients (2%), which was corrected by guide wire manipulation and asymmetry of the legs in 10 (5.4%). Insertion site hematoma occurred in one patient, and apical penetration of the cava during insertion occurred in a second patient. Both events were without sequelae. Follow-up examinations were performed at 30 days at which time 35 deaths had occurred. Recurrent embolism was suspected in six patients (3%) and two of three deaths were confirmed by autopsy. Filter movement greater than 9 mm was seen in 13 patients, (11%) and increase in base diameter greater than or equal to 5 mm was seen in 17 patients (14%). CT scanning showed evidence of caval penetration in only one patient (0.8%). Insertion site venous thrombosis was seen in 4/46 (8.7%) patients screened. The modified hook titanium Greenfield filter is inserted percutaneously or operatively through a sheath, eliminating concern for misplacement from premature discharge."
-What serious medical complications can arise from the use of traditional tribal enemas containing harmful substances like potassium dichromate?,"Colonic complications after toxic tribal enemas. Tribal enemas obtained from traditional healers are used widely in Southern Africa for a variety of indications. Inclusion of injurious substances such as potassium dichromate may cause serious colonic and renal complications. Nine such patients, in seven of whom chromate use was confirmed, presented after a mean delay of 7.3 days. All patients had bloody diarrhoea and vomiting and three underwent major colonic resection, requiring a total of ten procedures. One patient suffered mechanical perforation of the rectum, with subsequent necrotizing fasciitis, necessitating rectal excision. Eight patients had acute renal failure and seven required dialysis. One patient died. At follow-up one patient has chronic renal failure and only three are completely well. Although local medical practitioners are aware of the problem, the challenge of preventing harmful cultural practices remains."
-What are the potential advantages and limitations of intradermal hepatitis B vaccination compared to traditional intramuscular vaccination?,"Intradermal hepatitis B vaccination. The availability of vaccine since 1982 for immunization against hepatitis B virus (HBV) has had minimal impact on the disease; mass immunization has been suggested. Intradermal vaccination, which has precedent in prophylaxis of other infectious diseases, has been investigated as a low-cost alternative to traditional intramuscular HBV vaccination. Results of open and comparative trials indicate similar seroconversion rates for intradermal and intramuscular HBV vaccination routes in healthy adults. However, antibody titers and, presumably, duration of antibody protection appear to be decreased with intradermal HBV vaccination. Limited data suggest that demographic factors such as age and gender may affect vaccine responsiveness to intradermal HBV vaccine. Adverse skin reactions are common but do not represent a deterrent to continued intradermal HBV vaccination. There is a need for large-scale prospective comparative trials to substantiate the value of intradermal HBV vaccination. Nevertheless, the potential economic and epidemiologic benefit of intradermal vaccination justifies continued investigation for prevention of HBV infection."
-What novel diagnostic approach did the authors describe for obtaining tissue samples from Meckel cave lesions?,"Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology. The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction."
-What was the main objective of the study on outpatient pain clinics?,"Audit of outpatients: entering the loop. OBJECTIVE--To develop and test a method for routine data collection to observe current practice in outpatient pain clinics. DESIGN--Prospective questionnaire survey completed by consultants on each patient seen during October 1989 to May 1990. SETTING--Outpatient pain clinics of five teaching and five district general hospitals in Scotland and northern England. MAIN OUTCOME MEASURES--Number of new referrals and their source, and characteristics of pain at presentation. RESULTS--4354 forms were completed by 21 consultants over 29 weeks, corresponding to 2241 patients, of whom 981 were new referrals. The proportion of consultations at which new referrals were seen varied among the 10 clinics from 15% to 34%. The difference could not be accounted for by type of hospital. Sources of new referrals varied widely between the clinics (for example, range 22% to 78% for general practitioner referrals), as did new referrals by the type of pain (range 10.8% to 55.2% for low back pain, 10.5% to 32.5% for pain associated with surgery). However, these differences in types of patients seen could not be accounted for by variations in referral patterns among clinics. Problems identified in performing an audit of outpatients included the difficulty of obtaining firm diagnoses, the need for a method to link successive patient contacts, and the complexity of the presenting problem in many patients. CONCLUSIONS--It is possible to collect data for audit routinely in outpatient clinics. Observation of current practice in the clinics suggested possible unmet need or inappropriate management, which may require changes in practice."
-What were the two techniques used for aortic valve reconstruction in this study?,"Indications and limitations of aortic valve reconstruction. To elucidate the value of conservative operation for aortic regurgitation, all consecutive patients operated on between July 1988 and July 1990 were reviewed. Of 251 patients with aortic regurgitation, 107 (42.6%) had nonprosthetic operation. The mean age was 23 years, and 90 patients (84.1%) were rheumatic. Two techniques were used: repair (annular and leaflet plasties, 69 cases) and cusp extension with glutaraldehyde-treated pericardium (25 bovine, 13 autologous). There were two hospital deaths (1.8%), both in the repair group, and no late deaths or embolic events. Only 5 patients (4.7%) were anticoagulated. In the repair group there were 12 reoperations, four (5.9%) due to aortic and eight to mitral dysfunction. In the cusp extension group there were two reoperations due to mitral dysfunction. Echocardiographic follow-up showed better results with cusp extension. In conclusion, conservative operation for aortic regurgitation is possible in a high percentage of young rheumatic patients and does not require anticoagulation. Cusp extension is more reliable than repair in terms of early results, although its long-term durability is not yet known."
-How does HIV infection impact cell-mediated immunity in patients with chronic D hepatitis?,"Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis. To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication."
-What are the key anatomical features of the infrahyoid portion of the neck that make it suitable for axial imaging and differential diagnosis?,"Differential diagnosis of head and neck lesions based on their space of origin. 2. The infrahyoid portion of the neck. The infrahyoid portion of the neck can be considered as a series of contiguous fascial planes and intervening spaces that lend themselves well to axial imaging. These spaces can serve as a basis on which to formulate differential diagnoses for diseases in this region. This pictorial essay describes the fascia and fascial spaces of the infrahyoid portion of the neck. The contents of each space, the common abnormalities affecting the space, and the characteristic displacements produced by disease in each space are reviewed."
-What were the independent predictors of mortality identified in the multivariate analysis of patients with congestive heart failure?,"Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically."
-What were the primary prognostic factors identified in this study of carcinoid tumours in the gastrointestinal tract?,"Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome. This study represents retrospective analysis of 87 patients with a carcinoid tumour of the gastrointestinal tract seen and followed in the British Columbia Cancer Agency (BCCA) from 1960 to 1986. In 49 cases, the primary site was the small bowel. The rest of the cases were distributed as follows: 11 appendix, 10 rectum, 5 stomach, and 7 undetermined. We extrapolated the Dukes' and modified Astler-Coller surgicopathological classifications used for colorectal cancer for use in our cases of carcinoid tumour of the gastrointestinal tract. A strong correlation was found, using this staging, with disease-specific survival. Other prognostic factors included histologic differentiation, the presence of macroscopic residual disease after initial surgery, and level of 5-hydroxyindoleacetic acid (5-HIAA) in urine. Among 51 patients with surgically grossly removed disease, there was a tendency for the development of distant and distant/locoregional recurrence more often than locoregional recurrence alone. The liver was the commonest site of distant recurrence. Analysis of the effect of radiotherapy or chemotherapy on carcinoid tumour of the gastrointestinal tract proved unsuccessful because only a small portion of the patients had this treatment, and it was used mainly for palliation."
-What are the key characteristics and management strategies for neurofibromatosis-2?,"Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described."
-What were the most common tumor types observed in the study of children treated for brain tumors?,"Growth hormone deficiency following radiation therapy of primary brain tumors in children. The medical records of 123 patients treated for brain tumors at Children's Hospital and Medical Center, Seattle, Washington, between 1985 and 1987 were reviewed. The endocrinological complications of radiation therapy and the effectiveness of growth hormone (GH) replacement therapy were assessed. These were the first 2 years after synthetic GH became available. The disease pathology was confirmed at craniotomy or biopsy in 108 patients. Ninety-five children completed radiation therapy and 65 of these were alive at the time of review; these 65 children represent the study population. The most common tumor types were medulloblastoma, craniopharyngioma, and ependymoma. Endocrine evaluation was initiated with changes in the patients' growth velocity. Patient workup included skeletal x-ray films for determination of bone and analysis of thyroxin, thyroid-stimulating hormone, and somatomedin-C levels. Following 1-dopa and clonidine stimulation, provocative studies of GH levels were performed. Growth hormone failure and short stature were observed in 26 children, most commonly in the 2nd year after tumor treatment. Eight patients with GH failure were also hypothyroid. Hormone replacement therapy was initiated with recombinant GH, 0.05 mg/kg/day, and all children so treated showed an increase in height, with eight patients experiencing catch-up growth. There were no complications of therapy or tumor recurrence. Studies of baseline bone age and somatomedin-C levels on completion of radiation therapy are recommended. Comprehensive endocrine studies should follow changes in the patients' growth velocity. With early GH replacement, catch-up growth is possible and normal adult heights may be achieved."
-What is the prevalence and characteristics of subarachnoid hemorrhage (SAH) in patients with sickle-cell disease based on the University of Illinois study?,"Subarachnoid hemorrhage in sickle-cell disease. The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed."
-What defines the abnormal B-cell population in peripheral blood from multiple myeloma patients?,"Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage."
-What was the most effective body-support system for preventing heel ulcers in bedridden patients according to the study?,"Preventing heel ulcers: a comparison of prophylactic body-support systems. Five commercially available body-support systems used in the prevention of decubitus heel ulcers were objectively compared for their capacity to dissipate or decrease pressure concentration at the most prominent posterior aspect of the heel in bedridden, insensate patients. The Foot Drop Stop, a foam heel suspender, completely eliminated contact between the heel and the bed, and it was the most successful in decreasing pressure concentration. The space boot and foam heel protectors were far more successful than sheepskin rugs or polyester heel protectors, which provided little protection to the prominent heel."
-What are the potential causes of unilateral hydrocephalus identified in this prenatal sonographic study?,"Unilateral hydrocephalus: prenatal sonographic diagnosis. We studied six cases of unilateral hydrocephalus detected prenatally to analyze the sonographic features of the abnormality and to determine the cause and clinical outcome. In all cases, third-trimester sonograms showed marked unilateral lateral ventriculomegaly (mean atrial width, 4.4 cm) and normal contralateral lateral, third, and fourth ventricles. Five of the six cases had marked thinning of the cortical mantle on the affected side and shift of midline structures to the contralateral side. The causes of unilateral hydrocephalus were agenesis or stenosis of the foramen of Monro in three cases, transient obstruction of the foramen in one fetus with an intraventricular hematoma, underlying brain dysplasia in one fetus with a variant of holoprosencephaly, and undetermined in one case. All six neonates had placement of a ventriculoperitoneal shunt catheter; four of these have had normal cognitive development at follow-up. The remaining two infants have moderate to severe developmental impairment. Unilateral hydrocephalus is a rare anomaly that can be recognized by prenatal sonography. Even though unilateral ventriculomegaly may be marked, early diagnosis and treatment may result in a favorable clinical outcome."
-What is ankle arthrodesis and when should it be considered as a treatment option?,"An overview of ankle arthrodesis. Arthrodesis of the ankle can result in a painless, normal walking gait. However, complications in ankle arthrodesis can be major, and can occur when anatomy, deformity, or bony deficiency is not properly addressed. Nonoperative treatment should always be considered first, and, if possible, an open or arthroscopic ankle debridement can provide significant pain relief. Arthrodesis should be considered after conservative treatment fails. Infections, deformity, sensory deficiencies, and bony defects require special consideration. The use of bone graft and internal or external compression will enhance the likelihood of a successful arthrodesis."
-What is a glandular odontogenic cyst and when was it first described?,"Glandular odontogenic cyst: clinicopathologic analysis of three cases. The glandular odontogenic cyst is a rare cyst of odontogenic origin, first described in 1988 by Gardner et al. Three previously unreported glandular odontogenic cysts are presented; none recurred after the initial surgical treatment, and one example was associated with a squamous odontogenic tumor-like proliferation in the wall. Ten similar cases were found in the literature, and their clinical and roentgenographic features, and follow-up, have been compared with the present cases."
-What are the different clinical categories of scleral inflammation and their progression based on the study?,"Progression of scleral disease. The clinical features of 290 patients with scleral inflammation were reviewed to determine whether a classification based on the anatomical site and clinical appearance of the disease at presentation reflected its natural history. The authors' results confirm that the majority of patients remain in the same clinical category throughout the course of their disease. Of the 104 (35.9%) patients who experienced a recurrence of their disease, only 12 had progressed from diffuse to nodular disease, and 10 patients who originally had nodular disease developed scleral necrosis. Patients with necrotizing scleritis were older than patients in the other groups and more frequently had an associated systemic disease than patients with either diffuse or nodular disease; necrotizing scleritis was the most difficult disease to treat. Diffuse anterior scleritis had a lower incidence of visual loss (9%) than either nodular scleritis (26%) or necrotizing disease (74%), and, therefore, the authors consider nodular scleritis a disease of intermediate severity between diffuse scleritis and necrotizing disease. In this series, 12% of patients presented with posterior scleritis, and visual loss was most frequent in this group (84%)."
-How does a prolonged difference in diastolic blood pressure affect the risks of stroke and coronary heart disease?,"Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease. The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both."
-How do soluble and diffusible gases like helium and nitrous oxide affect the size of air emboli in pulmonary arterioles?,"Effect of ventilation with soluble and diffusible gases on the size of air emboli. Pulmonary hypertension resulting from venous air embolism is known to increase after ventilation with highly soluble and diffusible gases. Exacerbation of the hypertension could be due to further blockage of the circulation if the bubbles enlarge as a result of ingress of gas by diffusion. This mechanism has been frequently cited but lacks direct proof. To determine directly whether intravascular air bubbles actually enlarge when highly soluble and diffusible gases are inspired, we used microscopy to measure the size of gas emboli in vivo. When air bubbles were injected into the right atrium, the bubbles that appeared in pulmonary arterioles were larger during ventilation with helium or nitrous oxide than with air. Air bubbles injected into the pulmonary artery enlarged when the inspired gas was changed to helium or nitrous oxide. The direction, magnitude, and timing of changes in bubble size were consistent with a net diffusion of gas into the bubbles. These data support the idea that venous air emboli enlarge during ventilation with soluble and diffusible gases and thereby cause further vascular obstruction."
-How do platelets contribute to the resistance of thrombi to lysis in unstable angina?,"Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants."
-What are the different types of viruses that can cause hepatitis?,"Viral hepatitis. The new ABC's. Hepatitis may be caused by hepatitis A virus, hepatitis B virus, hepatitis C virus (classic non-A non-B viral hepatitis), hepatitis D virus (delta agent), and hepatitis E virus (epidemic non-A non-B viral hepatitis). Cytomegalovirus, Epstein-Barr virus, and herpes simplex virus may also occasionally cause hepatitis. Some forms of hepatitis carry the risks of chronic infection, cirrhosis, or hepatocellular carcinoma. Treatment options for viral hepatitis are limited and, in many cases, still under investigation. Prophylaxis is available for many forms of hepatitis and should be offered to those at risk."
-How did antibiotic therapy affect vitamin B12 absorption in subjects with atrophic gastritis?,"Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria."
-What is telangiectatic osteosarcoma and how has its prognosis changed over time?,"Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy."
-What medical complications can arise from large vessel occlusion in patients with systemic lupus erythematosus (SLE)?,"Large vessel occlusion with vasculitis in systemic lupus erythematosus. Patients with SLE may have acute large vessel occlusion due to vasculitis and/or circulating antiphospholipid antibodies, as illustrated by the case we have reported. Unfortunately, delayed medical attention led to gangrene of the foot and amputation. Early recognition and appropriate treatment may significantly decrease morbidity and mortality. Medical treatment may include corticosteroids, thrombolysis, anticoagulation, or immunosuppression."
-What are the key hemodynamic effects of ACE inhibitors in treating hypertension?,"Angiotensin converting enzyme inhibitors. Present and future. The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the ""more local"" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents."
-How does the Valsalva maneuver help in detecting left ventricular diastolic function abnormalities in patients with coronary artery disease or systemic hypertension?,"Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension. It has been suggested that changes in left atrial pressure may mask or mimic left ventricular diastolic function abnormalities detected by Doppler echocardiography. The effect of the Valsalva maneuver on the transmitral flow velocity profile was therefore studied in 28 patients without evidence of coronary artery disease (group 1, mean age +/- standard deviation 50 +/- 8 years) and in 94 patients with evidence of coronary artery disease or systemic hypertension (group 2, mean age 54 +/- 10 years). At baseline, group 2 patients had higher peak late diastolic filling velocity (A), lower peak early (E) to late diastolic filling velocity (E/A) ratio and longer isovolumic relaxation time than group 1, whereas heart rate, E velocity and E deceleration time were similar in both groups. During Valsalva, both groups had similar increases in heart rate and similar decreases in E velocity but E/A ratio decreased significantly only in group 2 because of a lesser decrease in A velocity. The E/A ratio was greater than or equal to 1.0 both before and during Valsalva in all but 1 patient in group 1, whereas in group 2, 32 patients had E/A greater than or equal to 1.0 at rest and during Valsalva, 33 patients had E/A greater than or equal to 1.0 at rest but less than 1.0 both at rest and during Valsalva. Using group 1 as controls, prevalence, specificity and positive predictive value of E/A less than 1.0 in group 2 were 31, 100 and 100% at rest and 66, 96 and 98% during Valsalva."
-How does the lipid membrane composition differ in the cerebral tissue of Rett syndrome patients compared to age-matched controls?,"Membrane cerebral lipids in Rett syndrome. The lipid membrane composition of cerebral tissue from 5 patients with classic Rett syndrome, ages 12-30 years, and from 14 age-matched controls was studied. The results demonstrated a selective loss of myelin-associated lipids and an enrichment of gangliosides in temporal white matter. The ganglioside pattern revealed an increase of astroglial cell-associated gangliosides and reduced proportions of gangliosides GD1a and GT1b. This latter finding may be crucial in synaptic function. The fatty acid compositions of ethanolamine phosphoglyceride, choline phosphoglyceride, and galactosylceramide were normal."
-How does inspiratory muscle fatigue affect subsequent high-intensity exercise performance?,"Effect of respiratory muscle fatigue on subsequent exercise performance. The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled to volitional exhaustion at 90% of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise."
-Does temporary occlusion of hypogastric arteries reduce blood loss during radical retropubic prostatectomy?,"Effect of temporary occlusion of hypogastric arteries on blood loss during radical retropubic prostatectomy. We report on a prospective, partially randomized study of 130 patients, examining the effect of temporary occlusion of the hypogastric arteries on intraoperative blood loss, perioperative blood replacement and change in preoperative to postoperative hematocrit. We observed no significant difference in any of these parameters when comparing patients who did and did not undergo intraoperative occlusion of the hypogastric arteries. These findings suggest that temporary occlusion of the hypogastric arteries during radical prostatectomy does not have a major effect on the blood loss associated with this operation. Extensive collateral circulation to the prostate and a substantial venous component of blood loss may explain these findings. Banking of 3 units of autologous blood preoperatively would have decreased the need for homologous transfusions in the majority of patients."
-What cross-resistance patterns were observed in the ACNU-resistant glioma sublines?,"Cross-resistance patterns in ACNU-resistant glioma sublines in culture. Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance."
-What are the key differences in management and recurrence rates between suprahyoid and infrahyoid cystic hygromas?,"Cervicofacial cystic hygroma. Patterns of recurrence and management of the difficult case. Cystic hygromas usually present in infancy or early childhood as compressible masses that may rapidly and intermittently enlarge. While they may arise in any anatomic location, hygromas of the head and neck are especially difficult to manage since enlargement may cause serious sequela such as airway obstruction, feeding difficulties, and speech pathology. Complete extirpation of these lesions is often impossible, and recurrence rates are accordingly high. We reviewed our 10-year experience in treating cervicofacial cystic hygromas. Of 34 patients, 21 had lesions cephalad to the hyoid and 13 had lesions caudal to the hyoid. While none of the 13 children with infrahyoid lesions demonstrated feeding or respiratory difficulties, eight of 21 children with suprahyoid involvement presented with dysphagia or airway compromise. The recurrence rates for infrahyoid and suprahyoid lesions were 15% and 81%, respectively. Those children with suprahyoid hygromas also experienced an increased operative complication rate compared with patients with infrahyoid involvement. Principles of management for suprahyoid and infrahyoid lesions are described, including the specific management of lingual, submandibular, parotid, and parotofacial hygromas."
-What is the primary goal of studying the mechanisms behind essential hypertension?,"Can essential hypertension be subclassified with respect to mechanism? Hypertension may result from a variety of abnormalities. The rise in blood pressure may trigger other secondary events that further influence cardiovascular homeostasis. The ability to measure some markers associated with hypertension or the responsiveness of blood pressure to nutritional interventions or to specific therapeutic agents may also have pathogenetic implications. The ultimate goal of further knowledge in this area should be to understand the fundamental abnormalities responsible for hypertension. Such insight would permit more effective treatment and, perhaps, primary prevention of this ubiquitous and multifaceted disorder."
-What was the primary objective of the study on imazodan for treating chronic congestive heart failure?,"Effectiveness of imazodan for treatment of chronic congestive heart failure. The Imazodan Research Group. A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo."
-What is the median weartime for the optimum anal continence plug design in the study?,"The anal continence plug: a disposable device for patients with anorectal incontinence. Anorectal incontinence is most commonly found in the elderly, but colorectal surgeons now see an increasing number of younger patients with this condition. Although medical and surgical treatments are available, a proportion of patients remain refractory to therapy. We investigated the efficacy of three designs of anal continence plug. 8 women and 2 men (mean age, 52 years) who were incontinent to both liquid and solid stool tested each plug for three consecutive weeks. 1 patients withdrew from the study. The median weartime for the optimum plug design was 12 h, and there were no episodes of incontinence in 82% of the periods during which the plug was in place. Patients required a median of eleven plugs per week, and in 82% of cases insertion was as easy as with a suppository. Plugs may have a place in the management of patients with anorectal incontinence."
-What were the survival rates for different stages of cervical cancer when treated with californium-252 neutron brachytherapy?,"A review of californium-252 neutron brachytherapy for cervical cancer. Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals."
-What were the key findings of the study comparing polyamide and polypropylene membranes for plasma separation?,Comparison of polyamide and polypropylene membranes for plasma separation. Plasma separation experiments were made with polyamide experimental prototype hollow-fiber plasma filters with surface areas between 0.025 m2 and 0.1090 m2 using bovine blood collected in acid citrate dextrose (ACD). The maximum filtration velocity rose with the wall shear rate gamma w as gamma w 0.72 +/- 0.02 and decreased with the length of fiber L as L-0.41 with a correlation coefficient of 0.97 +/- 0.02. The results were similar to those with polypropylene fibers. We also investigated the occurrence of hemolysis as a function of shear rate and transmembrane pressure. The free hemoglobin concentration of filtered plasma was checked using a U.V. spectrophotometer. It was concluded that polyamide membrane filters can be safely used for plasma separation from blood.
-How does chemotherapy affect natural killer (NK) cell activity in breast cancer patients?,"The relationship of chemotherapeutic and endocrine intervention on natural killer cell activity in human breast cancer. Peripheral blood natural killer (NK) activity against K562 target tumor cells was monitored in patients with breast cancer receiving no treatment, combination chemotherapy, and/or endocrine therapy. NK activity in untreated Stage I patients with no evidence of disease (ned) was significantly higher than in healthy controls. NK activity was shown to decline in individuals with cytotoxic drug therapy (P equals 0.036). There also were reduction in lymphocyte recoveries concomitant with chemotherapeutic intervention (P less than 0.001). Lymphocyte counts were incorporated in a calculation of absolute NK activity that more accurately reflected the significant reduction in NK activity that occurred in patients with localized and systemic disease on chemotherapy. Different chemotherapeutic agents were found to selectively affect NK activity. Stage II patients on phenylalanine mustard (P)/5-fluorouracil (F) (PF) and cyclophosphamide (C)/methotrexate (M)/5-fluorouracil (F) (CMF) protocols showed significant reductions in overall NK activity relative to healthy controls and Stage I patients with ned. Patients on P/doxorubicin (A)/F/tamoxifen (Tx) (PAFT) protocols showed reduced NK activity relative to Stage I patients. Patients on the short-dose C/A (CA) protocol showed normal levels of overall NK activity. High-risk Stage I patients on methotrexate (M)/F (MF)with sequential leucovorin rescue and patients with metastatic disease on endocrine therapy, i.e., Tx or megestrol acetate (Meg) showed overall NK activities in the range of healthy controls. Patients with systemic disease on CMF, CMF/vincristine/prednisone (CMFVP), vinblastine/A/thiotepa/fluoxymesterone (VATH), mitomycin/mitoxantrone (MtMx), and A regimens showed overall levels of absolute NK that were significantly less than either healthy controls or metastatic patients undergoing endocrine therapy. NK cytolytic data, monitored at multiple effector to target ratios, were subjected to exponential regression analysis. The elevation of NK cell responses in Stage I patients with ned and the decline of NK cell responses with cytotoxic chemotherapy were due to alterations in the maximal plateau levels of NK cell cytotoxicity represented by the A (asymptote) values. The k values obtained on regression analysis and indices of the relative killing capacities of individual NK cells remained unaltered in all populations. These results suggest that the cytolytic lymphocyte NK pool, elevated in Stage I patients with cancer, selectively declines as a result of cytotoxic therapy."
-How does the atrial natriuretic factor (ANF) hormonal system contribute to sodium excretion in dogs with experimental heart failure?,"The atrial natriuretic factor hormonal system in the regulation of sodium excretion in dogs with experimental heart failure. In response to a meat meal containing 125 mEq of sodium, conscious dogs (n = 5) with an arteriovenous (AV) fistula and chronic compensated heart failure exhibited temporally related increases in postprandial plasma immunoreactive atrial natriuretic factor (iANF), right atrial pressure, and sodium excretion. In separate experiments, two weeks of dietary sodium restriction produced similar marked stimulation of renin and aldosterone both in normal dogs (n = 5), and in AV fistula dogs (n = 5) with chronic high circulating levels of ANF. Plasma iANF did not change (P greater than .05) in either group. These results suggest that the ANF system is involved in the postprandial regulation of sodium excretion in the AV fistula dogs with compensated heart failure. In the postabsorptive state, however, the activity of the renin-aldosterone axis is closely related to dietary sodium intake and appears to function independently of the ANF system for the prevention of sodium loss."
-What are the key histologic and clinical characteristics of malignant blue nevus based on the analysis of 12 cases?,"Malignant blue nevus. To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm."
-What paraneoplastic syndrome was observed in the patient with pheochromocytoma and how was it potentially related to interleukin-6?,"Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production. Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome."
-What was the average cost of averting death or severe disability through neurosurgical intervention in this study?,"Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community."
-How was HLA class I antigen expression evaluated in patients with chronic hepatitis B?,"HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy."
-What factors were found to potentially delay malaria diagnosis in this urban emergency department study?,"Malaria in an urban emergency department: epidemiology and diagnostic features of 25 cases. This article presents a retrospective study of 25 patients diagnosed with malaria in an urban emergency department (ED) between June 1986 and June 1989. The mean annual case rate of malaria in this study group was more than three times the national rate. This may be ascribed to the notable ethnic diversity of the population. A history of travel to an area endemic for malaria was eventually elicited from all patients. The most common chief complaint was fever (56%) followed by abdominal pain (12%). Temperatures were elevated in 70% of the patients, with a mean temperature of 102.9 degrees F (39 degrees C). Gender was found to play a role in delaying diagnosis, with women accounting for 83% of a group of patients requiring multiple ED visits before diagnosis. The authors conclude that malaria must be considered when diagnosing patients in ethnically diverse populations. Gender may be associated with a delay in diagnosis. A careful travel history and a peripheral smear are aids in rapid diagnosis."
-What did the study reveal about interferon-alpha production in acute versus chronic hepatitis B virus infection?,"Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection. In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus."
-What factors were associated with the embolization of the prosthetic aortic valve in the young woman described in this case report?,"Death by embolization of prosthetic aortic valve. This report describes a case in which a young woman died from embolization of her prosthetic aortic valve. The discussion includes the embolization's association with chronic intravenous narcotism, recurrent bacterial endocarditis, and acute cocaine toxicity."
-What makes flunarizine unique among calcium antagonists in terms of its effects on the brain?,"Flunarizine in migraine: a minireview. Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena."
-What was the primary purpose of this study comparing ondansetron and metoclopramide?,"A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy."
-What was the outcome of thrombolytic therapy in patients with unstable angina in this study?,"Thrombosis and thrombolysis in unstable angina. Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures."
-"What is the relationship between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension?","Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system. An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based."
-What was the primary diagnostic challenge in identifying the cause of neurological deterioration in this 1-year-old male infant?,"Intracranial arteriovenous fistula manifesting as progressive neurological deterioration in an infant: case report. This 1-year-old male infant had been diagnosed with cerebral degenerative disease because he developed psychomotor regression, and brain atrophy was demonstrated on computed tomography. He underwent magnetic resonance imaging, which suggested a cerebrovascular malformation. Cerebral angiography disclosed an arteriovenous fistula, fed by an anterior cerebral artery and directly draining into a cortical vein. The occlusion of the feeding artery was followed by a satisfactory recovery. The mechanism of the neurological symptoms in this patient is thought to be caused by a steal phenomenon and compression of the brain stem by venous engorgement in the posterior fossa."
-What was the main finding of the study regarding low power laser biostimulation for chronic oro-facial pain?,Low power laser biostimulation of chronic oro-facial pain. A double-blind placebo controlled cross-over study in 40 patients. The efficacy of low power laser stimulation in the treatment of chronic oro-facial pain conditions was investigated in a double-blind placebo controlled modified cross-over study in 40 patients. The laser was an invisible infrared (IR) diode laser with an emission at 904 nanometer (nm). Treatment effect was evaluated by means of VAS-scales and global assessment of pain. Outcome of treatment was correlated to changes in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). The clinical impression was that placebo was superior to laser stimulation. No statistically significant difference between the analgesic effect of the laser and placebo irradiation was found on VAS-scales. A significant (P = 0.05) increase in 5-HIAA excretion was found in the placebo group. It is concluded that the possibility of a substantial placebo response should be taken into consideration using 904 nm (IR) lasers for pain treatment in patients with this type of chronic oro-facial pain.
-What was the frequency of dysplasia or cancer found in this colonoscopic screening of ulcerative colitis patients with more than 15 years of disease duration?,"Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question."
-What types of melanocytic nevi in children and adolescents may indicate an increased risk of malignant melanoma?,"Important melanocytic lesions in childhood and adolescence. Melanocytic nevi are common in children and adolescents, and the preponderance of these lesions are benign. Congenital melanocytic nevi, dysplastic nevi, and large numbers of common acquired nevi, however, may indicate an increased risk of malignant melanoma. With the exception, possibly, of giant congenital nevi, melanoma associated with these lesions generally occurs in adulthood. Nonetheless, some patients can be identified as being at increased risk for the development of melanoma during childhood. The poor prognosis associated with advanced melanoma and the curability of early lesions underscore the importance of prompt recognition of melanoma when it does occur in children. Furthermore, physicians who care for children are in a key position to decrease risk of melanoma throughout the lifespan by encouraging avoidance of excessive sun exposure during childhood."
-What was the dosage and administration method of metoclopramide used in this study for treating gastroparesis?,"Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. We investigated the safety and efficacy of short-term s.c. administration of metoclopramide in the treatment of symptomatic gastric stasis. Ten patients with gastroparesis, documented by abnormal solid phase radionuclide gastric emptying study, were treated with 10 mg (2 ml) of s.c. metoclopramide every 6 hr for 3 days. Patients gave themselves the injections as outpatients. Questionnaires were then completed concerning symptom relief, local side effects and adverse reactions. A repeat gastric emptying study was obtained immediately after the last dose of metoclopramide. Serum metoclopramide concentrations were obtained at trough, 1, 2, 3, 4 and 5 hr postadministration and serum prolactin levels at trough, 1 and 3 hr. Pharmacokinetic analysis showed mean peak metoclopramide concentration at 30 min of 99.7 +/- 47.1 ng/ml with measured levels of 93.9 +/- 106.83 ng/ml at 60 min and return to trough values by 4 hr; trough prolactins remained elevated above normal values. Gastric stasis improved from a base-line retention of 78.7% of radioisotope at 2 hr to 72.5% after 3 days of therapy (P = .65). Eight patients reported significant improvement in symptomology and two patients reported lessening of symptoms such as nausea, vomiting, bloating, abdominal pain, heartburn and vomiting. The side effects were minimal and did not interfere with completion of the protocol. We demonstrated that s.c. administration of metoclopramide was well accepted by patients and resulted in subjective and objective improvement of gastric stasis. In addition, serum metoclopramide concentrations were comparable with other parenteral routes of administration. Furthermore, serum prolactin levels may provide both a bioassay of efficacy and a marker for monitoring compliance."
-"How does 1,25-dihydroxyvitamin D3 affect the interferon-gamma-induced expression of MHC class II antigens on HEp-2 cells?","Differential enhancement of interferon-gamma-induced MHC class II expression of HEp-2 cells by 1,25-dihydroxyvitamin D3. Interferon-gamma (IFN-gamma) induces the expression of MHC class II antigens on non-lymphoid cells. In this study we investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the most active metabolite of vitamin D3, on the IFN-gamma-induced expression of MHC class II antigens on HEp-2 cells. We found that 1,25(OH)2D3 enhanced the IFN-gamma-induced expression of HLA-DR on these cells. Differential effects on the MHC class II antigens HLA-DR, -DQ and -DP were also observed."
-What were the most common late complications following abdominal aortic operation in this study?,"Reoperations for late complications following abdominal aortic operation. Fifty patients were identified who, following abdominal aortic operation, developed late complications affecting the vascular graft or endarterectomy and who underwent their first reoperation between 1979 and 1989. Thrombosis was the commonest complication affecting 28 (56 per cent) patients, followed by false aneurysm in 11 (22 per cent), enteric fistula in nine (18 per cent) and graft infection in two (4 per cent). The 30-day mortality rate for reoperation was 8 per cent; longer follow-up revealed mortality rates of 22, 50 and 63 per cent at 1, 3 and 5 years respectively. Thirty-four complications required reoperation within 5 years of the original surgery. Reoperation was needed for 35 patients whose original pathology was occlusive disease and for 15 whose original pathology was aneurysm. The nature of the complication was related to initial pathology; thrombosis was far commoner in those with occlusive disease, and enteric fistula and false aneurysm were commoner in those with aneurysmal disease."
-What was the cumulative percentage of patients free of arrhythmia after serial drug treatment in this study?,"Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events."
-How does the p53 gene mutation correlate with the progression of chronic myelocytic leukemia (CML) in this patient's case study?,Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
-What percentage of radiologic modalities showed inaccuracies in assessing lumbar spine fusions in this study?,"Correlation of radiologic assessment of lumbar spine fusions with surgical exploration. Although inspection of posterolateral lumbar fusion is the best method of determining its solidity, routine exploration of the fusion is somewhat impractical because of the morbidity and expense involved. Removal of internal fixation devices or implantable batteries or reoperation for failed back surgery enabled the exploration and assessment of lumbar spine fusions in 214 operations on 175 patients. The preoperative radiologic assessment (plain roentgenographs, polytomography, bending films, and computed tomographic scans) were correlated with surgical findings. This study indicated a significant percentage of inaccuracy of all radiologic modalities used. Noncorrelations were present in 36% of plain roentgenographs, 41% of polytomograms, 38% of bending films, and 43% of computed tomographic scans. Radiologic inaccuracy was manifest on both the positive and negative sides. Computed tomographic scanning presented the lowest percentage of inaccuracy (22%) and bending films the highest percentage (27%). Based on these findings, there exists the need for more accurate noninvasive methods to determine the solidity of spine fusions."
-What are the typical clinical features associated with cervicocranial arterial dissection?,"Cervicocranial arterial dissection. Dissection of the cervicocranial arteries is becoming more frequently recognized as a cause of neurological disorders. Typical clinical features seen with dissection include unilateral headache, oculosympathetic palsy, amaurosis fugax, and symptoms of focal brain ischemia. The diagnosis of carotid or intracranial dissection is usually best confirmed by angiography, although magnetic resonance imaging and computed tomography have been shown to visualize intimal dissection. The prognosis in cases of spontaneous dissection is generally benign unless the initial manifestation involves infarction with substantial deficit. The best approach to treatment appears to be the administration of the anticoagulant, heparin, followed by warfarin or antiplatelet therapy. Surgical intervention is reserved for cases of progressive or recurrent ischemic complication that occurs despite the administration of adequate doses of anticoagulants."
-What factors were significantly associated with an increased risk of cholelithiasis in childhood cancer patients after treatment?,"Cholelithiasis after treatment for childhood cancer. The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones."
-What were the key findings of the comparison between digital examination and anal endosonography in evaluating anal fistulae?,"Comparison between anal endosonography and digital examination in the evaluation of anal fistulae. A prospective trial was performed comparing the accuracy of digital examination and anal endosonography in defining the anatomy of anal fistulae. Before operation 38 consecutive patients were assessed by the consultant in charge of the case, by a research fellow and by anal endosonography involving two radiologists. These findings were compared with the operative findings. Consultants correctly identified 26 of 33 internal openings, 29 of 34 primary tracks and 15 of 21 secondary tracks. The research fellow correctly identified 26 internal openings, 24 primary tracks and 10 secondary tracks. There was no significant difference between the accuracy of consultants and the research fellow. Anal endosonography identified 10 internal openings based on initial criteria. This rose to 24 when revised ultrasonographic criteria were applied. There was no statistical difference between consultant assessment and anal ultrasonography in correctly identifying intersphincteric and transphincteric tracks. Ultrasonography is unable to assess primary superficial, suprasphincteric and extrasphincteric tracks or secondary supralevator and infralevator tracks. Consultant assessment of secondary supralevator and infralevator tracks was correct in 78 per cent of cases."
-What was the aim of the study in developing a test for gastric emptying and small bowel transit?,"Towards a less costly but accurate test of gastric emptying and small bowel transit. Our aim is to develop a less costly but accurate test of stomach emptying and small bowel transit by utilizing selected scintigraphic observations 1-6 hr after ingestion of a radiolabeled solid meal. These selected data were compared with more detailed analyses that require multiple scans and labor-intensive technical support. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected summaries of scintigraphic transit measurements. We studied 14 patients with motility disorders (eight neuropathic and six myopathic, confirmed by standard gastrointestinal manometry) and 37 healthy subjects. The patient group had abnormal gastric emptying (GE) and small bowel transit time (SBTT). The proportion of radiolabel retained in the stomach from 2 to 4 hr (GE 2 hr, GE 3 hr, GE 4 hr), as well as the proportion filling the colon at 4 and 6 hr (CF 4 hr, CF 6 hr) were individually able to differentiate health from disease (P less than 0.05 for each). From the logistic discriminant model, an estimated sensitivity of 93% resulted in similar specificities for detailed and selected transit parameters for gastric emptying (range: 62-70%). Similarly, combining selected observations, such as GE 4 hr with CF 6 hr, had a specificity of 76%, which was similar to the specificity of combinations of more detailed analyses. Based on the present studies and future confirmation in a larger number of patients, including those with less severe motility disorders, the 2-, 4-, and 6-hr scans with quantitation of proportions of counts in stomach and colon should provide a useful, relatively inexpensive strategy to identify and monitor motility disorders in clinical and epidemiologic studies."
-What was the 10- and 15-year actuarial survival rate for medulloblastoma patients in this study?,"Medulloblastoma: freedom from relapse longer than 8 years--a therapeutic cure? Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (greater than or equal to 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately."
-What was the treatment regimen used for patients with locally advanced paranasal sinus and nasopharynx tumors in this study?,"Locally advanced paranasal sinus and nasopharynx tumors treated with hyperfractionated radiation and concomitant infusion cisplatin. Fourteen patients with paranasal sinus complex and nasopharynx tumors were treated at State University of New York Health Science Center at Brooklyn (Brooklyn, NY) with a regimen of split-course hyperfractionated radiation (120 cGy/fraction) and concomitant cisplatin infusion (5 to 7 mg/m2/24 hours). All of the patients had T4 tumors or massively recurrent disease with base of skull or facial bone involvement. Twelve patients were treated with curative intent receiving total doses of 6000 to 6960 cGy (modal 6750 cGy), whereas two patients were treated with less than 5000 cGy as palliation. Eleven of the 12 patients (92%) achieved a complete response, and 7 of 12 (58%) are alive at 35 to 72 months (mean, 47 months). Five patients are alive with no evidence of disease, and two with a local recurrence. Three patients died of distant disease, and two died from a local recurrence. When the response to treatment was analyzed based on tumor volume and radiation dose, only two of nine lesions measuring between 4 to 10 cm failed locally. The two palliative patients had almost complete local clearance of the disease but died at 2 and 8 months, respectively. In nine patients, the eye or optic nerve was included in the treatment field and received between 2000 to 6960 cGy. Only one of these nine patients had ophthalmic complication and this was confined to the cornea."
-How does iloprost affect microvascular permeability in skeletal muscle after ischemia and reperfusion?,"Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion. Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified."
-How might exercise training potentially influence coronary collateral circulation?,"Exercise training and coronary collateral circulation. This review examines the potential for an exercise-induced increase in coronary collateral circulation, with specific reference to the role and functional significance of collateral vessels, highlighting animal and human studies in particular, and their inherent methodological limitations. Exercise training may enhance myocardial oxygen supply by promoting transient periods of myocardial ischemia, a potent trigger of collateral growth. Some human studies have shown that moderate-to-high intensity training can result in a higher double product at the onset of angina and/or ischemic ST-segment depression, suggesting that myocardial oxygen supply has increased. Attempts to use thallium-201 exercise scintigraphy to assess myocardial perfusion before and after a physical training program have produced conflicting data, whereas angiographic studies in group trials have, without exception, yielded disappointing results. Thus, direct evidence that exercise stimulates collateralization in humans is lacking."
-What percentage of bladder tumors showed positive signals for HPV type 16/18 DNA in this study?,"Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation. The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain."
-What is the significance of monosomy 7 in the reported case of erythroleukemia?,"Erythroleukemia in a child associated with monosomy 7. A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm."
-What rare condition can cause hypertension with increased renin concentrations in infants?,"Hypertension associated with increased renin concentrations in nephroblastoma. An infant with severe hypertension who had a nephroblastoma which was secreting active renin is described. Nephroblastoma must be included in the differential diagnosis of hypertension associated with increased renin concentrations, even in the absence of an abdominal mass."
-How do the hemodynamic effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) differ in experimental heart failure?,"Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure. S-nitrosothiols are potent in vitro vasodilators, but little is known about their in vivo action. In this study, we compared the effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) on left ventricular (LV) hemodynamics in congestive heart failure rats. By using a twoday crossover design, stepwise i.v. infusions of SNAP or NTG at 3, 5 and 8 micrograms/min were administered for 30 min each, followed by a dose of 10 micrograms/min over the next 10 h. LV end-diastolic and peak-systolic pressures (LVEDP and LVPSP, respectively) were measured at selected intervals. SNAP and NTG produced maximal LVEDP reductions of 46 and 44%, respectively, at the highest infusion rate. However, at the lower doses, greater reductions of LVEDP were seen with SNAP. NTG had a smaller effect on LVPSP (maximum 6% reduction) than SNAP (maximum reduction of 15%). During the 10-h infusion of NTG, LVEDP gradually returned to base-line values, indicating the development of tolerance, despite relatively constant plasma levels of NTG over the infusion period. Tolerance in LVEDP effects was not observed during the 10-h infusion of SNAP. In the presence of NTG tolerance, rats were still responsive to SNAP (mean reduction of LVEDP 24%), suggesting the absence of cross-tolerance between these two nitrovasodilators. These results suggest that SNAP is a more potent in vivo vasodilator than NTG, has more arterial action than NTG and is less prone to produce LV hemodynamic tolerance."
-What is the main focus of the case reports discussed in the context?,"Pattern of arterial involvement of the head, neck, and eyes in giant cell arteritis: three case reports. The findings of two post-mortem examinations and one CT scan of patients with biopsy proved giant cell arteritis (GCA) are presented. The presence or absence of intracranial involvement in GCA is discussed."
-What are coronary artery aneurysms and how are they typically detected?,"Coronary artery aneurysms--a case study and literature review. Coronary artery aneurysms are detected with increasing frequency owing to the advent of coronary angiographies. Although most patients with coronary artery aneurysms are asymptomatic, manifestations of myocardial ischemia may occur. The case described herein serves as a basis for a discussion of the pathogenesis, clinical manifestations, detection, and treatment of coronary artery aneurysms."
-What ethical considerations do physicians face when deciding whether to treat hypercalcemia in patients with advanced malignancy?,"Hypercalcemia of advanced malignancy: decision making and the quality of death. Hypercalcemia is a common complication of certain advanced malignancies and although not therapeutically difficult, its presence raises complex ethical issues. Treatment of this condition is most easily justified when the patient is not terminal, the benefits are tangible, and the patient agrees with therapy. Withholding treatment is defensible medically, legally, and morally when a terminal situation is present, when drawbacks exceed the benefits, and when an informed patient declines therapy. Hypercalcemia is one of a number of conditions of dying that can be controlled by the physician. The physician's decision to treat such a condition, in part, depends upon his or her view of a good death. Further study is needed to clarify and avoid those situations of dying which involve suffering. Physicians must begin this difficult analysis and dialogue if they are to fulfill their obligation to minimize suffering in all patients."
-What evidence suggests that interferon-alpha therapy can cause persistent neurotoxicity in cancer patients?,"Persistent neurotoxicity of systemically administered interferon-alpha. Fourteen cancer patients had evidence of persistent neurotoxicity of interferon-alpha therapy long after their treatment was discontinued. Although most of the cognitive symptoms were mild to moderate in severity, they were incapacitating to these individuals in their usual work. The neuropsychological test abnormalities were not attributable to subsequent therapy, disease status, or other medical problems. The pattern of deficits was consistent with frontal-subcortical dysfunction. Of the four patients who had follow-up assessment, two had improved and two had deteriorated. These findings suggest that in some cases interferon neurotoxicity is not reversible."
-What surgical procedure is described for treating lateral nasal wall neoplasms and what are its key characteristics?,"'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and ""medial maxillectomy,"" an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora."
-What was the overall prevalence of dementia in individuals 65 years and older in the East Baltimore Mental Health Survey?,"Dementia: case ascertainment in a community survey. The three-stage East Baltimore Mental Health Survey, conducted in 1981 as part of the Epidemiological Catchment Area Program, provided an opportunity to assess the prevalence of dementia and specific dementing disorders in a community-based, cross-sectional sample of the population. From the 3,841 households originally sampled, 810 individuals were selected for clinical psychiatric evaluation. Forty-one individuals were given a provisional diagnosis and referred to Stage 3 for differential diagnosis, with 32 individuals completing this evaluation. Thorough clinical evaluation of these cases resulted in an overall prevalence of dementia of 4.5% in those 65 years of age and older. The prevalence of specific dementing disorders was Alzheimer's disease (AD) (2.0%), Multi-Infarct Dementia (MID) (2.0%) and Mixed Dementia (MD) (0.5%). Prevalence increased with age for all dementias: Non-Whites had higher rates of dementia than Whites; females had higher rates of AD while males had higher rates of MID; and the prevalence of AD increased with increasing education, whereas the prevalence of MID decreased with increased education. Although this study includes only a small number of cases, necessitating some caution in interpreting the results, these figures do represent an estimate of the prevalence of severe dementing disorders and provide a basis for further community study."
-What is the key histological finding in the papular mucinosis associated with L-tryptophan-induced eosinophilia-myalgia syndrome?,"Papular mucinosis in L-tryptophan-induced eosinophilia-myalgia syndrome. Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses."
-What is fludarabine and in which types of leukemia has it shown potential effectiveness?,"Fludarabine: a review. The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels."
-What were the outcomes of endovascular treatment for brain arteriovenous malformations in this study?,"Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases. The authors report the results of treatment in 49 consecutive patients with brain arteriovenous malformations (AVM's) who underwent therapeutic embolization with liquid adhesive agents between 1984 and 1988 at the Toronto Western Hospital. Thirty-three patients had no other treatment and were followed up with angiography at 2 years and clinically from 2 to 6 years. Of the other 16 patients, 10 had adjunctive radiosurgery and six underwent surgical resection following embolization. Seven (14%) of the 49 patients had a morphological cure effected by embolization as evidenced on their 2-year follow-up angiograms: these have remained clinically stable. Twelve patients developed neurological deficits after embolization; eight (16% of the series) were transient and four (8%) were permanent. Two patients (4%) had a delayed hemorrhage after incomplete obliteration of their malformations. Endovascular treatment resulted in clinical improvement in 15 (33%) of the other 46 patients. None of the patients who initially presented with hemorrhage had a rebleed following embolization. It is concluded that endovascular treatment with liquid embolic material can be an integral part of the multidisciplinary treatment protocol for patients with brain AVM's."
-How does nonsteroidal anti-inflammatory drug (NSAID) usage impact upper gastrointestinal lesions in elderly patients?,"Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage. The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer."
-What were the key findings comparing restorative proctocolectomy with and without a covering ileostomy in patients with ulcerative colitis?,"Comparison of restorative proctocolectomy with and without covering ileostomy in ulcerative colitis. The experience of restorative proctocolectomy for ulcerative colitis is reported in 16 consecutive patients with no covering ileostomy (group 2) in comparison with 15 patients with a covering stoma (group 1); in each group a J pouch was constructed. All patients had pre- and postoperative clinical and manometric evaluations of the functional result up to 12 months. There were no deaths or permanent failures. The number of early complications was four in each group. Re-ileostomy was needed in one patient of group 1, and an ileostomy was constructed in three patients of group 2. At 1 year after operation the functional results did not differ between groups 1 and 2 in terms of daily frequency of defaecation (mean 5.6 and 5.4 in 24 h respectively), or in terms of anal basal or maximal squeeze pressures. There was a significant (P less than 0.01) saving in total hospital stay (median 11 days) and in operating theatre time (mean 41 min) in patients with no covering ileostomy. It is concluded that a covering ileostomy may be unnecessary in restorative proctocolectomy, at least in suitable cases with no technical difficulty at the time of operation."
-What percentage of severely hearing impaired adults in the audiology clinic had a mixed hearing impairment in their better hearing ear?,"Characterization of severely and profoundly hearing impaired adults attending an audiology clinic. Despite the fact that around 12 per cent of adult patients attending an audiology department will be severely hearing impaired (pure tone averages of 0.5, 1, 2 and 4 kHz of 70 dB HL or worse in the better hearing ear), their clinical and audiometric characteristics have not been well documented. These characteristics were collected prospectively in 132 adult patients attending a Severe Impairment Clinic, set up to manage their specific problems. The inability to provide sufficient masking makes audiometric assessment of the severity of the impairment uncertain in the poorer hearing ear in 52 per cent of these patients. In addition, the limited bone conduction output makes it almost invariably impossible to assess the masked bone conduction thresholds and hence the air-bone gap in the poorer ear. Hence, accurate characterization is only practical of the better hearing ear in such patients. In 67 per cent of the better hearing ears, there was a mixed hearing impairment, the air-bone gap being 20 dB or greater. The aetiology of the conductive component was almost equally otosclerosis and chronic otitis media. In only 19 per cent was the impairment of a pure sensorineural type, broken down as 6 per cent congenitally acquired, 5 per cent due to meningitis and 9 per cent being adult in onset. In the remaining 14 per cent of patients the type of impairment could not be classified as the bone conductive thresholds were off scale. Having had experience of managing these patients at a special clinic and knowing the workload involved, it is argued that consideration be given to setting up such clinics in most departments."
-What potential complication can cold-reacting autoantibodies cause during cardiac operations?,Agglutination of blood cardioplegia by cold-reacting autoantibodies. Cold-reacting autoantibodies occasionally occur in patients requiring cardiac operations. This report describes the clinical course of 1 patient with cold-reacting autoantibodies and intracoronary agglutination of the blood cardioplegia solution. Observations made in vivo and in vitro are considered in discussing recommendations for the management of extracorporeal circulation and cardioplegic arrest in patients with clinically silent cold-reacting autoantibodies.
-What are the key characteristics of Fibromyalgia Syndrome (FS) according to the context?,"Toward an integrated understanding of fibromyalgia syndrome. I. Medical and pathophysiological aspects. Fibromyalgia syndrome (FS) is a chronic pain disorder characterized by diffuse musculoskeletal soreness, stiffness, non-restorative sleep and psychological disturbance. At present, much about the etiology, pathological mechanisms and course of FS are unknown. Indeed, standardized diagnostic criteria have only been recently agreed upon. The present paper is the first of a two-part series which reviews the extant empirical literature concerning FS, with a view to arriving at an integrated understanding of the syndrome. The present paper describes the clinical presentation of FS and historical conceptualizations of the disorder. Available research on pathophysiological mechanisms in FS is then presented. In this section we have included literature concerning histology of muscle, sleep architecture, neurotransmitter anomalies and neuropeptide involvement in FS symptomatology."
-What is a peripheral ameloblastoma and how rare is this odontogenic tumor?,"Peripheral ameloblastoma: a clinical and histologic study of 11 cases. Peripheral ameloblastoma (PA) is a rare odontogenic tumor. Previously, only 39 cases of PA had been reported in the English literature. In this article 11 additional cases of PA are presented. Concordance with previous cases was evident with regard to race, clinical appearance, and site of predilection. However, differences were observed with regard to age, sex distribution, and predominant histologic pattern. The average age in the current cases is younger, there is no male bias, and the most common histologic pattern is plexiform rather than follicular or acanthomatous. Recurrence following simple excision is rare, but has been reported. Long-term postoperative follow-up is recommended."
-What is primary breast lymphoma (PBL) and how was it treated in the described cases?,"Primary breast lymphoma. Primary breast lymphoma (PBL) is a rare tumor of the breast. Three cases of PBL are being described. All three cases achieved remission following biopsy, chemotherapy, and/or radiotherapy. The literature is extensively reviewed with emphasis on true incidence of PBL and survival rates."
-What are some potential causes of high-attenuation mediastinal masses on unenhanced CT scans?,"High-attenuation mediastinal masses on unenhanced CT. On unenhanced CT scans, a variety of mediastinal masses contain areas with attenuation values higher than the attenuation value of the chest wall musculature. The increased attenuation may be diffuse or focal and may be a result of calcium deposition, high iodine content, or areas of acute hemorrhage. This report illustrates the gamut of high-attenuation mediastinal masses seen on unenhanced CT. Masses that are of high attenuation only on IV contrast-enhanced images (e.g., aberrant vessels) are not included."
-How does subeschar tissue fluid (STF) impact cell-mediated immune function in patients with severe thermal injury?,"Subeschar tissue fluid: a source of cell-mediated immune suppression in victims of severe thermal injury. Thermal injury results in pronounced physiologic alterations in microcirculation at the site of tissue damage. The consequence of these changes is an increase in microvascular permeability, leading to the accumulation of tissue edema, or subeschar tissue fluid (STF). One of the adverse properties of edema is its capacity in vitro to inhibit cell-mediated immune function. Since previous studies evaluated STF collected 5 to 7 days after thermal injury, the present study was designed to determine the time frame during which STF demonstrates its immune suppressive nature. Seven patients with severe thermal injury (30% to 100% total body surface area) were entered into the study. STF was collected in serial fashion, beginning as early as 9 hours after injury and continuing until fascial excision or patient death (maximum of 139 hours after injury). The addition of STF to cultures of lymphocytes obtained from healthy donors resulted in complete inhibition of mitogen-induced lymphocyte proliferation (MILP). Serum collected concomitantly from this group of patients was also capable of inhibiting MILP. From its inception, STF possesses the ability to inhibit MILP; this suppressive nature is stable, persisting for prolonged periods of time. The gradual absorption of STF likely contributes to the serologic evidence of cell-mediated immune suppression documented in victims of severe thermal injury."
-How do TGF alpha and TGF beta influence liver regeneration and hepatocyte proliferation?,"Protooncogenes and growth factors associated with normal and abnormal liver growth. Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF alpha, an autocrine, stimulatory growth factor, and TGF beta, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The expression of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF alpha and other growth factors and enter a proliferative phase. It is possible that TGF beta 1 serves as a stop signal for liver regeneration but the mechanisms by which TGF beta inhibits hepatocyte DNA synthesis are still unknown."
-How did psychopathology levels impact hospital stay length and medical service costs for inpatients in this study?,"Relation of psychopathology in general medical inpatients to use and cost of services. The authors investigated the relation between psychopathology in medically ill inpatients and use and cost of medical care services. Of 455 medical inpatients, the Medical Inpatient Screening Test identified 27.9% as very depressed, 27.5% as very anxious, 20.2% as having cognitive dysfunction, and 8.6% as having high pain levels. Overall, the test identified 51% of the patients as having high levels of psychopathology or pain. These subjects had a 40% longer median length of hospital stay and 35% greater mean hospital costs than those with low levels of psychopathology or pain. Patients with greater psychopathology also had higher hospital charges, more procedures during hospitalization, and more discharge diagnoses but did not differ from the other patients in sex, race, age, diagnosis-related group (DRG) major diagnostic category, or DRG weight."
-How does the presence of blood medium affect the pulsed-dye laser ablation of normal and atherosclerotic human aorta tissues?,"Enhancement of pulsed-dye laser ablation of arterial tissues with blood medium: effects of laser-induced shock waves. The influence of blood medium on tissue ablation by a pulsed dye laser and its selectivity for atheroma were investigated. The role of shock waves on tissue ablation was also evaluated. Normal and atherosclerotic human aortas were irradiated by a 480 nm pulsed dye laser activated at 5 Hz. The laser was coupled with a single 0.2 mm fiber (Uni-guide) (40 mjoules/pulse) or a multifiber catheter (14 x 150 microns) (100 mjoules/pulse). Shock waves were measured using a fluid-filled catheter connected to a strain gauge manometer. With the Uni-guide, pulse-dye lasing resulted in greater ablation of atheroma in blood (11.6 x 10(-3) mm3/joule, p less than 0.001 versus atheroma measured in saline and normal tissue in blood) followed by normal tissue in blood (2.5 x 10(-3)mm3/joule), atheroma in saline (1.71 x 10(-3)mm3/joule, p less than 0.05 versus normal tissue in saline), and normal tissue in saline (0.54 x 10(-3) mm3/joule). With the multifiber catheter, laser ablation was the greatest in atheroma in blood (0.55 +/- 0.26 mm3/joule p less than 0.001 versus atheroma in saline and normal tissue in blood), followed by normal tissue in blood (0.27 +/- 0.12 mm3/joule), atheroma in saline (0.14 +/- 0.15 mm3/joule, p less than 0.001 versus normal tissue in saline), and normal tissue in saline (0 mm3/joule). The ablation efficiency of the multifiber catheter was greater than that of the Uni-guide (p less than 0.0001)."
-What is the significance of the two case studies involving isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma?,Isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma. Two women developed apparently isolated recurrences of ovarian carcinoma involving prior incisions after receiving intraperitoneal radioactive chromic phosphate (P-32) adjuvant therapy for early epithelial ovarian carcinoma. Both are alive without evidence of disease at second-look laparotomy after surgical resection of the abdominal wall metastases and cisplatin-based combination chemotherapy. Mechanisms of cutaneous and incisional implantation metastases are discussed. Adjuvant therapy with intraperitoneal P-32 is unable to provide systemic therapy for occult metastatic disease. The favorable outcome in these cases probably reflects limited tumor burden at the time of recurrence and stands in stark contrast to other cases of soft tissue recurrences of ovarian carcinoma reported previously.
-How does blockade of ATP-sensitive potassium channels affect reactive hyperemia in the canine coronary circulation?,"Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 +/- 41%. After low-dose (0.8 mumol/min) and high-dose (3.7 mumol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 +/- 14% and 50 +/- 8%, respectively (p less than 0.05 compared with control for both). The decline in flow debt repayment was due to a significant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon."
-What are the key findings of the study regarding volume tests for chronic venous insufficiency?,"Volume tests for chronic venous insufficiency: an appraisal. Chronic venous disease is increasingly treated surgically with a variety of experimental procedures. Noninvasive volume tests are commonly used before surgery to select patients and after surgery to assess results. Rapid volume changes are considered to indicate regurgitation. Rigorous statistical validation of tests and the confounding nature of unmeasured arterial inflow are seldom considered. Volume changes were measured in 29 control limbs and 35 limbs with venous disease, with mercury-in-silicone rubber strain gauges, for both exercise and elevation. Normalization for arterial flow permitted calculation of the regurgitation rate. Normal (95% confidence) limits for measured and calculated parameters were determined. Specificity was shown by the percent of normal parameter values for control limbs and sensitivity by the percent of abnormal values for extremities with venous disease. Arterial flow significantly altered volume curves. Normalization increased specificity and sensitivity significantly. Calf exercise tests, even normalized, were too insensitive to be reliable. Elevation tests were significantly more sensitive for determining regurgitation. However, exercise tests were useful and supplied important information about the calf muscle pump. We conclude that, as currently used, many limb volume test procedures are unsuitable but could be improved significantly by normalization to reduce the confounding effect of regional arterial flow and use of an elevation test to measure regurgitation."
-What is the significance of the mutation in the porcine ryanodine receptor gene in relation to malignant hyperthermia in swine?,"Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs."
-What was the main objective of the study on phenytoin overdose?,"Severe oral phenytoin overdose does not cause cardiovascular morbidity. STUDY OBJECTIVE: To evaluate the potential for cardiovascular toxicity from severe oral phenytoin overdose. STUDY POPULATION: Fifty-seven patients admitted during a two-year period to an inner-city hospital for severe oral phenytoin overdose, which is defined as a peak level of 40 micrograms/mL or more. METHODS: Case records were reviewed retrospectively for symptoms and signs of phenytoin toxicity, especially circulatory effects. Baseline and toxic 12-lead ECGs, when available, were reviewed in detail. Continuous variables were compared using either paired or unpaired t tests, as appropriate. Significance was taken as P less than or equal to .05. RESULTS: Mean peak phenytoin level was 49.4 +/- 7.7 micrograms/mL. Continuous single-lead ECG monitoring in 36 patients (63%) for a mean of 26.5 +/- 21.6 hours revealed no incidents of dysrhythmia requiring treatment. ECGs recorded during toxicity in 52 cases (91%) revealed no clinically significant abnormalities attributable to phenytoin. ECGs during toxic and baseline states were available for detailed analysis in 15 cases. Ten patients exhibited an increase in PR interval (mean, 19 +/- 10 ms) when toxic, whereas five had a decrease (mean, 18 +/- 11 ms) compared with nontoxic records. No change in heart rate, QRS duration, or corrected QT interval was observed. There were no circulatory complications and no deaths. CONCLUSION: Cardiovascular toxicity is rarely a manifestation of oral phenytoin overdose. Routine management of stable patients with severe phenytoin overdose in a monitored setting is not mandatory."
-What neurotoxic effects were observed in patients treated with intraventricular alpha-interferon for leptomeningeal disease?,"Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease. Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment."
-How does positive end-expiratory pressure (PEEP) affect splanchnic circulation in experimental peritonitis?,"Effects of positive end-expiratory pressure on splanchnic circulation and function in experimental peritonitis. Splanchnic and central hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in anesthetized pigs using mechanical ventilatory assistance, with or without sepsis (fecal peritonitis). One hour after sepsis, PEEP (10 cm H2O) was applied (n = 6). Another group (n = 6) had sepsis without PEEP. In one group (n = 6) without sepsis, PEEP was applied after 1 hour, while a fourth group (n = 5), without sepsis or PEEP, served as a control. The group with PEEP and sepsis had reduced cardiac index, portal venous blood flow, and liver surface blood flow. The group with PEEP alone had reduced splanchnic circulation by increasing gastrointestinal vascular resistance, while the group with sepsis alone had increased portal vascular resistance. In a separate series with sepsis, intermittent PEEP, and vigorous fluid resuscitation, it was demonstrated that avoiding hypovolemia did not seem to protect from the PEEP effects on the splanchnic circulation. The combination of sepsis and PEEP was not additive on portal blood flow reduction but reduced bile production."
-What factors were associated with higher mortality rates in patients with ruptured abdominal aortic aneurysms in this study?,"Factors affecting survival of patients with ruptured abdominal aortic aneurysm in a West Virginia community. The hospital records for patients treated for ruptured abdominal aortic aneurysms in southern West Virginia during a recent five year period were reviewed. The over-all mortality rate was 62 per cent. Patients with intraperitoneal rupture had a higher mortality rate (97 per cent) than patients with retroperitoneal rupture (25 per cent). Patients at increased risk were more than 80 years of age, presented with syncope, experienced a short duration of symptoms before seeking medical attention, had preoperative systolic blood pressure levels of less than 90 millimeters of mercury and had a preoperative hemoglobin level of less than 8. Other factors associated with death were a delay in beginning surgical treatment, a larger total blood loss and amount of blood transfused. The results of multivariate analysis demonstrated that preoperative blood pressure, preoperative hemoglobin, presence of syncope and the amount of blood loss were, in large part, reflections of the type of rupture and had only slight independent relationship to mortality. The most effective method of preventing fatal outcome is elective resection of the aneurysms before rupture occurs."
-What were the anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A compared to other antiepileptic drugs?,"Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats. The anticonvulsant profiles of two potent and orally active gamma-aminobutyric acid (GABA) uptake inhibitors, 1-(4,4-diphenyl-3-butenyl)-3-piperidine-carboxylic acid hydrochloride (SK&F 89976-A) and 1-(4,4-diphenyl-3-butenyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (SK&F 100330-A), were determined with a battery of well-standardized tests in mice and rats and compared with the profiles of phenytoin (PHT), carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) when subjected to the same tests. ED50 values were calculated and compared with TD50 values for minimal motor impairment to provide protective indexes (PI = TD50/ED50). The anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A were similar and suggest that these compounds raise the threshold for seizure initiation rather than inhibit seizure spread. Like intraperitoneal (i.p.) PHT, CBZ, VPA, and CZP, SK&F 89976-A and SK&F 100330-A inhibited seizures in corneally kindled rats. The profiles of SK&F 89976-A and SK&F 100330-A were most similar to that of CZP and virtually opposite to that of PHT. Intraperitoneal SK&F 100330-A provided complete protection against pentylenetetrazol-induced seizures [subcutaneous (s.c.) PTZ] in mice but was ineffective against seizures induced by maximal electroshock (MES) at doses slightly greater than its TD50. SK&F 100330-A provided complete protection against picrotoxin-induced seizures (s.c. Pic) and against both clonus and forelimb tonic extension induced by NMDA N-methyl-D-aspartate [intracerebral ventricular (i.c.v.)-NMDA] in mice; however, SK&F 100330-A was ineffective against seizures induced by bicuculline (s.c. Bic) and strychnine (s.c. Strych) at doses slightly greater than its TD50. SK&F 89976-A was similar but provided partial protection against NMDA-induced clonus."
-How does substance P protect against the neurodegenerative effects of beta amyloid in the brain?,"An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P. Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta amyloid. Immunoblot analysis showed that beta amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta amyloid. Thus, beta amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P."
-How did technetium-99m-HMPAO labeled leukocyte imaging help in detecting the chronic prosthetic vascular graft infection in the 77-year-old patient?,Chronic prosthetic vascular graft infection visualized with technetium-99m-hexamethylpropyleneamine oxime-labeled leukocytes Technetium-99m-HMPAO labeled leukocytes demonstrated chronic femoro-femoral prosthetic vascular graft infection several times during an 18-mo period in a 77-yr-old man. The intensity and distribution of the uptake in the graft were fluctuating in different imaging occasions possibly indicating the strength and location of the infection. Gallium-67-citrate imaging showed negative results twice. The reason for negative 67Ga results remained obscure. The infected graft was removed and the patient did well 5 mo postoperatively.
-Does zidovudine have an effect on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection?,"No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection. Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity."
-How accurate is pneumothorax CT in evaluating chest wall and mediastinal invasion in lung cancer patients?,"Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT. For preoperative evaluation of chest wall and mediastinal invasion by lung cancer, computed tomography (CT), combined with artificial pneumothorax (pneumothorax CT), was performed in 43 patients with lung cancer in whom conventional CT scans showed that the mass was contiguous to the chest wall (n = 30) and/or mediastinum (n = 25) but without evidence of definite tumor invasion. Invasion was diagnosed on the basis of whether an air space existed between the mass and the adjacent structures. In three patients pneumothorax was not produced. After the procedure, four patients developed symptomatic pneumothorax, and one, subcutaneous emphysema. Comparison of diagnoses based on findings at pneumothorax CT, surgery, and pathologic examination showed that pneumothorax CT is 100% accurate for chest wall invasion and 76% accurate for mediastinal invasion. The authors conclude that this procedure is helpful in accurate evaluation of the T criterion in lung cancer, especially for patients in whom findings at conventional CT suggest tumor invasion of the chest wall and mediastinum."
-What is the relationship between alpha 2 macroglobulin complexes and the severity of acute pancreatitis?,"Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks. Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis."
-How does the depletion of factor XII-dependent fibrinolytic activity relate to the risk of early myocardial reinfarction after rt-PA therapy?,"Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction."
-What is the success rate of arthroscopic stapling for treating superior labral tears in young athletes?,"Arthroscopic stapling for detached superior glenoid labrum. Superior labral tears of the shoulder involve the biceps tendon and labrum complex which may be detached, displaced inferiorly, and interposed between the glenoid and the humeral head. We have treated ten young athletes with painful shoulders due to this lesion by arthroscopic stapling. Arthroscopy at the time of staple removal, after three to six months, showed that all the lesions had been stabilised. Clinical review at over 24 months showed an excellent or good result in 80%. The two relative failures were due in one to residual subacromial bursitis, and the other to multidirectional shoulder instability. Arthroscopic stapling can restore the shoulder anatomy, and it is recommended for active adolescent athletes with this lesion."
-What was the complication rate for intra-aortic balloon pump (IABP) insertion in different clinical scenarios according to the study?,"Percutaneous intra-aortic balloon pump: emphasis on complications. In a review of our 5-year experience with intra-aortic balloon pump (IABP) insertion I examined the complications of percutaneous IABP placement in 93 patients, and compared them with those reported in other studies in the literature. I analyzed several variables that may affect the complication rate. Of 78 patients in our series who had percutaneous IABP cardiac assist, 15 (19%) had complications, which falls into the acceptable range reported by others. Among 15 patients who had surgical placement of an IABP, the complication rate was similar at 20%. The complication rate after IABP insertions done by surgeons primarily in the operating room was compared with that from insertions done by cardiologists in the catheterization laboratory. The overall complication rate was found to be higher in the second group, 28.0% compared with 12.8%. The application of the IABP in cardiogenic shock was associated with a high complication rate (46%). On the other hand, its insertion before cardiac surgery was associated with a relatively low complication rate (9.5%)."
-What were the clinical outcomes for patients who underwent mitral prosthesis insertion with native leaflets left intact?,"Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: adverse clinical outcome in seven patients. Left ventricular (LV) outflow obstruction may result from retaining the anterior mitral leaflet when a mitral prosthesis is inserted in the mitral anulus. We retrospectively reviewed the echocardiograms (two-dimensional Doppler and Doppler color flow imaging, or transesophageal with color flow imaging) obtained in seven patients with preoperative mitral regurgitation who had a prosthesis implanted with the native mitral leaflets left intact. Systolic anterior motion of the native anterior mitral leaflet, as seen in dynamic LV outflow tract obstruction, was observed in six of seven patients. LV fractional shortening preoperatively was less than or equal to 0.25 in all (mean 0.20 +/- 0.04) and did not significantly (p = ns) increase postoperatively (mean 0.27 +/- 0.12). Color flow imaging revealed disturbed systolic flow in the LV outflow tract in five patients, and all had systolic anterior motion of the native anterior mitral leaflet. Continuous wave Doppler detected significant systolic LV outflow tract jets in five patients averaging 4.1 +/- 0.9 m/sec. Mitral prosthetic function was normal (pressure half-time of 81 +/- 25 msec and mean gradient of 7 +/- 3 mm Hg +/- SD) in five patients. Clinical follow-up revealed that all had died, six of them within 2 months of their operation. Thus systolic anterior motion of the native anterior mitral leaflet occurs commonly after prosthetic mitral valve insertion with the native leaflets left intact. Continuous wave Doppler often demonstrates increased systolic LV outflow tract velocities consistent with dynamic LV outflow obstruction."
-What was the treatment and outcome for the 40-year-old woman with periorbital necrobiotic xanthogranuloma and stage I multiple myeloma?,"Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma."
-What percentage of patients with failed back surgery syndrome experienced successful outcomes after spinal cord stimulator implantation at 2.2 and 5.0 years follow-up?,"Failed back surgery syndrome: 5-year follow-up after spinal cord stimulator implantation. Spinal cord stimulation, in use for more than 20 years, has evolved into an easily implemented technique, with percutaneous methods for electrode placement. We have reviewed our experience with this technique in treating ""failed back surgery syndrome,"" and have assessed patient and treatment characteristics as predictors of long-term outcome. A series of 50 patients with failed back surgery syndrome (averaging 3.1 previous operations), who underwent spinal cord stimulator implantation, was interviewed by impartial third parties, at mean follow-up intervals of 2.2 years and 5.0 years. Successful outcome (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in 53% of patients at 2.2 years and in 47% of patients at 5.0 years postoperatively. Ten of 40 patients who were disabled preoperatively returned to work. Improvements in activities of daily living were recorded in most patients for most activities; loss of function was rare. Most patients reduced or eliminated analgesic intake. Statistical analysis (including univariate and multivariate logistic regression) of patient characteristics as prognostic factors showed significant advantages for female patients and for those with programmable multi-contact implanted devices. These results, in patients with postsurgical lumbar arachnoid and epidural fibrosis and without surgically remediable lesions, compare favorably with the results in two separate series of patients with failed back surgery syndrome, in whom 1) surgical lesions were diagnosed and repeated operation performed; and 2) monoradicular pain syndromes were diagnosed and dorsal root ganglionectomies performed at our institution. This suggests the need for further assessment of selection criteria, critical analysis of treatment outcome, and prospective study of spinal cord stimulation and alternative approaches to failed back surgery syndrome."
-What clinical benefits did aspirin and heparin demonstrate in the treatment of unstable angina according to the clinical trials?,"Antiplatelet and antithrombotic therapy in unstable angina. In 4 well-controlled clinical trials, aspirin reduced the incidence of coronary events in unstable angina. The benefits were present during the acute, subacute and more chronic phases of the disease and were independent of the doses and of other protocol differences. This benefit of aspirin can be extended to some, but not all, other antiplatelet drugs. In 4 clinical trials, heparin used acutely added substantial benefit to the management of unstable angina, reducing the event rate and also the incidence of refractory angina more than aspirin. The long-term benefit of antithrombin therapy remains to be more thoroughly investigated. Despite these successes, the failure rate of aspirin and of heparin remains high, justifying a continuing search for more potent and safe antiplatelet and antithrombotic drugs."
-What was the primary purpose of using carbon dioxide laser ablation in treating cutaneous metastases from malignant melanoma?,"Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma. Multiple cutaneous and superficial subcutaneous metastases from malignant melanoma in 30 patients were treated palliatively by carbon dioxide laser ablation when lesions were to numerous, too large or recurring too rapidly for multiple local excisions. The number of lesions per patient ranged from three to 250 (median 30). Patients were treated under local or general anaesthetic and as day cases or inpatients. After a median follow-up interval of 8 months fewer than 1 per cent of lasered metastases have recurred locally. Sixteen patients have developed cutaneous metastases at other sites requiring further treatment. Approximately 2000 lesions have been treated on 64 occasions. Patients reported little or no pain after the operation and required only simple dry dressings. Wounds were completely healed in 2-6 weeks with good cosmetic results. This simple and effective treatment is becoming an alternative to isolated limb perfusion."
-How has endoscopy improved the diagnosis and treatment of peptic ulcer disease?,"Use of endoscopy in peptic ulcer disease. The diagnosis and treatment of acute bleeding caused by peptic ulcer disease has been greatly facilitated by fiberoptic endoscopy. The basic differentiation between malignant and benign gastric ulcer requires endoscopic confirmation with biopsy. The management of bleeding from peptic ulceration can be enhanced by endoscopic examination as can the prediction of risk for recurrent bleeding or need for surgical intervention. Various therapeutic maneuvers can be performed endoscopically, including monopolar and multipolar cautery, laser and heater probe therapy, and injection of vasoconstrictors to control bleeding. Endoscopic balloon dilation for the management of gastric outlet obstruction is often effective."
-What is the relationship between optic chiasmal neuritis and multiple sclerosis according to the given context?,"Optic chiasmal neuritis. In four of six patients with clinical optic chiasmal neuritis, MRI demonstrated abnormalities of the chiasm. Optic chiasmal neuritis may be the initial manifestation of multiple sclerosis, a reflection of established CNS demyelination, or an isolated clinical finding."
-What was the overall accuracy of MR imaging in staging endometrial carcinoma according to the NCI cooperative study?,"MR imaging evaluation of endometrial carcinoma: results of an NCI cooperative study. A prospective study to assess the usefulness of magnetic resonance (MR) imaging in the evaluation of endometrial carcinoma was undertaken by five institutions under the auspices of the National Cancer Institute. Six different MR imagers were used, ranging in magnetic field strength from 0.15 T to 1.5 T. For each unit, appropriate T1- and T2-weighted sequences in the transverse plane and T2-weighted sequences in the sagittal plane were used. Initially, 107 patients were entered in the study, but only 88 fulfilled all the criteria and provide the basis for this study. The abnormality within the endometrial cavity was demonstrated with MR imaging in 81% of the patients. The overall accuracy with MR imaging for staging endometrial carcinoma was 85%. In the evaluation of depth of myometrial invasion for stage I disease, overall accuracy with MR imaging was 74%. The accuracy of MR imaging in assessing tumors confined to endometrium or tumor with superficial myometrial invasion was 89% and decreased to 54% in assessing deep myometrial invasion. The results of this prospective study performed by multiple examiners with vastly different equipment demonstrate the inherent value of MR imaging in the evaluation of this neoplasm."
-"How did prazosin treatment affect blood pressure, HDL-cholesterol concentration, and apoprotein-AI/HDL kinetics in patients with mild hypertension?","Effect of prazosin treatment on HDL kinetics in patients with hypertension. The effect of prazosin treatment on blood pressure, plasma HDL-cholesterol concentration, and apoprotein-AI/HDL (apoAI/HDL) kinetics was studied in 11 patients with mild hypertension. Blood pressure (mean +/- SEM) fell from 143 +/- 1/96 +/- 1 to 134 +/- 1/86 +/- 1 mm Hg after 4 to 5 months of prazosin treatment (P less than .001), associated with an increase in plasma HDL-cholesterol concentration from 38 +/- 2 to 46 +/- 2 mg/dL (P less than .001). Both the fractional catabolic rate (FCR) and total synthetic rate of apoAI/HDL, which were higher than previous reported values for normal individuals, decreased from 0.36 +/- 0.02 to 0.30 +/- 0.02 L/day and 17.4 +/- 1.1 to 13.8 +/- 1.1 mg/kg/min, respectively. These changes were statistically significant, and the post-treatment values for both variables were now within the normal range. When the decay curve was further analyzed by nonlinear curve fitting, it was shown that the return to normal of the FCR of apoAI/HDL in patients treated with prazosin was accounted for by the decrease of the decay constants of the second [p(2)] and third [p(3)] components of the 125I-AI/HDL disappearance curve. In conclusion, abnormalities in HDL concentration and HDL kinetics exist in patients with very mild hypertension. These defects were significantly improved with prazosin treatment, and this may render the compound of particular clinical benefit in the treatment of patients with mild hypertension."
-What role does radiotherapy play in the treatment of paediatric haemangiomas?,"Paediatric haemangiomas: the role of radiotherapy. Radiotherapy currently maintains an occasional place in the therapy of complicated haemangiomas of childhood. Eight such childhood benign lesions have been so treated at St Bartholomew's Hospital in the last 10 years. The case histories are presented before being discussed in the context of other therapies available (no treatment, steroids, embolism and surgery), radiation technique used and radiation dose prescription advised."
-What is Human Cyclical Neutropenia and what are its key clinical characteristics?,"Fatal human cyclical neutropenia with unresolving tonsillitis and bilateral cervical abscesses. Human Cyclical Neutropenia is a rare haematological disorder, characterized by periodic oscillations in peripheral neutrophil levels from normal to neutropenic, during which patients experience ulcerative stomatitis, fever, malaise and occasional cutaneous and subcutaneous infections. We present our experience with a fatal case of Human Cyclical Neutropenia together with a brief review of the literature and diagnostic criteria. The paper aims to heighten the clinical awareness of the otolaryngologist to the condition. Close co-operation with the haematologist is essential both for diagnosis and management."
-What surgical procedure is described for treating lateral nasal wall neoplasms and what are its key characteristics?,"'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and ""medial maxillectomy,"" an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora."
-What was the primary purpose of the study on slow-release nifedipine in patients with variant angina?,"Efficacy of slow-release nifedipine on myocardial ischemic episodes in variant angina pectoris. To evaluate the efficacy of slow-release nifedipine (a single dose of 20 mg given at 10 P.M. or 2 doses of 20 mg at 10 P.M. and 6 A.M.) on ischemic episodes in patients with variant angina, a single-blind crossover study with ambulatory electrocardiographic monitoring was performed in 15 patients (13 men and 2 women, mean age 63 years). In all, there were 646 ischemic episodes detected with ambulatory electrocardiographic monitoring during the study period, and 618 episodes of them occurred during placebo periods with a circadian variation. Sixty-nine percent of the episodes in placebo periods were asymptomatic. The number of anginal attacks, nitroglycerin tablets taken, ST-segment elevation and the total ischemic duration significantly decreased during nifedipine therapy compared with results after the placebo therapy period, respectively (p less than 0.01 or 0.05). Twenty-eight ischemic episodes occurred during nifedipine therapy when the plasma level of nifedipine was low. Thus, asymptomatic ischemic episodes more frequently occur than symptomatic episodes and the administration of slow-release nifedipine is highly effective in suppressing not only symptomatic but also asymptomatic myocardial ischemia in patients with variant angina. The timing of the administration of slow-release nifedipine is an important factor in suppressing ischemic episodes."
-What is the main finding of this study regarding the natural course of hepatic haemangiomas in adults?,"Natural history of hepatic haemangiomas: clinical and ultrasound study. Hepatic haemangiomas are the most common benign tumours of the liver and commonly present as incidental findings on sonographic examination of the abdomen. Since little is known of the natural course of these tumours, we performed a clinical and sonographic follow up of 123 haemangioma patients. Our prospective study investigated clinical and sonographic findings in 158 haemangiomas for periods of 12 to 60 months. Ninety nine haemangiomas measured less than 2 cm and had an echogenic pattern; 40 were between 2 cm and 5 cm with a mainly echogenic structure; 19 measured greater than 5 cm and showed a mixed echo pattern. At the first examination only eight patients, all with giant haemangiomas, presented symptoms which could be attributed to the tumour. During follow up only one haemangioma changed in shape and size. One patient who was symptom free at the first examination experienced right upper abdominal quadrant pain during follow up. No deterioration occurred in any of the patients with symptoms at the first examination, and all had a satisfactory quality of life. No complications arose during the follow up period. This study shows that in adults haemangiomas remain stable in size and echo patterns rarely change. Only haemangiomas greater than 5 cm may cause symptoms. Prolonged clinical and sonographic follow up of small and medium sized haemangiomas is not warranted."
-What recent advances have been made in the treatment of breast cancer?,"Recent advances in the treatment of breast cancer. Multidisciplinary efforts have defined a number of prognostic factors and newer strategies to improve the outcome of patients with breast cancer. Conservative surgery has led to improved functional and cosmetic results. The development of a number of effective adjuvant regimens has led to improved survival. In patients with stage I disease, several biological characteristics of tumor have been identified that are associated with increased risk of relapse. A multimodality approach to patients with locally advanced disease and inflammatory cancer has resulted in improved survival. A number of hormonal and cytotoxic drug contaminations can palliate metastatic disease, with a small fraction of patients remaining in extended remission. Dose-intensive programs may lead to further improvements in survival of selected patients with this disease."
diff --git a/agentic-apps/agentic_rag_opensearch/output/antonette.md b/agentic-apps/agentic_rag_opensearch/output/antonette.md
deleted file mode 100644
index fe4a4a12..00000000
--- a/agentic-apps/agentic_rag_opensearch/output/antonette.md
+++ /dev/null
@@ -1,20 +0,0 @@
-# Antonette's Journey with Bell's Palsy
-
-## Basic Information
-- **Name:** Antonette M. Rivera
-- **Age:** 34
-- **Occupation:** Graphic Designer
-- **Condition:** Bell's Palsy (idiopathic facial paralysis)
-- **Key Treatment:** Eye protection to prevent corneal damage
-
-## The Story
-Antonette, a creative and detail-oriented graphic designer, woke up one morning with sudden facial numbness and drooping on her right side. She noticed she couldn’t blink her right eye fully and struggled to smile. Panicked, she rushed to the clinic, where her doctor confirmed Bell’s palsy—a diagnosis of exclusion requiring careful evaluation to rule out other causes.
-
-The physician emphasized the **most critical aspect of initial treatment**: **eye protection**. Antonette learned that her inability to close her right eyelid left her vulnerable to corneal drying and injury. To safeguard her vision, she was prescribed:
-- Artificial tears every 2 hours during the day
-- An eye patch at night
-- Lubricating ointment before sleep
-
-Though frustrated by the limitations, Antonette religiously followed the regimen. Over weeks, her facial muscles slowly regained strength. Her diligence paid off—no corneal damage occurred, and by 6 months, her smile was nearly back to normal.
-
-Antonette’s story underscores how **early, proactive eye care** can prevent irreversible harm in Bell’s palsy. Today, she advocates for awareness, sharing how prioritizing small daily steps saved her vision and quality of life.
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_opensearch/package.json b/agentic-apps/agentic_rag_opensearch/package.json
deleted file mode 100644
index 537f3765..00000000
--- a/agentic-apps/agentic_rag_opensearch/package.json
+++ /dev/null
@@ -1,37 +0,0 @@
-{
-  "name": "agentic-rag-opensearch",
-  "version": "1.0.0",
-  "description": "Multi-Agent RAG system with MCP and OpenSearch",
-  "main": "index.js",
-  "type": "module",
-  "scripts": {
-    "dev": "tsx src/index.ts",
-    "embed-knowledge": "tsx src/scripts/embedKnowledge.ts",
-    "test-agents": "tsx src/test-agents.ts",
-    "test": "echo \"Error: no test specified\" && exit 1"
-  },
-  "keywords": [
-    "rag",
-    "mcp",
-    "llm",
-    "agent",
-    "opensearch",
-    "multi-agent"
-  ],
-  "author": "",
-  "license": "ISC",
-  "dependencies": {
-    "@modelcontextprotocol/sdk": "^1.10.1",
-    "@modelcontextprotocol/server-filesystem": "^2025.3.28",
-    "@opensearch-project/opensearch": "^3.5.1",
-    "aws-sdk": "^2.1574.0",
-    "chalk": "^5.4.1",
-    "csv-parse": "^5.5.5",
-    "dotenv": "^16.4.5",
-    "langfuse": "^3.30.0",
-    "node-fetch": "^3.3.2",
-    "openai": "^4.28.4",
-    "tsx": "^4.7.1",
-    "typescript": "^5.3.3"
-  }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/pnpm-lock.yaml b/agentic-apps/agentic_rag_opensearch/pnpm-lock.yaml
deleted file mode 100644
index a10958d1..00000000
--- a/agentic-apps/agentic_rag_opensearch/pnpm-lock.yaml
+++ /dev/null
@@ -1,1841 +0,0 @@
-lockfileVersion: '9.0'
-
-settings:
-  autoInstallPeers: true
-  excludeLinksFromLockfile: false
-
-importers:
-
-  .:
-    dependencies:
-      '@modelcontextprotocol/sdk':
-        specifier: ^1.10.1
-        version: 1.10.2
-      '@modelcontextprotocol/server-filesystem':
-        specifier: ^2025.3.28
-        version: 2025.3.28(zod@3.24.2)
-      '@opensearch-project/opensearch':
-        specifier: ^3.5.1
-        version: 3.5.1
-      aws-sdk:
-        specifier: ^2.1574.0
-        version: 2.1692.0
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-        version: 5.4.1
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-        version: 16.4.7
-      langfuse:
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-        version: 3.37.4
-      node-fetch:
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-        version: 3.3.2
-      openai:
-        specifier: ^4.28.4
-        version: 4.91.1(zod@3.24.2)
-      tsx:
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-        version: 4.19.3
-      typescript:
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diff --git a/agentic-apps/agentic_rag_opensearch/setup-opensearch.sh b/agentic-apps/agentic_rag_opensearch/setup-opensearch.sh
deleted file mode 100755
index 4b0c4c3c..00000000
--- a/agentic-apps/agentic_rag_opensearch/setup-opensearch.sh
+++ /dev/null
@@ -1,328 +0,0 @@
-#!/bin/bash
-
-# Script to create an OpenSearch cluster for agentic RAG application
-
-set -e
-
-# Color codes for better readability
-GREEN='\033[0;32m'
-BLUE='\033[0;34m'
-RED='\033[0;31m'
-YELLOW='\033[0;33m'
-NC='\033[0m' # No Color
-
-# Function to display messages with timestamp
-log() {
-  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
-}
-
-warn() {
-  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
-}
-
-error() {
-  echo -e "${RED}[$(date '+%Y-%m-%d %H:%M:%S')] ERROR:${NC} $1"
-  exit 1
-}
-
-success() {
-  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
-}
-
-# Configuration variables
-DOMAIN_NAME="agentic-rag-opensearch"
-REGION="us-east-1"
-INSTANCE_TYPE="t3.small.search"
-INSTANCE_COUNT=1
-VOLUME_SIZE=20
-VOLUME_TYPE="gp3"
-OPENSEARCH_VERSION="2.11"
-
-# Check prerequisites
-check_prerequisites() {
-  log "Checking prerequisites..."
-  
-  # Check AWS CLI
-  if ! command -v aws &> /dev/null; then
-    error "AWS CLI is not installed. Please install it first."
-  fi
-  
-  # Check AWS credentials
-  if ! aws sts get-caller-identity &> /dev/null; then
-    error "AWS credentials not configured or invalid. Please configure AWS CLI."
-  fi
-  
-  # Get current AWS account ID and user ARN
-  ACCOUNT_ID=$(aws sts get-caller-identity --query Account --output text)
-  USER_ARN=$(aws sts get-caller-identity --query Arn --output text)
-  
-  log "AWS Account ID: $ACCOUNT_ID"
-  log "User ARN: $USER_ARN"
-  
-  success "All prerequisites satisfied."
-}
-
-# Get default VPC and subnet information
-get_vpc_info() {
-  log "Getting VPC and subnet information..."
-  
-  # Get default VPC
-  DEFAULT_VPC=$(aws ec2 describe-vpcs --filters "Name=is-default,Values=true" --query "Vpcs[0].VpcId" --output text --region $REGION)
-  
-  if [ "$DEFAULT_VPC" = "None" ] || [ -z "$DEFAULT_VPC" ]; then
-    error "No default VPC found. Please create a VPC first."
-  fi
-  
-  log "Using VPC: $DEFAULT_VPC"
-  
-  # Get subnets in the default VPC
-  SUBNETS=$(aws ec2 describe-subnets --filters "Name=vpc-id,Values=$DEFAULT_VPC" --query "Subnets[*].SubnetId" --output text --region $REGION)
-  
-  if [ -z "$SUBNETS" ]; then
-    error "No subnets found in VPC $DEFAULT_VPC"
-  fi
-  
-  # Convert to array and take first two subnets
-  SUBNET_ARRAY=($SUBNETS)
-  SUBNET_IDS="${SUBNET_ARRAY[0]}"
-  if [ ${#SUBNET_ARRAY[@]} -gt 1 ]; then
-    SUBNET_IDS="$SUBNET_IDS,${SUBNET_ARRAY[1]}"
-  fi
-  
-  log "Using subnets: $SUBNET_IDS"
-  
-  success "VPC information retrieved successfully."
-}
-# Create security group for OpenSearch
-create_security_group() {
-  log "Creating security group for OpenSearch..."
-  
-  # Check if security group already exists
-  EXISTING_SG=$(aws ec2 describe-security-groups --filters "Name=group-name,Values=opensearch-sg" "Name=vpc-id,Values=$DEFAULT_VPC" --query "SecurityGroups[0].GroupId" --output text --region $REGION 2>/dev/null || echo "None")
-  
-  if [ "$EXISTING_SG" != "None" ] && [ -n "$EXISTING_SG" ]; then
-    log "Security group already exists: $EXISTING_SG"
-    SECURITY_GROUP_ID=$EXISTING_SG
-  else
-    # Create security group
-    SECURITY_GROUP_ID=$(aws ec2 create-security-group \
-      --group-name opensearch-sg \
-      --description "Security group for OpenSearch cluster" \
-      --vpc-id $DEFAULT_VPC \
-      --query "GroupId" \
-      --output text \
-      --region $REGION)
-    
-    log "Created security group: $SECURITY_GROUP_ID"
-    
-    # Add inbound rule for HTTPS (port 443)
-    aws ec2 authorize-security-group-ingress \
-      --group-id $SECURITY_GROUP_ID \
-      --protocol tcp \
-      --port 443 \
-      --cidr 0.0.0.0/0 \
-      --region $REGION
-    
-    log "Added HTTPS inbound rule to security group"
-  fi
-  
-  success "Security group configured: $SECURITY_GROUP_ID"
-}
-
-# Check if OpenSearch domain already exists
-check_existing_domain() {
-  log "Checking if OpenSearch domain already exists..."
-  
-  EXISTING_DOMAIN=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION 2>/dev/null || echo "")
-  
-  if [ -n "$EXISTING_DOMAIN" ]; then
-    DOMAIN_STATUS=$(echo "$EXISTING_DOMAIN" | jq -r '.DomainStatus.Processing')
-    DOMAIN_ENDPOINT=$(echo "$EXISTING_DOMAIN" | jq -r '.DomainStatus.Endpoint')
-    
-    if [ "$DOMAIN_STATUS" = "false" ] && [ "$DOMAIN_ENDPOINT" != "null" ]; then
-      warn "OpenSearch domain '$DOMAIN_NAME' already exists and is active."
-      log "Domain endpoint: https://$DOMAIN_ENDPOINT"
-      
-      # Update .env file with existing endpoint
-      update_env_file "https://$DOMAIN_ENDPOINT"
-      
-      success "Using existing OpenSearch domain."
-      exit 0
-    else
-      warn "OpenSearch domain '$DOMAIN_NAME' exists but is still processing. Please wait for it to complete."
-      exit 1
-    fi
-  fi
-  
-  log "No existing domain found. Proceeding with creation..."
-}
-
-# Create OpenSearch domain
-create_opensearch_domain() {
-  log "Creating OpenSearch domain: $DOMAIN_NAME"
-  
-  # Create the domain configuration
-  cat > opensearch-domain-config.json << EOF
-{
-  "DomainName": "$DOMAIN_NAME",
-  "EngineVersion": "OpenSearch_$OPENSEARCH_VERSION",
-  "ClusterConfig": {
-    "InstanceType": "$INSTANCE_TYPE",
-    "InstanceCount": $INSTANCE_COUNT,
-    "DedicatedMasterEnabled": false
-  },
-  "EBSOptions": {
-    "EBSEnabled": true,
-    "VolumeType": "$VOLUME_TYPE",
-    "VolumeSize": $VOLUME_SIZE
-  },
-  "VPCOptions": {
-    "SubnetIds": ["$(echo $SUBNET_IDS | tr ',' '", "')"],
-    "SecurityGroupIds": ["$SECURITY_GROUP_ID"]
-  },
-  "AccessPolicies": "{\"Version\":\"2012-10-17\",\"Statement\":[{\"Effect\":\"Allow\",\"Principal\":{\"AWS\":\"$USER_ARN\"},\"Action\":\"es:*\",\"Resource\":\"arn:aws:es:$REGION:$ACCOUNT_ID:domain/$DOMAIN_NAME/*\"}]}",
-  "EncryptionAtRestOptions": {
-    "Enabled": true
-  },
-  "NodeToNodeEncryptionOptions": {
-    "Enabled": true
-  },
-  "DomainEndpointOptions": {
-    "EnforceHTTPS": true,
-    "TLSSecurityPolicy": "Policy-Min-TLS-1-2-2019-07"
-  },
-  "AdvancedSecurityOptions": {
-    "Enabled": false
-  }
-}
-EOF
-
-  # Create the domain
-  aws opensearch create-domain \
-    --cli-input-json file://opensearch-domain-config.json \
-    --region $REGION
-  
-  log "OpenSearch domain creation initiated..."
-  
-  # Clean up temporary file
-  rm -f opensearch-domain-config.json
-  
-  success "OpenSearch domain creation request submitted."
-}
-# Wait for domain to be ready
-wait_for_domain() {
-  log "Waiting for OpenSearch domain to be ready..."
-  
-  local max_attempts=60  # 30 minutes (30 seconds * 60)
-  local attempt=1
-  
-  while [ $attempt -le $max_attempts ]; do
-    log "Attempt $attempt/$max_attempts: Checking domain status..."
-    
-    DOMAIN_INFO=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION 2>/dev/null || echo "")
-    
-    if [ -n "$DOMAIN_INFO" ]; then
-      PROCESSING=$(echo "$DOMAIN_INFO" | jq -r '.DomainStatus.Processing')
-      ENDPOINT=$(echo "$DOMAIN_INFO" | jq -r '.DomainStatus.Endpoint')
-      
-      if [ "$PROCESSING" = "false" ] && [ "$ENDPOINT" != "null" ]; then
-        success "OpenSearch domain is ready!"
-        log "Domain endpoint: https://$ENDPOINT"
-        DOMAIN_ENDPOINT="https://$ENDPOINT"
-        return 0
-      fi
-    fi
-    
-    log "Domain is still processing. Waiting 30 seconds..."
-    sleep 30
-    ((attempt++))
-  done
-  
-  error "Domain failed to become ready within the expected time. Please check the AWS console."
-}
-
-# Update .env file with the new endpoint
-update_env_file() {
-  local endpoint=$1
-  log "Updating .env file with OpenSearch endpoint..."
-  
-  if [ -f ".env" ]; then
-    # Update existing OPENSEARCH_ENDPOINT line or add it
-    if grep -q "OPENSEARCH_ENDPOINT=" .env; then
-      sed -i.bak "s|OPENSEARCH_ENDPOINT=.*|OPENSEARCH_ENDPOINT=$endpoint|" .env
-    else
-      echo "OPENSEARCH_ENDPOINT=$endpoint" >> .env
-    fi
-    
-    # Update AWS_REGION if not present
-    if ! grep -q "AWS_REGION=" .env; then
-      echo "AWS_REGION=$REGION" >> .env
-    fi
-    
-    success ".env file updated with OpenSearch endpoint."
-  else
-    # Create new .env file
-    cat > .env << EOF
-OPENAI_API_KEY=your-openai-api-key
-OPENAI_BASE_URL=your-model-endpoint
-OPENSEARCH_ENDPOINT=$endpoint
-AWS_REGION=$REGION
-EOF
-    success "Created .env file with OpenSearch endpoint."
-  fi
-}
-
-# Verify the setup
-verify_setup() {
-  log "Verifying OpenSearch setup..."
-  
-  # Test connection (basic check)
-  log "Testing OpenSearch connectivity..."
-  
-  # Get domain info
-  DOMAIN_INFO=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION)
-  
-  if [ $? -eq 0 ]; then
-    success "OpenSearch domain is accessible via AWS CLI."
-    
-    # Display domain information
-    echo "$DOMAIN_INFO" | jq '.DomainStatus | {
-      DomainName: .DomainName,
-      Endpoint: .Endpoint,
-      Processing: .Processing,
-      InstanceType: .ClusterConfig.InstanceType,
-      InstanceCount: .ClusterConfig.InstanceCount,
-      VolumeSize: .EBSOptions.VolumeSize
-    }'
-  else
-    error "Failed to verify OpenSearch domain."
-  fi
-}
-
-# Main execution
-main() {
-  log "Starting OpenSearch cluster setup for agentic RAG application..."
-  
-  check_prerequisites
-  get_vpc_info
-  create_security_group
-  check_existing_domain
-  create_opensearch_domain
-  wait_for_domain
-  update_env_file "$DOMAIN_ENDPOINT"
-  verify_setup
-  
-  success "OpenSearch cluster setup completed successfully!"
-  log "Domain Name: $DOMAIN_NAME"
-  log "Endpoint: $DOMAIN_ENDPOINT"
-  log "Region: $REGION"
-  log ""
-  log "Next steps:"
-  log "1. Update your .env file with the correct OPENAI_API_KEY and OPENAI_BASE_URL"
-  log "2. Run 'pnpm install' to install dependencies"
-  log "3. Run 'pnpm embed-knowledge' to embed your knowledge documents"
-  log "4. Run 'pnpm dev' to start the agentic RAG application"
-}
-
-# Execute main function
-main
diff --git a/agentic-apps/agentic_rag_opensearch/src/Agent.ts b/agentic-apps/agentic_rag_opensearch/src/Agent.ts
deleted file mode 100644
index 2025d825..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/Agent.ts
+++ /dev/null
@@ -1,98 +0,0 @@
-import MCPClient from "./MCPClient";
-import ChatOpenAI from "./ChatOpenAI";
-import { logTitle } from "./utils";
-import { ToolCall } from "./ChatOpenAI";
-
-export default class Agent {
-    private mcpClients: MCPClient[];
-    private llm: ChatOpenAI | null = null;
-    private model: string;
-    private systemPrompt: string;
-    private context: string;
-
-    constructor(model: string, mcpClients: MCPClient[], systemPrompt: string = '', context: string = '') {
-        this.mcpClients = mcpClients;
-        this.model = model;
-        this.systemPrompt = systemPrompt;
-        this.context = context;
-    }
-
-    async init() {
-        logTitle('TOOLS');
-        for await (const client of this.mcpClients) {
-            await client.init();
-        }
-        const tools = this.mcpClients.flatMap(client => client.getTools());
-        this.llm = new ChatOpenAI(this.model, this.systemPrompt, tools, this.context);
-    }
-
-    async close() {
-        for await (const client of this.mcpClients) {
-            await client.close();
-        }
-    }
-
-    async invoke(prompt: string) {
-        if (!this.llm) throw new Error('Agent not initialized');
-        
-        try {
-            logTitle('AGENT EXECUTION');
-            console.log("Invoking LLM with tools...");
-            
-            // Start the conversation with the user prompt
-            let response = await this.llm.chat(prompt);
-            
-            // Continue the conversation until no more tool calls are needed
-            while (response.toolCalls && response.toolCalls.length > 0) {
-                logTitle('TOOL CALLS');
-                console.log(`Processing ${response.toolCalls.length} tool calls`);
-                
-                // Process each tool call
-                for (const toolCall of response.toolCalls) {
-                    await this.processToolCall(toolCall);
-                }
-                
-                // Continue the conversation with the tool results
-                response = await this.llm.chat();
-            }
-            
-            logTitle('FINAL RESPONSE');
-            console.log("Successfully completed request");
-            return response.content;
-        } catch (error) {
-            console.error("Error in agent execution:", error);
-            throw error;
-        }
-    }
-    
-    private async processToolCall(toolCall: ToolCall) {
-        try {
-            const { id, function: { name, arguments: argsString } } = toolCall;
-            console.log(`Executing tool call: ${name}`);
-            
-            // Parse the arguments
-            const args = JSON.parse(argsString);
-            
-            // Find the MCP client that can handle this tool
-            const toolName = name;
-            
-            // Find the appropriate client
-            const client = this.mcpClients[0]; // Since we only have one client
-            
-            if (!client) {
-                throw new Error(`No MCP client found for tool: ${name}`);
-            }
-            
-            // Call the tool and get the result
-            const result = await client.callTool(toolName, args);
-            console.log(`Tool result: ${JSON.stringify(result).substring(0, 100)}...`);
-            
-            // Append the tool result to the conversation
-            this.llm?.appendToolResult(id, JSON.stringify(result));
-        } catch (error) {
-            console.error(`Error processing tool call: ${error}`);
-            // Append the error as the tool result
-            this.llm?.appendToolResult(toolCall.id, JSON.stringify({ error: error.message }));
-        }
-    }
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_opensearch/src/ChatOpenAI.ts b/agentic-apps/agentic_rag_opensearch/src/ChatOpenAI.ts
deleted file mode 100644
index 470a875f..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/ChatOpenAI.ts
+++ /dev/null
@@ -1,220 +0,0 @@
-import OpenAI from "openai";
-import { Tool } from "@modelcontextprotocol/sdk/types.js";
-import 'dotenv/config'
-import { logTitle } from "./utils";
-import { createGeneration, isLangfuseEnabled } from "./LangfuseConfig";
-
-export interface ToolCall {
-    id: string;
-    function: {
-        name: string;
-        arguments: string;
-    };
-}
-
-export default class ChatOpenAI {
-    private llm: OpenAI;
-    private model: string;
-    private messages: OpenAI.Chat.ChatCompletionMessageParam[] = [];
-    private tools: Tool[];
-    private trace: any; // Langfuse trace
-
-    constructor(model: string, systemPrompt: string = '', tools: Tool[] = [], context: string = '', trace?: any) {
-        this.llm = new OpenAI({
-            apiKey: process.env.OPENAI_API_KEY,
-            baseURL: process.env.OPENAI_BASE_URL,
-            defaultHeaders: {
-                // Use only one authentication method to avoid conflicts
-                "Authorization": `Bearer ${process.env.OPENAI_API_KEY}`
-                // Removed "api-key" header to prevent double authentication
-            }
-        });
-        this.model = model;
-        this.tools = tools;
-        this.trace = trace;
-        if (systemPrompt) this.messages.push({ role: "system", content: systemPrompt });
-        if (context) this.messages.push({ role: "user", content: `Here is some context that might be helpful: \n\n${context}` });
-    }
-
-    async chat(prompt?: string): Promise<{ content: string, toolCalls: ToolCall[] }> {
-        logTitle('CHAT');
-        if (prompt) {
-            this.messages.push({ role: "user", content: prompt });
-        }
-        
-        // Debug the request
-        console.log('Sending request to model:', this.model);
-        console.log('Messages count:', this.messages.length);
-        console.log('Tools count:', this.tools.length);
-        
-        // Create Langfuse generation for tracing
-        const generation = createGeneration(
-            this.trace,
-            `chat-${this.model}`,
-            {
-                messages: this.messages.map(m => ({ role: m.role, content: typeof m.content === 'string' ? m.content.substring(0, 200) + '...' : '[complex content]' })),
-                tools: this.tools.map(t => t.name),
-                model: this.model
-            },
-            this.model,
-            {
-                messageCount: this.messages.length,
-                toolCount: this.tools.length,
-                hasSystemPrompt: this.messages.some(m => m.role === 'system')
-            }
-        );
-        
-        try {
-            // Create request options with tools if available
-            const requestOptions: OpenAI.Chat.ChatCompletionCreateParams = {
-                model: this.model,
-                messages: this.messages,
-                stream: false,
-            };
-            
-            // Add tools if available
-            if (this.tools.length > 0) {
-                requestOptions.tools = this.getToolsDefinition();
-                requestOptions.tool_choice = "auto";
-            }
-            
-            console.log('Sending request with options:', JSON.stringify({
-                ...requestOptions,
-                messages: `[${requestOptions.messages.length} messages]` // Don't log full messages
-            }, null, 2));
-            
-            const startTime = Date.now();
-            const completion = await this.llm.chat.completions.create(requestOptions);
-            const endTime = Date.now();
-            
-            // Extract the response content and tool calls
-            const message = completion.choices[0]?.message;
-            const content = message?.content || "";
-            const toolCalls = message?.tool_calls?.map(tc => ({
-                id: tc.id,
-                function: {
-                    name: tc.function.name,
-                    arguments: tc.function.arguments
-                }
-            })) || [];
-            
-            // Update Langfuse generation with results
-            if (generation && isLangfuseEnabled) {
-                generation.end({
-                    output: {
-                        content: content.substring(0, 500) + (content.length > 500 ? '...' : ''),
-                        toolCalls: toolCalls.map(tc => ({ name: tc.function.name, id: tc.id }))
-                    },
-                    usage: {
-                        promptTokens: completion.usage?.prompt_tokens,
-                        completionTokens: completion.usage?.completion_tokens,
-                        totalTokens: completion.usage?.total_tokens
-                    },
-                    metadata: {
-                        duration: endTime - startTime,
-                        finishReason: completion.choices[0]?.finish_reason,
-                        model: completion.model
-                    }
-                });
-            }
-            
-            // Add the response to messages
-            this.messages.push({
-                role: "assistant",
-                content: content,
-                tool_calls: message?.tool_calls
-            });
-            
-            // Log the response
-            if (toolCalls.length > 0) {
-                console.log(`Response includes ${toolCalls.length} tool calls`);
-                toolCalls.forEach(tc => console.log(`- Tool: ${tc.function.name}`));
-            } else {
-                console.log('Response content:', content.substring(0, 100) + (content.length > 100 ? '...' : ''));
-            }
-            
-            return {
-                content: content,
-                toolCalls: toolCalls,
-            };
-        } catch (error) {
-            // Update Langfuse generation with error
-            if (generation && isLangfuseEnabled) {
-                generation.end({
-                    output: null,
-                    metadata: {
-                        error: error.message || 'Unknown error',
-                        errorType: error.constructor.name
-                    }
-                });
-            }
-            
-            console.error('Error details:', error);
-            
-            // Enhanced error logging
-            console.error('Full error object:', JSON.stringify(error, null, 2));
-            
-            if (error.response) {
-                console.error('Response status:', error.response.status);
-                console.error('Response headers:', error.response.headers);
-                try {
-                    const responseText = await error.response.text();
-                    console.error('Response data:', responseText);
-                    try {
-                        // Try to parse as JSON for better readability
-                        const responseJson = JSON.parse(responseText);
-                        console.error('Response JSON:', JSON.stringify(responseJson, null, 2));
-                    } catch (parseError) {
-                        // If not valid JSON, the text version is already logged
-                    }
-                } catch (e) {
-                    console.error('Could not read response data:', e);
-                }
-            }
-            
-            // Log the exact request that was sent
-            console.error('Request that caused the error:');
-            console.error('- URL:', process.env.OPENAI_BASE_URL + '/chat/completions');
-            console.error('- Model:', this.model);
-            console.error('- Messages count:', this.messages.length);
-            console.error('- Tools count:', this.tools.length);
-            
-            throw error;
-        }
-    }
-
-    public appendToolResult(toolCallId: string, toolOutput: string) {
-        this.messages.push({
-            role: "tool",
-            content: toolOutput,
-            tool_call_id: toolCallId
-        });
-    }
-
-    public updateSystemPrompt(newSystemPrompt: string) {
-        // Remove existing system message if present
-        this.messages = this.messages.filter(msg => msg.role !== "system");
-        
-        // Add new system message at the beginning
-        this.messages.unshift({ role: "system", content: newSystemPrompt });
-    }
-
-    public clearMessages() {
-        this.messages = [];
-    }
-
-    public getMessageCount(): number {
-        return this.messages.length;
-    }
-
-    private getToolsDefinition(): OpenAI.Chat.Completions.ChatCompletionTool[] {
-        return this.tools.map((tool) => ({
-            type: "function",
-            function: {
-                name: tool.name,
-                description: tool.description,
-                parameters: tool.inputSchema,
-            },
-        }));
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/EmbeddingRetriever.ts b/agentic-apps/agentic_rag_opensearch/src/EmbeddingRetriever.ts
deleted file mode 100644
index 51486204..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/EmbeddingRetriever.ts
+++ /dev/null
@@ -1,116 +0,0 @@
-import { logTitle } from "./utils";
-import OpenSearchVectorStore from "./OpenSearchVectorStore";
-import 'dotenv/config';
-import fetch from 'node-fetch';
-
-export default class EmbeddingRetriever {
-    private embeddingModel: string;
-    private vectorStore: OpenSearchVectorStore;
-    private embeddingEndpoint: string;
-    private apiKey: string;
-    private readonly targetDimension: number = 384;
-
-    constructor(embeddingModel: string) {
-        this.embeddingModel = "llamacpp-embedding"; // Using llamacpp-embedding model
-        this.vectorStore = new OpenSearchVectorStore();
-        this.embeddingEndpoint = process.env.EMBEDDING_ENDPOINT;
-        this.apiKey = process.env.OPENAI_API_KEY;
-    }
-
-    async embedDocument(document: string) {
-        logTitle('EMBEDDING DOCUMENT');
-        const embedding = await this.embed(document);
-        await this.vectorStore.addEmbedding(embedding, document);
-        return embedding;
-    }
-
-    async embedQuery(query: string) {
-        logTitle('EMBEDDING QUERY');
-        const embedding = await this.embed(query);
-        return embedding;
-    }
-
-    private generateRandomEmbedding(): number[] {
-        return Array(this.targetDimension).fill(0).map(() => (Math.random() * 2 - 1));
-    }
-
-    private normalizeVector(vector: number[]): number[] {
-        const magnitude = Math.sqrt(vector.reduce((sum, val) => sum + val * val, 0));
-        return vector.map(val => val / magnitude);
-    }
-
-    private resizeEmbedding(embedding: number[]): number[] {
-        if (embedding.length === this.targetDimension) {
-            return embedding;
-        }
-
-        const result = new Array(this.targetDimension).fill(0);
-        const ratio = embedding.length / this.targetDimension;
-
-        for (let i = 0; i < this.targetDimension; i++) {
-            const start = Math.floor(i * ratio);
-            const end = Math.floor((i + 1) * ratio);
-            let sum = 0;
-            for (let j = start; j < end; j++) {
-                sum += embedding[j] || 0;
-            }
-            result[i] = sum / (end - start);
-        }
-
-        return this.normalizeVector(result);
-    }
-
-    private async embed(document: string): Promise<number[]> {
-        try {
-            console.log(`Sending embedding request to endpoint: ${this.embeddingEndpoint}`);
-            console.log(`Using model: ${this.embeddingModel}`);
-            console.log(`Document length: ${document.length} characters`);
-            
-            const response = await fetch(this.embeddingEndpoint, {
-                method: 'POST',
-                headers: {
-                    'Content-Type': 'application/json',
-                    'Authorization': `Bearer ${this.apiKey}`
-                },
-                body: JSON.stringify({
-                    model: this.embeddingModel,
-                    input: document
-                }),
-            });
-            
-            if (!response.ok) {
-                console.log(`HTTP error! Status: ${response.status}`);
-                const errorText = await response.text();
-                console.log(`Error response: ${errorText}`);
-                return this.generateRandomEmbedding();
-            }
-            
-            const responseBody = await response.json();
-            
-            // Check if we got a valid embedding in the expected OpenAI format
-            if (!responseBody || !responseBody.data || !responseBody.data[0] || !responseBody.data[0].embedding) {
-                console.log("Warning: Embedding API didn't return a valid embedding");
-                console.log("Response:", JSON.stringify(responseBody, null, 2));
-                return this.generateRandomEmbedding();
-            }
-            
-            // Get the embedding array from the OpenAI-compatible format
-            const embedding = responseBody.data[0].embedding;
-            
-            // Ensure we have a 384-dimensional vector
-            const resizedEmbedding = this.resizeEmbedding(embedding);
-            
-            console.log(`Successfully processed embedding with ${resizedEmbedding.length} dimensions`);
-            return resizedEmbedding;
-            
-        } catch (error) {
-            console.error("Error fetching embedding from endpoint:", error);
-            return this.generateRandomEmbedding();
-        }
-    }
-
-    async retrieve(query: string, topK: number = 3): Promise<string[]> {
-        const queryEmbedding = await this.embedQuery(query);
-        return this.vectorStore.search(queryEmbedding, topK);
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/LangfuseConfig.ts b/agentic-apps/agentic_rag_opensearch/src/LangfuseConfig.ts
deleted file mode 100644
index dbb81fcd..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/LangfuseConfig.ts
+++ /dev/null
@@ -1,86 +0,0 @@
-import { Langfuse } from 'langfuse';
-import 'dotenv/config';
-
-// Validate environment variables
-const publicKey = process.env.LANGFUSE_PUBLIC_KEY;
-const secretKey = process.env.LANGFUSE_SECRET_KEY;
-const host = process.env.LANGFUSE_HOST;
-
-if (!publicKey || !secretKey || !host) {
-  console.warn('Langfuse configuration incomplete. Some environment variables are missing:');
-  console.warn('- LANGFUSE_PUBLIC_KEY:', publicKey ? '✓' : '✗');
-  console.warn('- LANGFUSE_SECRET_KEY:', secretKey ? '✓' : '✗');
-  console.warn('- LANGFUSE_HOST:', host ? '✓' : '✗');
-  console.warn('Langfuse tracing will be disabled.');
-}
-
-// Initialize Langfuse client
-export const langfuse = publicKey && secretKey && host ? new Langfuse({
-  secretKey,
-  publicKey,
-  baseUrl: host,
-  flushAt: 1, // Send traces immediately for development
-}) : null;
-
-// Helper function to create a trace
-export function createTrace(name: string, input?: any, metadata?: any) {
-  if (!langfuse) {
-    console.warn('Langfuse not configured, skipping trace creation');
-    return null;
-  }
-  
-  return langfuse.trace({
-    name,
-    input,
-    metadata: {
-      ...metadata,
-      timestamp: new Date().toISOString(),
-      environment: 'development'
-    }
-  });
-}
-
-// Helper function to create a span within a trace
-export function createSpan(trace: any, name: string, input?: any, metadata?: any) {
-  if (!trace) {
-    return null;
-  }
-  
-  return trace.span({
-    name,
-    input,
-    metadata: {
-      ...metadata,
-      timestamp: new Date().toISOString()
-    }
-  });
-}
-
-// Helper function to create a generation (LLM call) within a trace
-export function createGeneration(trace: any, name: string, input?: any, model?: string, metadata?: any) {
-  if (!trace) {
-    return null;
-  }
-  
-  return trace.generation({
-    name,
-    input,
-    model,
-    metadata: {
-      ...metadata,
-      timestamp: new Date().toISOString()
-    }
-  });
-}
-
-// Helper function to flush traces (useful for cleanup)
-export async function flushLangfuse() {
-  if (langfuse) {
-    await langfuse.flushAsync();
-  }
-}
-
-// Export configuration status
-export const isLangfuseEnabled = !!langfuse;
-
-console.log(`Langfuse tracing: ${isLangfuseEnabled ? 'ENABLED' : 'DISABLED'}`);
diff --git a/agentic-apps/agentic_rag_opensearch/src/MCPClient.ts b/agentic-apps/agentic_rag_opensearch/src/MCPClient.ts
deleted file mode 100644
index 26910a47..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/MCPClient.ts
+++ /dev/null
@@ -1,62 +0,0 @@
-import { Client } from "@modelcontextprotocol/sdk/client/index.js";
-import { StdioClientTransport } from "@modelcontextprotocol/sdk/client/stdio.js";
-import { Tool } from "@modelcontextprotocol/sdk/types.js";
-
-export default class MCPClient {
-    public mcp: Client;
-    private command: string;
-    private args: string[]
-    private transport: StdioClientTransport | null = null;
-    private tools: Tool[] = [];
-
-    constructor(name: string, command: string, args: string[], version?: string) {
-        this.mcp = new Client({ name, version: version || "0.0.1" });
-        this.command = command;
-        this.args = args;
-    }
-
-    public async init() {
-        await this.connectToServer();
-    }
-
-    public async close() {
-        await this.mcp.close();
-    }
-
-    public getTools() {
-        return this.tools;
-    }
-
-    public callTool(name: string, params: Record<string, any>) {
-        return this.mcp.callTool({
-            name,
-            arguments: params,
-        });
-    }
-
-    private async connectToServer() {
-        try {
-            this.transport = new StdioClientTransport({
-                command: this.command,
-                args: this.args,
-            });
-            await this.mcp.connect(this.transport);
-
-            const toolsResult = await this.mcp.listTools();
-            this.tools = toolsResult.tools.map((tool) => {
-                return {
-                    name: tool.name,
-                    description: tool.description,
-                    inputSchema: tool.inputSchema,
-                };
-            });
-            console.log(
-                "Connected to server with tools:",
-                this.tools.map(({ name }) => name)
-            );
-        } catch (e) {
-            console.log("Failed to connect to MCP server: ", e);
-            throw e;
-        }
-    }
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_opensearch/src/OpenSearchVectorStore.ts b/agentic-apps/agentic_rag_opensearch/src/OpenSearchVectorStore.ts
deleted file mode 100644
index aeb8cef4..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/OpenSearchVectorStore.ts
+++ /dev/null
@@ -1,144 +0,0 @@
-import { Client } from '@opensearch-project/opensearch';
-import { VectorStore } from './VectorStore';
-import 'dotenv/config';
-import AWS from 'aws-sdk';
-import { AwsSigv4Signer } from '@opensearch-project/opensearch/aws';
-
-export default class OpenSearchVectorStore implements VectorStore {
-    private client: Client;
-    private indexName: string = 'rag_documents';
-    private dimension: number = 384; // Default dimension for embeddings
-
-    constructor() {
-        // Get configuration from environment variables
-        const region = process.env.AWS_REGION;
-        const opensearchEndpoint = process.env.OPENSEARCH_ENDPOINT;
-        
-        if (!region || !opensearchEndpoint) {
-            throw new Error('AWS_REGION and OPENSEARCH_ENDPOINT environment variables must be set');
-        }
-
-        // Create AWS credentials
-        const credentials = {
-            accessKeyId: process.env.AWS_ACCESS_KEY_ID || '',
-            secretAccessKey: process.env.AWS_SECRET_ACCESS_KEY || ''
-        };
-
-        // Initialize the OpenSearch client with AWS Signature V4 authentication
-        this.client = new Client({
-            ...AwsSigv4Signer({
-                region: region,
-                service: 'es',
-                credentials: credentials
-            }),
-            node: opensearchEndpoint
-        });
-        
-        this.initIndex();
-    }
-
-    private async initIndex() {
-        try {
-            // Check if index exists
-            const indexExists = await this.client.indices.exists({
-                index: this.indexName
-            });
-            
-            if (!indexExists.body) {
-                console.log(`Creating index ${this.indexName}`);
-                
-                // Create index with mapping for vector field
-                await this.client.indices.create({
-                    index: this.indexName,
-                    body: {
-                        settings: {
-                            "index.knn": true,
-                            "index.knn.space_type": "cosinesimil"
-                        },
-                        mappings: {
-                            properties: {
-                                embedding: {
-                                    type: 'knn_vector',
-                                    dimension: this.dimension,
-                                    method: {
-                                        name: 'hnsw',
-                                        space_type: 'cosinesimil',
-                                        engine: 'nmslib',
-                                        parameters: {
-                                            ef_construction: 128,
-                                            m: 16
-                                        }
-                                    }
-                                },
-                                document: {
-                                    type: 'text',
-                                    store: true
-                                }
-                            }
-                        }
-                    }
-                });
-                
-                console.log(`Index ${this.indexName} created successfully`);
-            } else {
-                console.log(`Index ${this.indexName} already exists`);
-            }
-        } catch (error) {
-            console.error('Error initializing OpenSearch index:', error);
-            throw error;
-        }
-    }
-
-    async addEmbedding(embedding: number[], document: string): Promise<void> {
-        try {
-            await this.client.index({
-                index: this.indexName,
-                body: {
-                    embedding: embedding,
-                    document: document
-                },
-                refresh: true // Make the document immediately searchable
-            });
-            console.log('Document added to OpenSearch');
-        } catch (error) {
-            console.error('Error adding embedding to OpenSearch:', error);
-            throw error;
-        }
-    }
-
-    async search(queryEmbedding: number[], topK: number = 3): Promise<string[]> {
-        try {
-            const searchResponse = await this.client.search({
-                index: this.indexName,
-                body: {
-                    size: topK,
-                    query: {
-                        knn: {
-                            embedding: {
-                                vector: queryEmbedding,
-                                k: topK
-                            }
-                        }
-                    },
-                    _source: ['document']
-                }
-            });
-            
-            // Extract documents from search results
-            const hits = searchResponse.body.hits.hits;
-            return hits.map((hit: any) => hit._source.document);
-        } catch (error) {
-            console.error('Error searching in OpenSearch:', error);
-            return [];
-        }
-    }
-
-    async close(): Promise<void> {
-        try {
-            await this.client.close();
-            console.log('OpenSearch connection closed');
-        } catch (error) {
-            console.error('Error closing OpenSearch connection:', error);
-        }
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/VectorStore.ts b/agentic-apps/agentic_rag_opensearch/src/VectorStore.ts
deleted file mode 100644
index 506339ea..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/VectorStore.ts
+++ /dev/null
@@ -1,10 +0,0 @@
-export interface VectorStoreItem {
-    embedding: number[];
-    document: string;
-}
-
-export interface VectorStore {
-    addEmbedding(embedding: number[], document: string): Promise<void>;
-    search(queryEmbedding: number[], topK: number): Promise<string[]>;
-    close?(): Promise<void>;
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/agents/KnowledgeAgent.ts b/agentic-apps/agentic_rag_opensearch/src/agents/KnowledgeAgent.ts
deleted file mode 100644
index 582a841a..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/agents/KnowledgeAgent.ts
+++ /dev/null
@@ -1,276 +0,0 @@
-import fs from "fs";
-import path from "path";
-import crypto from "crypto";
-import EmbeddingRetriever from "../EmbeddingRetriever";
-import { logTitle } from "../utils";
-
-interface FileMetadata {
-    path: string;
-    hash: string;
-    lastModified: number;
-    size: number;
-}
-
-export default class KnowledgeAgent {
-    private knowledgePath: string;
-    private metadataPath: string;
-    private embeddingRetriever: EmbeddingRetriever | null = null;
-    private lastKnownState: Map<string, FileMetadata> = new Map();
-
-    constructor() {
-        this.knowledgePath = path.join(process.cwd(), 'knowledge');
-        this.metadataPath = path.join(process.cwd(), '.knowledge-metadata.json');
-    }
-
-    async init() {
-        logTitle('INITIALIZING KNOWLEDGE AGENT');
-        
-        // Initialize embedding retriever with llamacpp-embedding model
-        this.embeddingRetriever = new EmbeddingRetriever("llamacpp-embedding");
-        
-        // Load existing metadata if available
-        await this.loadMetadata();
-        
-        console.log('Knowledge Agent initialized');
-    }
-
-    async close() {
-        // Save metadata before closing
-        await this.saveMetadata();
-        
-        // Close embedding retriever if needed
-        if (this.embeddingRetriever) {
-            // @ts-ignore - Access private property for cleanup
-            if (this.embeddingRetriever.vectorStore && typeof this.embeddingRetriever.vectorStore.close === 'function') {
-                // @ts-ignore
-                await this.embeddingRetriever.vectorStore.close();
-            }
-        }
-    }
-
-    async checkForChanges(): Promise<boolean> {
-        logTitle('CHECKING KNOWLEDGE CHANGES');
-        
-        if (!fs.existsSync(this.knowledgePath)) {
-            console.log(`Knowledge directory not found: ${this.knowledgePath}`);
-            return false;
-        }
-
-        const currentState = await this.scanKnowledgeDirectory();
-        const hasChanges = this.compareStates(currentState);
-        
-        if (hasChanges) {
-            console.log('Changes detected in knowledge files');
-            this.lastKnownState = currentState;
-        } else {
-            console.log('No changes detected in knowledge files');
-        }
-        
-        return hasChanges;
-    }
-
-    async embedKnowledge(): Promise<boolean> {
-        logTitle('EMBEDDING KNOWLEDGE FILES');
-        
-        if (!this.embeddingRetriever) {
-            console.error('Embedding retriever not initialized');
-            return false;
-        }
-
-        try {
-            // Get all knowledge files (including CSV)
-            const files = this.getAllKnowledgeFiles();
-            console.log(`Found ${files.length} knowledge files to embed`);
-            
-            let successCount = 0;
-            
-            // Process each file
-            for (const file of files) {
-                try {
-                    console.log(`Processing: ${path.basename(file)}`);
-                    
-                    const ext = path.extname(file).toLowerCase();
-                    
-                    if (ext === '.csv') {
-                        // Handle CSV files specially
-                        const csvSuccess = await this.processCsvFile(file);
-                        if (csvSuccess) successCount++;
-                    } else {
-                        // Handle regular text files
-                        const content = fs.readFileSync(file, 'utf-8');
-                        const enrichedContent = `File: ${path.basename(file)}\n\n${content}`;
-                        await this.embeddingRetriever.embedDocument(enrichedContent);
-                        successCount++;
-                    }
-                } catch (error) {
-                    console.error(`Error processing file ${file}:`, error);
-                }
-            }
-            
-            console.log(`Successfully embedded ${successCount}/${files.length} files`);
-            
-            // Save current state as metadata
-            await this.saveMetadata();
-            
-            return successCount > 0;
-        } catch (error) {
-            console.error('Error in knowledge embedding:', error);
-            return false;
-        }
-    }
-
-    private async scanKnowledgeDirectory(): Promise<Map<string, FileMetadata>> {
-        const state = new Map<string, FileMetadata>();
-        
-        if (!fs.existsSync(this.knowledgePath)) {
-            return state;
-        }
-        
-        const files = this.getAllKnowledgeFiles();
-        
-        for (const file of files) {
-            try {
-                const stats = fs.statSync(file);
-                const content = fs.readFileSync(file, 'utf-8');
-                const hash = crypto.createHash('md5').update(content).digest('hex');
-                
-                state.set(file, {
-                    path: file,
-                    hash,
-                    lastModified: stats.mtime.getTime(),
-                    size: stats.size
-                });
-            } catch (error) {
-                console.error(`Error scanning file ${file}:`, error);
-            }
-        }
-        
-        return state;
-    }
-
-    private compareStates(currentState: Map<string, FileMetadata>): boolean {
-        // If no previous state, consider it as changes
-        if (this.lastKnownState.size === 0) {
-            return currentState.size > 0;
-        }
-        
-        // Check for new or modified files
-        for (const [filePath, metadata] of currentState) {
-            const previousMetadata = this.lastKnownState.get(filePath);
-            
-            if (!previousMetadata || previousMetadata.hash !== metadata.hash) {
-                return true;
-            }
-        }
-        
-        // Check for deleted files
-        for (const filePath of this.lastKnownState.keys()) {
-            if (!currentState.has(filePath)) {
-                return true;
-            }
-        }
-        
-        return false;
-    }
-
-    private getAllKnowledgeFiles(): string[] {
-        if (!fs.existsSync(this.knowledgePath)) {
-            return [];
-        }
-        
-        const files: string[] = [];
-        const entries = fs.readdirSync(this.knowledgePath, { withFileTypes: true });
-        
-        for (const entry of entries) {
-            if (entry.isFile()) {
-                const filePath = path.join(this.knowledgePath, entry.name);
-                const ext = path.extname(entry.name).toLowerCase();
-                
-                // Support all knowledge file types including CSV
-                if (['.md', '.txt', '.json', '.csv'].includes(ext)) {
-                    files.push(filePath);
-                }
-            }
-        }
-        
-        return files;
-    }
-
-    private async processCsvFile(filePath: string): Promise<boolean> {
-        try {
-            const content = fs.readFileSync(filePath, 'utf-8');
-            const rows = content.split('\n').filter(row => row.trim());
-            
-            if (rows.length > 1) {
-                const headers = rows[0].split(',');
-                let processedRows = 0;
-                
-                // Process each row as a separate document
-                for (let i = 1; i < rows.length; i++) {
-                    const values = rows[i].split(',');
-                    const rowData = headers.map((header, index) => 
-                        `${header.trim()}: ${values[index]?.trim() || ''}`
-                    ).join('\n');
-                    
-                    const enrichedContent = `CSV File: ${path.basename(filePath)}\nRow ${i}:\n${rowData}`;
-                    await this.embeddingRetriever!.embedDocument(enrichedContent);
-                    processedRows++;
-                }
-                
-                console.log(`Processed ${processedRows} rows from CSV file`);
-                return true;
-            }
-            
-            return false;
-        } catch (error) {
-            console.error(`Error processing CSV file ${filePath}:`, error);
-            return false;
-        }
-    }
-
-    private getKnowledgeFiles(): string[] {
-        if (!fs.existsSync(this.knowledgePath)) {
-            return [];
-        }
-        
-        const files: string[] = [];
-        const entries = fs.readdirSync(this.knowledgePath, { withFileTypes: true });
-        
-        for (const entry of entries) {
-            if (entry.isFile()) {
-                const filePath = path.join(this.knowledgePath, entry.name);
-                const ext = path.extname(entry.name).toLowerCase();
-                
-                if (['.md', '.txt', '.json'].includes(ext)) {
-                    files.push(filePath);
-                }
-            }
-        }
-        
-        return files;
-    }
-
-    private async loadMetadata() {
-        try {
-            if (fs.existsSync(this.metadataPath)) {
-                const data = fs.readFileSync(this.metadataPath, 'utf-8');
-                const metadata = JSON.parse(data);
-                
-                this.lastKnownState = new Map(Object.entries(metadata));
-                console.log(`Loaded metadata for ${this.lastKnownState.size} files`);
-            }
-        } catch (error) {
-            console.error('Error loading metadata:', error);
-        }
-    }
-
-    private async saveMetadata() {
-        try {
-            const metadata = Object.fromEntries(this.lastKnownState);
-            fs.writeFileSync(this.metadataPath, JSON.stringify(metadata, null, 2));
-            console.log(`Saved metadata for ${this.lastKnownState.size} files`);
-        } catch (error) {
-            console.error('Error saving metadata:', error);
-        }
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/agents/MCPAgent.ts b/agentic-apps/agentic_rag_opensearch/src/agents/MCPAgent.ts
deleted file mode 100644
index ecaa58ea..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/agents/MCPAgent.ts
+++ /dev/null
@@ -1,263 +0,0 @@
-import MCPClient from "../MCPClient";
-import ChatOpenAI from "../ChatOpenAI";
-import { logTitle } from "../utils";
-import { ToolCall } from "../ChatOpenAI";
-import path from "path";
-import { createSpan, isLangfuseEnabled } from "../LangfuseConfig";
-
-export default class MCPAgent {
-    private mcpClients: MCPClient[];
-    private llm: ChatOpenAI | null = null;
-    private model: string;
-    private outPath: string;
-    private trace: any; // Langfuse trace
-
-    constructor(mcpClients: MCPClient[], model: string = 'Qwen/QwQ-32B-AWQ') {
-        this.mcpClients = mcpClients;
-        this.model = model;
-        this.outPath = path.resolve(process.cwd(), 'output');
-    }
-
-    async init() {
-        logTitle('INITIALIZING MCP AGENT');
-        
-        // Initialize all MCP clients
-        for (const client of this.mcpClients) {
-            await client.init();
-        }
-        
-        // Get all available tools
-        const tools = this.mcpClients.flatMap(client => client.getTools());
-        console.log(`Initialized ${this.mcpClients.length} MCP clients with ${tools.length} tools`);
-        
-        // Initialize LLM with tools but without system prompt and context yet
-        this.llm = new ChatOpenAI(this.model, '', tools, '');
-        
-        console.log('MCP Agent initialized');
-    }
-
-    async close() {
-        // Close all MCP clients
-        for (const client of this.mcpClients) {
-            await client.close();
-        }
-    }
-
-    async executeTask(query: string, context: string, trace?: any): Promise<string> {
-        logTitle('MCP AGENT TASK EXECUTION');
-        console.log(`Executing task with context length: ${context.length} characters`);
-        
-        // Store trace for use in tool calls
-        this.trace = trace;
-        
-        if (!this.llm) {
-            throw new Error('MCP Agent not initialized');
-        }
-
-        // Create system prompt with context
-        const systemPrompt = `You are a helpful assistant that can retrieve information and complete tasks.
-You have access to tools that can help you complete tasks.
-When asked to save files, always use the filesystem tool to write the content.
-Specifically, use the write_file tool to save files.
-The output path is ${this.outPath}.
-
-Context from knowledge base:
-${context}
-
-Use this context to inform your responses and complete the requested task.`;
-
-        // Get all available tools
-        const tools = this.mcpClients.flatMap(client => client.getTools());
-        
-        // Create a new ChatOpenAI instance with the trace for this specific task
-        const taskLLM = new ChatOpenAI(this.model, systemPrompt, tools, '', trace);
-
-        // Create span for MCP task execution
-        const taskSpan = createSpan(trace, 'mcp-task-execution', {
-            query,
-            contextLength: context.length,
-            model: this.model
-        });
-
-        try {
-            console.log("Starting conversation with LLM...");
-            
-            // Start the conversation with the user query
-            let response = await taskLLM.chat(query);
-            let toolCallCount = 0;
-            
-            // Continue the conversation until no more tool calls are needed
-            while (response.toolCalls && response.toolCalls.length > 0) {
-                logTitle('PROCESSING TOOL CALLS');
-                console.log(`Processing ${response.toolCalls.length} tool calls`);
-                
-                toolCallCount += response.toolCalls.length;
-                
-                // Create span for tool calls batch
-                const toolBatchSpan = createSpan(trace, 'tool-calls-batch', {
-                    batchSize: response.toolCalls.length,
-                    toolNames: response.toolCalls.map(tc => tc.function.name)
-                });
-                
-                // Process each tool call
-                for (const toolCall of response.toolCalls) {
-                    await this.processToolCall(toolCall, taskLLM);
-                }
-                
-                if (toolBatchSpan && isLangfuseEnabled) {
-                    toolBatchSpan.end({
-                        output: { processed: response.toolCalls.length }
-                    });
-                }
-                
-                // Continue the conversation with the tool results
-                response = await taskLLM.chat();
-            }
-            
-            logTitle('TASK COMPLETED');
-            console.log("Successfully completed task");
-            
-            // End task span with success
-            if (taskSpan && isLangfuseEnabled) {
-                taskSpan.end({
-                    output: {
-                        success: true,
-                        resultLength: response.content.length,
-                        toolCallsCount: toolCallCount,
-                        resultPreview: response.content.substring(0, 200) + '...'
-                    }
-                });
-            }
-            
-            return response.content;
-        } catch (error) {
-            console.error("Error in MCP agent execution:", error);
-            
-            // End task span with error
-            if (taskSpan && isLangfuseEnabled) {
-                taskSpan.end({
-                    output: {
-                        success: false,
-                        error: error.message || 'Unknown error',
-                        errorType: error.constructor.name
-                    }
-                });
-            }
-            
-            throw error;
-        }
-    }
-
-    async callTool(toolName: string, args: any): Promise<any> {
-        logTitle('DIRECT TOOL CALL');
-        console.log(`Calling tool: ${toolName}`);
-        console.log(`Arguments:`, args);
-        
-        // Find the appropriate MCP client for this tool
-        for (const client of this.mcpClients) {
-            const tools = client.getTools();
-            const tool = tools.find(t => t.name === toolName);
-            
-            if (tool) {
-                try {
-                    const result = await client.callTool(toolName, args);
-                    console.log(`Tool result:`, result);
-                    return result;
-                } catch (error) {
-                    console.error(`Error calling tool ${toolName}:`, error);
-                    throw error;
-                }
-            }
-        }
-        
-        throw new Error(`Tool ${toolName} not found in any MCP client`);
-    }
-
-    async listAvailableTools(): Promise<any[]> {
-        const allTools = this.mcpClients.flatMap(client => client.getTools());
-        return allTools;
-    }
-
-    private async processToolCall(toolCall: ToolCall, llm: ChatOpenAI) {
-        // Create span for individual tool call
-        const toolSpan = createSpan(this.trace, 'tool-call', {
-            toolName: toolCall.function.name,
-            toolId: toolCall.id
-        });
-        
-        try {
-            const { id, function: { name, arguments: argsString } } = toolCall;
-            console.log(`Executing tool call: ${name}`);
-            
-            // Parse the arguments
-            const args = JSON.parse(argsString);
-            
-            // Find the MCP client that can handle this tool
-            let result = null;
-            let toolFound = false;
-            
-            for (const client of this.mcpClients) {
-                const tools = client.getTools();
-                const tool = tools.find(t => t.name === name);
-                
-                if (tool) {
-                    toolFound = true;
-                    result = await client.callTool(name, args);
-                    break;
-                }
-            }
-            
-            if (!toolFound) {
-                throw new Error(`No MCP client found for tool: ${name}`);
-            }
-            
-            console.log(`Tool result: ${JSON.stringify(result).substring(0, 100)}...`);
-            
-            // End tool span with success
-            if (toolSpan && isLangfuseEnabled) {
-                toolSpan.end({
-                    output: {
-                        success: true,
-                        resultPreview: JSON.stringify(result).substring(0, 200) + '...',
-                        resultLength: JSON.stringify(result).length
-                    }
-                });
-            }
-            
-            // Append the tool result to the conversation
-            llm.appendToolResult(id, JSON.stringify(result));
-        } catch (error) {
-            console.error(`Error processing tool call: ${error}`);
-            
-            // End tool span with error
-            if (toolSpan && isLangfuseEnabled) {
-                toolSpan.end({
-                    output: {
-                        success: false,
-                        error: error.message || 'Unknown error',
-                        errorType: error.constructor.name
-                    }
-                });
-            }
-            
-            // Append the error as the tool result
-            llm.appendToolResult(toolCall.id, JSON.stringify({ error: error.message }));
-        }
-    }
-
-    getStats(): {
-        model: string;
-        clientCount: number;
-        toolCount: number;
-        initialized: boolean;
-    } {
-        const toolCount = this.mcpClients.flatMap(client => client.getTools()).length;
-        
-        return {
-            model: this.model,
-            clientCount: this.mcpClients.length,
-            toolCount,
-            initialized: this.llm !== null
-        };
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/agents/RAGAgent.ts b/agentic-apps/agentic_rag_opensearch/src/agents/RAGAgent.ts
deleted file mode 100644
index fe2bbf80..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/agents/RAGAgent.ts
+++ /dev/null
@@ -1,180 +0,0 @@
-import EmbeddingRetriever from "../EmbeddingRetriever";
-import { logTitle } from "../utils";
-
-export default class RAGAgent {
-    private embeddingRetriever: EmbeddingRetriever | null = null;
-    private model: string;
-
-    constructor(model: string = 'Qwen/QwQ-32B-AWQ') {
-        this.model = model;
-    }
-
-    async init() {
-        logTitle('INITIALIZING RAG AGENT');
-        
-        // Initialize the embedding retriever with llamacpp-embedding model
-        this.embeddingRetriever = new EmbeddingRetriever("llamacpp-embedding");
-        
-        console.log('RAG Agent initialized');
-    }
-
-    async close() {
-        // Close embedding retriever if needed
-        if (this.embeddingRetriever) {
-            // @ts-ignore - Access private property for cleanup
-            if (this.embeddingRetriever.vectorStore && typeof this.embeddingRetriever.vectorStore.close === 'function') {
-                // @ts-ignore
-                await this.embeddingRetriever.vectorStore.close();
-            }
-        }
-    }
-
-    async retrieveContext(query: string, topK: number = 5): Promise<string> {
-        logTitle('RAG CONTEXT RETRIEVAL');
-        console.log(`Query: ${query}`);
-        console.log(`Retrieving top ${topK} relevant documents`);
-        
-        if (!this.embeddingRetriever) {
-            throw new Error('RAG Agent not initialized');
-        }
-
-        try {
-            // Retrieve relevant documents
-            const documents = await this.embeddingRetriever.retrieve(query, topK);
-            
-            // Combine documents into context
-            const context = documents.join('\n\n---\n\n');
-            
-            console.log(`Retrieved ${documents.length} relevant documents`);
-            console.log('Context preview:', context.substring(0, 200) + '...');
-            
-            return context;
-        } catch (error) {
-            console.error('Error in context retrieval:', error);
-            throw error;
-        }
-    }
-
-    async retrieveContextWithMetadata(query: string, topK: number = 5): Promise<{
-        context: string;
-        documents: string[];
-        metadata: any[];
-    }> {
-        logTitle('RAG CONTEXT RETRIEVAL WITH METADATA');
-        console.log(`Query: ${query}`);
-        
-        if (!this.embeddingRetriever) {
-            throw new Error('RAG Agent not initialized');
-        }
-
-        try {
-            // Retrieve relevant documents
-            const documents = await this.embeddingRetriever.retrieve(query, topK);
-            
-            // For now, we don't have detailed metadata, but this structure allows for future enhancement
-            const metadata = documents.map((doc, index) => ({
-                index,
-                length: doc.length,
-                preview: doc.substring(0, 100)
-            }));
-            
-            const context = documents.join('\n\n---\n\n');
-            
-            console.log(`Retrieved ${documents.length} relevant documents with metadata`);
-            
-            return {
-                context,
-                documents,
-                metadata
-            };
-        } catch (error) {
-            console.error('Error in context retrieval with metadata:', error);
-            throw error;
-        }
-    }
-
-    async semanticSearch(query: string, filters?: any): Promise<string[]> {
-        logTitle('SEMANTIC SEARCH');
-        console.log(`Semantic search query: ${query}`);
-        
-        if (!this.embeddingRetriever) {
-            throw new Error('RAG Agent not initialized');
-        }
-
-        try {
-            // For now, use the standard retrieve method
-            // In the future, this could be enhanced with filtering capabilities
-            const documents = await this.embeddingRetriever.retrieve(query, 10);
-            
-            console.log(`Found ${documents.length} semantically similar documents`);
-            
-            return documents;
-        } catch (error) {
-            console.error('Error in semantic search:', error);
-            throw error;
-        }
-    }
-
-    async hybridSearch(query: string, keywordWeight: number = 0.3, semanticWeight: number = 0.7): Promise<string[]> {
-        logTitle('HYBRID SEARCH');
-        console.log(`Hybrid search query: ${query}`);
-        console.log(`Keyword weight: ${keywordWeight}, Semantic weight: ${semanticWeight}`);
-        
-        if (!this.embeddingRetriever) {
-            throw new Error('RAG Agent not initialized');
-        }
-
-        try {
-            // For now, this is just semantic search
-            // In a full implementation, this would combine keyword and semantic search
-            const documents = await this.embeddingRetriever.retrieve(query, 10);
-            
-            console.log(`Hybrid search returned ${documents.length} documents`);
-            
-            return documents;
-        } catch (error) {
-            console.error('Error in hybrid search:', error);
-            throw error;
-        }
-    }
-
-    async rerank(query: string, documents: string[], topK: number = 5): Promise<string[]> {
-        logTitle('DOCUMENT RERANKING');
-        console.log(`Reranking ${documents.length} documents for query: ${query}`);
-        
-        // Simple reranking based on query term frequency
-        // In a production system, this would use a more sophisticated reranking model
-        const scoredDocs = documents.map(doc => {
-            const queryTerms = query.toLowerCase().split(/\s+/);
-            const docLower = doc.toLowerCase();
-            
-            let score = 0;
-            for (const term of queryTerms) {
-                const matches = (docLower.match(new RegExp(term, 'g')) || []).length;
-                score += matches;
-            }
-            
-            return { doc, score };
-        });
-        
-        // Sort by score and return top K
-        const reranked = scoredDocs
-            .sort((a, b) => b.score - a.score)
-            .slice(0, topK)
-            .map(item => item.doc);
-        
-        console.log(`Reranked to top ${reranked.length} documents`);
-        
-        return reranked;
-    }
-
-    getStats(): {
-        model: string;
-        initialized: boolean;
-    } {
-        return {
-            model: this.model,
-            initialized: this.embeddingRetriever !== null
-        };
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/agents/SupervisorAgent.ts b/agentic-apps/agentic_rag_opensearch/src/agents/SupervisorAgent.ts
deleted file mode 100644
index 468ba937..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/agents/SupervisorAgent.ts
+++ /dev/null
@@ -1,249 +0,0 @@
-import { logTitle } from "../utils";
-import KnowledgeAgent from "./KnowledgeAgent";
-import RAGAgent from "./RAGAgent";
-import MCPAgent from "./MCPAgent";
-import MCPClient from "../MCPClient";
-import { createTrace, createSpan, flushLangfuse, isLangfuseEnabled } from "../LangfuseConfig";
-
-export interface AgentTask {
-    id: string;
-    type: 'knowledge_check' | 'embedding' | 'rag_query' | 'mcp_tool';
-    description: string;
-    data: any;
-}
-
-export interface AgentResult {
-    taskId: string;
-    success: boolean;
-    data?: any;
-    error?: string;
-}
-
-export default class SupervisorAgent {
-    private knowledgeAgent: KnowledgeAgent;
-    private ragAgent: RAGAgent;
-    private mcpAgent: MCPAgent;
-    private taskQueue: AgentTask[] = [];
-    private results: Map<string, AgentResult> = new Map();
-    private trace: any; // Langfuse trace
-
-    constructor(mcpClients: MCPClient[], model: string = 'Qwen/QwQ-32B-AWQ') {
-        this.knowledgeAgent = new KnowledgeAgent();
-        this.ragAgent = new RAGAgent(model);
-        this.mcpAgent = new MCPAgent(mcpClients, model);
-    }
-
-    async init() {
-        logTitle('INITIALIZING SUPERVISOR AGENT');
-        console.log('Initializing all sub-agents...');
-        
-        await Promise.all([
-            this.knowledgeAgent.init(),
-            this.ragAgent.init(),
-            this.mcpAgent.init()
-        ]);
-        
-        console.log('All agents initialized successfully');
-    }
-
-    async close() {
-        logTitle('CLOSING SUPERVISOR AGENT');
-        await Promise.all([
-            this.knowledgeAgent.close(),
-            this.ragAgent.close(),
-            this.mcpAgent.close()
-        ]);
-        
-        // Flush Langfuse traces before closing
-        if (isLangfuseEnabled) {
-            console.log('Flushing Langfuse traces...');
-            await flushLangfuse();
-        }
-    }
-
-    async executeWorkflow(userQuery: string): Promise<string> {
-        logTitle('EXECUTING MULTI-AGENT WORKFLOW');
-        console.log(`User Query: ${userQuery}`);
-
-        // Create main trace for the entire workflow
-        this.trace = createTrace(
-            'multi-agent-workflow',
-            { userQuery },
-            {
-                agentType: 'SupervisorAgent',
-                workflowType: 'multi-agent-rag',
-                timestamp: new Date().toISOString()
-            }
-        );
-
-        try {
-            // Step 1: Check knowledge and update if needed
-            const knowledgeSpan = createSpan(this.trace, 'knowledge-check', { step: 1 });
-            const knowledgeStatus = await this.checkAndUpdateKnowledge();
-            if (knowledgeSpan && isLangfuseEnabled) {
-                knowledgeSpan.end({ output: { hasChanges: knowledgeStatus } });
-            }
-            
-            // Step 2: Retrieve context using RAG
-            const ragSpan = createSpan(this.trace, 'rag-retrieval', { step: 2, userQuery });
-            const context = await this.retrieveContext(userQuery);
-            if (ragSpan && isLangfuseEnabled) {
-                ragSpan.end({ 
-                    output: { 
-                        contextLength: context.length,
-                        contextPreview: context.substring(0, 200) + '...'
-                    } 
-                });
-            }
-            
-            // Step 3: Execute task with MCP tools
-            const mcpSpan = createSpan(this.trace, 'mcp-execution', { step: 3, userQuery, contextLength: context.length });
-            const finalResult = await this.executeWithTools(userQuery, context);
-            if (mcpSpan && isLangfuseEnabled) {
-                mcpSpan.end({ 
-                    output: { 
-                        resultLength: finalResult.length,
-                        resultPreview: finalResult.substring(0, 200) + '...'
-                    } 
-                });
-            }
-
-            // End main trace with success
-            if (this.trace && isLangfuseEnabled) {
-                this.trace.update({
-                    output: {
-                        success: true,
-                        resultLength: finalResult.length,
-                        tasksCompleted: this.results.size
-                    }
-                });
-            }
-            
-            return finalResult;
-        } catch (error) {
-            console.error('Error in workflow execution:', error);
-            
-            // End main trace with error
-            if (this.trace && isLangfuseEnabled) {
-                this.trace.update({
-                    output: {
-                        success: false,
-                        error: error.message || 'Unknown error',
-                        errorType: error.constructor.name
-                    }
-                });
-            }
-            
-            throw error;
-        }
-    }
-
-    private async checkAndUpdateKnowledge(): Promise<boolean> {
-        logTitle('STEP 1: KNOWLEDGE CHECK & UPDATE');
-        
-        const task: AgentTask = {
-            id: 'knowledge-check-' + Date.now(),
-            type: 'knowledge_check',
-            description: 'Check for knowledge changes and update embeddings',
-            data: {}
-        };
-
-        const hasChanges = await this.knowledgeAgent.checkForChanges();
-        
-        if (hasChanges) {
-            console.log('Knowledge changes detected, updating embeddings...');
-            const embeddingResult = await this.knowledgeAgent.embedKnowledge();
-            
-            this.results.set(task.id, {
-                taskId: task.id,
-                success: embeddingResult,
-                data: { hasChanges, embeddingResult }
-            });
-            
-            return embeddingResult;
-        } else {
-            console.log('No knowledge changes detected');
-            this.results.set(task.id, {
-                taskId: task.id,
-                success: true,
-                data: { hasChanges: false }
-            });
-            
-            return true;
-        }
-    }
-
-    private async retrieveContext(query: string): Promise<string> {
-        logTitle('STEP 2: RAG CONTEXT RETRIEVAL');
-        
-        const task: AgentTask = {
-            id: 'rag-query-' + Date.now(),
-            type: 'rag_query',
-            description: 'Retrieve relevant context using RAG',
-            data: { query }
-        };
-
-        try {
-            const context = await this.ragAgent.retrieveContext(query);
-            
-            this.results.set(task.id, {
-                taskId: task.id,
-                success: true,
-                data: { context }
-            });
-            
-            return context;
-        } catch (error) {
-            this.results.set(task.id, {
-                taskId: task.id,
-                success: false,
-                error: error.message
-            });
-            
-            throw error;
-        }
-    }
-
-    private async executeWithTools(query: string, context: string): Promise<string> {
-        logTitle('STEP 3: MCP TOOL EXECUTION');
-        
-        const task: AgentTask = {
-            id: 'mcp-execution-' + Date.now(),
-            type: 'mcp_tool',
-            description: 'Execute task with MCP tools',
-            data: { query, context }
-        };
-
-        try {
-            const result = await this.mcpAgent.executeTask(query, context, this.trace);
-            
-            this.results.set(task.id, {
-                taskId: task.id,
-                success: true,
-                data: { result }
-            });
-            
-            return result;
-        } catch (error) {
-            this.results.set(task.id, {
-                taskId: task.id,
-                success: false,
-                error: error.message
-            });
-            
-            throw error;
-        }
-    }
-
-    getTaskResults(): Map<string, AgentResult> {
-        return this.results;
-    }
-
-    getWorkflowSummary(): string {
-        const results = Array.from(this.results.values());
-        const successful = results.filter(r => r.success).length;
-        const failed = results.filter(r => !r.success).length;
-        
-        return `Workflow Summary: ${successful} successful tasks, ${failed} failed tasks`;
-    }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/agents/index.ts b/agentic-apps/agentic_rag_opensearch/src/agents/index.ts
deleted file mode 100644
index 85af24e3..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/agents/index.ts
+++ /dev/null
@@ -1,6 +0,0 @@
-export { default as SupervisorAgent } from './SupervisorAgent';
-export { default as KnowledgeAgent } from './KnowledgeAgent';
-export { default as RAGAgent } from './RAGAgent';
-export { default as MCPAgent } from './MCPAgent';
-
-export type { AgentTask, AgentResult } from './SupervisorAgent';
diff --git a/agentic-apps/agentic_rag_opensearch/src/embedCSV.ts b/agentic-apps/agentic_rag_opensearch/src/embedCSV.ts
deleted file mode 100644
index e67579ec..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/embedCSV.ts
+++ /dev/null
@@ -1,75 +0,0 @@
-import fs from "fs";
-import path from "path";
-import { parse } from "csv-parse/sync";
-import EmbeddingRetriever from "./EmbeddingRetriever";
-import { logTitle } from "./utils";
-
-// Function to process and embed CSV data
-async function processCSVFile(filePath: string) {
-    logTitle('PROCESSING CSV FILE');
-    console.log(`Processing file: ${filePath}`);
-    
-    try {
-        // Read the CSV file
-        const fileContent = fs.readFileSync(filePath, 'utf-8');
-        
-        // Parse the CSV content
-        const records = parse(fileContent, {
-            columns: true,
-            skip_empty_lines: true
-        });
-        
-        console.log(`Found ${records.length} records in the CSV file`);
-        
-        // Initialize the embedding retriever with llamacpp-embedding model
-        const embeddingRetriever = new EmbeddingRetriever("llamacpp-embedding");
-        
-        // Process each record
-        let processedCount = 0;
-        for (const record of records) {
-            // Combine question and context for better retrieval
-            const documentText = `Question: ${record.question}\nContext: ${record.context}`;
-            
-            // Embed the document
-            await embeddingRetriever.embedDocument(documentText);
-            
-            processedCount++;
-            if (processedCount % 10 === 0) {
-                console.log(`Processed ${processedCount}/${records.length} records`);
-            }
-        }
-        
-        console.log(`Successfully embedded ${processedCount} records from the CSV file`);
-        
-        // Close OpenSearch connection when done
-        // @ts-ignore - Access private property for cleanup
-        if (embeddingRetriever.vectorStore && typeof embeddingRetriever.vectorStore.close === 'function') {
-            // @ts-ignore
-            await embeddingRetriever.vectorStore.close();
-        }
-        
-        return true;
-    } catch (error) {
-        console.error("Error processing CSV file:", error);
-        return false;
-    }
-}
-
-// Main function
-(async () => {
-    const csvFilePath = path.join(process.cwd(), '..', 'knowledge', 'q_c_data.csv');
-    
-    if (!fs.existsSync(csvFilePath)) {
-        console.error(`File not found: ${csvFilePath}`);
-        process.exit(1);
-    }
-    
-    const success = await processCSVFile(csvFilePath);
-    
-    if (success) {
-        console.log("CSV processing completed successfully");
-    } else {
-        console.error("CSV processing failed");
-        process.exit(1);
-    }
-})();
diff --git a/agentic-apps/agentic_rag_opensearch/src/embedKnowledge.ts b/agentic-apps/agentic_rag_opensearch/src/embedKnowledge.ts
deleted file mode 100644
index 4ff94c58..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/embedKnowledge.ts
+++ /dev/null
@@ -1,65 +0,0 @@
-import fs from "fs";
-import path from "path";
-import EmbeddingRetriever from "./EmbeddingRetriever";
-import { logTitle } from "./utils";
-
-// Function to process and embed knowledge files
-async function embedKnowledgeFiles() {
-    logTitle('EMBEDDING KNOWLEDGE FILES');
-    
-    const knowledgePath = path.join(process.cwd(), '..', 'knowledge');
-    
-    if (!fs.existsSync(knowledgePath)) {
-        console.error(`Knowledge directory not found: ${knowledgePath}`);
-        return false;
-    }
-    
-    try {
-        // Get all markdown files in the knowledge directory
-        const files = fs.readdirSync(knowledgePath)
-            .filter(file => file.endsWith('.md'));
-        
-        console.log(`Found ${files.length} markdown files in the knowledge directory`);
-        
-        // Initialize the embedding retriever with llamacpp-embedding model
-        const embeddingRetriever = new EmbeddingRetriever("llamacpp-embedding");
-        
-        // Process each file
-        for (const file of files) {
-            const filePath = path.join(knowledgePath, file);
-            console.log(`Processing file: ${file}`);
-            
-            // Read the file content
-            const content = fs.readFileSync(filePath, 'utf-8');
-            
-            // Embed the document
-            await embeddingRetriever.embedDocument(content);
-        }
-        
-        console.log(`Successfully embedded ${files.length} knowledge files`);
-        
-        // Close OpenSearch connection when done
-        // @ts-ignore - Access private property for cleanup
-        if (embeddingRetriever.vectorStore && typeof embeddingRetriever.vectorStore.close === 'function') {
-            // @ts-ignore
-            await embeddingRetriever.vectorStore.close();
-        }
-        
-        return true;
-    } catch (error) {
-        console.error("Error embedding knowledge files:", error);
-        return false;
-    }
-}
-
-// Main function
-(async () => {
-    const success = await embedKnowledgeFiles();
-    
-    if (success) {
-        console.log("Knowledge embedding completed successfully");
-    } else {
-        console.error("Knowledge embedding failed");
-        process.exit(1);
-    }
-})();
diff --git a/agentic-apps/agentic_rag_opensearch/src/index.ts b/agentic-apps/agentic_rag_opensearch/src/index.ts
deleted file mode 100644
index 8bd1f2fe..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/index.ts
+++ /dev/null
@@ -1,90 +0,0 @@
-import 'dotenv/config';
-import MCPClient from "./MCPClient";
-import { SupervisorAgent } from "./agents";
-import path from "path";
-import fs from "fs";
-import { logTitle } from "./utils";
-
-// Verify environment variables are loaded
-if (!process.env.AWS_REGION || !process.env.OPENSEARCH_ENDPOINT) {
-  throw new Error('Required environment variables AWS_REGION and OPENSEARCH_ENDPOINT are not set');
-}
-
-// Use the parent directory (where the command is run) instead of src directory
-const outPath = path.resolve(process.cwd(), 'output');
-const TASK = `
-Find information about "What is the most important aspect of initial treatment for Bell's palsy?". 
-Summarize this information and create a comprehensive story about Bell's palsy treatment.
-Save the story and important information to a file named "bells_palsy_treatment.md" in the output directory as a beautiful markdown file.
-Include sections for:
-1. Overview of Bell's palsy
-2. Most important initial treatment aspects
-3. Timeline for treatment
-4. Expected outcomes
-5. Additional recommendations
-`
-
-// Make sure output directory exists
-if (!fs.existsSync(outPath)) {
-  fs.mkdirSync(outPath, { recursive: true });
-}
-
-// Start the multi-agent application
-(async () => {
-  try {
-    logTitle('INITIALIZING MULTI-AGENT RAG SYSTEM');
-    
-    // Initialize the filesystem MCP client
-    const fileMCP = new MCPClient("filesystem", "npx", ['-y', '@modelcontextprotocol/server-filesystem', outPath]);
-    
-    await main(fileMCP);
-  } catch (error) {
-    console.error("Error in main:", error);
-    process.exit(1);
-  }
-})();
-
-async function main(fileMCP: MCPClient) {
-  let supervisor: SupervisorAgent | null = null;
-  
-  try {
-    // Initialize the supervisor agent with MCP clients
-    logTitle('INITIALIZING SUPERVISOR AGENT');
-    supervisor = new SupervisorAgent([fileMCP], 'Qwen/QwQ-32B-AWQ');
-    await supervisor.init();
-    
-    // Execute the complete workflow
-    logTitle('EXECUTING MULTI-AGENT WORKFLOW');
-    console.log('Task:', TASK);
-    
-    const result = await supervisor.executeWorkflow(TASK);
-    
-    // Display results
-    logTitle('WORKFLOW COMPLETED');
-    console.log('Final Result:', result);
-    
-    // Display workflow summary
-    const summary = supervisor.getWorkflowSummary();
-    console.log('\n' + summary);
-    
-    // Display detailed task results
-    const taskResults = supervisor.getTaskResults();
-    console.log('\nDetailed Task Results:');
-    for (const [taskId, result] of taskResults) {
-      console.log(`- ${taskId}: ${result.success ? 'SUCCESS' : 'FAILED'}`);
-      if (result.error) {
-        console.log(`  Error: ${result.error}`);
-      }
-    }
-    
-  } catch (error) {
-    console.error("Error in workflow execution:", error);
-    throw error;
-  } finally {
-    // Clean up resources
-    if (supervisor) {
-      logTitle('CLEANING UP');
-      await supervisor.close();
-    }
-  }
-}
diff --git a/agentic-apps/agentic_rag_opensearch/src/scripts/embedKnowledge.ts b/agentic-apps/agentic_rag_opensearch/src/scripts/embedKnowledge.ts
deleted file mode 100644
index dca6c5af..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/scripts/embedKnowledge.ts
+++ /dev/null
@@ -1,50 +0,0 @@
-import 'dotenv/config';
-import { KnowledgeAgent } from "../agents";
-import { logTitle } from "../utils";
-
-// Function to run knowledge embedding as a standalone script
-async function runKnowledgeEmbedding() {
-    logTitle('STANDALONE KNOWLEDGE EMBEDDING');
-    
-    let knowledgeAgent: KnowledgeAgent | null = null;
-    
-    try {
-        // Initialize the knowledge agent
-        knowledgeAgent = new KnowledgeAgent();
-        await knowledgeAgent.init();
-        
-        // Check for changes and embed if needed
-        const hasChanges = await knowledgeAgent.checkForChanges();
-        
-        if (hasChanges) {
-            console.log('Changes detected, embedding all knowledge files (including CSV)...');
-            
-            // Embed all knowledge files (markdown, text, JSON, and CSV)
-            const result = await knowledgeAgent.embedKnowledge();
-            console.log(`Knowledge embedding result: ${result ? 'SUCCESS' : 'FAILED'}`);
-            
-            if (result) {
-                console.log('Knowledge embedding completed successfully');
-            } else {
-                console.error('Knowledge embedding failed');
-                process.exit(1);
-            }
-        } else {
-            console.log('No changes detected in knowledge files');
-        }
-        
-    } catch (error) {
-        console.error('Error in knowledge embedding:', error);
-        process.exit(1);
-    } finally {
-        // Clean up
-        if (knowledgeAgent) {
-            await knowledgeAgent.close();
-        }
-    }
-}
-
-// Main execution
-(async () => {
-    await runKnowledgeEmbedding();
-})();
diff --git a/agentic-apps/agentic_rag_opensearch/src/scripts/index.ts b/agentic-apps/agentic_rag_opensearch/src/scripts/index.ts
deleted file mode 100644
index c075c0ad..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/scripts/index.ts
+++ /dev/null
@@ -1,3 +0,0 @@
-// Export scripts for programmatic usage if needed
-export * from './embedKnowledge';
-
diff --git a/agentic-apps/agentic_rag_opensearch/src/test-agents.ts b/agentic-apps/agentic_rag_opensearch/src/test-agents.ts
deleted file mode 100644
index 10df4826..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/test-agents.ts
+++ /dev/null
@@ -1,63 +0,0 @@
-import 'dotenv/config';
-import { KnowledgeAgent, RAGAgent, MCPAgent, SupervisorAgent } from "./agents";
-import MCPClient from "./MCPClient";
-import { logTitle } from "./utils";
-import path from "path";
-
-// Simple test to verify all agents can be initialized
-async function testAgents() {
-    logTitle('TESTING MULTI-AGENT SYSTEM');
-    
-    try {
-        // Test Knowledge Agent
-        console.log('Testing Knowledge Agent...');
-        const knowledgeAgent = new KnowledgeAgent();
-        await knowledgeAgent.init();
-        const hasChanges = await knowledgeAgent.checkForChanges();
-        console.log(`Knowledge changes detected: ${hasChanges}`);
-        await knowledgeAgent.close();
-        console.log('✓ Knowledge Agent test passed');
-        
-        // Test RAG Agent
-        console.log('\nTesting RAG Agent...');
-        const ragAgent = new RAGAgent();
-        await ragAgent.init();
-        const stats = ragAgent.getStats();
-        console.log('RAG Agent stats:', stats);
-        await ragAgent.close();
-        console.log('✓ RAG Agent test passed');
-        
-        // Test MCP Agent
-        console.log('\nTesting MCP Agent...');
-        const outPath = path.resolve(process.cwd(), 'output');
-        const fileMCP = new MCPClient("filesystem", "npx", ['-y', '@modelcontextprotocol/server-filesystem', outPath]);
-        const mcpAgent = new MCPAgent([fileMCP]);
-        await mcpAgent.init();
-        const mcpStats = mcpAgent.getStats();
-        console.log('MCP Agent stats:', mcpStats);
-        const tools = await mcpAgent.listAvailableTools();
-        console.log(`Available tools: ${tools.length}`);
-        await mcpAgent.close();
-        console.log('✓ MCP Agent test passed');
-        
-        // Test Supervisor Agent
-        console.log('\nTesting Supervisor Agent...');
-        const fileMCP2 = new MCPClient("filesystem", "npx", ['-y', '@modelcontextprotocol/server-filesystem', outPath]);
-        const supervisor = new SupervisorAgent([fileMCP2]);
-        await supervisor.init();
-        console.log('Supervisor Agent initialized successfully');
-        await supervisor.close();
-        console.log('✓ Supervisor Agent test passed');
-        
-        console.log('\n🎉 All agent tests passed successfully!');
-        
-    } catch (error) {
-        console.error('❌ Agent test failed:', error);
-        process.exit(1);
-    }
-}
-
-// Run the test
-(async () => {
-    await testAgents();
-})();
diff --git a/agentic-apps/agentic_rag_opensearch/src/test-langfuse.ts b/agentic-apps/agentic_rag_opensearch/src/test-langfuse.ts
deleted file mode 100644
index 80ada31a..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/test-langfuse.ts
+++ /dev/null
@@ -1,97 +0,0 @@
-import 'dotenv/config';
-import { createTrace, createSpan, createGeneration, flushLangfuse, isLangfuseEnabled } from './LangfuseConfig';
-
-async function testLangfuseIntegration() {
-    console.log('Testing Langfuse Integration...');
-    console.log('Langfuse enabled:', isLangfuseEnabled);
-    
-    if (!isLangfuseEnabled) {
-        console.log('Langfuse is not enabled. Please check your environment variables.');
-        return;
-    }
-    
-    // Create a test trace
-    const trace = createTrace(
-        'test-trace',
-        { message: 'Testing Langfuse integration' },
-        { testType: 'integration-test' }
-    );
-    
-    if (!trace) {
-        console.log('Failed to create trace');
-        return;
-    }
-    
-    console.log('Created trace successfully');
-    
-    // Create a test span
-    const span = createSpan(
-        trace,
-        'test-span',
-        { operation: 'test-operation' },
-        { spanType: 'test' }
-    );
-    
-    if (span) {
-        console.log('Created span successfully');
-        
-        // Simulate some work
-        await new Promise(resolve => setTimeout(resolve, 100));
-        
-        // End the span
-        span.end({
-            output: { result: 'test completed successfully' }
-        });
-        
-        console.log('Ended span successfully');
-    }
-    
-    // Create a test generation
-    const generation = createGeneration(
-        trace,
-        'test-generation',
-        { prompt: 'Test prompt' },
-        'test-model',
-        { generationType: 'test' }
-    );
-    
-    if (generation) {
-        console.log('Created generation successfully');
-        
-        // Simulate LLM response
-        await new Promise(resolve => setTimeout(resolve, 200));
-        
-        // End the generation
-        generation.end({
-            output: { response: 'Test response from LLM' },
-            usage: {
-                promptTokens: 10,
-                completionTokens: 5,
-                totalTokens: 15
-            }
-        });
-        
-        console.log('Ended generation successfully');
-    }
-    
-    // Update the main trace
-    trace.update({
-        output: {
-            success: true,
-            message: 'Test completed successfully'
-        }
-    });
-    
-    console.log('Updated trace successfully');
-    
-    // Flush traces
-    console.log('Flushing traces...');
-    await flushLangfuse();
-    console.log('Traces flushed successfully');
-    
-    console.log('Langfuse integration test completed!');
-    console.log('Check your Langfuse dashboard to see the test traces.');
-}
-
-// Run the test
-testLangfuseIntegration().catch(console.error);
diff --git a/agentic-apps/agentic_rag_opensearch/src/utils.ts b/agentic-apps/agentic_rag_opensearch/src/utils.ts
deleted file mode 100644
index 660eca95..00000000
--- a/agentic-apps/agentic_rag_opensearch/src/utils.ts
+++ /dev/null
@@ -1,9 +0,0 @@
-import chalk from "chalk";
-
-export function logTitle(message: string) {
-    const totalLength = 80;
-    const messageLength = message.length;
-    const padding = Math.max(0, totalLength - messageLength - 4); // 4 for the "=="
-    const paddedMessage = `${'='.repeat(Math.floor(padding / 2))} ${message} ${'='.repeat(Math.ceil(padding / 2))}`;
-    console.log(chalk.bold.cyanBright(paddedMessage));
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_opensearch/tsconfig.json b/agentic-apps/agentic_rag_opensearch/tsconfig.json
deleted file mode 100644
index e5f25ec9..00000000
--- a/agentic-apps/agentic_rag_opensearch/tsconfig.json
+++ /dev/null
@@ -1,17 +0,0 @@
-{
-  "compilerOptions": {
-    "target": "ES2020",
-    "module": "ESNext",
-    "moduleResolution": "Bundler",
-    "esModuleInterop": true,
-    "outDir": "./dist",
-    "rootDir": "./src",
-    "strict": true
-  },
-  "include": [
-    "src/**/*"
-  ],
-  "exclude": [
-    "node_modules"
-  ]
-}
\ No newline at end of file
diff --git a/agentic-apps/agentic_rag_opensearch/update-policy.json b/agentic-apps/agentic_rag_opensearch/update-policy.json
deleted file mode 100644
index f89b85f0..00000000
--- a/agentic-apps/agentic_rag_opensearch/update-policy.json
+++ /dev/null
@@ -1,37 +0,0 @@
-[
-  {
-    "Rules": [
-      {
-        "Resource": [
-          "collection/vectordb"
-        ],
-        "Permission": [
-          "aoss:CreateCollectionItems",
-          "aoss:DeleteCollectionItems",
-          "aoss:UpdateCollectionItems",
-          "aoss:DescribeCollectionItems"
-        ],
-        "ResourceType": "collection"
-      },
-      {
-        "Resource": [
-          "index/vectordb/*"
-        ],
-        "Permission": [
-          "aoss:CreateIndex",
-          "aoss:DeleteIndex",
-          "aoss:UpdateIndex",
-          "aoss:DescribeIndex",
-          "aoss:ReadDocument",
-          "aoss:WriteDocument"
-        ],
-        "ResourceType": "index"
-      }
-    ],
-    "Principal": [
-      "arn:aws:iam::412381761882:user/admin",
-      "arn:aws:iam::412381761882:root"
-    ],
-    "Description": "Rule 1"
-  }
-]
diff --git a/agentic-apps/single_agent/kubernetes/function_call.yaml b/agentic-apps/single_agent/kubernetes/function_call.yaml
deleted file mode 100644
index 62d2d964..00000000
--- a/agentic-apps/single_agent/kubernetes/function_call.yaml
+++ /dev/null
@@ -1,85 +0,0 @@
-apiVersion: v1
-kind: Secret
-metadata:
-  name: llm-credentials
-type: Opaque
-data:
-  # Base64 encoded value of your API key
-  # Replace with: echo -n "your-api-key" | base64
-  api-key: c2stMTIzNA==  # This is "sk-1234" encoded
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: weather-function-service
-spec:
-  replicas: 2
-  selector:
-    matchLabels:
-      app: weather-function-service
-  template:
-    metadata:
-      labels:
-        app: weather-function-service
-    spec:
-      nodeSelector:
-        kubernetes.io/arch: arm64
-      affinity:
-        nodeAffinity:
-          requiredDuringSchedulingIgnoredDuringExecution:
-            nodeSelectorTerms:
-            - matchExpressions:
-              - key: kubernetes.io/arch
-                operator: In
-                values:
-                - arm64
-      containers:
-      - name: weather-function-service
-        image: 412381761882.dkr.ecr.us-west-2.amazonaws.com/function:v5
-        ports:
-        - containerPort: 8000
-        env:
-        - name: LLM_SERVER_URL
-          value: ""
-        - name: LLM_MODEL
-          value: "Qwen/QwQ-32B-AWQ"
-        - name: LLM_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: llm-credentials
-              key: api-key
-        resources:
-          requests:
-            memory: "256Mi"
-            cpu: "100m"
-          limits:
-            memory: "512Mi"
-            cpu: "500m"
-        livenessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 30
-          periodSeconds: 10
-        readinessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 5
-          periodSeconds: 5
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: weather-function-service
-  annotations:
-    service.beta.kubernetes.io/aws-load-balancer-type: "external"
-    service.beta.kubernetes.io/aws-load-balancer-nlb-target-type: "ip"
-    service.beta.kubernetes.io/aws-load-balancer-scheme: "internet-facing"
-spec:
-  selector:
-    app: weather-function-service
-  ports:
-  - port: 80
-    targetPort: 8000
-  type: LoadBalancer
diff --git a/agentic-apps/single_agent/src/Dockerfile b/agentic-apps/single_agent/src/Dockerfile
deleted file mode 100644
index 2e9409f4..00000000
--- a/agentic-apps/single_agent/src/Dockerfile
+++ /dev/null
@@ -1,27 +0,0 @@
-FROM python:3.9-slim
-
-WORKDIR /app
-
-# Copy requirements first to leverage Docker cache
-COPY requirements.txt .
-
-# Install dependencies
-RUN pip install --no-cache-dir -r requirements.txt
-
-# Copy application code
-COPY server.py weather_service.py ./
-
-# Set environment variables with default values
-# These can be overridden when running the container
-ENV LLM_SERVER_URL="http://llm-service:8080/v1/chat/completions" \
-    LLM_API_KEY="sk-1234" \
-    LLM_MODEL="llama3" \
-    CONNECT_TIMEOUT=10 \
-    READ_TIMEOUT=300 \
-    LLM_MAX_RETRIES=3
-
-# Expose the port the app runs on
-EXPOSE 8000
-
-# Command to run the application
-CMD ["uvicorn", "server:app", "--host", "0.0.0.0", "--port", "8000"]
diff --git a/agentic-apps/single_agent/src/README.md b/agentic-apps/single_agent/src/README.md
deleted file mode 100644
index f590b829..00000000
--- a/agentic-apps/single_agent/src/README.md
+++ /dev/null
@@ -1,119 +0,0 @@
-# Weather Function Call Service for EKS
-
-This service provides a FastAPI application that uses LLM function calling capabilities to retrieve weather information. It's designed to run in an Amazon EKS cluster.
-
-## Features
-
-- Current weather information for any city
-- Weather forecasts for up to 16 days
-- LLM-powered chat interface with function calling capabilities
-- Health check endpoints
-
-## Environment Variables
-
-The application can be configured using the following environment variables:
-
-- `LLM_SERVER_URL`: URL of the LLM server (default: "http://llm-service:8080/v1/chat/completions")
-- `LLM_API_KEY`: API key for the LLM service (default: "sk-1234")
-- `LLM_MODEL`: Model name to use for inference (default: "llama3")
-- `CONNECT_TIMEOUT`: Connection timeout in seconds (default: 10)
-- `READ_TIMEOUT`: Read timeout in seconds (default: 300)
-- `LLM_MAX_RETRIES`: Maximum number of retries for LLM requests (default: 3)
-
-## Building and Running
-
-### Build the Docker image
-
-```bash
-docker build -t weather-function-service:latest .
-```
-
-### Run locally
-
-```bash
-docker run -p 8000:8000 \
-  -e LLM_SERVER_URL="http://your-llm-server:8080/v1/chat/completions" \
-  -e LLM_API_KEY="your-api-key" \
-  -e LLM_MODEL="llama3" \
-  weather-function-service:latest
-```
-
-## Deploying to EKS
-
-1. Push the image to a container registry (ECR, Docker Hub, etc.)
-2. Apply the Kubernetes deployment manifest
-
-```yaml
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: weather-function-service
-spec:
-  replicas: 2
-  selector:
-    matchLabels:
-      app: weather-function-service
-  template:
-    metadata:
-      labels:
-        app: weather-function-service
-    spec:
-      containers:
-      - name: weather-function-service
-        image: your-registry/weather-function-service:latest
-        ports:
-        - containerPort: 8000
-        env:
-        - name: LLM_SERVER_URL
-          value: "http://llm-service:8080/v1/chat/completions"
-        - name: LLM_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: llm-credentials
-              key: api-key
-        - name: LLM_MODEL
-          value: "llama3"
-        resources:
-          requests:
-            memory: "256Mi"
-            cpu: "100m"
-          limits:
-            memory: "512Mi"
-            cpu: "500m"
-        livenessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 30
-          periodSeconds: 10
-        readinessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 5
-          periodSeconds: 5
-```
-
-3. Create a service to expose the deployment
-
-```yaml
-apiVersion: v1
-kind: Service
-metadata:
-  name: weather-function-service
-spec:
-  selector:
-    app: weather-function-service
-  ports:
-  - port: 80
-    targetPort: 8000
-  type: ClusterIP
-```
-
-## API Endpoints
-
-- `POST /weather/current`: Get current weather for a city
-- `POST /weather/forecast`: Get weather forecast for a city
-- `POST /chat`: Chat with the LLM using weather functions
-- `GET /health`: Health check endpoint
-- `GET /health/llm`: LLM health check endpoint
diff --git a/agentic-apps/single_agent/src/requirements.txt b/agentic-apps/single_agent/src/requirements.txt
deleted file mode 100644
index fa94b791..00000000
--- a/agentic-apps/single_agent/src/requirements.txt
+++ /dev/null
@@ -1,6 +0,0 @@
-fastapi>=0.95.0
-uvicorn>=0.21.1
-pydantic>=1.10.7
-requests>=2.28.2
-urllib3>=1.26.15
-python-multipart>=0.0.6
diff --git a/agentic-apps/single_agent/src/server.py b/agentic-apps/single_agent/src/server.py
deleted file mode 100644
index 15ce922b..00000000
--- a/agentic-apps/single_agent/src/server.py
+++ /dev/null
@@ -1,372 +0,0 @@
-from fastapi import FastAPI, HTTPException
-from pydantic import BaseModel
-from typing import List, Optional, Dict, Any
-import requests
-from requests.adapters import HTTPAdapter
-from urllib3.util.retry import Retry
-import json
-import os
-import asyncio
-import logging
-import time
-from weather_service import WeatherService, WeatherData, ForecastData
-
-# Initialize FastAPI app
-app = FastAPI()
-
-# Configure logging
-logging.basicConfig(
-    level=logging.INFO,
-    format='%(asctime)s - %(name)s - %(levelname)s - %(message)s'
-)
-logger = logging.getLogger(__name__)
-
-# Configuration
-LLM_SERVER_URL = os.environ.get("LLM_SERVER_URL", "http://:8080/v1/chat/completions")
-LLM_API_KEY = os.environ.get("LLM_API_KEY", "sk-1234")
-LLM_MODEL = os.environ.get("LLM_MODEL", "llama3")
-CONNECT_TIMEOUT = int(os.environ.get("CONNECT_TIMEOUT", 10))
-READ_TIMEOUT = int(os.environ.get("READ_TIMEOUT", 300))
-LLM_MAX_RETRIES = int(os.environ.get("LLM_MAX_RETRIES", 3))
-
-# Pydantic models
-class WeatherRequest(BaseModel):
-    city: str
-
-class ForecastRequest(BaseModel):
-    city: str
-    days: Optional[int] = 5
-
-class Message(BaseModel):
-    role: str
-    content: str
-    name: Optional[str] = None
-
-class ChatRequest(BaseModel):
-    messages: List[Message]
-    model: Optional[str] = None
-
-class ChatResponse(BaseModel):
-    response: str
-    data: Optional[Dict] = None
-
-class CustomLLMClient:
-    def __init__(self, base_url: str, api_key: str, model: str = "llama3"):
-        self.base_url = base_url
-        self.model = model
-        self.headers = {
-            "Authorization": f"Bearer {api_key}",
-            "Content-Type": "application/json"
-        }
-        
-        # Configure retry strategy
-        retry_strategy = Retry(
-            total=LLM_MAX_RETRIES,
-            backoff_factor=1,
-            status_forcelist=[408, 429, 500, 502, 503, 504],
-        )
-        
-        # Create session with retry strategy
-        self.session = requests.Session()
-        adapter = HTTPAdapter(
-            max_retries=retry_strategy,
-            pool_connections=10,
-            pool_maxsize=100
-        )
-        self.session.mount("http://", adapter)
-        self.session.mount("https://", adapter)
-
-    async def create_chat_completion(self, messages: List[Dict], functions: List[Dict] = None, 
-                                   function_call: str = "auto", model: str = None) -> Dict:
-        try:
-            start_time = time.time()
-            payload = {
-                "model": model or self.model,
-                "messages": messages,
-                "temperature": 0.7,
-                "max_tokens": 1000
-            }
-            
-            # Only add functions if they are provided
-            if functions:
-                payload["functions"] = functions
-                payload["function_call"] = function_call
-
-            logger.info(f"Sending payload to LLM server: {json.dumps(payload, default=str)}")
-
-            loop = asyncio.get_event_loop()
-            response = await loop.run_in_executor(
-                None,
-                lambda: self.session.post(
-                    self.base_url,
-                    headers=self.headers,
-                    json=payload,
-                    timeout=(CONNECT_TIMEOUT, READ_TIMEOUT)
-                )
-            )
-            
-            response.raise_for_status()
-            duration = time.time() - start_time
-            logger.info(f"LLM request completed in {duration:.2f} seconds")
-            
-            # Log raw response text for debugging
-            logger.info(f"Raw response text: {response.text}")
-            
-            # Parse JSON response safely
-            try:
-                response_json = response.json()
-                return response_json
-            except json.JSONDecodeError as e:
-                logger.error(f"Failed to parse JSON response: {e}")
-                logger.error(f"Response text: {response.text}")
-                raise HTTPException(
-                    status_code=500,
-                    detail=f"Invalid JSON response from LLM server: {str(e)}"
-                )
-
-        except requests.exceptions.ConnectTimeout:
-            logger.error(f"Connection timeout after {CONNECT_TIMEOUT} seconds")
-            raise HTTPException(
-                status_code=504,
-                detail=f"Failed to connect to LLM server within {CONNECT_TIMEOUT} seconds"
-            )
-        except requests.exceptions.ReadTimeout:
-            logger.error(f"Read timeout after {READ_TIMEOUT} seconds")
-            raise HTTPException(
-                status_code=504,
-                detail=f"LLM server response timeout after {READ_TIMEOUT} seconds"
-            )
-        except requests.exceptions.RequestException as e:
-            logger.error(f"Request failed: {str(e)}")
-            raise HTTPException(
-                status_code=500,
-                detail=f"LLM Server Error: {str(e)}"
-            )
-
-# Initialize services
-weather_service = WeatherService()
-llm_client = CustomLLMClient(LLM_SERVER_URL, LLM_API_KEY, LLM_MODEL)
-
-# Function definitions for LLM
-weather_functions = [
-    {
-        "name": "get_current_weather",
-        "description": "Get the current weather for a specific city",
-        "parameters": {
-            "type": "object",
-            "properties": {
-                "city": {
-                    "type": "string",
-                    "description": "The city name to get weather for"
-                }
-            },
-            "required": ["city"]
-        }
-    },
-    {
-        "name": "get_weather_forecast",
-        "description": "Get the weather forecast for a specific city",
-        "parameters": {
-            "type": "object",
-            "properties": {
-                "city": {
-                    "type": "string",
-                    "description": "The city name to get forecast for"
-                },
-                "days": {
-                    "type": "integer",
-                    "description": "Number of days to forecast (max 16)",
-                    "minimum": 1,
-                    "maximum": 16
-                }
-            },
-            "required": ["city"]
-        }
-    }
-]
-
-# Function mapping
-def function_map(name: str, args: Dict[str, Any]) -> Any:
-    if name == "get_current_weather":
-        current_weather = weather_service.get_current_weather(args["city"])
-        if current_weather:
-            return {
-                "temperature": current_weather.temperature,
-                "description": current_weather.description,
-                "humidity": current_weather.humidity,
-                "wind_speed": current_weather.wind_speed
-            }
-        return None
-
-    elif name == "get_weather_forecast":
-        days = args.get("days", 5)
-        forecast = weather_service.get_forecast(args["city"], days)
-        if forecast:
-            return [{
-                "date": f.date,
-                "max_temp": f.max_temp,
-                "min_temp": f.min_temp,
-                "precipitation": f.precipitation,
-                "wind_speed": f.wind_speed
-            } for f in forecast]
-        return None
-
-    return None
-
-# API endpoints
-@app.post("/weather/current")
-async def current_weather(request: WeatherRequest):
-    result = weather_service.get_current_weather(request.city)
-    if not result:
-        raise HTTPException(status_code=404, detail="Weather data not found")
-    return result
-
-@app.post("/weather/forecast")
-async def weather_forecast(request: ForecastRequest):
-    result = weather_service.get_forecast(request.city, request.days)
-    if not result:
-        raise HTTPException(status_code=404, detail="Forecast data not found")
-    return result
-
-@app.post("/chat", response_model=ChatResponse)
-async def chat_endpoint(request: ChatRequest):
-    try:
-        # Convert Pydantic models to dictionaries
-        messages = [message.dict(exclude_none=True) for message in request.messages]
-        
-        # Use model from request if provided, otherwise use default
-        model = request.model if request.model else LLM_MODEL
-        
-        # Log the request being sent to the LLM server
-        logger.info(f"Sending request to LLM server: {LLM_SERVER_URL}")
-        logger.info(f"Using model: {model}")
-        logger.info(f"Request messages: {json.dumps(messages)}")
-        logger.info(f"Functions: {json.dumps(weather_functions)}")
-        
-        response = await llm_client.create_chat_completion(
-            messages=messages,
-            functions=weather_functions,
-            function_call="auto",
-            model=model
-        )
-        
-        # Log the raw response for debugging
-        logger.info(f"Raw LLM response: {json.dumps(response, default=str)}")
-        
-        # Check if response has the expected structure
-        if not response:
-            raise ValueError("LLM server returned None response")
-        if "choices" not in response:
-            raise ValueError(f"LLM response missing 'choices' field: {response}")
-        if not response["choices"] or len(response["choices"]) == 0:
-            raise ValueError(f"LLM response has empty 'choices' array: {response}")
-        if "message" not in response["choices"][0]:
-            raise ValueError(f"LLM response missing 'message' in first choice: {response['choices'][0]}")
-        
-        response_message = response["choices"][0]["message"]
-        
-        if "function_call" in response_message:
-            try:
-                # Function call detected, execute it and append result
-                function_name = response_message["function_call"]["name"]
-                
-                # Safely parse function arguments with better error handling
-                try:
-                    function_args_str = response_message["function_call"]["arguments"]
-                    function_args = json.loads(function_args_str)
-                except (KeyError, json.JSONDecodeError) as e:
-                    logger.error(f"Failed to parse function arguments: {e}")
-                    logger.error(f"Raw arguments: {response_message.get('function_call', {}).get('arguments', 'N/A')}")
-                    raise ValueError(f"Invalid function arguments: {str(e)}")
-                
-                logger.info(f"Function call detected: {function_name} with args: {function_args}")
-                
-                function_response = function_map(function_name, function_args)
-                
-                if function_response is None:
-                    logger.warning(f"Function {function_name} returned None response")
-                    function_response = {"error": f"No data found for {function_args.get('city', 'unknown location')}"}
-                
-                # Add function response to messages
-                messages.append({
-                    "role": "function",
-                    "name": function_name,
-                    "content": json.dumps(function_response)
-                })
-                
-                logger.info(f"Sending second request to LLM with function response")
-                second_response = await llm_client.create_chat_completion(
-                    messages=messages,
-                    model=model
-                )
-                
-                # Check second response structure with detailed error handling
-                if not second_response:
-                    raise ValueError("Second LLM request returned None response")
-                if "choices" not in second_response:
-                    raise ValueError(f"Second LLM response missing 'choices' field: {second_response}")
-                if not second_response["choices"] or len(second_response["choices"]) == 0:
-                    raise ValueError(f"Second LLM response has empty 'choices' array: {second_response}")
-                if "message" not in second_response["choices"][0]:
-                    raise ValueError(f"Second LLM response missing 'message' in first choice: {second_response['choices'][0]}")
-                
-                return ChatResponse(
-                    response=second_response["choices"][0]["message"]["content"],
-                    data=function_response
-                )
-            except Exception as e:
-                logger.error(f"Error processing function call: {str(e)}", exc_info=True)
-                # Fallback to original response if function call processing fails
-                return ChatResponse(
-                    response=f"I tried to get weather information, but encountered an error: {str(e)}. Please try again with a specific city name.",
-                    data={"error": str(e)}
-                )
-        
-        return ChatResponse(response=response_message["content"])
-    
-    except Exception as e:
-        logger.error(f"Chat endpoint error: {str(e)}", exc_info=True)
-        raise HTTPException(
-            status_code=500,
-            detail=f"Error processing request: {str(e)}"
-        )
-
-@app.get("/health")
-async def health_check():
-    return {"status": "healthy"}
-
-@app.get("/health/llm")
-async def llm_health_check():
-    try:
-        response = await llm_client.create_chat_completion(
-            messages=[{"role": "user", "content": "test"}]
-        )
-        # Check if response has expected structure
-        if not response or "choices" not in response or not response["choices"]:
-            return {
-                "status": "unhealthy", 
-                "reason": f"LLM server returned unexpected response format: {json.dumps(response, default=str)}"
-            }
-        return {"status": "healthy", "latency": response.get("latency", None)}
-    except Exception as e:
-        logger.error(f"LLM health check failed: {str(e)}", exc_info=True)
-        raise HTTPException(
-            status_code=503,
-            detail=f"LLM server unhealthy: {str(e)}"
-        )
-
-# Logging middleware
-@app.middleware("http")
-async def log_requests(request, call_next):
-    start_time = time.time()
-    response = await call_next(request)
-    duration = time.time() - start_time
-    logger.info(f"Path: {request.url.path} Duration: {duration:.2f}s Status: {response.status_code}")
-    return response
-
-# Startup message
-print(f"Server started with Connect Timeout: {CONNECT_TIMEOUT}s, Read Timeout: {READ_TIMEOUT}s")
-
-if __name__ == "__main__":
-    import uvicorn
-    uvicorn.run(app, host="0.0.0.0", port=8000)
diff --git a/agentic-apps/single_agent/src/weather_service.py b/agentic-apps/single_agent/src/weather_service.py
deleted file mode 100644
index 6f02b9b4..00000000
--- a/agentic-apps/single_agent/src/weather_service.py
+++ /dev/null
@@ -1,153 +0,0 @@
-# weather_service.py
-
-import requests
-from datetime import datetime
-from typing import Dict, Optional, List, Tuple
-from dataclasses import dataclass
-
-@dataclass
-class WeatherData:
-    temperature: float
-    description: str
-    humidity: float
-    wind_speed: float
-
-@dataclass
-class ForecastData:
-    date: str
-    max_temp: float
-    min_temp: float
-    precipitation: float
-    wind_speed: float
-
-class WeatherService:
-    def __init__(self):
-        self.geocoding_url = "https://geocoding-api.open-meteo.com/v1/search"
-        self.weather_url = "https://api.open-meteo.com/v1/forecast"
-    
-    def _get_coordinates(self, city: str) -> Optional[Tuple[float, float]]:
-        """
-        Get latitude and longitude for a given city name
-        """
-        try:
-            params = {
-                "name": city,
-                "count": 1,
-                "language": "en",
-                "format": "json"
-            }
-            
-            response = requests.get(self.geocoding_url, params=params, timeout=10)
-            response.raise_for_status()
-            data = response.json()
-            
-            if not data.get("results"):
-                print(f"City '{city}' not found")
-                return None
-            
-            location = data["results"][0]
-            return location["latitude"], location["longitude"]
-            
-        except requests.exceptions.RequestException as e:
-            print(f"Error getting coordinates: {e}")
-            return None
-
-    def get_current_weather(self, city: str) -> Optional[WeatherData]:
-        """
-        Get current weather for a given city
-        """
-        coordinates = self._get_coordinates(city)
-        if not coordinates:
-            return None
-        
-        lat, lon = coordinates
-        
-        try:
-            params = {
-                "latitude": lat,
-                "longitude": lon,
-                "current_weather": True,
-                "hourly": ["temperature_2m", "relative_humidity_2m", "windspeed_10m"],
-                "timezone": "auto"
-            }
-            
-            response = requests.get(self.weather_url, params=params, timeout=10)
-            response.raise_for_status()
-            data = response.json()
-            
-            current_hour = datetime.now().hour
-            
-            weather = WeatherData(
-                temperature=data["hourly"]["temperature_2m"][current_hour],
-                description=self._get_weather_description(
-                    data["hourly"]["temperature_2m"][current_hour]
-                ),
-                humidity=data["hourly"]["relative_humidity_2m"][current_hour],
-                wind_speed=data["hourly"]["windspeed_10m"][current_hour]
-            )
-            
-            return weather
-            
-        except requests.exceptions.RequestException as e:
-            print(f"Error fetching current weather: {e}")
-            return None
-
-    def get_forecast(self, city: str, days: int = 5) -> Optional[List[ForecastData]]:
-        """
-        Get weather forecast for a given city
-        """
-        if days > 16:
-            days = 16
-            print("Maximum forecast days is 16, adjusting to 16 days")
-            
-        coordinates = self._get_coordinates(city)
-        if not coordinates:
-            return None
-            
-        lat, lon = coordinates
-        
-        try:
-            params = {
-                "latitude": lat,
-                "longitude": lon,
-                "daily": ["temperature_2m_max", 
-                         "temperature_2m_min",
-                         "precipitation_sum",
-                         "windspeed_10m_max"],
-                "timezone": "auto",
-                "forecast_days": days
-            }
-            
-            response = requests.get(self.weather_url, params=params, timeout=10)
-            response.raise_for_status()
-            data = response.json()
-            
-            daily_data = data['daily']
-            forecast_list = []
-            
-            for i in range(days):
-                forecast = ForecastData(
-                    date=datetime.fromisoformat(daily_data['time'][i]).strftime('%Y-%m-%d'),
-                    max_temp=daily_data['temperature_2m_max'][i],
-                    min_temp=daily_data['temperature_2m_min'][i],
-                    precipitation=daily_data['precipitation_sum'][i],
-                    wind_speed=daily_data['windspeed_10m_max'][i]
-                )
-                forecast_list.append(forecast)
-                
-            return forecast_list
-            
-        except requests.exceptions.RequestException as e:
-            print(f"Error fetching forecast: {e}")
-            return None
-
-    def _get_weather_description(self, temperature: float) -> str:
-        """Simple helper to generate weather description based on temperature"""
-        if temperature > 30:
-            return "Hot"
-        elif temperature > 20:
-            return "Warm"
-        elif temperature > 10:
-            return "Mild"
-        else:
-            return "Cold"
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/.env.example b/agentic-apps/strandsdk_agentic_rag_opensearch/.env.example
deleted file mode 100644
index 2e446104..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/.env.example
+++ /dev/null
@@ -1,60 +0,0 @@
-# LiteLLM Configuration for Reasoning Models
-LITELLM_API_KEY=your-litellm-api-key
-LITELLM_BASE_URL=http://your-litellm-server:8080/v1
-REASONING_MODEL=qwen-qwq-32b-preview
-
-# Embedding Configuration (separate from reasoning)
-EMBEDDING_API_KEY=your-embedding-api-key
-EMBEDDING_BASE_URL=http://your-embedding-server:8080/v1
-EMBEDDING_MODEL=llamacpp-embedding
-
-
-# AWS Configuration  
-AWS_REGION=us-east-1
-OPENSEARCH_ENDPOINT=https://your-opensearch-domain.region.es.amazonaws.com
-
-# Tavily Web Search Configuration
-TAVILY_API_KEY=your-tavily-api-key
-
-# Optional: Langfuse for observability
-LANGFUSE_HOST=https://cloud.langfuse.com
-LANGFUSE_PUBLIC_KEY=your-public-key
-LANGFUSE_SECRET_KEY=your-secret-key
-
-# Application Settings
-KNOWLEDGE_DIR=knowledge
-OUTPUT_DIR=output
-VECTOR_INDEX_NAME=knowledge-embeddings
-TOP_K_RESULTS=5
-BYPASS_TOOL_CONSENT=true
-
-# Configuration Notes:
-# 
-# LITELLM_API_KEY: API key for your LiteLLM server hosting reasoning models
-# LITELLM_BASE_URL: Endpoint for LiteLLM server (e.g., http://localhost:8080/v1)
-# REASONING_MODEL: Model name for agent reasoning tasks (e.g., qwen-qwq-32b-preview)
-# 
-# EMBEDDING_API_KEY: API key for embedding service (can be same as LITELLM_API_KEY)
-# EMBEDDING_BASE_URL: Endpoint for embedding generation (can be same as LITELLM_BASE_URL)
-# EMBEDDING_MODEL: Model name for generating embeddings (e.g., llamacpp-embedding)
-# 
-# OPENAI_*: Legacy configuration for backward compatibility
-# DEFAULT_MODEL: Fallback model ID if LiteLLM fails
-# 
-# AWS_REGION: AWS region for OpenSearch and other AWS services
-# OPENSEARCH_ENDPOINT: Your AWS OpenSearch domain endpoint
-# 
-# TAVILY_API_KEY: API key for Tavily web search service (get from https://tavily.com)
-# 
-# LANGFUSE_*: Optional observability tracking (leave empty to disable)
-# 
-# KNOWLEDGE_DIR: Directory containing knowledge files to embed
-# OUTPUT_DIR: Directory for generated outputs and reports
-# VECTOR_INDEX_NAME: OpenSearch index name for vector storage
-# TOP_K_RESULTS: Default number of search results to return
-#
-# Model Usage:
-# - Reasoning Tasks (All Agents): Uses REASONING_MODEL via LiteLLM
-# - Embedding Tasks (RAG): Uses EMBEDDING_MODEL via embedding endpoint
-# - Web Search: Uses Tavily API for real-time information when RAG relevance is low
-# - Both LLM models can point to the same LiteLLM server with different model names
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/Dockerfile.main b/agentic-apps/strandsdk_agentic_rag_opensearch/Dockerfile.main
deleted file mode 100644
index c0d15447..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/Dockerfile.main
+++ /dev/null
@@ -1,52 +0,0 @@
-# Dockerfile for Main Application (FastAPI Server)
-FROM python:3.11-slim as base
-
-# Set environment variables
-ENV PYTHONUNBUFFERED=1
-ENV PYTHONDONTWRITEBYTECODE=1
-ENV DEBIAN_FRONTEND=noninteractive
-
-# Install system dependencies
-RUN apt-get update && apt-get install -y \
-    curl \
-    git \
-    build-essential \
-    && rm -rf /var/lib/apt/lists/*
-
-# Set working directory
-WORKDIR /app
-
-# Copy requirements first for better caching
-COPY requirements.txt .
-
-# Install Python dependencies
-RUN pip install --no-cache-dir -r requirements.txt
-
-# Install additional dependencies for the FastAPI server
-RUN pip install fastapi uvicorn python-dotenv httpx
-
-# Copy the entire application
-COPY . .
-
-# Create necessary directories
-RUN mkdir -p knowledge output logs
-
-# Set proper permissions
-RUN chmod +x scripts/*.py 2>/dev/null || true
-
-# Copy startup and health check scripts
-COPY startup-main.sh /app/startup-main.sh
-COPY healthcheck-main.sh /app/healthcheck-main.sh
-
-# Make startup and health check scripts executable
-RUN chmod +x /app/startup-main.sh /app/healthcheck-main.sh
-
-# Expose the FastAPI server port
-EXPOSE 8000
-
-# Add health check
-HEALTHCHECK --interval=30s --timeout=10s --start-period=60s --retries=3 \
-    CMD /app/healthcheck-main.sh
-
-# Set the default command
-CMD ["/app/startup-main.sh"]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/Dockerfile.mcp b/agentic-apps/strandsdk_agentic_rag_opensearch/Dockerfile.mcp
deleted file mode 100644
index f7d40aca..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/Dockerfile.mcp
+++ /dev/null
@@ -1,52 +0,0 @@
-# Dockerfile for MCP Server (Tavily Search Server)
-FROM python:3.11-slim as base
-
-# Set environment variables
-ENV PYTHONUNBUFFERED=1
-ENV PYTHONDONTWRITEBYTECODE=1
-ENV DEBIAN_FRONTEND=noninteractive
-
-# Install system dependencies
-RUN apt-get update && apt-get install -y \
-    curl \
-    git \
-    build-essential \
-    && rm -rf /var/lib/apt/lists/*
-
-# Set working directory
-WORKDIR /app
-
-# Copy requirements first for better caching
-COPY requirements.txt .
-
-# Install Python dependencies
-RUN pip install --no-cache-dir -r requirements.txt
-
-# Install additional dependencies for the MCP server
-RUN pip install python-dotenv httpx fastmcp
-
-# Copy the entire application
-COPY . .
-
-# Create necessary directories
-RUN mkdir -p logs
-
-# Set proper permissions
-RUN chmod +x scripts/*.py 2>/dev/null || true
-
-# Copy startup and health check scripts
-COPY startup-mcp.sh /app/startup-mcp.sh
-COPY healthcheck-mcp.sh /app/healthcheck-mcp.sh
-
-# Make startup and health check scripts executable
-RUN chmod +x /app/startup-mcp.sh /app/healthcheck-mcp.sh
-
-# Expose the MCP server port
-EXPOSE 8001
-
-# Add health check
-HEALTHCHECK --interval=30s --timeout=10s --start-period=60s --retries=3 \
-    CMD /app/healthcheck-mcp.sh
-
-# Set the default command
-CMD ["/app/startup-mcp.sh"]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/README.md b/agentic-apps/strandsdk_agentic_rag_opensearch/README.md
deleted file mode 100644
index 6472122f..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/README.md
+++ /dev/null
@@ -1,496 +0,0 @@
-# Multi-Agent RAG with Strands SDK and OpenSearch
-
-This project implements a sophisticated multi-agent Large Language Model (LLM) system using the **Strands SDK** that combines Model Context Protocol (MCP) for tool usage and Retrieval Augmented Generation (RAG) for enhanced context awareness, using OpenSearch as the vector database.
-
-## 🏗️ Architecture
-![Architecture Diagram](images/arch.png)
-
-The system is built with a modular multi-agent architecture using Strands SDK patterns with built-in OpenTelemetry tracing:
-
-```
-SupervisorAgent (Orchestrator) [with built-in tracing]
-├── KnowledgeAgent → Manages knowledge base and embeddings [traced]
-├── MCPAgent → Manages tool interactions via MCP protocol [traced]
-└── Strands SDK → Provides agent framework, tool integration, and OpenTelemetry tracing
-```
-
-## 🚀 Key Features
-
-### Multi-Agent Orchestration
-- **SupervisorAgent**: Main orchestrator with integrated RAG capabilities using Strands SDK
-- **KnowledgeAgent**: Monitors and manages knowledge base changes
-- **MCPAgent**: Executes tasks using MCP tools and file operations
-- **Built-in Tracing**: All agents include OpenTelemetry tracing via Strands SDK
-
-### Advanced RAG Capabilities
-- **OpenSearch Integration**: Vector storage and similarity search
-- **Embedding Generation**: Configurable embedding models and endpoints
-- **Multi-format Support**: Handles markdown, text, JSON, and CSV files
-- **Intelligent Search**: Vector similarity search with metadata and scoring
-- **Relevance Scoring**: Automatic relevance assessment for search results
-
-### External Web Search Integration 🌐
-- **Tavily API Integration**: Real-time web search via MCP server
-- **Automatic Triggering**: Web search activated when RAG relevance < 0.3
-- **News Search**: Dedicated recent news and current events search
-- **Hybrid Responses**: Combines knowledge base and web search results
-- **Smart Fallback**: Graceful degradation when web search unavailable
-
-### MCP Tool Integration
-- **Filesystem Operations**: Read, write, and manage files using Strands tools
-- **Web Search Tools**: Tavily-powered web and news search capabilities
-- **Extensible Architecture**: Easy to add new MCP servers
-- **Error Handling**: Robust tool execution with fallbacks
-- **Built-in Tools**: Integration with Strands built-in tools
-
-### Observability & Tracing
-- **OpenTelemetry Integration**: Native tracing through Strands SDK
-- **Multiple Export Options**: Console, OTLP endpoints, Jaeger, Langfuse
-- **Automatic Instrumentation**: All agent interactions are automatically traced
-- **Performance Monitoring**: Track execution times, token usage, and tool calls
-
-
-## 🏃‍♂️ Usage
-
-## Option 1, Container Deployment on Kubernetes
-
-For production deployments, use the containerized solution with Kubernetes:
-
-### 📋 Prerequisites
-
-- Python 3.9+
-- EKS cluster
-- TAVILY_API_KEY
-- AWS credentials configured
-
-### 🛠️ Installation
-
-#### 1. Build and Push Container Images
-
-```bash
-# Build Docker images and push to ECR
-./build-images.sh
-
-# This script will:
-# - Create ECR repositories if they don't exist
-# - Build main application and MCP server images
-# - Push images to ECR
-# - Update Kubernetes deployment files with ECR image URLs
-```
-
-#### 2. Deploy OpenSearch Cluster
-
-```bash
-# Deploy OpenSearch with CloudFormation and EKS Pod Identity
-./deploy-opensearch.sh [stack-name] [region] [namespace]
-
-# Example:
-./deploy-opensearch.sh strandsdk-rag-opensearch-stack us-east-1 default
-
-# This script will:
-# - Deploy OpenSearch cluster via CloudFormation
-# - Set up EKS Pod Identity for secure access
-# - Create the vector index automatically
-# - Configure IAM roles and policies
-```
-
-#### 3. Configure Kubernetes Secrets and ConfigMap
-
-Update the ConfigMap with your actual service endpoints and configuration:
-
-```bash
-# Apply the ConfigMap and Secrets
-kubectl apply -f k8s/configmap.yaml
-# Edit the ConfigMap with your actual values
-kubectl edit configmap app-config
-
-# Key values to update:
-# - LITELLM_BASE_URL: Your LiteLLM service endpoint
-# - EMBEDDING_BASE_URL: Your embedding service endpoint  
-# - OPENSEARCH_ENDPOINT: From OpenSearch deployment output
-# - LANGFUSE_HOST: Your Langfuse instance (optional)
-```
-
-Update secrets with your API keys:
-
-```bash
-# Update secrets with base64 encoded values
-kubectl edit secret app-secrets
-
-# To encode your keys:
-echo -n "your-api-key" | base64
-
-# Keys to update:
-# - litellm-api-key: Your LiteLLM API key
-# - embedding-api-key: Your embedding service API key
-# - tavily-api-key: Your Tavily API key for web search
-# - langfuse-public-key: Langfuse public key (optional)
-# - langfuse-secret-key: Langfuse secret key (optional)
-```
-
-#### 4. Deploy Kubernetes Applications
-
-```bash
-# Apply the service account (if not already created)
-kubectl apply -f k8s/service-account.yaml
-
-# Deploy the MCP server first
-kubectl apply -f k8s/tavily-mcp-deployment.yaml
-
-# Deploy the main application
-kubectl apply -f k8s/main-app-deployment.yaml
-
-# Check deployment status
-kubectl get pods -l app=tavily-mcp-server
-kubectl get pods -l app=strandsdk-rag-app
-
-# Check services and ingress
-kubectl get svc
-kubectl get ingress
-```
-
-#### 5. Test the Deployed System
-
-```bash
-# Get the Application Load Balancer endpoint
-ALB_ENDPOINT=$(kubectl get ingress strandsdk-rag-ingress-alb -o jsonpath='{.status.loadBalancer.ingress[0].hostname}')
-
-# Test the health endpoint
-curl -X GET "http://${ALB_ENDPOINT}/health"
-
-# Test a simple query
-curl -X POST "http://${ALB_ENDPOINT}/query" \
-  -H "Content-Type: application/json" \
-  -d '{
-    "query": "What is Bell'\''s palsy?",
-    "include_web_search": true
-  }'
-
-# Test knowledge embedding
-curl -X POST "http://${ALB_ENDPOINT}/embed-knowledge" \
-  -H "Content-Type: application/json"
-
-# Test with a more complex medical query
-curl -X POST "http://${ALB_ENDPOINT}/query" \
-  -H "Content-Type: application/json" \
-  -d '{
-    "question": "Find information about \"What was the purpose of the study on encainide and flecainide in patients with supraventricular arrhythmias\". Summarize this information and create a comprehensive story.Save the story and important information to a file named \"test1.md\" in the output directory as a beautiful markdown file.",
-    "top_k": 3
-  }' \
-  --max-time 600
-```
-
-
-## Option 2: Local Development
-
-### 📋 Prerequisites
-
-- Python 3.9+
-- EKS cluster
-- TAVILY_API_KEY
-- Public facing Opensearch cluster
-- AWS credentials configured
-
-### 🛠️ Installation
-
-```bash
-# Clone the repository
-git clone <repository-url>
-cd strandsdk_agentic_rag_opensearch
-
-# Create virtual environment
-python3 -m venv venv
-source venv/bin/activate  # On Windows: venv\Scripts\activate
-
-# Install dependencies
-pip install -r requirements.txt
-
-# Set up environment variables
-cp .env.example .env
-# Edit .env with your configuration
-```
-
-### ⚙️ Configuration
-
-Create a `.env` file with the following variables:
-
-```env
-# OpenAI Configuration
-OPENAI_API_KEY=your-openai-api-key
-OPENAI_BASE_URL=https://api.openai.com/v1
-DEFAULT_MODEL=us.anthropic.claude-3-7-sonnet-20250219-v1:0
-
-# AWS Configuration  
-AWS_REGION=us-east-1
-OPENSEARCH_ENDPOINT=https://your-opensearch-domain.region.es.amazonaws.com
-
-# Tavily Web Search Configuration
-TAVILY_API_KEY=your-tavily-api-key
-
-# Tracing Configuration (Optional)
-OTEL_EXPORTER_OTLP_ENDPOINT=http://localhost:4318
-OTEL_EXPORTER_OTLP_HEADERS=key1=value1,key2=value2
-STRANDS_OTEL_ENABLE_CONSOLE_EXPORT=true
-
-# Optional: Langfuse for observability
-LANGFUSE_HOST=https://cloud.langfuse.com
-LANGFUSE_PUBLIC_KEY=your-public-key
-LANGFUSE_SECRET_KEY=your-secret-key
-
-# Application Settings
-KNOWLEDGE_DIR=knowledge
-OUTPUT_DIR=output
-VECTOR_INDEX_NAME=knowledge-embeddings
-TOP_K_RESULTS=5
-```
-
-### 🏃‍♂️ Deploy
-
-
-#### 1. Start Tavily MCP Server (for Web Search)
-
-```bash
-# Start the Tavily web search server
-python scripts/start_tavily_server.py
-
-# Or run directly
-python src/mcp_servers/tavily_search_server.py
-```
-
-#### 2. Embed Knowledge Documents
-
-```bash
-# Process and embed all knowledge documents
-python -c "from src.agents.knowledge_agent import knowledge_agent; print(knowledge_agent('Please embed all knowledge files'))"
-```
-
-#### 3. Run the Multi-Agent System
-
-```bash
-# Standard mode (with built-in tracing)
-source venv/bin/activate
-python -m src.main
-
-# Clean mode (async warnings suppressed)
-python run_main_clean.py
-
-# Single query - standard mode
-python -c "from src.main import run_single_query; print(run_single_query('What is Bell\'s palsy?'))"
-
-# Single query - clean mode
-python run_single_query_clean.py "What is Bell's palsy?"
-
-# Single query - ultra clean mode (completely suppressed stderr)
-python run_completely_clean.py "What is Bell's palsy?"
-```
-
-#### 4. Test the System
-
-```bash
-# Run comprehensive tests including web search integration
-python -m src.test_agents
-
-# Test the enhanced RAG system with chunk relevance evaluation
-python test_enhanced_rag.py
-
-# Test web search integration specifically
-python src/test_web_search_integration.py
-
-# Run tests with clean output (async warnings filtered)
-python run_clean_test.py
-```
-
-**Note**: The enhanced system uses RAGAs for chunk relevance evaluation, which may generate harmless async cleanup warnings. Use `run_clean_test.py` for a cleaner testing experience.
-
-
-#### Container Deployment Architecture
-
-```
-┌─────────────────────────────────────────────────────────────┐
-│                    Application Load Balancer                │
-│                    (ALB Ingress Controller)                 │
-└─────────────────────┬───────────────────────────────────────┘
-                      │
-┌─────────────────────┴───────────────────────────────────────┐
-│                 Kubernetes Cluster (EKS)                   │
-│                                                             │
-│  ┌─────────────────────┐    ┌─────────────────────────────┐ │
-│  │   Main Application  │    │     MCP Server              │ │
-│  │   (Port 8000)       │◄──►│   (Tavily Web Search)       │ │
-│  │                     │    │     (Port 8001)             │ │
-│  └─────────────────────┘    └─────────────────────────────┘ │
-│              │                                              │
-│              ▼                                              │
-│  ┌─────────────────────────────────────────────────────────┐ │
-│  │              OpenSearch Cluster                         │ │
-│  │         (Vector Database + Search)                      │ │
-│  └─────────────────────────────────────────────────────────┘ │
-└─────────────────────────────────────────────────────────────┘
-```
-
-#### Container Features
-
-- **Auto-scaling**: Kubernetes HPA for dynamic scaling
-- **Health Checks**: Built-in health endpoints for monitoring
-- **Service Discovery**: Internal service communication via Kubernetes DNS
-- **Security**: EKS Pod Identity for secure AWS service access
-- **Observability**: OpenTelemetry tracing with multiple export options
-- **Load Balancing**: ALB for external traffic distribution
-- **Configuration Management**: ConfigMaps and Secrets for environment-specific settings
-
-## 🔍 Observability & Tracing
-
-The system includes comprehensive observability through Strands SDK's built-in OpenTelemetry integration:
-
-### Automatic Tracing
-- **All agents** are automatically traced using Strands SDK
-- **Tool calls**, **LLM interactions**, and **workflows** are captured
-- **Performance metrics** including token usage and execution times
-
-### Trace Export Options
-- **Console Output**: Set `STRANDS_OTEL_ENABLE_CONSOLE_EXPORT=true` for development
-- **OTLP Endpoint**: Configure `OTEL_EXPORTER_OTLP_ENDPOINT` for production
-- **Langfuse**: Use Langfuse credentials for advanced observability
-- **Jaeger/Zipkin**: Compatible with standard OpenTelemetry collectors
-
-### Local Development Setup
-```bash
-# Pull and run Jaeger all-in-one container
-docker run -d --name jaeger \
-  -e COLLECTOR_OTLP_ENABLED=true \
-  -p 16686:16686 \
-  -p 4317:4317 \
-  -p 4318:4318 \
-  jaegertracing/all-in-one:latest
-
-# Access Jaeger UI at http://localhost:16686
-```
-
-## 🧠 Agent Workflows
-
-### Knowledge Management Workflow
-1. **File Monitoring**: Scans knowledge directory for changes
-2. **Change Detection**: Uses file hashes and timestamps
-3. **Document Processing**: Handles multiple file formats
-4. **Embedding Generation**: Creates vector embeddings
-5. **Vector Storage**: Stores in OpenSearch with metadata
-
-### RAG Retrieval Workflow  
-1. **Query Processing**: Analyzes user queries
-2. **Embedding Generation**: Converts queries to vectors
-3. **Similarity Search**: Finds relevant documents in OpenSearch
-4. **Context Formatting**: Structures results for LLM consumption
-5. **Relevance Ranking**: Orders results by similarity scores
-
-### MCP Tool Execution Workflow
-1. **Tool Discovery**: Connects to available MCP servers
-2. **Context Integration**: Combines RAG context with user queries
-3. **Tool Selection**: Chooses appropriate tools for tasks
-4. **Execution Management**: Handles tool calls and responses
-5. **Result Processing**: Formats and returns final outputs
-
-## 🔧 Extending the System
-
-### Adding New Agents
-
-### Adding New Agents
-
-```python
-from strands import Agent, tool
-from src.utils.strands_langfuse_integration import create_traced_agent
-
-# Define tools for the agent
-@tool
-def my_custom_tool(param: str) -> str:
-    """Custom tool implementation."""
-    return f"Processed: {param}"
-
-# Create the agent with built-in tracing
-my_agent = create_traced_agent(
-    Agent,
-    model="us.anthropic.claude-3-7-sonnet-20250219-v1:0",
-    tools=[my_custom_tool],
-    system_prompt="Your specialized prompt here",
-    session_id="my-agent-session",
-    user_id="system"
-)
-```
-
-### Adding New MCP Servers
-
-```python
-from fastmcp import FastMCP
-
-mcp = FastMCP("My Custom Server")
-
-@mcp.tool(description="Custom tool description")
-def my_custom_tool(param: str) -> str:
-    """Custom tool implementation."""
-    return f"Processed: {param}"
-
-if __name__ == "__main__":
-    mcp.run(transport="streamable-http", port=8002)
-```
-
-## 📊 Monitoring and Observability
-
-The system includes comprehensive observability features:
-
-- **OpenTelemetry Integration**: Native tracing through Strands SDK
-- **Multiple Export Options**: Console, OTLP endpoints, Jaeger, Langfuse
-- **Workflow Summaries**: Detailed execution reports
-- **Performance Metrics**: Duration and success tracking
-- **Error Handling**: Comprehensive error reporting and recovery
-
-## 🧪 Example Use Cases
-
-### Medical Knowledge Query
-```python
-query = "What are the symptoms and treatment options for Bell's palsy?"
-result = supervisor_agent(query)
-print(result['response'])
-```
-
-### Document Analysis and Report Generation
-```python
-query = "Analyze the medical documents and create a summary report saved to a file"
-result = supervisor_agent(query)
-# System will retrieve relevant docs, analyze them, and save results using MCP tools
-```
-
-## 🔍 Architecture Benefits
-
-1. **Modularity**: Each agent has specific responsibilities
-2. **Scalability**: Agents can be scaled independently  
-3. **Reliability**: Isolated failures don't affect the entire system
-4. **Extensibility**: Easy to add new capabilities
-5. **Observability**: Comprehensive monitoring and tracing via Strands SDK
-6. **Standards Compliance**: Uses MCP for tool integration and OpenTelemetry for tracing
-
-## 🔧 Key Improvements
-
-### Unified Architecture
-- **Single Codebase**: No separate "enhanced" versions - all functionality is built into the standard agents
-- **Built-in Tracing**: OpenTelemetry tracing is automatically enabled through Strands SDK
-- **Simplified Deployment**: One main application with all features included
-- **Consistent API**: All agents use the same tracing and configuration patterns
-
-### Enhanced Developer Experience
-- **Automatic Instrumentation**: No manual trace management required
-- **Multiple Export Options**: Console, OTLP, Jaeger, Langfuse support out of the box
-- **Environment-based Configuration**: Easy setup through environment variables
-- **Clean Code Structure**: Removed duplicate wrapper functions and complex manual tracing
-- **Async Warning Management**: Clean test runner filters harmless async cleanup warnings
-- **Robust Error Handling**: Fallback mechanisms ensure system reliability
-
-## 🤝 Contributing
-
-1. Fork the repository
-2. Create a feature branch
-3. Make your changes
-4. Add tests for new functionality
-5. Submit a pull request
-
-## 📄 License
-
-This project is licensed under the MIT License - see the LICENSE file for details.
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/build-images.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/build-images.sh
deleted file mode 100755
index 599dc2e0..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/build-images.sh
+++ /dev/null
@@ -1,161 +0,0 @@
-#!/bin/bash
-
-# Build script for separate Docker images with ECR integration and automatic Kubernetes manifest updates
-set -e
-
-# Detect OS and set sed command for cross-platform compatibility
-if [[ "$OSTYPE" == "darwin"* ]]; then
-    # macOS (BSD sed)
-    SED_INPLACE() { sed -i "" "$@"; }
-    OS_NAME="macOS"
-else
-    # Linux (GNU sed)
-    SED_INPLACE() { sed -i "$@"; }
-    OS_NAME="Linux"
-fi
-
-echo "Detected OS: ${OS_NAME}"
-echo "Using appropriate sed syntax for cross-platform compatibility"
-echo ""
-
-# Configuration
-AWS_REGION="us-east-1"  # Change to your preferred region
-AWS_ACCOUNT_ID=$(aws sts get-caller-identity --query Account --output text)
-ECR_REGISTRY="${AWS_ACCOUNT_ID}.dkr.ecr.${AWS_REGION}.amazonaws.com"
-TAG="latest"
-
-# Repository names
-MAIN_REPO_NAME="strandsdk-agentic-rag-main"
-MCP_REPO_NAME="strandsdk-agentic-rag-mcp"
-
-echo "Building Strands SDK Agentic RAG Docker Images with ECR Integration..."
-echo "======================================================================"
-echo "AWS Account ID: ${AWS_ACCOUNT_ID}"
-echo "AWS Region: ${AWS_REGION}"
-echo "ECR Registry: ${ECR_REGISTRY}"
-echo ""
-
-# Function to create ECR repository if it doesn't exist
-create_ecr_repo() {
-    local repo_name=$1
-    echo "Checking if ECR repository '${repo_name}' exists..."
-    
-    if aws ecr describe-repositories --repository-names ${repo_name} --region ${AWS_REGION} >/dev/null 2>&1; then
-        echo "✅ ECR repository '${repo_name}' already exists"
-    else
-        echo "Creating ECR repository '${repo_name}'..."
-        aws ecr create-repository \
-            --repository-name ${repo_name} \
-            --region ${AWS_REGION} \
-            --image-scanning-configuration scanOnPush=true \
-            --encryption-configuration encryptionType=AES256
-        echo "✅ ECR repository '${repo_name}' created successfully"
-    fi
-}
-
-# Authenticate Docker to ECR
-echo "Authenticating Docker to ECR..."
-aws ecr get-login-password --region ${AWS_REGION} | docker login --username AWS --password-stdin ${ECR_REGISTRY}
-echo "✅ Docker authenticated to ECR successfully"
-
-# Create ECR repositories
-create_ecr_repo ${MAIN_REPO_NAME}
-create_ecr_repo ${MCP_REPO_NAME}
-
-echo ""
-
-# Build Main Application Image
-echo "Building Main Application Image..."
-docker build -f Dockerfile.main -t ${MAIN_REPO_NAME}:${TAG} .
-docker tag ${MAIN_REPO_NAME}:${TAG} ${ECR_REGISTRY}/${MAIN_REPO_NAME}:${TAG}
-echo "✅ Main Application Image built and tagged successfully"
-
-# Build MCP Server Image
-echo "Building MCP Server Image..."
-docker build -f Dockerfile.mcp -t ${MCP_REPO_NAME}:${TAG} .
-docker tag ${MCP_REPO_NAME}:${TAG} ${ECR_REGISTRY}/${MCP_REPO_NAME}:${TAG}
-echo "✅ MCP Server Image built and tagged successfully"
-
-echo ""
-echo "Images built and tagged successfully:"
-echo "- ${ECR_REGISTRY}/${MAIN_REPO_NAME}:${TAG}"
-echo "- ${ECR_REGISTRY}/${MCP_REPO_NAME}:${TAG}"
-echo ""
-
-# Push images to ECR
-echo "Pushing Main Application Image to ECR..."
-docker push ${ECR_REGISTRY}/${MAIN_REPO_NAME}:${TAG}
-echo "✅ Main Application Image pushed to ECR successfully"
-
-echo "Pushing MCP Server Image to ECR..."
-docker push ${ECR_REGISTRY}/${MCP_REPO_NAME}:${TAG}
-echo "✅ MCP Server Image pushed to ECR successfully"
-
-echo ""
-echo "All images pushed to ECR successfully!"
-echo ""
-
-# Update Kubernetes deployment files with ECR image names
-echo "Updating Kubernetes deployment files with ECR image URLs..."
-
-# Update main app deployment
-if [ -f "k8s/main-app-deployment.yaml" ]; then
-    SED_INPLACE "s|image: .*strandsdk-agentic-rag-main:.*|image: ${ECR_REGISTRY}/${MAIN_REPO_NAME}:${TAG}|g" k8s/main-app-deployment.yaml
-    echo "✅ Updated main-app-deployment.yaml with ECR image URL"
-else
-    echo "⚠️  k8s/main-app-deployment.yaml not found"
-fi
-
-# Update MCP server deployment
-if [ -f "k8s/tavily-mcp-deployment.yaml" ]; then
-    SED_INPLACE "s|image: .*strandsdk-agentic-rag-mcp:.*|image: ${ECR_REGISTRY}/${MCP_REPO_NAME}:${TAG}|g" k8s/tavily-mcp-deployment.yaml
-    echo "✅ Updated tavily-mcp-deployment.yaml with ECR image URL"
-else
-    echo "⚠️  k8s/tavily-mcp-deployment.yaml not found"
-fi
-
-echo ""
-echo "✅ Kubernetes deployment files updated with ECR image URLs!"
-echo ""
-
-# Clean up local images to save space
-echo "Cleaning up local Docker images..."
-docker rmi ${MAIN_REPO_NAME}:${TAG} ${ECR_REGISTRY}/${MAIN_REPO_NAME}:${TAG} || true
-docker rmi ${MCP_REPO_NAME}:${TAG} ${ECR_REGISTRY}/${MCP_REPO_NAME}:${TAG} || true
-echo "✅ Local Docker images cleaned up"
-
-echo ""
-echo "======================================================================"
-echo "✅ BUILD AND DEPLOYMENT PREPARATION COMPLETE!"
-echo "======================================================================"
-echo ""
-echo "ECR Repositories created:"
-echo "- ${ECR_REGISTRY}/${MAIN_REPO_NAME}"
-echo "- ${ECR_REGISTRY}/${MCP_REPO_NAME}"
-echo ""
-echo "Images pushed to ECR:"
-echo "- ${ECR_REGISTRY}/${MAIN_REPO_NAME}:${TAG}"
-echo "- ${ECR_REGISTRY}/${MCP_REPO_NAME}:${TAG}"
-echo ""
-echo "Next steps:"
-echo "1. Update your ConfigMap secrets with actual values:"
-echo "   kubectl apply -f k8s/configmap.yaml"
-echo ""
-echo "2. Deploy the applications:"
-echo "   kubectl apply -f k8s/tavily-mcp-deployment.yaml"
-echo "   kubectl apply -f k8s/main-app-deployment.yaml"
-echo ""
-echo "3. Check deployment status:"
-echo "   kubectl get pods -l app=tavily-mcp-server"
-echo "   kubectl get pods -l app=strandsdk-rag-app"
-echo ""
-echo "4. Get the ALB endpoint:"
-echo "   kubectl get ingress strandsdk-rag-ingress-alb"
-echo ""
-echo "Current ECR image URLs in deployments:"
-if [ -f "k8s/main-app-deployment.yaml" ]; then
-    echo "Main App: $(grep 'image:' k8s/main-app-deployment.yaml | head -1 | awk '{print $2}')"
-fi
-if [ -f "k8s/tavily-mcp-deployment.yaml" ]; then
-    echo "MCP Server: $(grep 'image:' k8s/tavily-mcp-deployment.yaml | head -1 | awk '{print $2}')"
-fi
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/cleanup-opensearch.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/cleanup-opensearch.sh
deleted file mode 100755
index 882ba3c1..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/cleanup-opensearch.sh
+++ /dev/null
@@ -1,166 +0,0 @@
-#!/bin/bash
-
-# Script to cleanup OpenSearch cluster and related resources
-
-set -e
-
-# Color codes for better readability
-GREEN='\033[0;32m'
-BLUE='\033[0;34m'
-RED='\033[0;31m'
-YELLOW='\033[0;33m'
-NC='\033[0m' # No Color
-
-# Function to display messages with timestamp
-log() {
-  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
-}
-
-warn() {
-  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
-}
-
-error() {
-  echo -e "${RED}[$(date '+%Y-%m-%d %H:%M:%S')] ERROR:${NC} $1"
-  exit 1
-}
-
-success() {
-  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
-}
-
-# Configuration variables
-DOMAIN_NAME="agentic-rag-opensearch"
-REGION="us-east-1"
-SECURITY_GROUP_NAME="opensearch-sg"
-
-# Check prerequisites
-check_prerequisites() {
-  log "Checking prerequisites..."
-  
-  # Check AWS CLI
-  if ! command -v aws &> /dev/null; then
-    error "AWS CLI is not installed. Please install it first."
-  fi
-  
-  # Check AWS credentials
-  if ! aws sts get-caller-identity &> /dev/null; then
-    error "AWS credentials not configured or invalid. Please configure AWS CLI."
-  fi
-  
-  success "All prerequisites satisfied."
-}
-
-# Delete OpenSearch domain
-delete_opensearch_domain() {
-  log "Checking for OpenSearch domain: $DOMAIN_NAME"
-  
-  EXISTING_DOMAIN=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION 2>/dev/null || echo "")
-  
-  if [ -n "$EXISTING_DOMAIN" ]; then
-    log "Deleting OpenSearch domain: $DOMAIN_NAME"
-    
-    aws opensearch delete-domain \
-      --domain-name $DOMAIN_NAME \
-      --region $REGION
-    
-    log "OpenSearch domain deletion initiated. This may take several minutes..."
-    
-    # Wait for deletion to complete
-    local max_attempts=30  # 15 minutes
-    local attempt=1
-    
-    while [ $attempt -le $max_attempts ]; do
-      log "Attempt $attempt/$max_attempts: Checking if domain is deleted..."
-      
-      DOMAIN_CHECK=$(aws opensearch describe-domain --domain-name $DOMAIN_NAME --region $REGION 2>/dev/null || echo "DELETED")
-      
-      if [ "$DOMAIN_CHECK" = "DELETED" ]; then
-        success "OpenSearch domain deleted successfully!"
-        break
-      fi
-      
-      log "Domain still exists. Waiting 30 seconds..."
-      sleep 30
-      ((attempt++))
-    done
-    
-    if [ $attempt -gt $max_attempts ]; then
-      warn "Domain deletion is taking longer than expected. Please check AWS console."
-    fi
-  else
-    log "OpenSearch domain '$DOMAIN_NAME' not found. Skipping deletion."
-  fi
-}
-
-# Delete security group
-delete_security_group() {
-  log "Checking for security group: $SECURITY_GROUP_NAME"
-  
-  # Get default VPC
-  DEFAULT_VPC=$(aws ec2 describe-vpcs --filters "Name=is-default,Values=true" --query "Vpcs[0].VpcId" --output text --region $REGION)
-  
-  if [ "$DEFAULT_VPC" = "None" ] || [ -z "$DEFAULT_VPC" ]; then
-    log "No default VPC found. Skipping security group deletion."
-    return
-  fi
-  
-  EXISTING_SG=$(aws ec2 describe-security-groups --filters "Name=group-name,Values=$SECURITY_GROUP_NAME" "Name=vpc-id,Values=$DEFAULT_VPC" --query "SecurityGroups[0].GroupId" --output text --region $REGION 2>/dev/null || echo "None")
-  
-  if [ "$EXISTING_SG" != "None" ] && [ -n "$EXISTING_SG" ]; then
-    log "Deleting security group: $EXISTING_SG"
-    
-    # Try to delete the security group
-    if aws ec2 delete-security-group --group-id $EXISTING_SG --region $REGION 2>/dev/null; then
-      success "Security group deleted successfully!"
-    else
-      warn "Failed to delete security group. It may still be in use or have dependencies."
-      log "You may need to delete it manually from the AWS console."
-    fi
-  else
-    log "Security group '$SECURITY_GROUP_NAME' not found. Skipping deletion."
-  fi
-}
-
-# Clean up .env file
-cleanup_env_file() {
-  log "Cleaning up .env file..."
-  
-  if [ -f ".env" ]; then
-    # Remove or comment out OPENSEARCH_ENDPOINT
-    if grep -q "OPENSEARCH_ENDPOINT=" .env; then
-      sed -i.bak 's/^OPENSEARCH_ENDPOINT=/#OPENSEARCH_ENDPOINT=/' .env
-      success ".env file updated (OPENSEARCH_ENDPOINT commented out)."
-    else
-      log "OPENSEARCH_ENDPOINT not found in .env file."
-    fi
-  else
-    log ".env file not found. Nothing to clean up."
-  fi
-}
-
-# Main execution
-main() {
-  log "Starting OpenSearch cluster cleanup..."
-  
-  warn "This will delete the OpenSearch domain and related resources."
-  read -p "Are you sure you want to continue? (y/N): " -n 1 -r
-  echo
-  
-  if [[ ! $REPLY =~ ^[Yy]$ ]]; then
-    log "Cleanup cancelled."
-    exit 0
-  fi
-  
-  check_prerequisites
-  delete_opensearch_domain
-  delete_security_group
-  cleanup_env_file
-  
-  success "OpenSearch cluster cleanup completed!"
-  log "All resources have been cleaned up."
-  log "Note: It may take a few minutes for all AWS resources to be fully removed."
-}
-
-# Execute main function
-main
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/deploy-opensearch.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/deploy-opensearch.sh
deleted file mode 100755
index dd25c451..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/deploy-opensearch.sh
+++ /dev/null
@@ -1,295 +0,0 @@
-#!/bin/bash
-
-# Deploy OpenSearch CloudFormation Stack with EKS Pod Identity mapping
-# Usage: ./deploy-opensearch.sh [stack-name] [region] [namespace]
-
-set -e
-
-STACK_NAME=${1:-"strandsdk-rag-opensearch-stack"}
-REGION=${2:-"us-east-1"}
-NAMESPACE=${3:-"default"}
-TEMPLATE_FILE="opensearch-cluster-simple.yaml"
-
-echo "🚀 Deploying OpenSearch CloudFormation Stack with EKS Pod Identity..."
-echo "Stack Name: $STACK_NAME"
-echo "Region: $REGION"
-echo "Namespace: $NAMESPACE"
-echo "Template: $TEMPLATE_FILE"
-echo ""
-
-# Get EKS cluster name from current kubeconfig context
-echo "🔍 Reading EKS cluster name from kubeconfig..."
-if ! command -v kubectl &> /dev/null; then
-    echo "❌ kubectl is not installed or not in PATH"
-    exit 1
-fi
-
-CURRENT_CONTEXT=$(kubectl config current-context 2>/dev/null || echo "")
-if [ -z "$CURRENT_CONTEXT" ]; then
-    echo "❌ No current kubectl context found"
-    echo "Please set your kubectl context to point to your EKS cluster"
-    exit 1
-fi
-
-# Extract cluster name from context (format: arn:aws:eks:region:account:cluster/cluster-name)
-EKS_CLUSTER_NAME=$(echo $CURRENT_CONTEXT | sed 's/.*cluster\///')
-if [ -z "$EKS_CLUSTER_NAME" ]; then
-    echo "❌ Could not extract EKS cluster name from context: $CURRENT_CONTEXT"
-    exit 1
-fi
-
-echo "✅ Found EKS cluster: $EKS_CLUSTER_NAME"
-echo ""
-
-# Check if AWS CLI is configured
-if ! aws sts get-caller-identity > /dev/null 2>&1; then
-    echo "❌ AWS CLI is not configured or credentials are invalid"
-    echo "Please run 'aws configure' first"
-    exit 1
-fi
-
-# Check if template file exists
-if [ ! -f "$TEMPLATE_FILE" ]; then
-    echo "❌ Template file $TEMPLATE_FILE not found"
-    exit 1
-fi
-
-# Check if EKS cluster exists
-echo "🔍 Verifying EKS cluster exists..."
-if ! aws eks describe-cluster --name $EKS_CLUSTER_NAME --region $REGION > /dev/null 2>&1; then
-    echo "❌ EKS cluster $EKS_CLUSTER_NAME not found in region $REGION"
-    echo "Please ensure the EKS cluster exists and your kubeconfig is correct"
-    exit 1
-fi
-
-# Check if EKS cluster has Pod Identity addon enabled
-echo "🔍 Checking EKS Pod Identity addon..."
-POD_IDENTITY_STATUS=$(aws eks describe-addon \
-    --cluster-name $EKS_CLUSTER_NAME \
-    --addon-name eks-pod-identity-agent \
-    --region $REGION \
-    --query 'addon.status' \
-    --output text 2>/dev/null || echo "NOT_FOUND")
-
-if [ "$POD_IDENTITY_STATUS" != "ACTIVE" ]; then
-    echo "⚠️  EKS Pod Identity addon is not active on cluster $EKS_CLUSTER_NAME"
-    echo "Installing EKS Pod Identity addon..."
-    aws eks create-addon \
-        --cluster-name $EKS_CLUSTER_NAME \
-        --addon-name eks-pod-identity-agent \
-        --region $REGION \
-        --resolve-conflicts OVERWRITE
-    
-    echo "⏳ Waiting for Pod Identity addon to become active..."
-    aws eks wait addon-active \
-        --cluster-name $EKS_CLUSTER_NAME \
-        --addon-name eks-pod-identity-agent \
-        --region $REGION
-    echo "✅ Pod Identity addon is now active"
-fi
-
-# Validate the template
-echo "🔍 Validating CloudFormation template..."
-aws cloudformation validate-template \
-    --template-body file://$TEMPLATE_FILE \
-    --region $REGION
-
-if [ $? -eq 0 ]; then
-    echo "✅ Template validation successful"
-else
-    echo "❌ Template validation failed"
-    exit 1
-fi
-
-# Deploy the stack
-echo ""
-echo "📦 Deploying CloudFormation stack..."
-aws cloudformation deploy \
-    --template-file $TEMPLATE_FILE \
-    --stack-name $STACK_NAME \
-    --region $REGION \
-    --capabilities CAPABILITY_NAMED_IAM \
-    --parameter-overrides \
-        ClusterName=strandsdk-rag-opensearch \
-        ServiceAccountName=strandsdk-rag-service-account \
-        EKSClusterName=$EKS_CLUSTER_NAME \
-        KubernetesNamespace=$NAMESPACE
-
-if [ $? -eq 0 ]; then
-    echo ""
-    echo "✅ Stack deployment successful!"
-    echo ""
-    echo "📋 Getting stack outputs..."
-    aws cloudformation describe-stacks \
-        --stack-name $STACK_NAME \
-        --region $REGION \
-        --query 'Stacks[0].Outputs[*].[OutputKey,OutputValue]' \
-        --output table
-    
-    echo ""
-    echo "🔐 To get the master password, run:"
-    echo "aws secretsmanager get-secret-value --secret-id strandsdk-rag-opensearch-master-password --region $REGION --query SecretString --output text | jq -r .password"
-    
-    echo ""
-    echo "🌐 OpenSearch Dashboards will be available at:"
-    ENDPOINT=$(aws cloudformation describe-stacks \
-        --stack-name $STACK_NAME \
-        --region $REGION \
-        --query 'Stacks[0].Outputs[?OutputKey==`OpenSearchDomainEndpoint`].OutputValue' \
-        --output text)
-    echo "https://$ENDPOINT/_dashboards"
-    
-    echo ""
-    echo "🔗 EKS Pod Identity Association created:"
-    echo "Cluster: $EKS_CLUSTER_NAME"
-    echo "Namespace: $NAMESPACE"
-    echo "Service Account: strandsdk-rag-service-account"
-    
-    echo ""
-    echo "⏳ Waiting for OpenSearch cluster to be ready..."
-    echo "This may take 15-20 minutes..."
-    
-    # Wait for OpenSearch cluster to be ready
-    CLUSTER_STATUS=""
-    WAIT_COUNT=0
-    MAX_WAIT=60  # 60 * 30 seconds = 30 minutes max wait
-    
-    while [ "$CLUSTER_STATUS" != "Active" ] && [ $WAIT_COUNT -lt $MAX_WAIT ]; do
-        sleep 30
-        CLUSTER_STATUS=$(aws opensearch describe-domain \
-            --domain-name strandsdk-rag-opensearch \
-            --region $REGION \
-            --query 'DomainStatus.Processing' \
-            --output text 2>/dev/null)
-        
-        if [ "$CLUSTER_STATUS" = "False" ]; then
-            CLUSTER_STATUS="Active"
-        fi
-        
-        WAIT_COUNT=$((WAIT_COUNT + 1))
-        echo "   Waiting... ($WAIT_COUNT/60)"
-    done
-    
-    if [ "$CLUSTER_STATUS" = "Active" ]; then
-        echo "✅ OpenSearch cluster is ready!"
-        
-        # Setup OpenSearch index
-        echo ""
-        echo "🔧 Setting up OpenSearch index..."
-        
-        # Install required dependencies if not already installed
-        echo "📦 Installing required dependencies (opensearch-py, boto3, requests-aws4auth)..."
-        INSTALL_SUCCESS=false
-        
-        # Check if all dependencies are already installed
-        if python3 -c "import opensearchpy, boto3; from requests_aws4auth import AWS4Auth" 2>/dev/null; then
-            echo "✅ All required dependencies are already installed"
-            INSTALL_SUCCESS=true
-        else
-            echo "   Required dependencies not found, installing..."
-            
-            # Try different installation methods
-            if [[ "$VIRTUAL_ENV" != "" ]]; then
-                echo "   Using virtual environment: $VIRTUAL_ENV"
-                if pip install opensearch-py boto3 requests-aws4auth; then
-                    INSTALL_SUCCESS=true
-                fi
-            elif command -v pip3 &> /dev/null; then
-                echo "   Trying pip3 with --user flag..."
-                if pip3 install --user opensearch-py boto3 requests-aws4auth; then
-                    INSTALL_SUCCESS=true
-                elif pip3 install --break-system-packages opensearch-py boto3 requests-aws4auth; then
-                    echo "   Installed with --break-system-packages flag"
-                    INSTALL_SUCCESS=true
-                fi
-            elif command -v python3 -m pip &> /dev/null; then
-                echo "   Trying python3 -m pip..."
-                if python3 -m pip install --user opensearch-py boto3 requests-aws4auth; then
-                    INSTALL_SUCCESS=true
-                elif python3 -m pip install --break-system-packages opensearch-py boto3 requests-aws4auth; then
-                    echo "   Installed with --break-system-packages flag"
-                    INSTALL_SUCCESS=true
-                fi
-            fi
-            
-            if [ "$INSTALL_SUCCESS" = false ]; then
-                echo "⚠️  Failed to install dependencies automatically"
-                echo "   Please install them manually before running index setup:"
-                echo "   pip3 install --user opensearch-py boto3 requests-aws4auth"
-                echo "   or activate a virtual environment and run: pip install opensearch-py boto3 requests-aws4auth"
-                echo "   or use: pip3 install --break-system-packages opensearch-py boto3 requests-aws4auth"
-            else
-                echo "✅ Dependencies installed successfully"
-            fi
-        fi
-        
-        # Check if setup_opensearch_index.py exists and opensearch-py is available
-        if [ -f "setup_opensearch_index.py" ] && [ "$INSTALL_SUCCESS" = true ]; then
-            # Get the service account role ARN from CloudFormation output
-            SERVICE_ACCOUNT_ROLE_ARN=$(aws cloudformation describe-stacks \
-                --stack-name $STACK_NAME \
-                --region $REGION \
-                --query 'Stacks[0].Outputs[?OutputKey==`ServiceAccountRoleArn`].OutputValue' \
-                --output text)
-            
-            # Set environment variables for the index setup
-            export OPENSEARCH_ENDPOINT="https://$ENDPOINT"
-            export AWS_REGION="$REGION"
-            export VECTOR_INDEX_NAME="knowledge-embeddings"
-            export EMBEDDING_DIMENSION="384"
-            export SERVICE_ACCOUNT_ROLE_ARN="$SERVICE_ACCOUNT_ROLE_ARN"
-            
-            # Run the index setup script
-            if python3 setup_opensearch_index.py; then
-                echo "✅ OpenSearch index created successfully!"
-            else
-                echo "⚠️  OpenSearch index setup failed, but you can run it manually later:"
-                echo "   First install dependencies: pip3 install --user opensearch-py boto3 requests-aws4auth"
-                echo "   Then run:"
-                echo "   export OPENSEARCH_ENDPOINT=https://$ENDPOINT"
-                echo "   export AWS_REGION=$REGION"
-                echo "   export SERVICE_ACCOUNT_ROLE_ARN=$SERVICE_ACCOUNT_ROLE_ARN"
-                echo "   python3 setup_opensearch_index.py"
-            fi
-        elif [ -f "setup_opensearch_index.py" ] && [ "$INSTALL_SUCCESS" = false ]; then
-            echo "⚠️  setup_opensearch_index.py found but required dependencies not available"
-            echo "   Install dependencies first, then run index setup manually:"
-            echo "   pip3 install --user opensearch-py boto3 requests-aws4auth"
-            echo "   export OPENSEARCH_ENDPOINT=https://$ENDPOINT"
-            echo "   export AWS_REGION=$REGION"
-            SERVICE_ACCOUNT_ROLE_ARN=$(aws cloudformation describe-stacks \
-                --stack-name $STACK_NAME \
-                --region $REGION \
-                --query 'Stacks[0].Outputs[?OutputKey==`ServiceAccountRoleArn`].OutputValue' \
-                --output text)
-            echo "   export SERVICE_ACCOUNT_ROLE_ARN=$SERVICE_ACCOUNT_ROLE_ARN"
-            echo "   python3 setup_opensearch_index.py"
-        else
-            echo "⚠️  setup_opensearch_index.py not found, skipping index creation"
-            echo "   You can create the index manually later"
-        fi
-    else
-        echo "⚠️  OpenSearch cluster is still processing after 30 minutes"
-        echo "   You can check the status in the AWS console and run index setup later"
-    fi
-    
-    echo ""
-    echo "📝 Next steps:"
-    echo "If index setup failed, run manually:"
-    echo "   pip3 install --user opensearch-py boto3 requests-aws4auth"
-    echo "   export OPENSEARCH_ENDPOINT=https://$ENDPOINT"
-    echo "   export AWS_REGION=$REGION"
-    SERVICE_ACCOUNT_ROLE_ARN=$(aws cloudformation describe-stacks \
-        --stack-name $STACK_NAME \
-        --region $REGION \
-        --query 'Stacks[0].Outputs[?OutputKey==`ServiceAccountRoleArn`].OutputValue' \
-        --output text 2>/dev/null || echo "")
-    if [ -n "$SERVICE_ACCOUNT_ROLE_ARN" ]; then
-        echo "   export SERVICE_ACCOUNT_ROLE_ARN=$SERVICE_ACCOUNT_ROLE_ARN"
-    fi
-    echo "   python3 setup_opensearch_index.py"
-    
-else
-    echo "❌ Stack deployment failed"
-    exit 1
-fi
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/healthcheck-main.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/healthcheck-main.sh
deleted file mode 100755
index 00f798cf..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/healthcheck-main.sh
+++ /dev/null
@@ -1,19 +0,0 @@
-#!/bin/bash
-
-# Health check script for Main Application (FastAPI Server)
-
-# Load environment variables from ConfigMap or local file
-if [ -f "/app/config/.env" ]; then
-    export $(grep -v '^#' /app/config/.env | xargs) 2>/dev/null || true
-elif [ -f "/app/.env" ]; then
-    export $(grep -v '^#' /app/.env | xargs) 2>/dev/null || true
-fi
-
-# Check if the FastAPI server is responding
-if curl -f -s http://localhost:8000/health > /dev/null 2>&1; then
-    echo "FastAPI Server: Running"
-    exit 0
-else
-    echo "FastAPI Server: Not responding"
-    exit 1
-fi
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/healthcheck-mcp.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/healthcheck-mcp.sh
deleted file mode 100755
index 0b937729..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/healthcheck-mcp.sh
+++ /dev/null
@@ -1,19 +0,0 @@
-#!/bin/bash
-
-# Health check script for MCP Server
-
-# Load environment variables from ConfigMap or local file
-if [ -f "/app/config/.env" ]; then
-    export $(grep -v '^#' /app/config/.env | xargs) 2>/dev/null || true
-elif [ -f "/app/.env" ]; then
-    export $(grep -v '^#' /app/.env | xargs) 2>/dev/null || true
-fi
-
-# Check if the MCP server is responding
-if curl -f -s http://localhost:8001/mcp/ > /dev/null 2>&1; then
-    echo "MCP Server: Running"
-    exit 0
-else
-    echo "MCP Server: Not responding"
-    exit 1
-fi
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/images/arch.png b/agentic-apps/strandsdk_agentic_rag_opensearch/images/arch.png
deleted file mode 100644
index 2cf8c9cc..00000000
Binary files a/agentic-apps/strandsdk_agentic_rag_opensearch/images/arch.png and /dev/null differ
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/configmap.yaml b/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/configmap.yaml
deleted file mode 100644
index c6f2bc12..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/configmap.yaml
+++ /dev/null
@@ -1,78 +0,0 @@
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: app-config
-  labels:
-    app: strandsdk-rag
-data:
-  .env: |
-    # LiteLLM Configuration for Reasoning Models
-    LITELLM_BASE_URL=http://your-litellm-loadbalancer.us-east-1.elb.amazonaws.com/v1
-    REASONING_MODEL=vllm-server-qwen3
-    
-    # Embedding Configuration (separate from reasoning)
-    EMBEDDING_BASE_URL=http://your-litellm-loadbalancer.us-east-1.elb.amazonaws.com/v1/embeddings
-    EMBEDDING_MODEL=llamacpp-embedding
-    
-    # AWS Configuration  
-    AWS_REGION=us-east-1
-    OPENSEARCH_ENDPOINT=https://your-opensearch-domain.us-east-1.es.amazonaws.com
-    
-    # Tavily MCP Service Configuration
-    TAVILY_MCP_SERVICE_URL=http://tavily-mcp-service:8001/mcp
-    
-    # Optional: Langfuse for observability
-    LANGFUSE_HOST=http://your-langfuse-loadbalancer.us-east-1.elb.amazonaws.com
-    
-    # Application Settings
-    KNOWLEDGE_DIR=knowledge
-    OUTPUT_DIR=output
-    VECTOR_INDEX_NAME=knowledge-embeddings
-    TOP_K_RESULTS=3
-  
-  # Individual config values for environment variables
-  litellm-base-url: "http://your-litellm-loadbalancer.us-east-1.elb.amazonaws.com/v1"
-  reasoning-model: "vllm-server-qwen3"
-  embedding-base-url: "http://your-litellm-loadbalancer.us-east-1.elb.amazonaws.com/v1/embeddings"
-  embedding-model: "llamacpp-embedding"
-  opensearch-endpoint: "https://your-opensearch-domain.us-east-1.es.amazonaws.com"
-  aws-region: "us-east-1"
-  vector-index-name: "knowledge-embeddings"
-  tavily-mcp-service-url: "http://tavily-mcp-service:8001/mcp"
-  langfuse-host: "http://your-langfuse-loadbalancer.us-east-1.elb.amazonaws.com"
-  knowledge-dir: "knowledge"
-  output-dir: "output"
-  top-k-results: "3"
----
-apiVersion: v1
-kind: Secret
-metadata:
-  name: app-secrets
-  labels:
-    app: strandsdk-rag
-type: Opaque
-data:
-  # Base64 encoded secrets - replace with your actual base64 encoded values
-  # To encode: echo -n "your-api-key" | base64
-  litellm-api-key: <BASE64_ENCODED_LITELLM_API_KEY>
-  embedding-api-key: <BASE64_ENCODED_EMBEDDING_API_KEY>
-  tavily-api-key: <BASE64_ENCODED_TAVILY_API_KEY>
-  langfuse-public-key: <BASE64_ENCODED_LANGFUSE_PUBLIC_KEY>
-  langfuse-secret-key: <BASE64_ENCODED_LANGFUSE_SECRET_KEY>
----
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: knowledge-base
-  labels:
-    app: strandsdk-rag
-data:
-  # Add your knowledge base files here
-  # Example:
-  # sample-doc.txt: |
-  #   This is sample knowledge base content
-  #   Add your actual knowledge documents here
-  README.md: |
-    # Knowledge Base
-    This ConfigMap contains knowledge base documents for the RAG application.
-    Add your knowledge documents as data entries in this ConfigMap.
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/main-app-deployment.yaml b/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/main-app-deployment.yaml
deleted file mode 100644
index 1d1e5552..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/main-app-deployment.yaml
+++ /dev/null
@@ -1,204 +0,0 @@
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: strandsdk-rag-app
-  labels:
-    app: strandsdk-rag-app
-    component: main-app
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: strandsdk-rag-app
-  template:
-    metadata:
-      labels:
-        app: strandsdk-rag-app
-        component: main-app
-    spec:
-      serviceAccountName: strandsdk-rag-service-account
-      containers:
-      - name: strandsdk-rag-app
-        image: 412381761882.dkr.ecr.us-east-1.amazonaws.com/strandsdk-agentic-rag-main:latest
-        ports:
-        - containerPort: 8000
-          name: http
-        env:
-        # LiteLLM Configuration
-        - name: LITELLM_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: litellm-api-key
-        - name: LITELLM_BASE_URL
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: litellm-base-url
-        - name: REASONING_MODEL
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: reasoning-model
-        # Embedding Configuration
-        - name: EMBEDDING_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: embedding-api-key
-        - name: EMBEDDING_BASE_URL
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: embedding-base-url
-        - name: EMBEDDING_MODEL
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: embedding-model
-        # AWS Configuration
-        - name: OPENSEARCH_ENDPOINT
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: opensearch-endpoint
-        - name: AWS_REGION
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: aws-region
-        # Tavily Configuration
-        - name: TAVILY_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: tavily-api-key
-        - name: TAVILY_MCP_SERVICE_URL
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: tavily-mcp-service-url
-        # Langfuse Configuration
-        - name: LANGFUSE_HOST
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: langfuse-host
-        - name: LANGFUSE_PUBLIC_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: langfuse-public-key
-        - name: LANGFUSE_SECRET_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: langfuse-secret-key
-        # Application Settings
-        - name: VECTOR_INDEX_NAME
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: vector-index-name
-        - name: KNOWLEDGE_DIR
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: knowledge-dir
-        - name: OUTPUT_DIR
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: output-dir
-        - name: TOP_K_RESULTS
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: top-k-results
-        resources:
-          requests:
-            memory: "512Mi"
-            cpu: "200m"
-          limits:
-            memory: "2Gi"
-            cpu: "1000m"
-        livenessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 60
-          periodSeconds: 60  # Increased from 30 to 60 seconds
-          timeoutSeconds: 15  # Increased from 10 to 15 seconds
-          failureThreshold: 5  # Increased from 3 to 5 failures
-        readinessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 30
-          periodSeconds: 30  # Increased from 10 to 30 seconds
-          timeoutSeconds: 10  # Increased from 5 to 10 seconds
-          failureThreshold: 5  # Increased from 3 to 5 failures
-        volumeMounts:
-        - name: app-config
-          mountPath: /app/config
-          readOnly: true
-        - name: knowledge-volume
-          mountPath: /app/knowledge
-          readOnly: true
-      volumes:
-      - name: app-config
-        configMap:
-          name: app-config
-      - name: knowledge-volume
-        configMap:
-          name: knowledge-base
-      restartPolicy: Always
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: strandsdk-rag-service
-  labels:
-    app: strandsdk-rag-app
-    component: main-app
-spec:
-  selector:
-    app: strandsdk-rag-app
-  ports:
-  - name: http
-    port: 80
-    targetPort: 8000
-    protocol: TCP
-  type: ClusterIP
----
-apiVersion: networking.k8s.io/v1
-kind: Ingress
-metadata:
-  name: strandsdk-rag-ingress-alb
-  annotations:
-    kubernetes.io/ingress.class: alb
-    alb.ingress.kubernetes.io/scheme: internet-facing
-    alb.ingress.kubernetes.io/target-type: ip
-    alb.ingress.kubernetes.io/healthcheck-path: /health
-    alb.ingress.kubernetes.io/healthcheck-port: "8000"
-    alb.ingress.kubernetes.io/listen-ports: '[{"HTTP": 80}]'
-    # Increase ALB idle timeout to 15 minutes for long-running agentic queries
-    alb.ingress.kubernetes.io/load-balancer-attributes: idle_timeout.timeout_seconds=900
-    # Increase target group timeout and health check settings for better handling
-    alb.ingress.kubernetes.io/target-group-attributes: deregistration_delay.timeout_seconds=30,slow_start.duration_seconds=0,stickiness.enabled=false
-    # Add health check configuration for better reliability
-    alb.ingress.kubernetes.io/healthcheck-interval-seconds: "30"
-    alb.ingress.kubernetes.io/healthcheck-timeout-seconds: "10"
-    alb.ingress.kubernetes.io/healthy-threshold-count: "2"
-    alb.ingress.kubernetes.io/unhealthy-threshold-count: "3"
-spec:
-  rules:
-    - http:
-        paths:
-          - path: /
-            pathType: Prefix
-            backend:
-              service:
-                name: strandsdk-rag-service
-                port:
-                  number: 80
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/service-account.yaml b/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/service-account.yaml
deleted file mode 100644
index 767393d5..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/service-account.yaml
+++ /dev/null
@@ -1,6 +0,0 @@
-apiVersion: v1
-kind: ServiceAccount
-metadata:
-  name: strandsdk-rag-service-account
-  namespace: default
-
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/tavily-mcp-deployment.yaml b/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/tavily-mcp-deployment.yaml
deleted file mode 100644
index bac9c8da..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/k8s/tavily-mcp-deployment.yaml
+++ /dev/null
@@ -1,104 +0,0 @@
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: tavily-mcp-server
-  labels:
-    app: tavily-mcp-server
-    component: mcp-server
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: tavily-mcp-server
-  template:
-    metadata:
-      labels:
-        app: tavily-mcp-server
-        component: mcp-server
-    spec:
-      containers:
-      - name: tavily-mcp-server
-        image: 412381761882.dkr.ecr.us-east-1.amazonaws.com/strandsdk-agentic-rag-mcp:latest
-        # Fixed command to run MCP server directly with proper host binding
-        command:
-        - python
-        - -c
-        - |
-          from dotenv import load_dotenv
-          import os
-          # Load environment variables from ConfigMap or local file
-          if os.path.exists('/app/config/.env'):
-              load_dotenv('/app/config/.env')
-              print('Loaded environment from ConfigMap')
-          elif os.path.exists('/app/.env'):
-              load_dotenv('/app/.env')
-              print('Loaded environment from local file')
-          # Import and run MCP server with host binding to 0.0.0.0
-          from src.mcp_servers.tavily_search_server import mcp
-          mcp.run(transport='streamable-http', port=8001, host='0.0.0.0')
-        ports:
-        - containerPort: 8001
-          name: http
-        env:
-        # Tavily Configuration
-        - name: TAVILY_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: tavily-api-key
-        # LiteLLM Configuration (for potential future use)
-        - name: LITELLM_API_KEY
-          valueFrom:
-            secretKeyRef:
-              name: app-secrets
-              key: litellm-api-key
-        - name: LITELLM_BASE_URL
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: litellm-base-url
-        # AWS Configuration
-        - name: AWS_REGION
-          valueFrom:
-            configMapKeyRef:
-              name: app-config
-              key: aws-region
-        # Server Configuration
-        - name: PORT
-          value: "8001"
-        - name: HOST
-          value: "0.0.0.0"
-        resources:
-          requests:
-            memory: "128Mi"
-            cpu: "50m"
-          limits:
-            memory: "256Mi"
-            cpu: "200m"
-        # Health checks removed as not needed for MCP server
-        volumeMounts:
-        - name: app-config
-          mountPath: /app/config
-          readOnly: true
-      volumes:
-      - name: app-config
-        configMap:
-          name: app-config
-      restartPolicy: Always
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: tavily-mcp-service
-  labels:
-    app: tavily-mcp-server
-    component: mcp-server
-spec:
-  selector:
-    app: tavily-mcp-server
-  ports:
-  - name: http
-    port: 8001
-    targetPort: 8001
-    protocol: TCP
-  type: ClusterIP
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/knowledge/q_c_data.csv b/agentic-apps/strandsdk_agentic_rag_opensearch/knowledge/q_c_data.csv
deleted file mode 100644
index e84c39dd..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/knowledge/q_c_data.csv
+++ /dev/null
@@ -1,2003 +0,0 @@
-question,context
-What were the surgical complications observed in patients who underwent excision of limbal dermoids?,"Excision of limbal dermoids. We reviewed the clinical files of 10 patients who had undergone excision of unilateral epibulbar limbal dermoids. Preoperatively, all of the affected eyes had worse visual acuity (P less than .02) and more astigmatism (P less than .01) than the contralateral eyes. Postoperatively, every patient was cosmetically improved. Of the eight patients for whom both preoperative and postoperative visual acuity measurements had been obtained, in six it had changed minimally (less than or equal to 1 line), and in two it had improved (less than or equal to 2 lines). Surgical complications included persistent epithelial defects (40%) and peripheral corneal vascularization and opacity (70%). These complications do not outweigh the cosmetic and visual benefits of dermoid excision in selected patients."
-What is the most important aspect of initial treatment for Bell's palsy?,"Bell's palsy. A diagnosis of exclusion. In cases of acute unilateral facial weakness, a careful and systematic evaluation is necessary to identify the cause. Idiopathic facial paralysis (Bell's palsy) is a diagnosis of exclusion. It is also the most common cause of unilateral facial weakness seen by primary care physicians. The most important aspect of initial treatment is eye protection. Administration of systemic oral corticosteroids may lessen severity and duration of symptoms."
-How did steroid therapy help in the removal of the retained foreign body in the endobronchial region?,"Retained endobronchial foreign body removal facilitated by steroid therapy of an obstructing, inflammatory polyp. Oral and topical steroids were used to induce regression in an inflammatory, obstructing endobronchial polyp caused by a retained foreign body. The FB (a peanut half), which had been present for over six months, was then able to be easily and bloodlessly retrieved with fiberoptic bronchoscopy."
-What unusual complication of Crohn's disease was observed in the patient described in this case report?,"Recurrent buccal space abscesses: a complication of Crohn's disease. A patient is described with generalized gastrointestinal involvement by Crohn's disease. Symptoms of recurrent ulceration and mucosal tags are well-described oral manifestations of Crohn's disease; however, in our patient recurrent facial abscesses, which required extraoral drainage, also developed. This complication has not previously been reported."
-What are the key characteristics and management recommendations for intracranial fibromatosis based on the given context?,"Intracranial fibromatosis. Fibromatoses are uncommon infiltrative lesions affecting musculoaponeurotic structures, most often of the limbs and trunk. Lesions involving the cranial cavity are rare and require the same aggressive surgical management as elsewhere in the body. This case illustrates their clinical and neuroradiological features and underscores the necessity for aggressive resection to avoid recurrence. The literature is reviewed."
-What was the effect of intrathecally administered morphine sulfate on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) in awake patients?,"The effect of intrathecal morphine on somatosensory evoked potentials in awake humans. Although the effect of systemic opioids on somatosensory evoked potentials has been well described, little is known about the interaction between intrathecally administered opioid analgesics and somatosensory evoked potentials. Accordingly, the influence of intrathecally administered morphine on posterior tibial nerve somatosensory cortical evoked potentials (PTSCEPs) was investigated in 22 unpremedicated, awake, neurologically normal patients scheduled to undergo elective abdominal or pelvic procedures. Patients were randomly assigned to receive either preservation-free intrathecal morphine sulfate (ITMS) or placebo. After baseline PTSCEP, heart rate and, mean blood pressure were recorded, ITMS (15 micrograms.kg-1) was injected via standard dural puncture with the patient in the lateral position. PTSCEPs, heart rate, and mean blood pressure were recorded again at 5, 10, 20, 30, 60, 90, and 120 min. Control patients were treated identically (including position, sterile preparation, and subcutaneous tissue infiltration with local anesthetic), except for lumbar puncture, and were unaware of their randomization. Before administration of ITMS, PTSCEP P1, N1, P2, N2, and P3 latencies were 39.4 +/- 3.2, 47.6 +/- 3.9, 59.2 +/- 3.2, 70.4 +/- 3.7, and 84.6 +/- 5.5 ms, (mean +/- standard deviation), respectively. The corresponding P1-N1, N1-P2, and P2-N2 amplitudes were 2.4 +/- 1.1, 2.4 +/- 1.1, and 2.3 +/- 0.9 microV, respectively. There were no significant changes over time between the control and ITMS groups. PTSCEPs resulting from left-sided stimulation were not different from those elicited by right-sided stimulation. All ITMS patients had intense postoperative analgesia for at least 24 h. It is concluded that ITMS does not affect PTSCEP waveforms in the 35-90 ms latency range during the awake state."
-What is the key message of the 29th Rovenstine lecture regarding the ongoing education and approach of anesthesiologists?,"The 29th Rovenstine lecture: clinical challenges for the anesthesiologist. In conclusion, I hope that my comments have reaffirmed your biases or, even more importantly, stimulated you to think in a different way about the information explosion in our specialty and medicine in general. I believe our specialty is in a golden era that will benefit from the past and be nourished by new discoveries and understanding. We as clinicians must accept the challenge of recognizing what new information deserves incorporation into our practice, what old information deserves to be sustained, and what merits new scrutiny and perhaps should be discarded. If I had one wish, it would be that anesthesiologists would never lose their zeal to be students--their thirst for new information--as the continuum of anesthesia education is indeed a life-long process. That wish, ladies and gentlemen, is my challenge to all anesthesiologists."
-What was the purpose of the study on encainide and flecainide in patients with supraventricular arrhythmias?,"Mortality in patients treated with flecainide and encainide for supraventricular arrhythmias. In a recent clinical trial, the class Ic antiarrhythmic drugs encainide and flecainide were found to be associated with an increased mortality risk in patients with new myocardial infarction and ventricular arrhythmias. The purpose of this study was to assess whether an increased mortality risk also accompanied the use of these drugs to treat patients with supraventricular arrhythmias. Data were obtained from the respective pharmaceutical sponsors on the mortality observed with each drug in United States and foreign protocols enrolling patients with supraventricular arrhythmias. Mortality in the encainide population (343 patients) and the flecainide population (236 patients) was compared with that in a research arrhythmia clinic, the Duke population (154 patients). Nine deaths occurred in the combined encainide-flecainide population and 10 deaths occurred in the Duke population; the follow-up periods averaged 488 days and 1,285 days, respectively. The 6-year survival functions of these 2 populations, estimated by the Kaplan-Meier technique, did not differ significantly (p = 0.62). The hazard ratio for the combined encainide-flecainide population relative to the Duke population was estimated to be 0.6 with a 95% confidence interval of 0.2, 1.7. These descriptive comparisons did not demonstrate any excess mortality when flecainide and encainide were used in patients with supraventricular arrhythmias."
-How do lymphokines contribute to the potential immunotherapy of cancer?,"Approaches to immunotherapy of cancer: characterization of lymphokines as second signals for cytotoxic T-cell generation. Lymphokines, the soluble molecules produced by cells of the immune system, regulate cell-cell interactions and, consequently, the functional status of the immune system. Altering immunoregulatory pathways with lymphokines in vivo may provide a mechanism for controlling a variety of immunologic disorders. Although normally produced in vivo in very small quantities, the widespread availability of recombinant lymphokines has made it possible to study the molecular signals involved in production of lymphocyte effectors with activity against tumor. For example, interleukin-2-based cancer immunotherapy programs have, in certain clinical situations, suggested that immunologic intervention can influence the regression of metastatic cancer. Ultimately the successful application of these biologic agents requires an understanding of the interaction between the immune system and tumor on a molecular level. To induce a given biologic effect, it is necessary both to classify the required lymphokines and to identify the relevant effector cell populations. This review will examine the progress made in identifying the requirements for lymphokine-induced cytotoxic T-lymphocyte function."
-What was the clinical progression and outcome of the 71-year-old woman's retinal condition associated with non-Hodgkin's large cell lymphoma?,"Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma). A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma."
-How did morphine and naloxone affect pain-related behaviors in rats with peripheral mononeuropathy?,"The 'tonic' pain-related behaviour seen in mononeuropathic rats is modulated by morphine and naloxone. This study investigated the sensitivity to pharmacological manipulations of a rating method, adapted from the formalin test, to measure the tonic component of the pain-related behaviour induced by creating a peripheral mononeuropathy with 4 loose ligatures around the common sciatic nerve. Although the adequacy of opioid substances in alleviating neuropathic pain is highly controversial, the effects of morphine (1 mg/kg i.v.) and naloxone (1 mg/and 3 micrograms/kg i.v.) were tested 1-2 weeks after the nerve ligatures were established, when pain-related behaviours were well developed. Morphine (1 mg/kg i.v.) induced a potent and prolonged decrease in the pain-rating score at week 2 after surgery. Either at week 1 or week 2, naloxone elicited a bidirectional dose-dependent action: a further increase in the pain-rating score with the high dose (1 mg/kg i.v.), and a paradoxical decrease in the score with the low dose of 3 micrograms/kg i.v. These effects are comparable to those already described in several rat models of inflammatory pain and, in the same model of neuropathy, using a phasic nociceptive test, the measure of the vocalization to paw pressure. A few differences in the effects of naloxone on tonic and phasic pain are noted and discussed."
-What cardiovascular changes were observed in patients during upper gastrointestinal endoscopy with deep sedation?,"Examination of cardiorespiratory changes during upper gastrointestinal endoscopy. Comparison of monitoring of arterial oxygen saturation, arterial pressure and the electrocardiogram. Critical events including hypoxaemia, arrhythmias and myocardial ischaemia may occur more frequently during endoscopic procedures than during anaesthesia. A study was undertaken to assess the cardiovascular changes and to evaluate suitable monitoring techniques to detect critical events during sedation and endoscopy. Twenty patients scheduled to undergo a prolonged endoscopic procedure which required deep sedation were studied. Continuous recordings of electrocardiogram, heart rate and arterial oxygen saturation were made and arterial pressure was recorded at one-minute intervals. The study commenced immediately before administration of sedatives, continued for the duration of the examination and for one hour following the examination. Oxygen saturation decreased in all patients during the examination to a mean of 82.9% (SD 11.9), and remained below baseline for the duration of the examination and into the recovery period. Statistically significant increases and reductions of systolic arterial pressure and rate-pressure product were found during the procedures compared with baseline values recorded before administration of sedatives. Sixteen of the 20 patients developed tachycardia during the examination. Ten patients developed ectopic foci which were supraventricular, ventricular or both in origin. Electrocardiogram changes resolved during the recovery period. Myocardial ischaemia was assessed by S-T segment depression and a significant correlation was found between S-T segment depression and hypoxaemia, although the magnitude of the S-T depression was small and may not have been detected clinically. No correlation was found between S-T segment depression and arterial pressure, heart rate or rate-pressure product."
-How did the presence of 4-methylpyrazole affect blood alcohol levels and methionine metabolism in the experimental groups of Golden Syrian hamsters?,"Hepatic transmethylation and blood alcohol levels. Golden Syrian hamsters that have elevated hepatic alcohol dehydrogenase activity were divided into four groups and group-fed on four different liquid diets for five weeks. Group I was fed a control diet formulated for hamsters. Group II was fed the control diet containing 20 micrograms of 4 methylpyrazole per litre. Group III was fed the hamster ethanol liquid diet (ethanol amounting to 36% of total calories). Group IV was fed the ethanol diet to which 4-methylpyrazole (20 micrograms/litre) was added. Groups I, II and III were group-fed the amount consumed by Group IV on a daily basis. Upon killing the animals, blood alcohol levels were found to be elevated in Group IV but not in Group III. Hepatic methionine synthetase (MS) was inhibited in Group IV. Betaine-homocysteine methyltransferase was induced in this group to compensate for the MS inhibition and liver betaine was lowered reflecting this induction. None of these changes were seen in Group III. Since none of the animals showed an aversion to their respective diets and gained weight normally, these data indicate that it was the elevated blood levels of ethanol rather than nutritional factors that were related to the changes in methionine metabolism."
-What are the key characteristics of memory T cells in liver inflammation?,"Memory T cells represent the predominant lymphocyte subset in acute and chronic liver inflammation. T cells can be divided into two main phenotypic subpopulations-i.e., the CD45RA-positive (2H4-positive) ""naive"" subset and the CD45RO-positive (UCHL1-positive) ""memory"" subset. In light of this recent functional reinterpretation of T-lymphocyte subpopulations, we reinvestigated the composition of the inflammatory infiltrate in liver biopsy specimens from patients with acute and chronic hepatitis. In normal liver, the few scattered mononuclear cells present in portal tracts and in the intralobular parenchyma consisted of both CD45RA-positive (2H4-positive) naive and CD45RO-positive (UCHL1-positive) memory T cells. In inflammatory liver diseases, portal tract and periportal and intralobular areas of inflammation consisted virtually only of CD45RO-positive (UCHL1-positive) memory T cells, which strongly expressed the CDw29 (4B4) antigen, and the adhesion molecules LFA-1, CD2, LFA-3, CD44 and VLA-4 and the activation marker human leukocyte antigen-DR. These results indicate that activated memory T cells represent the predominant subpopulation of lymphocytes in areas of liver inflammation. Memory T cells strongly express various homing receptors and adhesion molecules, which probably allow them to accumulate at inflammatory sites and to strengthen interaction with target cells. Furthermore, the increased number of memory T cells with enhanced interferon-gamma production in areas of liver inflammation may contribute to the maintenance and up-regulation of immune responses occurring in inflammatory liver diseases."
-What ultrastructural changes were observed in endothelial cells after intracutaneous injection of NAP-1/IL-8?,"Inflammatory properties of neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8) in human skin: a light- and electronmicroscopic study. Neutrophil-activating protein-1/interleukin 8 (NAP-1/IL-8), purified to homogeneity from lipopolysaccharide-stimulated human peripheral blood monocytes, was injected intracutaneously into human skin. Sequential biopsy specimens were taken in order to investigate the sequence of ultrastructural changes induced by the cytokine. Whereas intracutaneous injection of 100 ng of NAP-1/IL-8 per site caused no macroscopic changes, by histology infiltration with polymorphonuclear leukocytes (PMN) and monocytes was present within 1 h and increased at 3 and 5 h. No lymphocyte infiltration was noted. The first ultrastructural changes (30 min) consisted of the presence of cytoplasmic 7-nm microfilament bundles, as well as numerous protrusions of the luminal plasma membrane of endothelial cells (EC). As a striking feature, multiple 100- to 160-nm electron lucent vesicles could be observed in the EC cytoplasm. These structures differed from plasmalemmal vesicles and suggest secretory activity. When PMN and monocytes appeared in the vascular lumen (1 h and later), the number of 100-160-nm electron-lucent vesicles had decreased significantly. In contrast to C5a-injected skin sites, mast cell degranulation was absent."
-What percentage of patients in the study had squamous cell carcinoma?,"Bronchogenic carcinoma with chest wall invasion. Bronchogenic carcinoma with chest wall involvement continues to present a major clinical challenge. We have treated 52 patients since 1973, excluding those with superior sulcus tumors. There were 37 male and 15 female patients with an average age of 62.9 years. Chest pain was an initial symptom in 37%. All patients had negative mediastinoscopy results. Squamous cell carcinoma was present in 53% and adenocarcinoma in 35%. The median number of ribs resected was two (range, one to six), and only 2 patients required chest wall reconstruction. Pathologic staging was T3 N0 M0 in 83% and T3 N1 M0 in 17%. Operative mortality was 3.8%. Absolute 5-year survival was 26.3%. Patients who had N1 disease had a 5-year survival of only 11%. Radiation therapy was employed in 46% for positive nodes or close margins. Bronchogenic carcinoma with chest wall invasion remains potentially curable if N2 nodes are not involved. The role of radiation therapy has not been clearly defined. Morbidity and mortality should be minimal."
-What are the two most common electronic weapons discussed in the context?,"Electronic weaponry--a question of safety [published erratum appears in Ann Emerg Med 1991 Sep;20(9):1031] Electronic weapons represent a new class of weapon available to law enforcement and the lay public. Although these weapons have been available for several years, there is inadequate research to document their safety or efficacy. Two of the most common, the TASER and the stun gun, are reviewed. The electronic weapon was initially and still is approved by the US Consumer Product Safety Commission; its approval was based on theoretical calculations of the physical effects of damped sinusoidal pulses, not on the basis of animal or human studies. These devices are widely available and heavily promoted, despite limited research into their safety or efficiency and despite recent animal studies documenting their potential for lethality."
-What was the primary objective of surgical management for acoustic tumors in this study?,"Operative management of acoustic neuromas: the priority of neurologic function over complete resection. The objective of surgical management of acoustic tumors is to remove them entirely and preserve facial nerve function and hearing when possible. A dilemma arises when it is not possible to remove the entire tumor without incurring additional neurologic deficits. Twenty patients who underwent intentional incomplete surgical removal of an acoustic neuroma to avoid further neurologic deficit were retrospectively reviewed. They were divided into a subtotal group (resection of less than 95% of tumor) and a near-total group (resection of 95% or more of tumor) and were followed yearly with either computed tomography or magnetic resonance imaging. The subtotal group was planned and consisted of elderly patients (mean age, 68.5 years) with large tumors (mean, 3.1 cm). The near-total group consisted of younger patients (mean age, 45.8 years) and smaller tumors (mean, 2.3 cm). The mean length of followup for all patients was 5.0 years. Ninety percent of patients had House grade I or II facial function post-operatively. Radiologically detectable tumor regrowth occurred in only one patient, who was in the subtotal resection group. Near-total resection of acoustic tumor was not associated with radiologic evidence of regrowth of tumor for the period of observation. Within the limits of the follow-up period of this study, subtotal resection of acoustic neuroma in elderly patients was not associated with clinically significant recurrence in most patients and produced highly satisfactory rates of facial preservation with low surgical morbidity."
-What is the potential drug interaction described in the context that may lead to cardiotoxicity?,"Torsades de pointes occurring in association with terfenadine use. Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval. Although found in many clinical settings, torsades de pointes is most often drug induced. This report describes the first association (exclusive of drug overdose) of symptomatic torsades de pointes occurring with the use of terfenadine in a patient who was taking the recommended prescribed dose of this drug in addition to cefaclor, ketoconazole, and medroxyprogesterone. Measured serum concentrations of terfenadine and its main metabolite showed excessive levels of parent terfenadine and proportionately reduced concentrations of metabolite, suggesting inhibition of terfenadine metabolism. We believe that a drug interaction between terfenadine and ketoconazole resulted in the elevated terfenadine levels in plasma and in the cardiotoxicity previously seen only in cases of terfenadine overdose."
-What is the prevalence of celiac or superior mesenteric artery stenoses among male veterans evaluated for peripheral vascular disease?,"Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients."
-What were the key findings of the brain-stem auditory evoked responses (BAER's) analysis in patients with acoustic neurinoma?,"Brain-stem auditory evoked responses in 56 patients with acoustic neurinoma. The brain-stem auditory evoked responses (BAER's) recorded from 56 patients with acoustic neurinomas were analyzed. Ten of the patients had intracanalicular tumors and 46 had extracanalicular tumors. It was possible to obtain BAER's following stimulation of the affected side in 28 patients and after stimulation of the unaffected side in all 56. Five patients (11%) had normal BAER's following stimulation of both sides; three of these patients had intracanalicular tumors. Among BAER's obtained following stimulation of the affected ear, the mean interpeak latency (IPL) for peaks I to III associated with extracanalicular tumors was significantly prolonged relative to controls (p less than 0.001), and linear regression analysis revealed a significant positive correlation between tumor size and IPL of peaks I to III (p less than 0.05). Analysis of the 56 BAER's recorded after stimulation of the unaffected side revealed a significant positive correlation between the IPL's of peaks III to V and tumor size (p less than 0.001). This correlation was not strengthened when accounting for the degree of brain-stem compression. Finally, evidence of preserved function within the auditory pathway, even in the presence of partial hearing loss, is presented. This finding suggests that more patients might benefit from surgical procedures that spare the eighth cranial nerve."
-What was the first successful heterotransplantation of a human carcinoid tumor into nude mice?,"First heterotransplantation of a human carcinoid tumor into nude mice. The first successful heterotransplantation of a human carcinoid tumor into nude mice is reported. CSH, a voluminous hepatic metastasis of a primary bronchial carcinoid tumor (CSB) was resected and transplanted into three irradiated nude (Swiss-nu/nu) mice both by subcutaneous (SC) and intramuscular (IM) routes; the success rate was five of six. Heterotransplanted tumors took 4 to 5 months to appear in the mice and 1 month to attain a width of 0.5 cm. Both human and mouse tumors (named CSH-SC and CSH-IM) were studied by light and electron microscopy. They were Grimelius-positive, neuron-specific enolase-positive, and bombesin-negative by immunocytochemistry. Furthermore, CSH-SC cells presented characteristic (pear-shaped, rod-shaped, or tadpole-shaped) neurosecretory granules. Although CSB and CSH were slightly serotonin positive by immunocytochemistry, only a few serotonin-positive cells were found in CSH-SC and none in CSH-IM, suggesting partial loss of differentiation or an increase in serotonin catabolism during transplantation."
-What was the purpose of the study on signal-averaged electrocardiogram (SAECG) reproducibility?,"A prospective evaluation of the immediate reproducibility of the signal-averaged ECG. The purpose of this investigation was to prospectively evaluate the immediate reproducibility of the signal-averaged electrocardiogram (SAECG). A total of 114 patients undergoing evaluation for ventricular arrhythmias were enrolled in this protocol. Two consecutive SAECG's (40 Hz bidirectional high-pass filtering with a computer-automated system) were performed 10 minutes apart. Abnormal SAECG parameters were defined as (1) vector QRS duration more than 120 msec, (2) terminal root mean square (RMS) voltage less than 20 microV, and (3) low-amplitude signal (LAS) duration more than 40 msec. An SAECG was defined as abnormal if at least one vector parameter was abnormal. There was close correlation between vector parameters during the two SAECG observations: QRS duration had the highest reproducibility (r2 = 0.97, p less than 0.001) followed by terminal RMS voltage (r2 = 0.92, p less than 0.001), and LAS duration (r2 = 0.90, p less than 0.001). The mean (+/- SD) percentage of change between the two recordings was 2% +/- 2% of the QRS duration, 13% +/- 22% for terminal RMS voltage, and 7% +/- 11% for LAS duration. The reproducibility of an initially normal SAECG was 92% and of an initially abnormal SAECG, 96%. Seventeen patients (15%) had a change in one of the three vector parameters between the two recordings. There were no clinically significant differences between the 17 patients in whom the SAECG was nonreproducible and the 97 patients in whom the SAECG was reproducible. However, reproducibility was significantly higher in patients with an initially normal versus an initially abnormal SAECG (92% vs 76%, p = 0.03)."
-What were the independent risk factors for stroke identified in this Chinese population study?,"Hypertension, lipoprotein(a), and apolipoprotein A-I as risk factors for stroke in the Chinese. We analyzed the serum concentrations of lipids and lipoproteins and the prevalence of other risk factors in a case-control study of 304 consecutive Chinese patients with acute stroke (classified as cerebral infarction, lacunar infarction, or intracerebral hemorrhage) and 304 age- and sex-matched controls. For all strokes we identified the following risk factors: a history of ischemic heart disease, diabetes mellitus, or hypertension; the presence of atrial fibrillation or left ventricular hypertrophy; a glycosylated hemoglobin A1 concentration of greater than 9.1%; a fasting plasma glucose concentration 3 months after stroke of greater than 6.0 mmol/l; a serum triglyceride concentration 3 months after stroke of greater than 2.1 mmol/l; and a serum lipoprotein(a) concentration of greater than 29.2 mg/dl. We found the following protective factors: a serum high density lipoprotein-cholesterol concentration of greater than 1.59 mmol/l and a serum apolipoprotein A-I concentration of greater than or equal to 106 mg/dl. The patterns of risk factors differed among the three stroke subtypes. When significant risk factors were entered into a multiple logistic regression model, we found a history of hypertension, a high serum lipoprotein(a) concentration, and a low apolipoprotein A-I concentration to be independent risk factors for all strokes. The attributable risk for hypertension was estimated to be 24% in patients aged greater than or equal to 60 years. In this population, in which cerebrovascular diseases are the third commonest cause of mortality, identification of risk factors will allow further studies in risk factor modification for the prevention of stroke."
-What percentage of lung cancers showed an air bronchogram or air bronchiologram on CT scans and histologic sections in this study?,"Prevalence of air bronchograms in small peripheral carcinomas of the lung on thin-section CT: comparison with benign tumors. Despite improved techniques--such as bronchoscopy and percutaneous needle biopsy--to evaluate pulmonary nodules, there are still many cases in which surgical resection is necessary before carcinoma can be differentiated from benign lesions. The present study was undertaken to determine if the presence of an air bronchogram or air bronchiologram (patent visible bronchus or bronchiole) is useful in distinguishing small lung cancers from benign nodules. Thin-section chest CT scans were obtained in patients with 20 peripheral lung cancers less than 2 cm in diameter (18 adenocarcinomas, one squamous cell carcinoma, and one large cell carcinoma) and 20 small benign nodules (eight hamartomas, seven tuberculomas, two foci of aspergillosis, one focus of cryptococcosis, one chronic focal interstitial pneumonitis, and one plasma cell granuloma). The images were compared with regard to the patency of any bronchus or bronchiole within the lesions. After surgical resection, the specimens were inflated with agar and sectioned transversely to correlate gross morphology and low-power histologic sections with the CT appearance. An air bronchogram or air bronchiologram was seen in the tumors on 65% of CT scans and 70% of histologic sections. Benign nodules had a patent bronchus or bronchiole on CT scans and histologic sections in only one case (5%). These findings suggest that the presence of an air bronchogram in a lung nodule is a useful finding to help differentiate adenocarcinomas from benign lesions."
-What were the most frequent complications observed in patients receiving long-term spinal morphine administration via Port-A-Cath?,"Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study. Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases)."
-How accurate is real-time ultrasound in detecting deep venous thrombosis (DVT) compared to contrast venography?,"Real-time ultrasound for the detection of deep venous thrombosis. PURPOSE: Accurate diagnosis of deep venous thrombosis (DVT) is a clinical problem in emergency practice. A prospective trial was conducted comparing real-time ultrasound with contrast venography in the diagnosis of proximal DVT. METHODS: Seventy patients whose clinical presentations mandated diagnostic evaluation for DVT had real-time ultrasound of the involved leg followed by contrast venography. Initial readings of ultrasound and venography were compared with each other and with final readings to assess reliability of interpretation. RESULTS: Final ultrasound readings agreed with final venogram readings in all patients. Negative initial ultrasound readings agreed with final venogram readings in 56 of 56 patients (negative predictive value, 100%; 95% confidence interval, 94 to 100). Eighteen patients had positive initial ultrasound readings compared with 14 who had positive final venogram readings (positive predictive value, 78%; 95% confidence interval, 55 to 91). CONCLUSION: Negative real-time ultrasonography reliably excludes proximal DVT. Positive ultrasound reliably diagnoses proximal DVT only in experienced hands."
-How does dual-chamber sensor-driven pacing compare to single-chamber pacing in terms of cardiac output for patients with chronotropic incompetence?,"Single- versus dual-chamber sensor-driven pacing: comparison of cardiac outputs. Previous studies have shown that single-chamber sensor-driven pacing improves exercise tolerance for patients with chronotropic incompetence. However, long-term single-chamber pacing has a number of inherent problems that limit its usefulness. Although sensor-driven dual-chamber pacing largely obviates the problems inherent with single-chamber sensor-driven pacing, the physiologic benefit of dual-chamber sensor-driven pacing has not yet been demonstrated. Accordingly, the purpose of this study was to compare exercise-induced cardiac output for patients with chronotropic incompetence, after programming their pacemakers to either a simulated sensor-driven single or simulated dual-chamber mode. Cardiac output was measured noninvasively at rest and peak exercise using standard Doppler-derived measurements, obtained in a blinded fashion. At rest the Doppler-derived resting VVI and DDD cardiac outputs were 4.49 +/- 0.3 L/min and 4.68 +/- 0.3 L/min, respectively. At peak exercise, the DDD cardiac output was 5.07 +/- 0.5 L/min, whereas the simulated activity VVI and DDD cardiac outputs were 6.33 +/- 0.6 L/min and 7.41 +/- 0.70 L/min, respectively. Analysis of variance showed that there was an overall significant difference in cardiac output from rest to peak exercise (p less than 0.001). However, only the simulated activity DDD cardiac output was significantly different from its respective control value (p less than 0.05). Thus this study shows for the first time that the addition of rate responsiveness to dual-chamber pacing results in a significant improvement in cardiac output for patients with chronotropic incompetence."
-How does D-dimer affect the secretion of interleukin and other substances in the NOMO-1 human promonocytic leukemia cell line?,"FDP D-dimer induces the secretion of interleukin-1, urokinase-type plasminogen activator, and plasminogen activator inhibitor-2 in a human promonocytic leukemia cell line. We studied the effect of fibrinogen degradation products D, E, and D-dimer on a human promonocytic leukemia cell line, NOMO-1. After exposure to a 10(-5)-mol/L fragment D or D-dimer, the cells displayed macrophage-like characteristics, such as adherence to plastic surfaces, and showed approximately a twofold increase in response to the nitroblue tetrazolium reduction test. The secretion of interleukin-1 alpha (IL-1 alpha) into the medium was markedly stimulated by a 10(-5)-mol/L fragment D, E, and D-dimer, whereas a significant increase in IL-1 beta secretion was observed only in D-dimer-stimulated cells. In addition, D-dimer induced a rapid increase in urokinase-type plasminogen activator on day 1 (0.52 +/- 0.02 ng/mL v 0.07 +/- 0.01 ng/mL in the control culture) and a slow increase in plasminogen activator inhibitor-2 on day 5 (3.9 +/- 1.6 ng/mL v 1.2 +/- 0.2 ng/mL in the control culture). An increase in tissue factor (TF) was also demonstrated on the cell surface of NOMO-1 cells exposed to fragment D or D-dimer by indirect immunofluorescence using an anti-TF monoclonal antibody. Scatchard plot analysis showed that fragment D and D-dimer bound to the NOMO-1 cells with a kd of 3.3 nmol/L and 2.7 nmol/L, respectively. These results suggest that fragment D-dimer specifically stimulates cells of monocyte-macrophage lineage to secrete key substances that regulate blood coagulation, fibrinolysis, and inflammation."
-What factors predict the success of stereotactic aspiration for colloid cysts?,"Stereotactic management of colloid cysts: factors predicting success. Stereotactic aspiration is a valuable surgical alternative for colloid cysts when used alone or in conjunction with microsurgical resection. Since 1981, the authors have performed computerized tomography (CT)-guided stereotactic aspiration as the initial procedure in 22 patients with colloid cysts; stereotactic aspiration alone was successful in 11 patients (50%). Of the 11 patients in whom aspiration failed, stereotactic endoscopic resection was attempted in three and was successful in one. Seven patients required a craniotomy and microsurgical removal of the cyst performed via a transcortical approach. The preoperative CT appearance in eight cases of a hypodense or isodense cyst correlated favorably with successful aspiration of the cyst in six patients. A hyperdense appearance on the preoperative CT scan in 14 cases was associated with subtotal aspiration in 13 patients; five required craniotomy for removal. Preoperative magnetic resonance (MR) imaging in eight patients provided excellent anatomical definition of the cyst and its relationship to other structures of the third ventricle, but it was not possible to correlate successful aspiration with cyst appearance on MR images with short or long relaxation time sequences. The authors' 9-year experience suggests that preoperative CT studies accurately determine size, predict viscosity, and help to define a group of colloid cyst patients for whom stereotactic cyst aspiration will likely be successful. Unsuccessful stereotactic aspiration was related to two features: the high viscosity of the intracystic colloid material (nine patients), or deviation of the cyst away from the aspiration needle due to small cyst volume (two patients). Because of its simplicity and low risk, stereotactic surgery can be offered to selected patients as the initial procedure of choice. Craniotomy can be reserved for those whose imaging studies predict failure or for those whose cyst cannot be aspirated."
-What percentage of patients with chronic demyelinating polyneuropathy showed MRI changes suggestive of demyelination?,"Cranial magnetic resonance imaging in chronic demyelinating polyneuropathy. Twenty one patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and five patients with chronic demyelinating polyneuropathy associated with benign monoclonal paraproteinaemia none of whom had signs or symptoms of central nervous system disease, had cranial magnetic resonance imaging (MRI) on a 1.5 Tesla unit. Areas of increased white matter signal intensity were seen in one of 10 patients aged less than 50 years and in five of 16 patients aged more than 50 years. In only two of the patients (8%), neither of whom had paraproteinaemia, did the appearance strongly suggest demyelination. The only clinical variable that predicted MRI changes was age (p less than 0.01)."
-How did the bleeding patterns differ between postmenopausal women receiving estradiol and norethisterone acetate versus estradiol and cyproterone acetate?,"Bleeding patterns during continuous combined estrogen-progestogen therapy. Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding."
-How does liver cirrhosis affect the metabolism and processing of lysophosphatidylcholine in rats?,"Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis. Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance."
-How many additional metastatic lymph nodes were found through serial sectioning in this study?,"The value of single versus multiple sections for detection of lymph node metastasis. This study was undertaken to determine the value of serial sectioning of lymph nodes as an aid in optimally examining cervical specimens for metastasis. The presence or absence of lymph node metastasis in 802 lymph nodes obtained from 51 consecutive neck dissection specimens were initially determined by the routine method, examination of one section from each node. This examination revealed 40 lymph nodes with metastatic involvement. Further study of the 716 lymph nodes that were initially interpreted as free of tumor by serial sectioning added only two positive nodes. Thus, serial sectioning did not contribute significantly to the detection of lymph node metastasis."
-What was the observed difference in hemolytic activity between plasma from ALS patients and normal controls?,"Cytotoxic activity in plasma from patients with amyotrophic lateral sclerosis. The present study evaluates an assay of cytotoxic effect of plasma from patients with amyotrophic lateral sclerosis. Plasma from 20 recently diagnosed ALS patients induced hemolysis of normal red blood cells with a significantly greater intensity than that of normal controls. After at least 1 month of treatment with prednisone and azathioprine, the hemolytic activity of ALS plasma was reduced but was still higher than that of control plasma."
-What are the MR imaging characteristics of giant cell tumors in patients with Paget disease of bone?,"Multiple giant cell tumors and Paget disease of bone: radiographic and clinical correlations. The clinical and radiographic findings of four patients with multicentric giant cell tumor (GCT) of bone and Paget disease were retrospectively reviewed. Three patients underwent magnetic resonance (MR) imaging evaluation; all patients underwent computed tomography (CT). The MR characteristics of the bone component in pagetic GCT appeared to reflect the pagetic phase; a sclerotic pattern was largely represented by hypointense marrow signal intensity on images obtained with both long and short repetition times (TRs) and echo times (TEs). Conversely, a tumor appearing in a mixed pagetic phase demonstrated more heterogeneous signal intensity with all pulse sequences. Extensive soft-tissue components, noted in all cases, showed largely intermediate signal intensity on short TR/TE images and foci of increased signal intensity on longer TR/TE images. In most cases, dramatic reduction in tumor bulk was noted with the use of steroids alone. An awareness of this entity is important because the appearance of lytic lesions with soft-tissue extension in patients with Paget disease does not necessarily imply a grave prognosis. Serial CT or MR imaging is helpful in monitoring the remissions and exacerbations that reflect response to therapy in Paget disease and GCT."
-What are the key MRI findings and considerations when assessing the postoperative spine in patients with degenerative disc disease?,"Magnetic resonance assessment of the postoperative spine. Degenerative disc disease. The magnetic resonance (MR) imaging findings in patients after surgery for degenerative disc disease in the lumbar and cervical spine are discussed. In the lumbar spine, changes seen in the immediate postoperative period, use of Gd-DTPA in distinguishing scar and disc and postoperative complications are reviewed. In the cervical spine, operative approaches and types, the appearance of bony stenosis, and disc herniations are demonstrated."
-What are the advantages and outcomes of using the pedicled island flap technique for repairing complicated urethral strictures?,"Urethroplasty using the pedicled island flap technique in complicated urethral strictures. Many techniques have been described for the repair of recurrent urethral strictures. Experience with 1-stage correction of hypospadias and epispadias, using a vascularized island flap technique, has led to its increased application for complicated adult urethral strictures. The advantage of the vascularized island flap technique is that reconstruction can be completed with only 1 operation, and it provides good subjective and objective results. Analysis of 50 consecutive cases treated by this approach has proved its validity. Of the 50 cases fistulas occurred in 20%, of which 12% required surgical correction, and stricture recurred in 32%. The largest proportion of recurrence was noted in patients who were primarily treated with 3 or more urethrotomies within a short time. Therefore, we recommend open surgical repair when 1 or 2 internal urethrotomies fail to produce a good result."
-What percentage of HIV-seropositive patients were found to have bullous pemphigoid (BP)-type autoantibodies in the study?,"Bullous pemphigoid autoantibodies, HIV-1 infection and pruritic papular eruption. Bullous pemphigoid (BP)-type autoantibodies were found by Western blot (WB) analysis of epidermal extracts in the serum of 38% of HIV-seropositive patients compared with 21% of HIV-seronegative patients with chronic pruritus and 76% of patients with BP. They were further identified as BP autoantibodies (BPab) by immunoprecipitation and immunoelectron microscopy. Their incidence increased from 21% in HIV infection stage II to 37% and 43% in stages III and IV, respectively. Of the patients suffering from HIV-related chronic pruritic papulovesicular eruption. 75% showed circulating BPab as compared with 29% in those without skin problems (P = 0.0066) and, among them, 30% met the diagnostic criteria for BP when histology, WB, immunofluorescence and immunoelectron microscopy techniques were used. In conclusion, this study identifies an autoimmune skin reaction that may account for, or be related to, the distressing pruritic eruptions occurring in HIV-infected patients."
-What is the significance of the DNA segment isolated from the agouti locus in mice?,Molecular characterization of a region of DNA associated with mutations at the agouti locus in the mouse. Molecular characterization of a radiation-induced agouti (a)-locus mutation has resulted in the isolation of a segment of DNA that maps at or near the a locus on chromosome 2 in the mouse. This region of DNA is deleted in several radiation- or chemical-induced homozygous-lethal a-locus mutations and is associated with specific DNA structural alterations in two viable a-locus mutations. We propose that DNA probes from this region of chromosome 2 will be useful for ultimately characterizing the individual gene or genes associated with a-locus function.
-How do fish oils (EPA and DHA) affect platelet aggregation induced by nitrogen microbubbles?,"Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles. Platelet aggregation induced by N2 microbubbles (simulating microbubbles developed during deep diving) was measured in seven volunteers before and after intake of ethyl-eicosapentaenoate (-EPA, 3.5 g/day) and ethyl-docosahexaenoate (-DHA, 2.5 g/day) for 2 wk. The relative content of arachidonic acid (AA) decreased in platelets from all individuals, whereas the content of EPA and DHA increased. The decrease of AA was almost identical with the increase of EPA plus DHA. In plasma the AA content was unchanged, while EPA and DHA increased. The N2 microbubble-induced aggregation showed a significant negative correlation with the DHA content both in platelets and in plasma. Less aggregation was also observed with high EPA content in platelets or plasma. A significant correlation between AA content in platelets and aggregation was seen. Intake of marine oils may be beneficial to divers under deep diving and to patients during extracorporeal circulation, because this may reduce the microbubble-induced aggregation."
-What is midventricular obstruction and how does it relate to chronic systemic hypertension?,"Midventricular obstruction associated with chronic systemic hypertension and severe left ventricular hypertrophy. Midventricular obstruction is an uncommon finding previously defined by catheterization and angiographic techniques in patients with hypertrophic cardiomyopathy. This study describes the clinical and echocardiographic findings of 10 consecutive patients (mean age 73 years) with severe concentric left ventricular (LV) hypertrophy and the unusual finding of a dynamic systolic obstruction located in the midportion of the left ventricle. All patients were known to have chronic hypertension, and none had a history or family history of hypertrophic cardiomyopathy. In each case, a well-defined, high velocity, turbulent jet was identified by Doppler color flow imaging and subsequently confirmed with conventional Doppler techniques. Septal and posterior wall thickness averaged 1.67 and 1.57 cm, respectively. Mean LV mass index was 199 g/m2 and ejection fraction averaged 78%. Peak systolic velocity obtained by continuous-wave Doppler averaged 2.7 m/s and appeared as either a ""late-peaking"" or a ""spike and dome"" configuration. Seven of 10 patients gave a history of syncope or severe presyncope at the time of echocardiographic examination. At a mean follow-up of 1 year, syncope or presyncope had resolved in 5 patients in whom medication was adjusted based on the ultrasound study, but persisted in 2 patients in whom diuretic therapy was continued. It is concluded that obstruction to systolic flow can occur at the mid-LV level in some patients with severe concentric LV hypertrophy and avoidance of medication known to lower LV volume may relieve symptoms of transient inadequate cardiac output."
-How do blood type differences impact waiting times and graft survival in cadaveric renal transplantation?,"The impact of nonidentical ABO cadaveric renal transplantation on waiting times and graft survival. Blood type O recipients of cadaveric renal transplants have longer pretransplant waiting periods than blood type A, B, and AB recipients. To evaluate reasons for and consequences of this discrepancy, we studied both the frequency of various donor and recipient blood type combinations and their outcomes. Among 37,659 cadaveric renal transplants performed during 1983 through 1989, there were 2,625 transplants (7%) received by patients of compatible but nonidentical blood types. Of 18,575 type O donor organs, 16,784 were received by type O patients for a recipient to donor ratio of 0.9. The corresponding ratios were greater than 1.0 for all other blood types (1.02 for blood type A, 1.14 for type B, and 2.18 for type AB). This causes blood type O patients to have a lower access to transplantation and to have significantly longer waiting times than patients of all other blood types. This inequality of access diminished significantly (P less than 0.001) over the years, but did not resolve by 1989. Analysis of relative risk for first graft loss by multiple regression (Cox) showed that transplantation across compatible blood types had a 9.1% higher risk (P less than 0.1) than that of transplantation among identical blood types. Cadaveric renal transplantation within identical blood types optimizes access to transplantation and avoids further aggravating past disadvantages for blood type O recipients."
-What were the key findings of the study comparing streptokinase and recombinant tissue plasminogen activator (rTPA) in treating acute lower limb ischaemia?,"Results of a recently instituted programme of thrombolytic therapy in acute lower limb ischaemia. Twenty-eight patients with acute lower limb ischaemia received low dose intra-arterial thrombolytic therapy over a 2-year period. Eighteen patients received streptokinase and ten patients received recombinant tissue plasminogen activator (rTPA). Indications included arterial thromboemboli and graft failures. Mean ischaemic times were similar in both groups. Treatment time to achieve lysis was significantly less with rTPA (P less than 0.01). Subsequent vascular procedures, including angioplasty or reconstruction, were undertaken in 36 per cent of patients. Arterial puncture site bleeding occurred in eight (29 per cent) patients. Three (11 per cent) patients suffered rethrombosis after initial successful lysis. All rethromboses were successfully lysed with rTPA. There were two major amputations. Five (18 per cent) patients died, all lytic failures in the streptokinase treatment group. There were no cerebral haemorrhagic events and no patient died as a result of thrombolytic therapy. Good clinical outcome was obtained in nine of 18 patients treated with streptokinase and in nine of ten patients treated with rTPA. Intra-arterial thrombolysis provides effective therapy with high rates of limb salvage and a low mortality rate. This study suggests that rTPA may be a more effective agent, causing less morbidity, than streptokinase."
-What rare cardiac condition did the woman present with due to metastatic melanoma?,"Metastatic melanoma to the heart presenting with ventricular tachycardia. Intraventricular tumors in adults are uncommon, and the association of these with ventricular tachycardia is even more rare. We report a case of an intracardiac metastatic melanoma in a woman who presented with syncope due to ventricular tachycardia."
-What clinical methods are used for risk stratification in patients after a myocardial infarction?,"Risk stratification after myocardial infarction. Clinical overview. Many patients with an acute myocardial infarction can be stratified into subgroups that are at high risk for morbidity and mortality on the basis of clinical characteristics that indicate recurrent myocardial ischemia, persistent left ventricular dysfunction, and/or recurrent cardiac arrhythmias. In patients with uncomplicated myocardial infarction the assessment of symptoms, physical findings, and ECG changes during predischarge exercise testing often identifies patients at increased risk for further cardiac events. Because of the suboptimum sensitivity and specificity of the exercise ECG for detecting myocardial ischemia, myocardial perfusion imaging with 201Tl and/or assessment of global and segmental ventricular function by two-dimensional echocardiography or radionuclide cineangiography during or immediately after exercise are often added to the predischarge risk stratification."
-What is the clinical significance of recurrent pericarditis in hypocomplementemic urticarial vasculitis syndrome?,"Recurrent pericarditis and cardiac tamponade in a patient with hypocomplementemic urticarial vasculitis syndrome. We describe a patient with hypocomplementemic urticarial vasculitis syndrome complicated by recurrent pericarditis and cardiac tamponade. The episodes of pericarditis were associated with urticarial vasculitis, hypocomplementemia, and circulating IgG antibodies to the collagen-like region of Clq. Histopathologic examination of the skin and pericardium demonstrated vasculitis associated with immunoglobulin and complement deposition suggesting an immune complex mediated etiology. Recurrent pericarditis should be included in the clinical spectrum of hypocomplementemic urticarial vasculitis syndrome."
-How did supplemental oxygen affect breathlessness and oxygen saturation in patients with chronic obstructive airway disease (COAD) and interstitial lung disease (ILD)?,"Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease. We have compared the symptomatic benefit of air and oxygen at rest in hypoxemic patients with chronic obstructive airway disease (COAD) or interstitial lung disease (ILD). A total of 12 severely disabled patients with COAD (mean +/- SEM, PaO2, 50.3 +/- 3.7 mm Hg) and 10 with ILD (PaO2, 48.0 +/- 3.1 mm Hg) received 28% oxygen and air by Venturi face mask, each gas on two occasions, in a double-blind randomized fashion. SaO2 increased (p less than 0.01) in both groups during oxygen breathing: COAD, 85.1 +/- 2.3% versus 93.1 +/- 1.4%; ILD, 85.5 +/- 1.7% versus 94.7 +/- 0.9%. The patients with COAD stated that air helped their breathing on 15 of 24 occasions and that oxygen helped on 22 of 24 occasions (p less than 0.05). In the patients with ILD the values were 6 of 20 and 13 of 20 occasions, respectively (p less than 0.05). In both groups of patients the severity of breathlessness recorded on a 100-mm visual analog scale was significantly (p less than 0.05) lower during oxygen breathing: COAD, 29.6 +/- 4.5 versus 45.6 +/- 6.0; ILD, 30.2 +/- 5.1 versus 48.1 +/- 4.4. Ventilation measured by magnetometers was significantly lower during oxygen breathing in the patients with COAD (8.2 +/- 1.0 versus 9.3 +/- 1.1 L/min; p less than 0.05), but the difference between oxygen and air in patients with ILD was not statistically significant (9.3 +/- 1.3 versus 11.2 +/- 1.6 L/min; p greater than 0.05)."
-What was the impact of mitomycin C (MMC) as an adjuvant treatment on survival rates in patients with resected gastric cancer after a 10-year follow-up?,"Mitomycin C as an adjuvant treatment to resected gastric cancer. A 10-year follow-up. Seventy consecutive patients were entered in a two-arm randomized trial after surgical resection for locally advanced gastric cancer. In the first arm, 37 patients were included as a control group, receiving no further treatment after surgery. In the second arm, 33 patients were treated with adjuvant chemotherapy consisting of mitomycin C (MMC), 20 mg/m2 administered intravenously once every 6 weeks for four consecutive cycles. All patients in both arms were followed in the same way for 5 years. At 5 years 23 of 37 patients in the control arm and 7 of 33 patients in the treatment arm were dead because of relapse. Actuarial survival curve was statistically significant in favor of patients given adjuvant MMC (p less than 0.001). After 10 years follow-up, 31 of 37 patients in the control arm and 16 out of 33 patients in the treatment arm were dead because of relapse, the statistical differences continuing in the actuarial survival curve in favor of treated patients (p less than 0.01). The best advantages of adjuvant treatment were observed in the T3N0M0 stage. The most frequent relapse site was the peritoneal cavity and the relapse pattern shows special decrease in liver metastases in treated patients. Toxicity was acute and mild. No delayed toxicity or second malignancies were observed. These data suggest that adjuvant MMC after resected surgery of gastric cancer is a successful treatment and its effects are still evident after 10 years of follow-up."
-What are the key histological and histochemical characteristics of mucin-producing tumors in the pancreas?,"Mucin-producing tumor of the pancreas. A new pancreatic tumor, called mucin-producing tumor, has received great attention in Japan. These tumors are found inside the pancreatic duct and produce large quantities of copious mucus. The authors examined 22 cases of these tumors histologically and histochemically. In 12 malignant cases, the tumors inside the ducts consisted of cancerous lesions over small areas along with papillary or atypical hyperplasia. Tumors in ten benign cases mainly consisted of papillary hyperplasia. Except for three patients with carcinoma in situ, cancerous tumors infiltrated the pancreatic parenchyma and, in some cases, were observed invading the bile duct or duodenum. A mucous histochemical study showed evidence of sialomucin in malignant cases; neutral mucin was dominant in benign cases. Characteristics of this disease were also compared with 13 cases of mucinous cystic neoplasm. From the results, it was concluded that these two diseases can be classified into the same conceptual category."
-How was acute massive hepatic injury induced in rats in this experimental model?,"A rat model of acute liver necrosis induced by a monoclonal antibody to liver-specific antigen and complement. Acute massive hepatic injury was induced in rats by a monoclonal antibody against a rat liver-specific membrane antigen, and its histological characteristics were investigated. A single intravenous injection of murine ascites containing a monoclonal antibody produced numerous hemorrhagic foci of degenerated and necrotic liver cells predominantly in zones 1 (the periportal area) and 2 (the area of transition between the periportal zone and the perivenular zone) of the liver lobule within 10 min. Massive hepatocellular necroses were observed 1 hr later, but no inflammatory cell infiltration occurred in and around the necrotic foci. Immunohistological study demonstrated marked deposition of the third component of the complement system in the necrotic area. Serum complement activity was sharply decreased immediately after the injection of the antibody, suggesting that the hepatic necrosis is ascribable to a complement-mediated immune attack on the liver cell membrane induced by the antigen-antibody reaction. The hepatic necrosis in response to monoclonal-antibody injection did not progress to a chronic disease and healed almost completely, changing to scar tissues within 2 wk. Although it is not clear whether this hepatic injury has any clinical relevance, this antibody/complement model may be useful for investigating the cause and therapy of hepatic diseases such as fulminant hepatitis."
-What unique observation was made about the lateral rectus muscle after the silicone band transection in this case report?,"Preserved action of a rectus muscle after transection by an encircling solid silicone band. We present a case of anterior migration of a solid silicone band through a lateral rectus muscle. In this patient the action of the lateral rectus was preserved, and this is demonstrated photographically. The possible reasons for this rare complication and the possible mechanism by which lateral rectus activity remained intact are explained."
-What is the primary histologic reaction pattern in Behcet's disease?,"Clinical features of Behcet's disease. Report of four cases. Behcet's disease is a multisystem inflammatory disorder of unknown etiology. The unifying histologic reaction pattern is a leukocytoclastic vasculitis that affects predominantly the skin, oral mucosa, and eyes. Many other sites of involvement have been reported but are inconsistently found in individual patients. Early recognition and treatment of Behcet's disease may help prevent devastating permanent sequelae such as blindness. Because oral involvement is often the first manifestation of this disorder, dental practitioners are in a unique position to help these patients. We report four cases of Behcet's disease in North American patients. Diagnostic criteria and treatment options are reviewed."
-How did recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) impact neutrophil recovery and patient outcomes in autologous bone marrow transplantation for lymphoid cancer?,"Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid cancer. BACKGROUND. The period of neutropenia after autologous bone marrow transplantation results in substantial morbidity and mortality. The results of previous phase I-II clinical trials suggest that recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) may accelerate neutrophil recovery and thereby reduce complications in patients after autologous bone marrow transplantation. METHODS. We conducted a randomized, double-blind, placebo-controlled trial at three institutions. The study design and treatment schedules were identical, and the results were pooled for analysis. One hundred twenty-eight patients were enrolled. Sixty-five patients received rhGM-CSF in a two-hour intravenous infusion daily for 21 days, starting within four hours of the marrow infusion, and 63 patients received placebo. RESULTS. No toxic effects specifically ascribed to rhGM-CSF were observed. The patients given rhGM-CSF had a recovery of the neutrophil count to 500 x 10(6) per liter 7 days earlier than the patients who received placebo (19 vs. 26 days, P less than 0.001), had fewer infections, required 3 fewer days of antibiotic administration (24 vs. 27 days, P = 0.009), and required 6 fewer days of initial hospitalization (median, 27 vs. 33 days; P = 0.01). There was no difference in the survival rate at day 100. CONCLUSIONS. In patients undergoing autologous bone marrow transplantation for lymphoid neoplasia, rhGM-CSF significantly lessens morbidity. Further studies will be required to establish its optimal dosage and schedule of administration."
-What differences were observed between Candida tropicalis and Candida albicans fungemia in children with leukemia?,"Candida tropicalis and Candida albicans fungemia in children with leukemia. The records were reviewed for all patients hospitalized at a pediatric oncology center for complications of leukemia (n = 822) or lymphoma (n = 290) during an 8-year period. The results of surveillance cultures (throat, rectal, and urine) and blood cultures were analyzed to identify cases of Candida tropicalis and C. albicans colonization and/or fungemia. None of the patients with lymphoma who had positive surveillance cultures for C. albicans (n = 89) or C. tropicalis (n = 23) had fungemia. Among patients with leukemia, significant fungal infection was documented in 12 of 107 colonized with C. tropicalis (11.2%) versus 14 of 700 (2%) colonized with C. albicans (P less than 0.001). The two groups of children with fungemia were similar in primary diagnoses (predominantly acute lymphoblastic leukemia) and in the frequency of several known risk factors for infection, including the duration of neutropenia (absolute neutrophil counts, less than 500/microliters). Patients with C. tropicalis fungemia all had disseminated disease compared with nine of 14 patients with C. albicans fungemia. Also, subcutaneous abscesses were unique to patients with C. tropicalis in this series. Two patients in each group died of their infection; central nervous system involvement was present in both fatal cases of C. tropicalis fungemia. A high index of suspicion and the early institution of appropriate antifungal therapy are critical to the successful management of these infections in patients with leukemia."
-What was the relationship between the degree of coronary stenosis and mortality in patients who survived an anterior wall Q-wave acute myocardial infarction?,"Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05)."
-What are the contributing factors that may lead to late bleeding after rhytidectomy?,"Late bleeding after rhytidectomy from injury to the superficial temporal vessels. Five healthy, normotensive women, whose mean age was 49.8 years, developed expanding hematomas between 8 and 10 days (average 9 days) after rhytidectomy. In each patient, the bleeding vessel could be identified: In two, it was the parietal branch of the superficial temporal artery; in two, it was the parietal branch of the superficial temporal vein; and in one, it was the superficial temporal artery immediately before its branching. Contributing factors may have been sudden physical exertion in four of the five patients and in another salicylate ingestion. Several measures can help avoid late bleeding from the superficial temporal vessels or their branches; not using a too potent vasoconstrictive agent (epinephrine) in the local anesthetic so that the vessels will be easier to visualize; not injecting the local anesthetic too deeply or incising to deeply; dividing and ligating the superficial temporal vessel and its major branches if injured; using bipolar coagulation on small branches; and instructing patients repeatedly not to engage in strenuous activity or to ingest salicylates for at least 2 weeks after operation."
-What is the current understanding of dietary fiber's effectiveness in managing constipation and diarrhea in tube-fed patients?,"Dietary fiber and bowel function in tube-fed patients. In tube-fed patients, dietary fiber is often used to manage constipation/diarrhea. Dietary fiber consists of water-soluble and insoluble plant compounds that are resistant to digestion by small-bowel enzymes but are fermented to varying degrees by colonic bacteria. Many physiologic effects of fiber may be related to the degree of fermentation. Few controlled studies of fiber-containing tube feedings have been performed. These studies have limitations and are nondefinitive as to whether fiber prevents or controls constipation/diarrhea. Constipation in tube-fed patients has not been shown to respond to mixed soluble/insoluble fiber in the few studies performed to date. Likewise, fiber may be of only limited benefit in controlling diarrhea in acute illness because of such factors as stress or medication. Fiber does play a role in maintaining gut integrity in all patients, whether they have diarrhea or not. Fiber may be recommended as part of a standard tube-feeding regimen to help assure gut mucosal integrity but not specifically to treat constipation/diarrhea. Further studies are necessary before the role of fiber in the management of constipation/diarrhea in tube-fed patients is determined."
-What was the effectiveness of fluconazole in treating hepatosplenic candidiasis in patients who did not respond to previous antifungal treatments?,"Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy."
-What abnormal vascular responses were observed in patients with hypertrophic cardiomyopathy during exercise?,"Abnormal vascular responses to supine exercise in hypertrophic cardiomyopathy. BACKGROUND. Exercise hypotension has been documented in hypertrophic cardiomyopathy. It is not the result of an inability to augment cardiac output but instead relates to an inappropriate and exaggerated decrease in systemic vascular resistance at high work loads. METHODS AND RESULTS. To enable us to examine the behavior of the peripheral vasculature during exercise, 103 consecutive patients underwent maximal symptom-limited supine bicycle exercise with measurement of forearm blood flow. A minimum reduction of 12% from the basal value was defined as a normal response based on the study of 25 normal controls. In the patients, two patterns of forearm blood flow were observed. Sixty-four patients had an appropriate reduction in forearm blood flow of 40 +/- 16% from resting flow. In 39 patients, the forearm blood flow either failed to decrease or increased with exercise by 45 +/- 105% of the resting value. Patients with an abnormal forearm vasodilator response were younger (31 +/- 13 versus 46 +/- 14 years), and more of them had a family history of hypertrophic cardiomyopathy and sudden death than did those with a normal vasoconstrictor response (16 of 39 versus eight of 64). Left ventricular end-diastolic cavity dimensions were smaller in those with an abnormal forearm blood flow response, but other clinical, echocardiographic, and arrhythmic variables were similar. To assess the relation of abnormal peripheral vascular responses to erect exercise blood pressure response, patients underwent treadmill exercise testing with careful monitoring of systolic blood pressure response. Thirty-eight patients had significant exercise hypotension with failure of the systolic blood pressure to increase during progressive exercise (n = 6) or an abrupt decrease in systolic blood pressure (20-60 mm Hg) from the peak value (n = 32); 65 patients had a normal exercise blood pressure response, but 18 of these patients had an oscillation in systolic blood pressure of 10 mm Hg or more early in the recovery phase. Thirty-one of 39 patients with an abnormal forearm blood flow response demonstrated exercise hypotension during the erect exercise testing, and the remaining eight patients had a normal exercise blood pressure response; however, five of these eight had abnormal oscillations in blood pressure during recovery (r = 0.61, p less than 0.001). CONCLUSIONS. The relation of abnormal peripheral vascular responses to exercise hypotension confirms the observation of hemodynamic instability in patients with hypertrophic cardiomyopathy. The finding of abnormal vascular responses in patients known to be at increased risk (young age and a family history of hypertrophic cardiomyopathy and sudden death) suggests that hemodynamic mechanisms may be important in the occurrence of sudden death in hypertrophic cardiomyopathy."
-What were the significant predictors of death on the first day in the Surgical Intensive Care Unit (SICU)?,"Surgical intensive care unit resource use in a specialty referral hospital: I. Predictors of early death and cost implications. The rationing of medical care prioritizes the need for early predictors of death in the surgical intensive care unit (SICU). We prospectively studied 100 consecutive SICU admissions, looking for predictors of early death in the SICU and the cost implications of these findings. Serial APACHE II scores on days 1, 3, and 5 were subjected to multinomial logistic regression analysis to determine significant predictors of death in the SICU on day 1. Survivors had significantly lower (p less than 0.05) mean day-1 APACHE II scores than had nonsurvivors (13.6 vs 22.1). Half of the patients with scores greater than 18 died, and all patients with scores on day 1 of 25 or greater died. Significant predictors of death on SICU day 1 were APACHE II scores, Acute Physiology Score, Glasgow Coma Score, creatinine level, and Chronic Health Evaluation Score. Forty-one patients had been transferred from community hospitals as a results of acute illness; this population accounted for two thirds of the deaths in the SICU. Ten of 18 nonsurvivors were predicted on day 1, with these patients incurring a total cost of approximately $1 million. If therapy had been modified on days 5, 10, or 15, the potential cost savings would have been $340,000, $240,000, or $140,000, respectively. Integration of the results of this study into the management decision-making process and treatment guidelines may reduce the cost of care in the SICU."
-What potential complications can arise from percutaneous insertion of an intra-aortic balloon pump?,"Aortoiliac dissection after percutaneous insertion of an intra-aortic balloon pump. Aortic or aortoiliac dissection may complicate percutaneous intra-aortic balloon pump insertion in various ways. Thrombosis can escape clinical recognition if no major obstruction develops. Death due to perforation after dissection is not uncommon. In this case study, aortoiliac dissection led to bilateral iliac artery stenosis, an unusual complication of percutaneous femoral cannulation for insertion of a balloon pump."
-How does heart rate affect pulmonary artery acceleration time in different levels of pulmonary artery pressure?,"Effects of heart rate and pulmonary artery pressure on Doppler pulmonary artery acceleration time in experimental acute pulmonary hypertension. Chronic pulmonary hypertension in humans is characterized by shortening of the pulmonary artery acceleration time as measured by Doppler echocardiography, such that the higher the pulmonary artery pressure, the shorter the pulmonary acceleration time. Increases in heart rate are also known to produce decreases in the pulmonary artery acceleration time. To explore the relationship between mean pulmonary artery pressure, heart rate, and Doppler pulmonary artery acceleration time, experimental acute pulmonary hypertension was created in nine Duroc swine, either by infusion of Sephadex beads with embolization of the pulmonary arterial circulation or by partially occluding the main pulmonary artery 8 to 10 cm distal to the pulmonic valve. Pulmonary artery Doppler flow velocity recordings and invasive pressure measurements were made at baseline and at paced atrial rates ranging from 60 to 160 beats per minute, in 20-beat increments. The results in this acute animal model reveal that increases in heart rate produced significant decreases in Doppler pulmonary artery acceleration time at mean pressures below 25 mm Hg. However, with mean pulmonary artery pressures greater than 25 mm Hg, both heart rate and increases in pulmonary artery pressure had no significant effect on acceleration time."
-How does hypertension and elevated cholesterol affect the fibrinolytic system?,"Hypo-fibrinolysis in patients with hypertension and elevated cholesterol. To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI."
-"How does Doppler ultrasound help in identifying a small, clinically undetectable ductus arteriosus?","Doppler ultrasound and the silent ductus arteriosus. A clinically undetectable, small ductus arteriosus was identified by Doppler ultrasonography in 21 individuals. Infants were excluded from the study and no patient had pulmonary hypertension. Persistence of the ductus arteriosus is likely to be more common than shown by less sensitive diagnostic methods. Some patients considered to have infective endocarditis with a normal heart may have a silent ductus arteriosus. Evidence of such an association would justify ligation or antibiotic cover as prophylactic measures."
-What may cause tears in the retinal pigment epithelium according to the context?,Tears of the retinal pigment epithelium: occurrence in association with choroidal effusion. Two patients developed large tears of the retinal pigment epithelium associated with choroidal effusion. One tear occurred after combined cataract/filtration surgery complicated by postoperative choroidal detachment; the second developed in a patient with idiopathic uveal effusion syndrome. Weakness of the junctions of the pigment epithelial cells secondary to the accumulation of fluid in the subretinal or suprachoroidal space may result in tearing of the retinal pigment epithelium as it is stretched.
-How did different nutritional regimens affect the cell kinetic activity of gastrointestinal tumors in this preliminary study?,"Cell kinetics of gastrointestinal tumors after different nutritional regimens. A preliminary report. Forty-four cases of different untreated gastrointestinal tumors were studied with regard to cell kinetic activity. As a pilot experiment, we also determined the 3H-TdR Labeling Index (LI) in 28 patients in basal conditions and after 15 days of nutritional manipulation with prevalently lipid-based or glucose-based feeding to ascertain whether selective nutritional regimens could affect tumor proliferation. Preliminary results from this study indicate that a kinetic perturbation is induced in tumor cells by nutritional manipulation. Lipid-based feeding seems to produce effects similar to those of chemical or physical anticancer agents, thus suggesting a possible supporting role of nutritional manipulation in cancer treatment strategy."
-What was the interval between HBV infection and HCC appearance in the three reported cases?,"HBV-DNA-related hepatocellular carcinoma occurring in childhood. Report of three cases. In a series of 325 HBV chronically infected children observed over an 18-year period, three developed HCC. These three children were born in southern Italy, a region characterized by a high endemic HBV infection rate; each had been infected perinatally, developed an acute hepatitis, and became a chronic carrier. Two of the three with cirrhosis were HBsAg positive at the time their HCC was detected. The remaining case had seroconverted to HBsAb but HBV-DNA integration could be demonstrated in the absence of cirrhosis; moreover HBV antigens were not expressed in the tissue of this case. The interval between HBV infection and HCC appearance in these three cases ranged from six to 11 years. A similarity between these three Italian cases and the majority of HCC arising in chronically infected children in the Far East is noted."
-"What is the medical condition described in the context, and how long has the patient been experiencing recurrent symptoms?",Localized recurrent postoperative pernio associated with leukocytoclastic vasculitis. A patient with recurrent pernio of the right ankle for 21 years after surgery had a leukocytoclastic vasculitis localized in the area. We suggest that the various histologic descriptions of pernio in the literature and in this case represent different levels of severity of the disease.
-What advantages does the microvascular peritoneal flap offer for intraoral reconstruction?,"Intraoral reconstruction with a microvascular peritoneal flap. The microvascular peritoneal flap offers a new reconstructive option for closure of intraoral defects. The flap is easy to raise, and donor-site morbidity is low. Unlike fascial flaps, in which the raw surface may take weeks to ""mucosalize,"" the peritoneal surface heals primarily. Finally, the rectus muscle effectively covers all forms of mandibular reconstruction, and the reliable skin paddle makes possible the closure of substantial cutaneous defects."
-How does transcutaneous electrical nerve stimulation (TENS) therapy affect uterine activity in women with primary dysmenorrhea?,"Interrelation of analgesia and uterine activity in women with primary dysmenorrhea. A preliminary report. The interrelation between uterine activity and pain from primary dysmenorrhea has been of interest for many years. Objective studies of uterine activity during non-steroidal antiinflammatory drug therapy have supported the assertion that uterine activity causes pain and that reducing that activity leads to pain reduction. Unfortunately, those studies could not refute the counter-assertion that reductions in uterine activity come about because of reduced pain through central analgesia and not by direct pharmacologic action. In an effort to clarify this question, a small number of women were studied using intrauterine pressure recording and analysis to evaluate objective changes in uterine physiology during transcutaneous electrical nerve stimulation (TENS) therapy for dysmenorrhea. The preliminary studies indicated that despite successful subjective therapy with TENS, intrauterine pressure parameters remained steady or showed signs of worsening. These findings indicate that TENS provides pure analgesia by an alteration of the body's ability to receive or perceive the pain signal rather than by a direct uterine effect. It appears that the reduction in uterine activity seen in objective drug studies represents direct drug action rather than a change from reduced pain through central analgesic effects."
-What was the purpose of the laboratory study on psyllium hydrophilic mucilloid (PHM) added to enteral feeding formula?,"Flow characteristics of enteral feeding with psyllium hydrophilic mucilloid added. One therapy for managing diarrhea in patients in intensive care units who are receiving enteral nutrition is administration of psyllium hydrophilic mucilloid (PHM). This laboratory study was conducted to determine whether the addition of PHM (Metamucil) to enteral feeding formula (Entrition) adversely affected the flow characteristics of the feeding formula through a small-bore feeding tube. Descriptive data were obtained from 72 trials of feeding formula with varied infusion rates, formula osmolality and temperature, and PHM concentrations. Two thirds (n = 48) of the trials were successful (PHM did not clog the tubing and obstruct flow). The remaining one third of the trials (n = 24) were unsuccessful. Successful formula infusion was influenced by formula temperature and osmolality but not by infusion rate, PHM concentration, or flow interruption. If formula with PHM was followed by formula without PHM, the infusion was successful regardless of infusion rate or formula osmolality. Thus, the data from this laboratory study indicate that when therapeutic doses of PHM are prescribed, it is feasible for PHM to be mixed in room-temperature feeding formula and infused without clogging the feeding tube."
-How does growth hormone influence kidney growth and scarring in experimental models?,"The role of growth hormone and insulin-like growth factor-I in experimental renal growth and scarring. Recent evidence suggests a causal link between early renal/glomerular hypertrophy and late kidney scarring and glomerular sclerosis. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide likely to play a role in the development of kidney growth. We observed an increased renal IGF-I content in two experimental models of accelerated kidney growth in the rat. By contrast, diabetic renal hypertrophy is abolished in the absence of growth hormone (GH). Dietary protein manipulations affect the expression of compensatory renal growth (CRG), as well as renal IGF-I content. The renotrophic effect of a high-protein diet on CRG seems GH-dependent and IGF-I-mediated. GH also appears to have a permissive role on the development of progressive renal scarring following extensive renal ablation in rats, as dwarf rats seem somewhat resistant to the development of accelerated scarring and renal failure."
-What was the 20-year survival probability for patients with T2N0M0 stage I breast carcinoma in this long-term follow-up study?,"Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients."
-How do serum endothelin-1 (ET-1) concentrations differ between subjects with primary Raynaud's phenomenon and control subjects during cold provocation?,"Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6] degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml) than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder."
-What is the key finding of this study regarding the treatment of arteriovenous malformations with peripheral aneurysms?,"Embolization of arteriovenous malformations with peripheral aneurysms using ethylene vinyl alcohol copolymer. Report of three cases. The authors report three cases of arteriovenous malformations (AVM's) with aneurysms arising from the feeding artery; all were successfully treated with a new nonadhesive liquid embolic material, ethylene vinyl alcohol copolymer (EVAL). In two patients the AVM's were totally removed without difficulty, and in one the AVM was managed conservatively after embolization. No new neurological deficits appeared during or after embolization. After road-mapping techniques, EVAL was injected slowly until the feeding artery and aneurysm were completely obliterated. This embolic agent is easy to handle and is considered safe compared with other adhesive liquid embolic agents, such as isobutyl-2-cyanoacrylate or n-butyl cyanoacrylate. It is concluded that EVAL is an excellent agent for embolizing an AVM with a peripheral aneurysm on the feeding artery."
-What complication did the 36-year-old mentally retarded patient experience with his Foley catheter gastrostomy tube?,"Duodenal obstruction by a nondeflating Foley catheter gastrostomy tube. We report the case of a 36-year-old mentally retarded man who presented to our emergency department after one day of vomiting and one episode of coffee-ground emesis. The Foley catheter used as his gastrostomy tube was found to be obstructing the duodenum, and the balloon could not be deflated. Removal was accomplished by rupturing the balloon by endoscopy. Our case illustrates one of many possible complications of feeding gastrostomy tubes."
-What were the most common histologic types of soft tissue sarcomas found in the chest wall in this study?,"Soft tissue sarcomas of the chest wall. Results of surgical resection. Primary soft tissue sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. Most studies have categorized these tumors as truncal sarcomas and inferred a poor prognosis. To assess the results of surgical treatment, we reviewed our 40-year experience. Methods: Records of 189 patients admitted to our institution from 1948 to 1988 were reviewed. Pathologic material was available for review in the 149 cases (79%) that comprise this report. Survival was calculated by the Kaplan-Meier method, with comparisons by log-rank analysis and significance defined as p less than 0.05. Results: Ages ranged from 3 weeks to 86 years (median, 38 years); the ratio of male to female patients was 2:1. The initial complaint was mass or pain in 97% of the cases. Ninety sarcomas (60%) were high grade and 59 (40%) were low grade. Histologic types were as follows: desmoid tumor (n = 32, 21%); liposarcoma (n = 23, 15%); rhabdomyosarcoma (n = 18, 12%); fibrosarcoma (n = 17, 11%); embryonal rhabdomyosarcoma (n = 14, 9%); malignant peripheral nerve tumor (n = 13, 9%); malignant fibrous histiocytoma (n = 11, 7%); spindle cell sarcoma (n = 4, 3%); tenosynovial sarcoma (n = 3, 3%); hemangiopericytoma (n = 3, 3%); alveolar soft part sarcoma (n = 3, 3%); and other types (n = 12, 9%). Resection was the primary treatment in 140 cases (94%). Local recurrence developed in 27%. Metastases occurred in 52 (35%) of the cases (metachronous in 42, synchronous in 10) and were more common in patients with high-grade disease (46/90, 51%) than in those with low-grade disease (6/59, 10%). Overall 5-year survival was 66%. Five-year survival rate for those with high-grade sarcomas (49%) was significantly lower than that for low-grade sarcomas (90%, p less than 0.0001). Tumor size and age of patient were not prognostic. Conclusions: Survival of patients with primary soft tissue sarcomas of the chest wall after resection is similar to that of patients with sarcomas of the extremities. Resection alone provides acceptable survival (90% at 5 years) for those with low-grade sarcomas, but adjuvant treatment should be considered for those with high-grade sarcomas."
-"How do cephalometric measurements differ between patients with sleep apnoea, non-apnoeic snorers, and non-snoring control subjects?","Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age."
-How effective are intravascular stents in managing superior vena cava syndrome?,"Intravascular stents in the management of superior vena cava syndrome. Superior vena cava syndrome can be effectively palliated with the use of intravascular stents. Adjunctive modalities which may be utilized prior to stent placement are thrombolytic therapy and balloon angioplasty. Six patients with an underlying malignancy were treated with these modalities. Complete resolution of symptoms occurred in five patients, and partial resolution occurred in the sixth. Two of the patients who had initial, complete resolution of symptoms had recurrences. One involved rethrombosis of the superior vena cava which occurred twice and required percutaneous thrombectomy, and the second involved restenosis requiring a percutaneous transluminal angioplasty of the SVC just distal to the stent. Both of these patients with second procedures, again, had complete resolution of symptoms. Intravascular stents are a valuable additional treatment of superior vena cava syndrome."
-"How do environmental chemicals and pollution impact public health in developing countries, particularly in relation to malnutrition and infectious diseases?","Chemicals and environmentally caused diseases in developing countries. This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of ""developing countries,"" the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries."
-What did the multivariate analysis reveal about prognostic indicators in acute spinal cord injury?,"Acute spinal cord injury: magnetic resonance imaging correlated with myelopathy. Thirty-one patients (29 males and two females, 13-87 years of age (mean, 46.7 years] with acute spinal cord injury were studied by MR (magnetic resonance) imaging and the results were correlated with neurological findings. Magnetic resonance images were obtained with a 0.5 T superconductive MR scanner (Phillips Gyroscan S5). Initial imaging was performed within 24 hours after trauma in 13 patients, 1-7 days in 13 patients and 7-14 days in five patients. Twenty-six patients underwent follow-up examinations with MR imaging. Cord abnormalities including cord compression (23 patients), cord swelling (seven patients), and abnormal signal intensities on either T1 or T2-weighted images (26 patients) were observed on initial examination. Multivariate analysis showed that cord compression and abnormal intensities on T1-weighted images were important prognostic indicators. Hyperintensity on T2-weighted images was non-specific but correlated well with clinical recovery. Magnetic resonance imaging is useful in predicting the prognosis and for planning treatment following spinal cord injuries."
-Can vitamin D deficiency cause an unusual pain syndrome with hyperesthetic characteristics?,"Can vitamin D deficiency produce an unusual pain syndrome? An unusual pain occurred in five patients in the presence of compromised vitamin D status and resolved 5 to 7 days after supplementation with vitamin D in the form of ergocalciferol. The pain had a hyperesthetic quality and did not respond to the use of analgesics, including opiate derivatives. Treatment with therapeutic levels of a tricyclic antidepressant did not bring relief of symptoms. In one case, months after treatment and subsequent improvement of vitamin D status and pain, the vitamin D status again declined and the pain recurred. The pain again resolved with vitamin D replacement and improvement of levels. There may be a pain syndrome associated with vitamin D depletion that appears as hyperesthesia worsened by light, superficial pressure or even small increments of movement. This pain restricts mobility and function and may lead to further complications, such as pressure sores."
-What was the success rate of operations for dividing atrioventricular accessory pathways in patients with Wolff-Parkinson-White syndrome?,"Operations for Wolff-Parkinson-White syndrome. Forty-six patients with symptomatic tachycardia underwent operations to divide 55 atrioventricular accessory pathways. Mean age was 29 years (range 11 to 63). Ten patients (22%) had associated cardiac disease, including two with a congenital diverticulum of the coronary sinus and six (13%) who had concomitant surgical procedures. A bipolar hand-held electrode was used in 22 operations, and simultaneous multisite mapping in the last 24 operations. Ten patients (22%) had multiple accessory pathways. A modified endocardial approach was used. The overall patient success rate was 93% with 91% to 93% of accessory pathways successfully divided. The perioperative morbidity was 17%. There were two reoperations. There were no early or late deaths. Patients have been followed up for a mean of 16 months. There were five recurrences of preexcitation (two early, three late). Two of these patients (both with a congenital diverticulum of the coronary sinus) had reoperation. One patient had late recurrence of atrial fibrillation. Operation for the Wolff-Parkinson-White syndrome has a high probability of success with a low operative risk."
-How do oral contraceptives potentially impact metabolic risk markers related to coronary heart disease?,"Oral contraceptives and coronary heart disease. In industrialized countries, coronary heart disease (CHD) is a major public health problem for both men and women. Preventive strategies for reducing the excessive mortality and morbidity associated with CHD involve the identification and modification of metabolic factors believed to be involved in the disease process. Three major areas of concern are lipid metabolism, carbohydrate metabolism and the hemostatic system. The steroid hormones contained in oral contraceptives (OCs) have been shown to interfere in all three areas. In many instances OCs have been shown to alter metabolic markers for CHD in directions associated with increased risk. Although evidence is lacking that such changes induce CHD in users of modern, low-dose OCs, it would be prudent to develop formulations with a minimal impact on metabolic risk markers. There is increasing evidence that many of the metabolic disturbances seen in CHD patients share a common origin, and the development of risk-free OCs is likely to require investigation into complex interrelationships."
-What was the purpose of this pilot study involving Fluosol and emergency coronary angioplasty in patients with anterior myocardial infarction?,"Demonstration of myocardial reperfusion injury in humans: results of a pilot study utilizing acute coronary angioplasty with perfluorochemical in anterior myocardial infarction. Reperfusion may limit the amount of potentially salvageable myocardium through the introduction of cellular elements into previously ischemic but viable myocardium (reperfusion injury). It has been demonstrated that intracoronary infusion of a 20% intravascular perfluorochemical emulsion (Fluosol) significantly reduces infarct size and results in improved left ventricular function in the canine model. This pilot study was performed to explore the existence of myocardial reperfusion injury in humans. Utilizing Fluosol as a probe in conjunction with emergency coronary angioplasty, 26 patients presenting within 4 h with a first anterior myocardial infarction were randomized to emergency angioplasty or angioplasty followed by a 30-min intracoronary infusion of Fluosol at 40 ml/min. Global and regional ventricular function were assessed immediately and a mean of 12 days after successful angioplasty with contrast ventriculography. Infarct size was semiquantitated with thallium-201 single-photon emission computed tomography (SPECT) images before discharge. Twelve patients (six undergoing angioplasty alone, six treated with angioplasty and Fluosol) had an occluded infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] grade 0 to 1) at the time of emergency catheterization and were included in the final analysis. At 12 days after successful angioplasty, the improvement in regional ventricular function was greater in patients receiving adjunctive therapy with intracoronary Fluosol versus those undergoing angioplasty alone utilizing both the radial shortening and centerline method, respectively (23 +/- 3.1% vs. 8 +/- 2.3%, p less than 0.02; and -1.6 +/- 0.4 vs. -2.9 +/- 0.2 SD/chord, p less than 0.05)."
-What are the advantages of using the rectus abdominis free flap in head and neck reconstruction?,"The rectus abdominis free flap in head and neck reconstruction. The rectus abdominis musculocutaneous free flap, based on the deep inferior epigastric artery and vein, has been used widely in reconstruction of the breast and extremities. The number of reports on its applications in the head and neck is limited. The rectus abdominis free flap is one of the most versatile soft-tissue flaps. The deep inferior epigastric artery and vein are long, large-diameter vessels that are ideal for microvascular anastomoses. The area of skin that can be transferred is probably the largest of all flaps presently in use. The versatility of this donor site is due to the ability to transfer large areas of skin with varying thicknesses and varying amounts of underlying muscle. We have successfully used this flap in 15 consecutive patients to reconstruct defects of the neck, face, mouth, pharynx, skull base, and scalp. No major complications involving either the recipient or donor sites occurred. The literature on the use of the rectus abdominis flap in head and neck reconstruction is reviewed in detail. The advantages and disadvantages of this soft-tissue free flap are thoroughly discussed in an effort to better define its proper place among the reconstructive options available to the head and neck surgeon."
-How did the protein and fat intake affect glomerular filtration rate and urinary protein loss in patients with membranous nephropathy?,"Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome. Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake."
-How did oral ofloxacin compare to parenteral antibiotics in treating chronic osteomyelitis?,"Ofloxacin versus parenteral therapy for chronic osteomyelitis. We conducted a randomized comparison of oral ofloxacin (400 mg twice a day) and parenteral agents (cefazolin, 1.0 g intravenously every 8 h, or ceftazidime, 2.0 g intravenously every 12 h) in biopsy-confirmed, nonprosthesis osteomyelitis. A total of 19 subjects received ofloxacin for an average of 8 weeks, and 14 received parenteral antibiotics for an average of 4 weeks; both therapies were well tolerated. Infections were due to Staphylococcus aureus (40%), Enterococcus spp. (3%), Pseudomonas aeruginosa (15%), and other gram-negative organisms (42%). At the completion of therapy, one P. aeruginosa infection in the ofloxacin group persisted and the organism acquired resistance, accompanied by a resistant Acinetobacter superinfection. In the parenteral group, one S. aureus infection persisted, and there was a resolved superinfection due to S. aureus as well. Eighteen-month follow-up data have been obtained. Among those treated with ofloxacin, four subjects whose initial response to therapy was successful suffered relapses of infection, three due to S. aureus and one due to P. aeruginosa, while in the parenteral group, one subject with a P. aeruginosa infection relapsed. Long-term response to therapy was successful for 14 of 19 (74%) subjects who received ofloxacin and 12 of 14 (86%) who received parenteral antibiotics; the difference was not significant. Oral ofloxacin appears comparable to parenteral antibiotics in chronic osteomyelitis due to susceptible organisms, and oral ofloxacin offers advantages in economics and convenience."
-What are the two most common procedures used for screening hearing loss in newborns or intensive care nurseries?,"Auditory screening of infants. Within the last 20 years, infant hearing screening has progressed from a laudable goal to a state-mandated reality in many areas of the United States. The high risk register provides a means by which history and neonatal physical examination can be used to identify the infant at risk for hearing loss. Two procedures (crib-O-gram and auditory brainstem-evoked response) have been the most common methods of screening for hearing loss in the newborn or in intensive care nurseries. Evoked cochlear emissions reportedly are identifiable in 90 to 100% of normal-hearing infants. This observation has lead to the use of evoked otoacoustic emissions as a hearing screening procedure with infants."
-What was the main objective of the SWIFT trial in treating acute myocardial infarction?,"SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. OBJECTIVE--To see whether early elective angiography with a view to coronary angioplasty or bypass grafting of a stenosed infarct related vessel would improve outcome in acute myocardial infarction treated by thrombolysis with anistreplase. DESIGN--Randomised study of two treatment strategies with analysis of results over 12 months. SETTING--21 district hospitals and regional cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients presenting with clinical and electrocardiographic features of acute myocardial infarction up to three hours after the onset of major symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units followed by a standard regimen of heparin, warfarin, and timolol and (in patients so randomised) early angiography plus appropriate intervention. MAIN OUTCOME MEASURE--Death or reinfarction within 12 months. RESULTS--397 patients were randomised to receive early angiography plus appropriate intervention (coronary angioplasty in 169 cases, coronary grafting in 59) and 403 patients to receive conservative care (of these, 12 had angioplasty and seven bypass grafting during the initial admission). By 12 months mortality (5.8% (23 patients) in the intervention group v 5.0% (20) in the conservative care group; p = 0.6) and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4) were similar in the two groups. No significant differences in rates of angina or rest pain were found at 12 months. Left ventricular ejection fraction at three and 12 months was the same in both groups. Median hospital stay was longer in the intervention group (11 days v 10 days; p less than 0.0001). CONCLUSION--For most patients given thrombolytic treatment for acute myocardial infarction a strategy of angiography and intervention is appropriate only when required for clinical indications."
-What are the characteristic radiographic features of chondromyxoid fibroma that help in its identification?,"Chondromyxoid fibroma: radiographic appearance in 38 cases and in a review of the literature [published erratum appears in Radiology 1991 Aug;180(2):586] Thirty-eight cases of histologically confirmed chondromyxoid fibroma were reviewed and their radiographic features recorded. These findings, coupled with a review of the English-language medical literature, suggest that this rare, benign bone tumor has a characteristic but not specific radiographic appearance and may often mimic more common tumors. Chondromyxoid fibroma may occur anywhere in the skeleton, but almost half of the cases occur around the knee. The possibility of chondromyxoid fibroma should always be considered when a focal bone lesion is evaluated that has geographic bone destruction, a sclerotic rim, lobulated margins, and septation. The diagnosis of chondromyxoid fibroma is most likely when the patient is in the 2nd decade of life."
-How do bile acids contribute to splanchnic hemodynamics in portal hypertension?,"Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia."
-What percentage of falls resulted in a major injury in this prospective study of elderly community-dwelling persons?,"Risk factors for injurious falls: a prospective study. We conducted a prospective study of the consequences of falls in 325 elderly community-dwelling persons, all of whom had fallen in the previous year. We contacted subjects every week for one year to ascertain falls and to determine the circumstances and consequences of falls. Only 6% of 539 falls resulted in a major injury (fracture, dislocation, or laceration requiring suture), but over half (55%) resulted in minor soft tissue injury. One in ten falls left the faller unable to get up for at least 5 minutes, and one in four falls caused subjects to limit their activities. The risk of injury per fall was about the same regardless of the number of falls a person had during follow-up. The risk of major injury was increased (age- and sex-adjusted odds ratio: 5.9, 95% confidence interval: 2.3-14.9) in falls associated with loss of consciousness compared to nonsyncopal falls. In multivariate analyses of nonsyncopal falls, the risk of major injury per fall was higher in persons having a previous fall with fracture (6.7; 2.1-21.5), a slower Trail Making B time (1.9; 1.1-3.2), and in Whites (18.4; 7.5-44.6). The risk that a nonsyncopal fall would result in minor injury (versus no injury) was increased in persons with a slower hand reaction time (1.8; 1.0-3.2) decreased grip strength (1.5; 1.0-2.3), in Whites (2.0; 1.0-3.7), in falls while using stairs and steps (2.2; 1.0-5.0), and turning around or reaching (3.5; 1.7-7.3). Our findings suggest that neuromuscular and cognitive impairment, as well as the circumstances of falls, affect the risk of injury when a fall occurs."
-What was the main purpose of the study on nitroglycerin patches in patients with chronic stable angina?,"The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration. This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical."
-What were the five-year cure rates for T1 glottic squamous cell carcinoma patients who underwent laser cordectomy with and without prior radiation treatment?,"Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure."
-What is the unique aspect of the obturator foramen bypass described in this case report?,Crossover ilioprofunda reconstruction: an expanded role for obturator foramen bypass. The standard obturator foramen bypass extends from the aorta or iliac artery to the ipsilateral superficial femoral or popliteal artery. This operation has been both effective and versatile as an indirect bypass procedure for circumventing difficult vascular problems in the femoral triangle. A case is presented of a patient whose limb was salvaged by an obturator foramen bypass from the contralateral iliac artery to the profunda femoris artery. This unique case is compared to other published cases to emphasize the potential advantages of the profunda femoris as the preferred graft outflow in selected cases of arterial reconstruction through the obturator foramen.
-When is antibiotic treatment recommended for bacterial gastroenteritis?,"Antibiotic treatment of bacterial gastroenteritis. Antibiotic treatment is important in certain etiologies of bacterial gastroenteritis, both for clinical improvement and for eradication of the causative organism from stools, which is important epidemiologically. The etiology, however, is seldom known at presentation in sporadic cases of diarrhea. Thus the decision to initiate antibiotic therapy and the choice of the specific antimicrobial agents should be made on a clinical basis, before culture results are available."
-How does CD45 potentially regulate signal transduction in B cells?,"Regulation of B cell antigen receptor signal transduction and phosphorylation by CD45. CD45 is a member of a family of membrane proteins that possess phosphotyrosine phosphatase activity, and is the source of much of the tyrosine phosphatase activity in lymphocytes. In view of its enzymatic activity and high copy number, it seems likely that CD45 functions in transmembrane signal transduction by lymphocyte receptors that are coupled to activation of tyrosine kinases. The B cell antigen receptor was found to transduce a Ca(2+)-mobilizing signal only if cells expressed CD45. Also, both membrane immunoglobulin M (mIgM) and CD45 were lost from the surface of cells treated with antibody to CD45, suggesting a physical interaction between these proteins. Finally, CD45 dephosphorylated a complex of mIg-associated proteins that appears to function in signal transduction by the antigen receptor. These data indicate that CD45 occurs as a component of a complex of proteins associated with the antigen receptor, and that CD45 may regulate signal transduction by modulating the phosphorylation state of the antigen receptor subunits."
-What was the effect of isradipine on systolic and diastolic blood pressure in patients with mild-to-moderate hypertension?,"Multicenter evaluation of efficacy, tolerability and safety of a new first-line antihypertensive drug, isradipine, in a Latin-American population. Isradipine, a new antihypertensive dihydropyridine calcium antagonist, was evaluated for its efficacy, tolerability, and safety in 91 ambulatory patients who had mild-to-moderate hypertension. The design of the present study included a two-week wash-out period after confirmation of disease, followed by 12 weeks of active treatment with 2.5 mg isradipine twice daily. Patients were switched from other antihypertensive drugs, mainly diuretics and beta-blockers. The dose of isradipine remained virtually unchanged throughout the study and resulted in a mean decrease of 22 mm Hg in systolic blood pressure (SBP) (P less than .00001) and 19 mm Hg in diastolic blood pressure (DBP) (P less than .00001). Heart rate was unchanged (difference of -1 beats/min), as was the mean body weight of the study patients. Isradipine was generally well tolerated. Side effects were few and, when present, tended to diminish and eventually disappear during the treatment period. All of the clinical laboratory parameters tested and electrocardiograph intervals remained unchanged. In conclusion, these results indicate that isradipine is a novel drug which is highly effective and well tolerated in the treatment of mild to moderate hypertension in this group of patients."
-What are the potential complications for pregnancies complicated by chronic hypertension?,"Diagnosis and management of chronic hypertension in pregnancy. Pregnancies complicated by chronic hypertension are at increased risk for the development of superimposed preeclampsia, abruptio placentae, and poor perinatal outcome. The frequency of these complications is particularly increased in patients with severe hypertension and those with preexisting cardiovascular and renal disease. Such women should receive appropriate antihypertensive therapy and frequent evaluations of maternal and fetal well-being. In contrast, in patients with mild essential chronic hypertension, the maternal and perinatal benefits from antihypertensive medications are highly controversial. A review of the literature revealed two placebo-controlled studies, four trials comparing treatment versus no medication, and three comparisons of methyldopa and oxprenolol. In only one of these studies were subjects randomized in the first trimester. No differences in pregnancy outcome were found with the use of antihypertensive drugs. Evaluation of the woman with chronic hypertension who is considering pregnancy should begin before conception to establish the cause and severity of the hypertension. Appropriate management should include frequent evaluation of maternal and fetal well-being; antihypertensive medications may be useful in patients with severe disease as well as in those with target organ involvement."
-How can the relationship between gastroesophageal reflux (GER) and upper airway diseases impact patient diagnosis and treatment?,"Gastroesophageal reflux and upper airway diseases. GER can have important impacts on the upper airway passages, and in turn, upper airway obstruction can certainly aggravate reflux. This relationship should be considered in the newborn or young infant, faced with a sudden life-threatening event, and in the older child or adult presenting with chronic head and neck complaints, either unexplained or unresponsive to adequate medical therapy. A causal relationship may be difficult to establish, based first on clinical expertise as a guideline, on laboratory tests, among which pharyngeal pH monitoring could be promising, and on response to medical antireflux therapy. A better understanding of the significance of high levels of reflux and defective acid clearance, as well as a more precise knowledge of the maturation and functioning of upper airway protective mechanisms, would open the way to more accurate diagnostic procedures, to a more reliable definition of the abnormal, and to greater efficiency in the management of these patients."
-What are the potential causes and techniques for removing a Foley catheter when its balloon cannot be deflated?,"Emergency management of the nondeflating Foley catheter balloon. Inability to remove a self-retaining (Foley) catheter may result from failed attempts to deflate its balloon. In this article, the authors review the causes of inability to deflate Foley catheters as well as the various techniques for their removal."
-What was the primary finding of the study regarding the mechanism of post-prandial worsening of angina?,"Post-prandial worsening of angina: all due to changes in cardiac output? BACKGROUND--The precise mechanism leading to the post-prandial worsening of angina has yet to be adequately defined. It has been attributed to an increase in double product but is perhaps more likely to be related to an increase in cardiac output after food. This study was designed to evaluate the effects of food on patients' exercise tolerance and compare these with changes in haemodynamic variables. METHODS--23 patients with chronic stable angina who had post-prandial worsening of their angina were studied. The patients were evaluated on two occasions and at each visit they underwent two symptom limited treadmill exercise tests. They remained fasting on the first visit and were given a 1400 kcal meal 60 minutes before the second exercise test on the second visit. Time to onset of 1 mm ST segment depression, heart rate, systemic arterial blood pressure, and cardiac output were measured at rest and during exercise. RESULTS--There were no differences in any of the variables during the two exercise tests on the day the patients remained fasting. After the meal exercise tolerance fell significantly by 136 seconds and the stage at which 1 mm ST segment depression was first seen was also significantly reduced. Resting cardiac output increased significantly by 0.86 1/min with the patients sitting and by 0.89 1/min standing. The exercise times after food were significantly related to cardiac output even when fasting times were taken into account. Resting heart rate increased significantly by 8.3 beats per minute sitting and 10.4 beats per minute standing. There was little change in blood pressure and no evidence that the double product predicted the post-prandial exercise time. CONCLUSIONS--Worsening of angina was related to the increase in cardiac output after a meal and successful treatment will depend upon the prevention of this increase."
-What types of headaches were observed in patients with Arnold-Chiari malformation (ACM) in this study?,"Headache spectrum in Arnold-Chiari malformation. Exertional headaches in patients with Arnold-Chiari malformation (ACM) are well described. We report four patients with Type I ACM and recurrent headaches. These patients presented, respectively, with low spinal fluid pressure headache, migraine without aura, migraine with aura, and migraine with prolonged aura. This report suggests the need for observing patients with recurrent headaches for any physical stigmata of craniovertebral junction anomalies, and the need to exclude ACM in such patients. Possible implications of the association between ACM and different types of headaches are discussed."
-What were the key findings regarding the performance of different types of prostheses in combined mitral-aortic valve replacement after a 14-year follow-up?,"Influence of type of prosthesis on late results after combined mitral-aortic valve replacement. The influence of type of prosthesis on the late outcome of patients with combined mitral-aortic valve replacement was analyzed by comparing, at a 14-year follow-up, patients receiving two biological prostheses (group 1; n = 135), two mechanical prostheses (group 2; n = 221), or a mechanical prosthesis in the aortic position and a bioprosthesis in the mitral position (group 3; n = 97). No difference was found among the three groups in terms of actuarial survival and incidence of and freedom from valve-related deaths, thromboemboli, and hemorrhages. Patients with biological prostheses had a significantly greater incidence of structural valve deterioration, reoperations, and overall complications when compared with patients with only mechanical prostheses. The results of an extended follow-up of patients with combined mitral-aortic valve replacement indicate that mechanical prostheses perform better in the long-term owing to their superior durability when compared with biological valves. The use of bioprostheses should be confined to old patients with limited life expectancy because of their cardiac disease, provided that anticoagulants are not used. Combination of mechanical and biological prostheses in the same patient should be avoided because the advantages of each type of prosthesis are lost."
-What changes in CT scan appearance can be observed in a traumatized spleen during nonoperative management?,"CT appearance of splenic injuries managed nonoperatively. This essay illustrates the appearance of the traumatized spleen on CT scans obtained during the course of conservative treatment. Although the CT appearance of acute rupture of the spleen has been adequately described, little has been reported about the appearance of the spleen as it heals after trauma. Examples of CT studies of splenic injuries illustrate the various changes in appearance over time in the traumatized spleen that is treated nonoperatively."
-What significant legislative act was passed in 1971 that helped advance cancer research and treatment?,"Progress in cancer. Definite progress has been made against cancer since the National Cancer Act was passed in 1971. Physicians are giving increased attention to cancer prevention. The exciting changes in molecular biology provide increased knowledge about basic mechanisms in tumor growth and metastases. Detailed discussions of two common solid cancers--breast and colorectal--attest to continuing advances in cancer diagnosis and treatment. All of these augur well for further progress in oncology. Continued research, basic and clinical, is mandatory."
-What was the success rate of the percutaneous posterolateral lumbar discectomy procedure in this study?,"Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise."
-What was the overall success rate of endoprosthesis insertion for proximal malignant biliary obstruction in this study?,"Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion. For four years up to December 1987, 190 patients (median age 73 years) with proximal malignant biliary obstruction were treated by endoscopic endoprosthesis insertion. Altogether 101 had cholangiocarcinoma, 21 gall bladder carcinoma, 20 local spread of pancreatic carcinoma, and 48 metastatic malignancy. Fifty eight patients had type I, 54 type II, and 78 type III proximal biliary strictures (Bismuth classification). All patients were either unfit or unsuitable for an attempt at curative surgical resection. A single endoprosthesis was placed initially, with a further stent being placed only if relief of cholestasis was insufficient or sepsis developed in undrained segments. The combined percutaneous-endoscopic technique was used to place the endoprosthesis when appropriate, after failed endoscopic endoprosthesis insertion or for second endoprosthesis placement. Full follow up was available in 97%.Thirteen patients were still alive at the time of review and all but one had been treated within the past six months. Initial endoprosthesis insertion succeeded technically at the first attempt in 127 patients, at the second in 30, and at a combined procedure in a further 13 (cumulative total success rate 89% - type I: 93%; type II: 94%; and type III: 84%). There was adequate biliary drainage after single endoprosthesis insertion in 152 of the 170 successful placements, giving an overall successful drainage rate of 80%. Three patients had a second stent placed by combined procedure because of insufficient drainage, giving an overall successful drainage rate of 82% (155 of 190). The final overall drainage success rates were type I: 91%; type II: 83%; and type III: 73%. The early complication rates were type I: 7%; type II: 14%; and type III: 31%."
-What serious complications can occur after intravesical instillation of bacillus Calmette-Guerin (BCG)?,"Complications after intravesical instillation of bacillus Calmette-Guerin: rhabdomyolysis and metastatic infection. Two cases of adverse reaction to bacillus Calmette-Guerin (BCG) bladder instillations are reported. In both cases transient fevers and systemic symptoms developed following the instillations. After an additional instillation 1 patient had high fevers, severe myalgias and profound weakness followed by rhabdomyolysis and anuric renal failure, which required 3 weeks of hemodialysis before recovery. Extensive evaluation revealed no cause other than the BCG instillations. In the other patient a firm subcutaneous nodule gradually developed on the chest wall, which contained nonviable acid fast bacilli."
-How does the severity of prior salpingitis episodes impact the recurrence rate of ectopic pregnancy in women with a prior uterine pregnancy?,"Recurrence of ectopic pregnancy: the role of salpingitis. We evaluated the role of salpingitis on the recurrence of ectopic pregnancy from a historical cohort of 2501 women who had undergone laparoscopic examination for acute salpingitis. We used pregnancy (N = 2899) as the unit of analysis and a modified conditional logistic regression to estimate a pairwise odds ratio as a measure of the recurrence of ectopic pregnancy. Among the second or higher order of pregnancy, the recurrence was 21.7%. For pregnancies with a prior uterine pregnancy, the ectopic pregnancy rate increased with prior salpingitis scores constructed from a combination of prior salpingitis episodes and severity (0 score, 2.7%; 1 to 2 scores, 4.8%; and greater than or equal to 3 scores, 12.1%). For those with a prior ectopic pregnancy, the rate did not increase with prior salpingitis scores (score 0, 20.0%; score 1 or 2, 19.2%; and score greater than or equal to 3, 26.9%). The adjusted pairwise odds ratio was 2.2 and was practically unchanged (2.1) after additional adjustment with prior salpingitis scores. These findings confirm salpingitis as a risk factor for first ectopic pregnancy, but once a woman had an ectopic pregnancy, previous salpingitis might not add any incremental risk."
-What percentage of patients reported pain relief after receiving nitrous oxide in this rural EMS system study?,"Effectiveness of nitrous oxide in a rural EMS system. Prehospital systems need a safe, effective analgesic agent for the treatment of patients suffering from pain. Recent studies have documented the efficacy of nitrous oxide in urban and rural settings. This study reviews the findings on 200 patients (157 trauma, 23 medical, 18 musculoskeletal problems) who received nitrous oxide during a 28-month period in a rural EMS system. Eighty-five percent of the patients reported pain relief. Only minor side effects were noted. Patient satisfaction was high, and there was no abuse noted among personnel."
-What is an iatrogenic epidermoid cyst and how can it occur in the parotid region following ear surgery?,Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed.
-What is an epidural blood patch and how was it used to treat subarachnoid-cutaneous fistula in the described cases?,Epidural blood patch for treatment of subarachnoid fistula in children. A subarachnoid-cutaneous fistula developed in two children after the placement of a catheter in the subarachnoid space for drainage of cerebrospinal fluid. The management of this iatrogenic complication with epidural blood patch is described.
-How does the estrogen receptor (ER) level correlate with response to tamoxifen treatment in advanced breast cancer?,"The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer."
-What were the two drugs used in the study for treating patients with Raynaud's phenomenon?,"Regional intravenous ketanserin and guanethidine therapy in Raynaud's phenomenon. The authors report the results of a study of 25 patients with Raynaud's phenomenon (primary, posttraumatic, and secondary to diffuse connective tissue diseases) treated with regional intravenous injections of guanethidine or ketanserin. These two drugs were chosen because of the different etiopathologic profiles of the conditions. All the patients showed a substantial clinical improvement with a remission of trophic lesions. Conditions secondary to connective tissue disorders did not demonstrate much improvement based on instrumental data alone, possibly because of the intrinsic limitations of the techniques used for evaluating peripheral blood flow. This specific type of pharmaceutical treatment appeared to be especially suitable for this disease owing to a combination of therapeutic efficacy and a substantial reduction in the total dosage for each patient."
-What are the two fracture patterns associated with the anteroinferior cervical vertebral body corner (teardrop) fracture?,"The axial load teardrop fracture. A biomechanical, clinical and roentgenographic analysis. The anteroinferior cervical vertebral body corner fracture was originally described by Schneider and Cann as the ""teardrop"" fracture. This report analyzes the biomechanical, clinical, and roentgenographic features of 55 such fractures obtained from the National Football Head and Neck Injury Registry. Teardrop fractures resulting from tackle football characteristically occurred in players attempting to make a tackle in which initial contact was made with the top or crown of the helmet. There were two fracture patterns associated with the anteroinferior corner (teardrop) fracture fragment: 1) the isolated fracture, which is usually not associated with permanent neurologic sequelae; and 2) the three-part, two-plane fracture in which there is an associated sagittal vertebral body fracture as well as fracture of the posterior neural arch. This latter pattern was almost always associated with permanent neurologic sequelae, specifically quadriplegia. Axial loading of the cervical spine was clearly identified as a mechanism of injury for both fracture patterns. Roentgenographic examination must include both anteroposterior and lateral views with computed tomography or tomography as necessary to determine the presence of the sagittal vertebral body fracture and the integrity of the posterior neural arch."
-What were the key findings of the study comparing clinical and photographic methods for assessing facial weakness?,"Facial weakness. A comparison of clinical and photographic methods of observation. The search for an internationally acceptable facial grading system has resulted in an assessment of existing methods by several investigators. These studies were based on observations of video film taken of patients with varying degrees of facial malfunction. Although the grading systems were evaluated, the use of videotape has never been compared with clinical examination and its suitability for this type of work is, therefore, unknown. We used nine facial grading systems to compare the results of clinical observation with those of photographic methods of presentation. The latter included videotape, photographic slides, and a combination of the two. The correlation between clinical examination findings and findings of any of the photographic methods was poor, suggesting the need for a standard form of presentation when grading patients. The most consistent results were found with either clinical examination or photographic slides; videotape was the least reliable."
-How do the patterns of soft palate oscillations differ between nasal and mouth snoring?,"Pattern of simulated snoring is different through mouth and nose. Cineradiography of the pharynx during simulated snoring was done in 6 healthy volunteers, and supraglottic pressure and flow rate were recorded in 12 others. We observed, immediately before snoring, a decrease in the sagittal diameter of the oropharynx followed, during snoring, by high-frequency oscillations of soft palate and pharyngeal walls. The pattern of soft palate oscillations was different while snoring through the nose or mouth. During inspiratory snoring through the nose, the soft palate remained in close contact with the back of the tongue and only the uvula presented high-frequency oscillations. Snoring through the mouth resulted in ample high-frequency oscillations of the whole soft palate. Frequency of airflow and supraglottic pressure oscillations was less (P less than 0.05) during mouth (28.2 +/- 7.5 Hz) than during nasal snoring (77.8 +/- 36.7 Hz). This difference may be related to the smaller oscillating mass (i.e., uvula) during nasal snoring. At variance with our previous data, which showed that snoring during sleep, in both heavy (nonapneic) snorers and obstructive sleep apnea patients, was systematically preceded by flow limitation, this was not true during simulated snoring."
-What potential risks were identified in the study regarding self-administered sublingual nitroglycerin?,"Defining the proper role for self-administered sublingual nitroglycerin. A survey of physicians and patients. Within a half-year period, we encountered six cases of patients harmed by the adverse effects of self-administered nitroglycerin--syncope, delayed definitive medical care, and the worsening of nonischemic symptoms. We therefore surveyed 112 patients after a remote myocardial infarction, and 121 cardiologists and internists, regarding the use of sublingual nitroglycerin. Of the physicians, 84 percent routinely prescribed nitroglycerin to patients after a myocardial infarction, and 79 percent of the patients had the tablets available (83 percent of these, at all times). Most patients used the tablets less than once per month, and 37 percent of the patients who always carried nitroglycerin had not used it at all during the preceding year. Although 89 percent of the patients claimed to know when to use the drug, 57 percent had used it or would use it for symptoms such as dizziness, rapid heartbeat, or presyncope. All patients having nitroglycerin claimed it relieved their symptoms, even if the relief was only partial, the time elapsed until relief could not be specified, and the symptoms were of a type unlikely to be relieved by the drug. We suggest that the practice of routinely prescribing nitroglycerin to patients after a myocardial infarction should be reassessed."
-What was the average age of patients with osteonecrosis in the femoral condyle of the knee in this study?,"Clinical course and roentgenographic changes of osteonecrosis in the femoral condyle under conservative treatment. The history of osteonecrosis in the femoral condyle of the knee was observed in 15 knees in 14 patients, averaging 62.8 years in age (range, 23-79 years). There were nine women and five men. The average follow-up period was 4.9 years (range, one to 12 years). Spontaneous osteonecrosis was found in 11 patients and steroid-induced osteonecrosis in three. The medial femoral condyles were involved in 13 knees and the lateral femoral condyles in two. The maximum width of the lesion was measured on anteroposterior roentgenograms and an osteonecrotic lesion less than 10 mm wide was rated as small. Cases of small osteonecrotic lesions displayed no remarkable changes with respect to stages and limb alignment. The average size of the steroid-induced osteonecrotic lesions was significantly larger than that of the spontaneous type. The size of the osteonecrotic lesions at the follow-up examination was compared to that observed at the initial diagnosis in 12 knees. Eight of these lesions displayed increases in dimension of more than 18% over the initial size at diagnosis."
-What were the potential benefits of performing combined coronary angiography and angioplasty in this study?,"Safety and cost effectiveness of combined coronary angiography and angioplasty. If coronary angioplasty can be safely performed at the time of the initial diagnostic catheterization, it may result in shorter hospitalization stays and lower overall costs. Combined coronary angiography and angioplasty was performed electively on 733 patients between January 1, 1984, and September 1, 1988. These patients were divided into three major subgroups based upon their indications for angioplasty: 444 (61%) procedures were performed for restenosis; 190 (26%) procedures were performed in patients for unstable angina; and 99 (13%) procedures were performed in patients without unstable angina or previous angioplasty. A subset of 219 patients from this study who underwent elective combined coronary angiography and angioplasty during 1986 were compared with a matched population of 191 patients from the angiography and angioplasty as separate procedures). The success and complication rates were similar for both of these groups. Patients who underwent the combined procedure were hospitalized for a mean of 4.6 days with average total charges of $11,128, compared with 8.0 days and $13,160 for patients undergoing separate procedures (p less than 0.001). Significant savings were also realized with respect to total contrast dose, fluoroscopic time, and total procedural time. Thus in informed patients with suitable coronary anatomy, the strategy of combined angiography and angioplasty may present an opportunity for decreasing hospitalization stay, reducing total charges for revascularization, and reducing radiation exposure without compromising the safety or effectiveness of the procedure."
-What was the mean follow-up period for the porous-coated total hip prostheses in this study?,"Prospective study of porous-coated anatomic total hip arthroplasty. Seventy-five uncemented porous-coated total hip prostheses were implanted in 64 patients. The results were reviewed after a mean follow-up period of 47 months (range, 40-64 months). The mean preoperative rating was fair, and the mean postoperative rating was excellent. There were six dislocations. Ten patients had mild thigh pain at one year; by two years, the pain had resolved in six patients. Neither moderate nor severe limp nor significant loosening of beads was observed. Only one patient had progressive radiolucent lines. The high rate of dislocation may be related to a compromise of acetabular position to obtain bony fixation in acetabula early in the series. The clinical results were encouraging."
-How did the natriuretic response of torasemide compare to furosemide in nonazotemic cirrhotic patients with ascites?,"Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study. In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed."
-How did early thrombolytic therapy affect the incidence of ventricular late potentials in patients after acute myocardial infarction?,"Reduction in the frequency of ventricular late potentials after acute myocardial infarction by early thrombolytic therapy. Ventricular late potentials are strong predictors of arrhythmic events after acute myocardial infarction (AMI). To assess the effect of intravenous thrombolysis on the incidence of ventricular late potentials, 223 consecutive patients surviving a first AMI were included in the present study: 59 patients (53 men, 6 women, mean age +/- standard deviation 55 +/- 10 years) received intravenous recombinant tissue-type plasminogen activator (100 mg over 3 hours, group A) and 164 patients (123 men, 41 women, mean age 61 +/- 11 years) received conventional medical treatment (group B). A time-domain signal-averaged electrocardiogram and a high-resolution beat-to-beat recording (gain 10(6), filters 100 to 300 Hz) were performed at 10 +/- 3 days after AMI. There was no difference between group A and B patients in terms of AMI location (anterior in 28 of 59 vs 80 of 164, difference not significant [NS]), mean left ventricular ejection fraction (55 +/- 10 vs 55 +/- 13%, NS), or presence of heart failure (New York Heart Association class III or IV in 12 of 59 vs 40 of 164, NS). The incidence of ventricular late potentials was 10% (6 of 59) in group A and 24% (39 of 164) in group B (p less than 0.05). Among the 146 patients who underwent coronary arteriography, the incidence of ventricular late potentials was 13% (10 of 80) in patients with a patent infarct-related artery and 26% (17 of 66) in patients with an occluded infarct-related artery (p less than 0.05)."
-What was the efficacy of aztreonam in preventing urinary tract infections following transurethral resection of the prostate (TURP) in this multicenter study?,"Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study. The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure."
-What is the significance of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in Turcot syndrome and related conditions?,"Ocular findings in Turcot syndrome (glioma-polyposis). Turcot syndrome is a hereditary condition characterized by multiple, adenomatous gastrointestinal polyps associated with neuroepithelial tumors of the central nervous system. The authors examined a patient with Turcot syndrome who had multiple regions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) with areas of surrounding hypopigmentation in the fundi of both eyes. Multiple, bilateral patches of CHRPE have been reported in patients with familial adenomatous polyposis and Gardner syndrome. This finding is thought to be a sensitive and specific clinical marker for these conditions and useful for predicting the presence and development of colorectal polyposis. Our findings provide further evidence that familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome may be related conditions representing the variable phenotypic expression of a single, autosomal dominant genetic disorder. Children and young adults with multiple patches of CHRPE and a family history of adenomatous polyposis may be at increased risk for the development of central nervous system tumors as well as gastrointestinal polyps."
-What is the rare complication observed in this patient with mixed connective tissue disease?,Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease.
-What was the most common symptom among patients with lower esophageal mucosal rings in this study?,"Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring."
-What is the sensitivity and specificity of duplex scanning in detecting atherosclerotic renal artery stenosis?,"Role of duplex scanning for the detection of atherosclerotic renal artery disease. To assess the accuracy of renal artery duplex scanning for the purpose of diagnosing atherosclerotic renal artery stenosis, we compared the findings of renal arteriograms to the results of duplex scanning in 41 patients. Using an increase of renal artery peak systolic flow velocity of greater than 180 cm/sec, duplex scanning was able to discriminate normal from diseased renal arteries with a sensitivity of 95% and a specificity of 90%. Using the principle that blood flow velocity across a stenosis is roughly proportional to the degree of stenosis, it appeared that a ratio of the peak velocity in the renal artery to the aorta (RAR) of greater 3.5 predicted a greater than 60% diameter reduction of that renal artery, which is felt to be a significant stenosis. Forty-eight vessels were classified as having a greater than 60% diameter reduction by arteriography. Using the RAR of greater than 3.5, duplex scanning agreed in 44 renal arteries (sensitivity 92%). In the 26 renal arteries where arteriography showed a less than 60% diameter reduction, duplex scanning agreed in 16 vessels and correctly detected a focal narrowing in nine of the remaining ten vessels. Ten of 11 occluded renal arteries were correctly identified by duplex scanning. Duplex scanning determined the location of the renal artery lesion with an accuracy of 95% (kappa 0.74). Since duplex scanning can accurately demonstrate and locate focal renal artery stenosis, we believe it may become an accurate screening test for renovascular hypertension."
-How accurate was the high frequency epicardial echocardiography in measuring coronary artery dimensions and detecting atherosclerotic lesions compared to histopathological results?,"Histopathological validation of high frequency epicardial echocardiography of the coronary arteries in vitro. The accuracy and reliability of measurement of coronary artery dimensions and detection of atherosclerotic lesions by high frequency epicardial echocardiography were compared with histopathological results. Ten pressure perfused human hearts were examined in vitro with a 10 MHz (Diasonics) transducer and a 7.5 MHz (Vingmed/Sonotron) transducer. There was close agreement between ultrasound and pathological measurements of coronary artery luminal diameter. Qualitative changes in wall structure such as diffuse wall thickening and calcification were readily identified; however, the resolution of the transducers was not high enough accurately to measure wall dimensions in normal coronary arteries. Coefficient of variation measurements for intra and inter observer variability (5.2% and 6.9% respectively) showed excellent reproducibility. The technique was accurate in identifying atherosclerotic lesions, imaging arteries distal to an occlusion, locating deeply sited arteries, and identifying complete obliteration of an artery. Intraoperative video playback and transducer miniaturisation may minimise problems caused by cardiac movement and restricted access. With these developments intraoperative assessment of coronary artery disease may become a real possibility."
-What is the typical progression and prognosis of diabetic femoral neuropathy based on this study?,"The natural history of diabetic femoral neuropathy Diabetic femoral neuropathy is an uncommon, unpleasant and sometimes disabling condition, on account of both pain and muscular atrophy, whose long-term prognosis has not previously been documented. We have reviewed a group of 27 patients up to 14 years (median 62 months) after diagnosis; 18 of these were re-examined after an average of nearly 4 years (median 45 months). The condition was more common in non-insulin-dependent diabetics (88 per cent), in men (59 per cent) and in older patients (median age at diagnosis 64 years). The neuropathy was bilateral (10 cases) or unilateral (17 cases); five patients with unilateral neuropathy developed femoral neuropathy on the opposite side, usually within a few weeks of the first episode. Recovery was apparent after 3 months and usually complete by 18 months; only two of the 27 patients had severe relapses. No patients remained disabled, although there were minor residual symptoms and signs in half of the patients (2 cm reduction in thigh circumference and diminished reflexes). The outlook for femoral neuropathy, even in its most severe form, is therefore very good: residual features are demonstrable but do not cause symptoms, and relapses after the first few weeks are very rare."
-How did participation in a cardiac rehabilitation program affect patients' psychosocial function six months after an acute cardiac event?,"Effects of a multidimensional cardiopulmonary rehabilitation program on psychosocial function. The effects of participation in a structured, outpatient cardiac rehabilitation program on psychosocial function after acute myocardial infarction or coronary artery bypass surgery, or both, were evaluated prospectively in 141 patients who were married or living with ""a significant other"" (89% men, mean [+/- standard deviation] age 63 +/- 9 years old). Forty-one patients who were participants in a 3-month cardiac rehabilitation program were compared with 100 patients who did not participate in a formal program. On average, patients in both groups were well educated, older Caucasians who had minimal cardiac dysfunction (New York Heart Association class I or II). Patients in the 2 groups were not different at baseline in sociodemographic or clinical characteristics or in any of the dependent measures of anxiety, depression, psychosocial adjustment to illness or marital adjustment. Six months after initial testing, patients who attended cardiac rehabilitation were significantly less anxious (F[1,139] = 5.09, p = 0.03), less depressed (F[1,139] = 8.39, p = 0.004), had better psychosocial adjustment (F[1,139] = 5.87, p = 0.02), and were more satisfied with their marriages (F[1,139] = 8.6, p = 0.004) than nonparticipants. The findings support the effectiveness of group cardiac rehabilitation for this subgroup of patients in facilitating their psychosocial recovery after an acute cardiac event."
-How do the adrenal glands contribute to plasma norepinephrine concentrations during cardiopulmonary resuscitation in dogs?,"Plasma norepinephrine concentrations during resuscitation in the dog. The objective of this study was to evaluate whether the adrenal glands contribute to the increase in plasma norepinephrine concentrations during cardiopulmonary resuscitation, by releasing norepinephrine and/or by secreting epinephrine that facilitates the release of norepinephrine from sympathetic nerve endings via stimulation of presynaptic beta receptors. The experiments were performed in adrenalectomized and in sham-operated dogs. In adrenalectomized dogs the increase in plasma norepinephrine concentrations during cardiopulmonary arrest and basic life support (BLS) was markedly smaller than in sham-operated dogs. Intravenous infusion of physiologic doses of epinephrine during BLS in adrenalectomized animals did not influence the plasma norepinephrine concentrations. These data indicate that, as suggested by others, the marked increase in plasma norepinephrine concentrations during BLS in dogs is mainly of adrenomedullary origin. They also suggest that presynaptic facilitation of norepinephrine release by epinephrine is not important, but further experiments using higher doses of epinephrine are necessary."
-What defects were observed in the lymphokine-activated killer (LAK) cell generation and activity among acute leukemia patients?,"Defective lymphokine-activated killer cell generation and activity in acute leukemia patients with active disease. In 26 myeloid and lymphoid acute leukemia patients at presentation the capacity to generate interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells effective against the natural killer (NK)-resistant Raji cell line, as well as the susceptibility of the blasts to normal peripheral blood (PB) LAK cells and to autologous LAK effectors was analyzed. The overall PB LAK activity against Raji cells was significantly lower in acute leukemia patients compared with normal controls (mean, 1,473 +/- 971 SD LU/10(8) LAK effectors v 3,340 +/- 1,862; P less than .001). The sensitivity of the blasts to autologous LAK cells was also significantly lower than to normal LAK effectors (517 +/- 593 LU/10(8) LAK effectors v 1,304 +/- 1,066; P less than .01). When the data were analyzed independently, four patterns of behavior could be recognized. The relatively largest group (9 of 26) included patients in whom effective LAK cells could be generated against the Raji line, but in whom the blasts were resistant to autologous PB-LAK effectors while being susceptible to normal LAK cells (defective specific LAK activity). In 5 of 26 cases, an incapacity to generate LAK activity against both allogeneic and autologous target cells was observed (defective LAK generation). In six further cases, the blasts were resistant to both allogeneic and autologous LAK populations, though the latter were effective against the Raji line (resistant blasts). The same defects could also be shown with bone marrow-derived LAK cells. Only in six cases did the leukemic blasts appear susceptible to autologous and allogeneic LAK cells. In four patients the analysis could be repeated at remission, and in three a restoration of the LAK function against the primary blasts was recorded. In the 10 cases studied at relapse, the blasts were resistant to autologous LAK effectors in nine and to normal LAK in seven. These data demonstrate that in most acute leukemia patients with active disease, a defect of the LAK machinery, either a deficient generation of LAK cells or the resistance of the blasts to LAK effectors, may be documented, pointing therefore to a possible contributory role of the LAK system in the control of leukemic cell growth. In view of the frequent normalization of the autologous LAK activity at the time of remission, immunotherapy with IL-2/LAK cells should be primarily aimed to patients with minimal residual disease."
-What are the two unusual features of the pharyngeal pouch carcinoma cases reported in this study?,"Pharyngeal pouch carcinoma: two unusual cases. Two patients with carcinomata arising in pharyngeal pouches are reported. In one, the tumour was detected preoperatively by a contrast radiographic study. In the second the lesion was a carcinoma in situ. The English literature is reviewed with reference to these two unusual features."
-How do middle ear inflammatory mediators potentially cause sensorineural hearing loss?,"Middle ear inflammatory mediators and cochlear function. Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study."
-What percentage of patients experienced experienced cerebrospinal fluid leaks after acoustic neuroma surgery in this study?,"Cerebrospinal fluid leaks and meningitis in acoustic neuroma surgery. Cerebrospinal fluid leaks and associated meningitis are the most common life-threatening complications of surgery for acoustic neuromas. This retrospective study reviews 319 patients who had surgery for 321 acoustic tumors at the Sunnybrook Health Sciences Center, University of Toronto, from April 1975 to March 1990. Cerebrospinal fluid leaks occurred after 13.4% of primary tumor operations. Surgical repair was required in 6.2% of all patients; 4.4% needed more than one operation. Meningitis occurred in 5.3% of all patients. These complications were more common in larger tumors and after the combined translabyrinthine middle fossa approach. Transnasopharyngeal eustachian tube obliteration was used to stop recurrent cerebrospinal fluid leaks in two patients."
-What restriction endonucleases were used to detect polymorphisms in the progesterone receptor gene in this study?,"Progesterone receptor gene restriction fragment length polymorphisms in human breast tumors. We examined the progesterone receptor (PgR) gene in tissue from both primary human breast tumors and normal placentas, detecting restriction fragment length polymorphisms (RFLPs) with the restriction endonucleases Pst I/Sst I and HindIII. There was a general agreement of the Pst I and Sst I polymorphisms in any individual tumor, suggesting that they define two alleles in the human PgR locus, one being characterized by a deletion of about 300 base pairs with respect to the other. Both primary human breast tumor specimens (n = 36) and human term placentas (n = 48) displayed similar allele frequencies and typical mendelian distribution of these Pst I/Sst I alleles. The previously reported HindIII PgR RFLP was also investigated in 132 breast tumors. The HindIII PgR gene RFLP did not display typical mendelian distribution in the breast tumors; the factors affecting the HindIII allele frequencies are presently unknown. Neither the HindIII RFLP nor the deletion defined by Pst I and Sst I correlated with PgR expression as determined by a ligand-binding assay, suggesting that neither is related to the heterogeneity of PgR expression seen in breast tumors."
-What treatment is recommended when there is clinical or investigative evidence suggesting the presence of a demyelinating disease?,"Destructive lesions in demyelinating disease. Three cases are presented in which clinical and radiological features suggested the diagnosis of glioma but surgical biopsy revealed a demyelinating process, with tissue destruction and cyst formation in two. One patient had clinically definite multiple sclerosis. Two had probable acute disseminated encephalomyelitis. Treatment with high dose steroids is appropriate when there is clinical or investigative evidence to suggest the presence of demyelinating disease, before deciding on biopsy."
-How do T1 and T2 relaxation times change in different myocardial layers following ischemia and reperfusion?,"Transmural distribution of myocardial edema by NMR relaxometry following myocardial ischemia and reperfusion. To determine the distribution and extent of myocardial edema resulting from ischemia and reperfusion, seven open-chest dogs underwent occlusion of the left circumflex coronary artery for 2 hours (group I), and 10 underwent occlusion for 2 hours and reperfusion for 2 hours (group II). Proton nuclear magnetic resonance spectroscopy (T1 and T2 relaxation times) and percent water content were determined to quantitate the amount of edema. There was a transmural increase of the T1 relaxation time of the central ischemic zone in groups I and II, although this increase was significantly greater in group II in both the subendocardium (group I = 707.8 +/- 12.5 msec, group II = 813.2 +/- 36.2 msec; p less than 0.01) and subepicardium (group I = 641.7 +/- 20.5 msec, group II = 760.5 +/- 34.7 msec; p less than 0.01). These increases were also observed in the T2 weighted relaxation time in the subendocardium (group I = 54.7 +/- 0.8 msec, group II = 78.7 +/- 6.3 msec; p less than 0.005) and subepicardium (group I = 54.0 +/- 1.4 msec, group II = 73.1 +/- 4.0 msec; p less than 0.001). Transmural differences were evident between the myocardial layers with increased T1 relaxation times (p less than 0.01) in the subendocardium in both groups. Similar increases were noted in the percent water content of the myocardium. Thus T1 and T2 relaxation times lengthened with an increase in myocardial water content following occlusion, and these relaxation times were augmented by reperfusion. We conclude that ischemia-induced edema occurs in a transmural distribution from subendocardium to subepicardium following occlusion, and this edema is further enhanced by reperfusion."
-What potential complication can occur in the fallopian tubes following an inguinal hernia repair?,"Tubal occlusion after inguinal hernia repair. A case report. Midtubal occlusion and infertility occurred subsequent to an inguinal hernia repair. Recognition of the traumatic etiology is important because other causes of midtubal obstruction, such as endometriosis, tuberculosis and adenomatoid tumor of the oviduct, may be considered contraindications to reconstructive surgery. Once recognized, the condition is highly amendable to microsurgical reconstruction."
-How did the use of fine catheter peritoneal cytology (FCPC) and laparoscopy help improve the management of patients with acute abdominal pain in this study?,"Role of fine catheter peritoneal cytology and laparoscopy in the management of acute abdominal pain. Laparoscopy and fine catheter peritoneal cytology (FCPC) have been advocated as aids in the assessment of acute abdominal pain. In all, 411 patients admitted to a district general hospital during a 10-month period were managed using a standard protocol incorporating these techniques. After initial assessment by a surgical registrar, 151 patients were excluded from further progress through the protocol (age less than 16 years, definite diagnosis made or contraindication to FCPC. The remaining 260 patients were placed in one of four management groups: (A) urgent operation (23 patients); (B) 'look and see' (40 patients); (C) 'wait and see' (59 patients); (D) urgent operation not indicated (138 patients). Eighty-eight of 99 patients (88 per cent) in groups B and C, where the need for operation was uncertain, underwent successful FCPC and 39 patients (39 per cent) underwent laparoscopy. In these patients the initial registrar management decision proved to be incorrect in 33 cases (33 per cent), but by following the protocol the number of management errors actually made was reduced to 13 (13 per cent, P less than 0.001). This would have been reduced to 8 per cent if the protocol had not been violated in five patients. This study demonstrates the effectiveness of a protocol using FCPC and laparoscopy to improve the management of patients with acute abdominal pain."
-"What is the association between HIV infection and Salmonella typhi or Salmonella paratyphi infections in the study conducted in Lima, Peru?","Association between the acquired immunodeficiency syndrome and infection with Salmonella typhi or Salmonella paratyphi in an endemic typhoid area. Eight cases of typhoid and paratyphoid fever were identified during a 4-year period in a cohort of 117 patients who were positive for human immunodeficiency virus in Lima, Peru. Asymptomatic patients with human immunodeficiency virus infection and patients with the lymphadenopathy syndrome had a typical clinical presentation and response to therapy. Patients with the acquired immunodeficiency syndrome who were culture positive for Salmonella typhi or Salmonella paratyphi presented with fulminant diarrhea and/or colitis; the two patients for whom at least 2 months of follow-up were available relapsed. In our cohort there were 0.06 cases of typhoid or paratyphoid per patient year of observation; this rate is approximately 60 times that in the general population in Lima, and 25 times that in the 15- to 35-year-old age group. Our data indicate that patients who are positive for human immunodeficiency virus are at significantly increased risk for infection with S typhi and S paratyphi, and suggest that the clinical presentation of these diseases in patients with the acquired immunodeficiency syndrome differs from that seen immunocompetent hosts."
-What are the comparative outcomes of extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrostolithotomy in treating stone-containing caliceal diverticula?,"The roles of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy in the management of pyelocaliceal diverticula. Various combinations of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy were used in the treatment of 40 stone-containing caliceal diverticula in 39 patients (16 men and 23 women). Only 1 of 26 patients (4%) treated with ESWL as a single modality became stone-free, although 9 (36%) became asymptomatic. Ten patients undergoing ESWL primarily eventually required percutaneous nephrostolithotomy due to persistence of symptoms and all became stone-free. A total of 14 patients underwent a percutaneous approach as a single modality, and the diverticula in 13 of these patients became stone-free, although 2 patients did have residual parenchymal fragments. Therefore, 21 of 24 patients (87.5%) became completely free of stones using the percutaneous approach. All patients managed with percutaneous nephrostolithotomy became free of symptoms. The complex nature of access during percutaneous nephrostolithotomy favors a 1-stage approach with direct puncture into the stone-containing diverticulum. Simultaneous fulguration of the diverticulum at percutaneous nephrostolithotomy is favored, since all 17 patients in whom this technique was used had complete obliteration of the diverticulum on followup contrast studies. These data suggest that caliceal diverticula should be managed with percutaneous nephrostolithotomy, since ESWL monotherapy is unlikely to produce a stone-free or symptom-free status."
-What was the impact of optimal debulking surgery on survival rates in patients with advanced ovarian cancer across different chemotherapy trials?,"Five-year survival for cisplatin-based chemotherapy versus single-agent melphalan in patients with advanced ovarian cancer and optimal debulking surgery. The purpose of this study was to evaluate 5-year survival and 5-year progression-free survival in previously untreated patients with advanced ovarian cancer treated with single-agent melphalan in which very few patients underwent optimal debulking surgery (less than 2 cm residual) as compared with the patients treated with Cisplatin-based chemotherapy in which most patients underwent optimal debulking surgery. Significant increases in 5-year survival and 5-year progression-free survival were noted as we changed from the melphalan trial, in which only 14% underwent optimal debulking surgery, to PAC-H, in which 57% and the PAC trial in which 90%, respectively, underwent optimal debulking surgery. However, for those patients whose tumors were optimally debulked in the three trials, there were no statistically significant differences in median survival, median progression-free survival, 5-year survival, or 5-year progression-free survival in those patients treated with melphalan, PAC-H, or PAC. Without optimal debulking surgery, Cisplatin-based multiagent chemotherapy offered a small survival advantage. These results are similar to that reported by Gruppo Interregionale Cooperativo Oncologico Ginecologia, in which survival curves were identical for all the subgroups of chemotherapy regimens for those patients with residual disease less than 2 cm at the onset of chemotherapy whether they received (1) cyclophosphamide; (2) cyclophosphamide and Adriamycin; (3) cyclophosphamide, Adriamycin, and Cisplatin; (4) cyclophosphamide, Adriamycin, and hexamethylmelamine; (5) Cisplatin and cyclophosphamide; (6) low-dose Cisplatin; (7) high-dose Cisplatin; or (8) carboplatin."
-What are the most common menstrual symptoms associated with pelvic endometriosis according to the study?,"Menstrual symptoms in women with pelvic endometriosis. OBJECTIVE--To investigate menstrual symptoms in relation to pelvic pathology. DESIGN--A prospective questionnaire-based study. SETTING--Aberdeen Royal Infirmary, Scotland. SUBJECTS--1250 questionnaires were sent out prior to planned admission and 1200 women (96%) brought the completed questionnaires. They comprised 598 women undergoing laparoscopic sterilization, 312 having laparoscopy because of infertility, 156 having laparoscopy because of chronic pelvic pain and 134 women undergoing abdominal hysterectomy for dysfunctional uterine bleeding. MAIN OUTCOME MEASURES--The occurrence of dysmenorrhoea, menorrhagia, menstrual regularity, premenstrual spotting, deep dyspareunia and pelvic pain in women with either endometriosis and post infective pelvic adhesions or a normal pelvis. RESULTS--Menorrhagia, menstrual irregularity and premenstrual spotting occurred with equal frequency in all groups. Deep dyspareunia, pain after intercourse and recurrent pain unrelated to menstruation or coitus was more common in women with endometriosis and those with post infective pelvic adhesions than in those with a normal pelvis. Dysmenorrhoea appears to be more prevalent among women having endometriosis. CONCLUSIONS--Menstrual symptoms, while raising a high index of suspicion for endometriosis, are not entirely reliable as indicators of disease. Dysmenorrhoea is the most common reported symptom in endometriosis sufferers. Diagnostic laparoscopy should be considered before institution of treatment in women complaining of pelvic pain and menstrual symptoms."
-How do the surface markers of monocytes change during in vitro maturation to macrophages?,"In vitro maturation of mononuclear phagocytes and susceptibility to HIV-1 infection. In the present report, we have studied the in vitro transition of normal blood monocytes to macrophages by changes in cell morphology, and the expression of surface antigens with a panel of monoclonal antibodies. The maturation process was accompanied by notable changes in cell-surface markers in a time-dependent manner. The percentage of cells expressing CD11c, ICAM-1, HLA-DR, and Fc receptor class III increased while the CD4 and CD35 expression was markedly decreased. After demonstrating that in vitro monocytes mature to macrophages in a recognizable manner, we studied the susceptibility to HIV-1 infection at time points representing different stages of cell maturation. The results show that monocyte/macrophages are susceptible to HIV-1 infection at all stages of differentiation. However, the kinetics of virus replication depends on the degree of maturation at the time of infection. Two major patterns of replication were observed: Infection of monocytes resulted in efficient virus production measurable by reverse transcriptase activity in culture supernatant, whereas infection of fully differentiated macrophages yielded low but sustained virus release only demonstrable by p24 antigen assay. We were not able to detect differences in the capacity of the virus to infect and replicate in monocyte/macrophages with respect to cellular origin of the virus isolate and whether the viruses were laboratory-adapted strains or low-passaged patient isolates."
-What was the main strategy used for managing distal ileal Crohn's disease in this study?,"Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy."
-What potential risks are associated with topical diphenhydramine administration in children with varicella-zoster infection?,"Diphenhydramine toxicity in three children with varicella-zoster infection. Diphenhydramine hydrochloride is an antihistamine with anticholinergic properties that is frequently used both orally and topically for the temporary relief of pruritus. Significant systemic absorption may occur following topical administration of diphenhydramine in patients with varicella-zoster lesions. We describe three children with varicella-zoster infection (VZI) who developed bizarre behavior as well as visual and auditory hallucinations following topical applications of large amounts of diphenhydramine to the majority of skin surfaces. In two cases, oral diphenhydramine was also administered. Serum diphenhydramine concentrations approximated or exceeded those previously reported. In each case, a complete resolution of mental status abnormalities occurred within 24 hours after discontinuation of all diphenhydramine-containing products. Pharmacists and other health professionals should be aware of the potential toxicity of topical diphenhydramine in patients with VZI."
-What medical conditions were the patients treated for before experiencing cerebral vasospasm?,Symptomatic cerebral vasospasm following tumor resection: report of two cases. The authors report two cases of symptomatic cerebral vasospasm following resection of an acoustic neuroma and a left sphenoid wing meningioma. Vascular spasm was documented by transcranial Doppler and angiography studies. Both patients responded to hypervolemic therapy. Possible mechanisms contributing to this rare complication are discussed.
-How does the posterior cricoarytenoid (PCA) muscle activity change during different breathing conditions in normal adults?,"Posterior cricoarytenoid activity in normal adults during involuntary and voluntary hyperventilation. The effect of isocapnic hypoxia and hyperoxic hypercapnia on the electrical activity of the posterior cricoarytenoid (PCA) muscle was determined in eight normal adult humans by use of standard rebreathing techniques and was compared with PCA activity during voluntary hyperventilation performed under isocapnic and hypocapnic conditions. PCA activity was recorded with intramuscular hooked-wire electrodes implanted through a fiberoptic nasopharyngoscope. During quiet breathing in all subjects, the PCA was phasically active on inspiration and tonically active throughout the respiratory cycle. At comparable increments in respiratory output, hypercapnia, hypoxia, and voluntary hyperventilation appeared to be associated with similar increases in phasic or tonic PCA activity. During quiet breathing, the onset of phasic PCA activity usually occurred before inspiratory airflow and extended beyond the start of expiratory airflow. The duration of phasic PCA preactivation and postinspiratory phasic PCA activity remained unchanged during progressive hypercapnia and progressive hypoxia. The results, in combination with recent findings for vocal cord adductors, suggest that vocal cord position throughout the respiratory cycle during hyperpnea is actively controlled by simultaneously acting and antagonistic intrinsic laryngeal muscles."
-What was the diagnostic approach and treatment for the patient with isolated adrenal cryptococcosis?,"Isolated cryptococcosis of the adrenal gland. A case of isolated adrenal cryptococcosis is reported. A patient with a history of diabetes mellitus had symptoms of left flank pain. Roentgenological and sonographic findings of the adrenal gland were indicative of a malignant tumour. Tissue obtained from surgery showed fungal granuloma and a poorly encapsulated cryptococcal organism was identified by special stains. A post-operative serum cryptococcal antigen test was positive, and the patient was successfully treated with surgery and a course of amphotericin B. After a 7-month follow-up period, there is no evidence of recurrence or dissemination."
-What was the primary finding of the multicenter trial regarding dexamethasone therapy in neonates with chronic lung disease?,"Dexamethasone therapy in neonatal chronic lung disease: an international placebo-controlled trial. Collaborative Dexamethasone Trial Group. In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups."
-What were the hemodynamic effects of desmopressin administration in patients undergoing coronary artery bypass grafting?,"Hemodynamic consequences of desmopressin administration after cardiopulmonary bypass. Desmopressin acetate is used to reduce blood loss after cardiac surgery. However, there have been reports that hypotension can occur with infusion of desmopressin and that postoperative blood loss is not reduced. In this randomized, double-blinded study, we investigated the effects of desmopressin on hemodynamics, coagulation, and postoperative blood loss in patients undergoing primary elective coronary artery bypass grafting (CABG). After reversal of heparin effect, 20 patients received desmopressin 0.3 micrograms.kg-1, infused over 15 min, and 20 patients received a placebo. Desmopressin produced a small but significant decrease in diastolic blood pressure when compared with the placebo (50.8 mmHg vs. 57.6 mmHg for the desmopressin- and placebo-treated groups, respectively; P = 0.0372). A 20% or greater decrease in mean arterial pressure was observed in 7 of 20 patients receiving desmopressin, whereas only one patient in the placebo-treated group experienced a decrease of this magnitude (P = 0.0177). Reductions in arterial pressure were secondary to decreases in systemic vascular resistance (SVR) (mean SVR before and after the drug infusion, 1,006 and 766 dyn.s.cm-5, respectively, for the desmopressin-treated group; and 994 and 1,104 dyn.s.cm-5, respectively, for the placebo-treated group; P = 0.0078)."
-What makes cutaneous metastasis from papillary thyroid carcinoma rare and challenging to diagnose?,"Cutaneous metastasis from papillary carcinoma of the thyroid gland. Cutaneous metastases from carcinoma of the thyroid gland are rare. We present the clinical, histologic, and immunohistochemical features of a solitary metastasis from papillary carcinoma of the thyroid. Our results indicate that this tumor can produce epithelial mucin and, therefore, must be differentiated from other metastatic carcinomas and from primary apocrine tumors of the skin. Positive staining for thyroglobulin confirmed the diagnosis in this case."
-What were the main findings of the histopathologic analysis of 204 fibrous gingival lesions?,"Fibrous lesions of the gingiva: a histopathologic analysis of 204 cases. Two hundred four cases of fibrous lesions of the gingiva were studied histologically for the presence of calcified tissue, the nature of the connective tissue, the type of keratinization, and the degree of epithelial thickness. Initially these lesions were subcategorized into four specific entities, namely fibrous epulis, fibroepithelial polyp, calcifying fibroblastic granuloma, and ossifying fibrous epulis. It was found that 46.5% of the lesions contained calcifications. The connective tissue was represented predominantly by either the collagenous type (50.5%) or the mixed (cellular and collagenous) type (44.6%). It was also found that 36% of the lesions were ulcerated, and, of these, 79.5% were associated with the cellular type of connective tissue and calcifications. In an attempt to subcategorize the fibrous lesions into specific entities, it was found that 32 cases (15.7%) had mixed features. This fact supports the suggestion that these lesions are stages in the spectrum of a single disease process and should collectively be termed fibroblastic gingival lesions. However, it is also suggested that the two terms, namely peripheral fibroma and fibrous epulis with and without ossification, should be retained whereas the usage of other terminologies should be avoided."
-What is the significance of ipsilateral breast tumour recurrence (IBTR) in relation to distant disease risk after breast cancer treatment?,"Significance of ipsilateral breast tumour recurrence after lumpectomy. Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy."
-What was the prevalence of peripheral neuropathy in the Parsi community of Bombay according to the survey?,"Prevalence of peripheral neuropathy in the Parsi community of Bombay. We carried out a door-to-door survey to screen for neurologic diseases, including peripheral neuropathy, in a community of 14,010 Parsis living in housing colonies in Bombay, India. The most common neurologic disorder was peripheral neuropathy with 334 cases (2,384 cases/100,000 population). The most common neuropathy was compressive, with diabetes the most common noncompressive etiology. There was no leprosy, and nutritional neuropathies were rare."
-What was the response rate to preoperative chemotherapy in patients with esophageal adenocarcinoma in this pilot study?,"A pilot study of neoadjuvant chemotherapy with 5-fluorouracil and cisplatin with surgical resection and postoperative radiation therapy and/or chemotherapy in adenocarcinoma of the esophagus. Fifteen patients with potentially resectable adenocarcinoma of the esophagus were treated with two cycles of preoperative chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP). Response to chemotherapy was evaluated by comparative barium swallow, computerized chest tomography, esophagoscopy, and change in clinical symptomatology. Eleven patients (73%) were resected, two (13%) were explored and found inoperable, and two (13%) were not subjected to surgery (one because of death related to toxicity and one due to progressive disease). Ten of eleven patients (91%) had gross residual tumor. One patient (9%) had residual microscopic disease only. One patient (7%) had complete clinical responses (CCR), five (33%) had partial clinical response (PCR), and nine (60%) had no response (NR). Five of 15 patients (or 45% of resected patients) remain free of disease. Median survival time was 18.47 months for all patients and 23.83 months for resected patients."
-What are the characteristic symptoms of a duodenobronchial fistula?,"Duodenobronchial fistula. Duodenobronchial fistulas are an extremely rare subgroup of abdominobronchial fistulas, which include bronchobiliary, gastrobronchial, enterobronchial, colobronchial, and splenobronchial fistulas. Only one case of a duodenobronchial fistula has been previously reported. Duodenobronchial fistulas occur as a complication of a duodenal injury. The characteristic symptoms are a cough that produces copious bilious secretions, shortness of breath, and fever. The diagnosis is made by contrast gastrointestinal studies. Treatment requires an abdominal approach with interruption of the fistula at its duodenal origin and control of the inciting inflammatory process. With prompt diagnosis and treatment, thoracic drainage or pulmonary resection should not be needed."
-What is a peritoneopericardial diaphragmatic hernia and how was it discovered in this particular case?,"Peritoneopericardial diaphragmatic hernia discovered at coronary bypass operation. A 68-year-old man was discovered to have a large peritoneopericardial hernia when operated on for coronary artery bypass. Such hernias are very unusual. The pathogenesis, clinical presentation, and management of this problem are discussed."
-What is the mortality rate and morbidity rate in the study of 23 patients with acute necrotizing pancreatitis?,"Acute necrotizing pancreatitis: management by planned, staged pancreatic necrosectomy/debridement and delayed primary wound closure over drains. We reviewed our recent experience with management of 23 consecutive patients with acute necrotizing pancreatitis. All patients had documented necrotizing pancreatitis with parenchymal or peripancreatic necrosis. Our method of treatment has evolved from our previous approach of controlled open lesser sac drainage (marsupialization) to staged necrosectomy/debridement with delayed primary closure over drains. With this latter approach, hospital mortality was 4 of 23 patients (17 per cent), but significant morbidity still occurred in 12 of 23 patients (52 per cent). However, recurrent intra-abdominal abscess before discharge occurred in only one patient. We believe that this operative approach toward the severely ill patient with acute necrotizing pancreatitis who requires operative intervention will minimize the occurrence of intra-abdominal sepsis."
-What makes CT imaging of pancreatic diseases in children different from adults?,"CT of the pancreas in children. CT has become a frequently used imaging method for evaluating suspected pancreatic disease in children. Although the spectrum of CT findings in pancreatic disease is well documented in adults, there is a paucity of such information in children. Familiarity with CT patterns of pancreatic disease in childhood is important for diagnosis. In this essay, we illustrate the CT findings of pancreatic lesions in children."
-What surgical technique improvements were made in treating pectus excavatum over a 15-year period?,"Pectus excavatum: a 15-year perspective. Pectus excavatum is relatively uncommon. Our experience with 177 children during a 15-year period produced changes in our surgical technique, which now includes a small transverse incision, minimal subcutaneous flap elevation, a muscle-relaxing incision over the fifth costal cartilage, complete resection of involved cartilage, use of Adkins' strut, suspension of sternum to strut, taut reefing of intercostal muscle, no tubes or drains, epidural analgesia, a patient-controlled analgesia device postoperatively, and eventual strut removal. Use of the evolved technique gives excellent cosmetic results, good functional results with minimal discomfort, and a shorter convalescent period."
-What is a false aneurysm of the right internal mammary artery and how is it related to median sternotomy?,False aneurysm of the right internal mammary artery. False aneurysm of the internal mammary artery is an uncommon complication of median sternotomy. Clinical and radiological findings of 2 such cases are presented. At operative exploration neither was directly related to the presence of a sternal wire.
-How does the concentration of inspired CO2 (FICO2) affect cardiac resuscitation in the experimental rat model?,"Hypercarbic acidosis reduces cardiac resuscitability. BACKGROUND AND METHODS: Marked increases in myocardial hypercarbia and acidosis accompany cardiac arrest and resuscitation. To investigate whether hypercarbic acidosis independent of oxygenation is of itself detrimental to cardiac resuscitation, three groups of six Sprague-Dawley rats were ventilated with gas mixtures containing concentrations of inspired CO2 (FICO2) of 0.0, 0.3, or 0.5, with oxygen fractions held constant at 0.5. After 4 mins of ventricular fibrillation, mechanical chest compressions were initiated with a pneumatic thumper; 2 mins later, transthoracic defibrillation was attempted. RESULTS: Each animal ventilated with FICO2 of 0.0 or 0.3 was successfully resuscitated. However, none of the animals ventilated with FICO2 of 0.5, in which aortic pH was less than 6.67 and aortic PCO2 was greater than 200 torr (greater than 26.7 kPa), was resuscitated (p less than .001). This finding contrasted with a second control group of seven identically treated animals which, in the absence of cardiac arrest, demonstrated no adverse effects after ventilation with an FICO2 of 0.5. CONCLUSIONS: Increases in FICO2 to levels of 0.5 under conditions of constant arterial oxygenation and controlled coronary perfusion pressure preclude successful resuscitation in this rodent model of CPR."
-What is the effectiveness of endoscopic balloon dilatation in managing intestinal strictures caused by Crohn's disease?,"Endoscopic balloon dilatation as a therapeutic option in the management of intestinal strictures resulting from Crohn's disease. Endoscopic balloon dilatation was undertaken in seven patients who presented with obstructive symptoms resulting from Crohn's disease. Five patients had strictures from recurrent disease at the site of an ileotransverse anastomosis, one had duodenal stenosis and one a colonic stricture. The procedures were performed under intravenous sedation on one to four occasions (median 2) and were uncomplicated. Sustained improvement over an 18-24-month follow-up period was achieved in five patients, but dilatation was unsuccessful in two cases. Endoscopic balloon dilatation is a safe and effective option in selected patients with intestinal strictures resulting from Crohn's disease and may overcome the need for surgery."
-What method is considered the definitive study for evaluating the integrity of breast implants?,"Definitive diagnosis of breast implant rupture by ultrasonography. Silicone breast implantation is entering its fourth decade. Our ability to monitor the integrity of ""old"" prostheses is questioned. Clinical and mammographic examinations are reliable indicators of implant rupture only if there has been gel migration away from the implant pocket. Ultrasonography is presented as a reliable, sensitive method of evaluation of implant integrity. It should be considered the definitive study of prosthesis integrity. When sonography is added to mammographic and clinical examination, the preoperative evaluation of symptomatic augmented breasts is complete. Ultrasonography may be considered with mammography in the routine breast examination of all previously augmented patients."
-What are the key principles of managing external abdominal fistulas arising from the digestive tract?,"External fistulas arising from the digestive tract. External abdominal fistulas that arise from the digestive tract are associated with high mortality and prolonged morbidity in terms of infection, malnutrition, and skin excoriation. Such external fistulas most commonly follow anastomotic leak after gastrointestinal surgery. We identified 58 patients seen over a 5-year period at the University of Louisville Hospitals because of external abdominal fistulas that arose from the stomach (8), duodenum (4), small intestine (26), colon (14), biliary tract (9), and pancreas (7). Fifteen patients had multiple fistulas and 32 had high-output fistulas (greater than 200 mL/day). Closure was achieved in 48 patients, and eight of the 10 patients whose fistulas remained open died. Overall mortality was 19%. Principles of management include control of infection, correction of fluid and electrolyte imbalance, nutritional support, proper wound care, and often operative intervention. Multiple staged operations over many months were particularly important in managing complex wounds with large abdominal wall defects and multiple fistulas. Fistula closure is the ultimate goal, and patience is important to achieve it."
-What treatment was found to be effective in managing neurogenic pulmonary edema in a patient with subarachnoid hemorrhage?,"Neurogenic pulmonary edema: treatment with dobutamine. In the case of a patient with complicating subarachnoid hemorrhage, an infusion of dobutamine was followed by a massive diuresis and regression of severe neurogenic pulmonary edema. It is suggested that the reduction in total peripheral vascular resistance and the increase in cardiac contractility accounts for the observed beneficial effect and indicate that dobutamine is a suitable drug for the treatment of neurogenic pulmonary edema."
-What complications did the patient develop after receiving a continuous IV infusion of vasopressin?,"Rhabdomyolysis and cutaneous necrosis following intravenous vasopressin infusion. A continuous IV infusion of vasopressin was administrated to a patient with cirrhosis of the liver and acute gastrointestinal bleeding from esophageal varices. In the first 24 hours, the patient developed rhabdomyolysis and cutaneous necrosis. Stopping vasopressin infusion resulted in relief of these lesions. The rarity of these complications suggests an idiosyncratic reaction of susceptible individuals that may be related to previous vascular disease or a failure in baroreceptor regulation."
-What are the key mental health benefits of regular aerobic exercise?,"Health benefits of aerobic exercise. Regular aerobic exercise has significant cardiovascular benefits, including a reduction in incidence of and mortality from coronary artery disease--probably because of positive effects on blood lipid levels and blood pressure. Aerobic exercise can also be an important adjunct to a weight-loss program. Many persons who continue an exercise program do so because of its positive mental benefits, including reduction in anxiety and depression and modulation of stress levels. Aerobic exercise has a place in the management of diabetes, pregnancy, and aging. The problems associated with aerobic exercise are minimal compared with its benefits."
-What makes low back pain a challenging diagnosis in emergency department settings?,"Low back pain: review of diagnosis and therapy. Low back pain is a patient complaint frequently encountered in the emergency department setting. The disease entity is often a diagnostic challenge with a subtle presentation, but can be accompanied by significant neurovascular complications. Current topics of controversy include the utility of radiologic evaluation, pharmacologic and holistic treatment strategies, as well as guidelines for urgent referral of patients with lumbar pain."
-How does Color Doppler imaging help in assessing orbital blood flow in carotid artery disease?,"Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease. Color Doppler imaging was used to evaluate the hemodynamics of the ophthalmic vasculature in a case of complete internal carotid artery occlusion. This procedure, which allows rapid, noninvasive imaging, showed a partial ophthalmic artery obstruction with absent flow in the central retinal artery, central retinal vein, and nasal posterior ciliary arteries. Although altered perfusion of the retinal vessels may be evaluated clinically, assessment of blood flow in the ophthalmic and ciliary arteries previously could be evaluated only indirectly by intravenous fluorescein angiography. The color Doppler imaging findings were confirmed by intravenous fluorescein angiography and carotid arteriography. Color Doppler imaging represents a noninvasive method to diagnose abnormal blood flow of the ophthalmic artery and its branches and to evaluate serial changes of the circulation in a noninvasive manner."
-What CT scan findings are associated with a higher probability of hypovolemia in patients with subarachnoid hemorrhage?,"Association of hypovolemia after subarachnoid hemorrhage with computed tomographic scan evidence of raised intracranial pressure. Hypovolemic patients are more likely to suffer delayed cerebral ischemia and infarction after a subarachnoid hemorrhage (SAH). Prompt recognition and correction of hypovolemia may improve the outcome. We have identified computed tomographic (CT) scan findings that increase the probability of a patient presenting with hypovolemia soon after an SAH. The plasma volume (PV) of 25 patients admitted within 96 hours of an SAH was measured using radioiodinated serum albumin. The normal PVs were measured in an outpatient setting 6 months later or predicted from their total body water. Nine patients (36%) were found to be hypovolemic, defined as a fall in PV exceeding 10% of the normal PV (mean fall, 18 +/- 2%). Sixteen patients were normovolemic or hypervolemic (mean PV, +9 +/- 2%). The basal cisterns were compressed or obliterated on the CT scans of all hypovolemic patients compared with 12.5% of normovolemic patients (chi-square, 14.52; P less than 0.01). The probabilities of a patient being hypovolemic if the CT scan indicated raised intracranial pressure were high: hydrocephalus, P = 0.80; compression of the basal cisterns, P = 0.82; and compression of the basal cisterns associated with intracerebral hematoma or midline shift, P = 1.00. Patients with an SAH and radiological evidence of raised intracranial pressure should be considered at particular risk for systemic hypovolemia."
-What are the key differences in spinal nerve sheath tumors between patients with neurofibromatosis type 1 and type 2?,"Benign spinal nerve sheath tumors: their occurrence sporadically and in neurofibromatosis types 1 and 2. Benign spinal nerve sheath tumors (neurofibromas and schwannomas) often occur on dorsal nerve roots sporadically or in neurofibromatosis types 1 and 2. These are histologically benign tumors, and distinction between them is frequently not made by clinicians. To determine if there is a correlation between the histological pattern of benign spinal nerve sheath tumors and the type of neurofibromatosis, the clinical and pathological features of these tumors (86 surgical specimens and five autopsies) in 68 patients were reviewed. The patients were classified into one of four categories: neurofibromatosis type 1, neurofibromatosis type 2, uncertain, or sporadic. The diagnostic criteria used for neurofibromatosis types 1 and 2 were established by the National Institutes of Health. Patients who did not fulfill criteria for either neurofibromatosis type 1 or 2 but who had multiple nervous system tumors or other stigmata of neurofibromatosis were designated ""uncertain."" Spinal nerve sheath tumors were considered sporadic in 42 cases (40 schwannomas and two neurofibromas). In the 14 patients with neurofibromatosis type 1, all spinal nerve sheath tumors were neurofibromas. In six of the seven patients with neurofibromatosis type 2, all spinal nerve sheath tumors were schwannomas. One patient with neurofibromatosis type 2 had a spinal nerve sheath schwannoma and a tumor with features of both tumor types. The authors conclude that spinal nerve sheath tumors in patients with neurofibromatosis type 1 are neurofibromas. In contrast, spinal nerve sheath tumors occurring in neurofibromatosis type 2 or sporadically are most frequently schwannomas. The distinct histological features of these tumors may reflect different pathogenetic mechanisms even though they arise at identical sites in neurofibromatosis types 1 and 2."
-What were the key findings comparing surgically treated and untreated patients with spinal stenosis?,"The effect of decompression on the natural course of spinal stenosis. A comparison of surgically treated and untreated patients. The clinical course of 19 untreated patients with spinal stenosis (mean age, 60 years) was compared with that of 44 patients treated surgically (mean age, 65 years). The time of follow-up was 31 and 53 months, respectively. About 80% of the patients had neurogenic intermittent claudication. In the follow-up, one third of the treated and one half of the untreated patients still had neurogenic claudication. By visual analogue-scale estimation, 60% of those treated surgically and 33% of the untreated patients felt better. Fifty-eight percent of the untreated patients were unchanged. Neurophysiologic changes showed progression in almost all cases; it was more pronounced in the treated patients. No proof of severe deterioration was found in the untreated patients, and observation for 2-3 years seems to be a good alternative to surgery."
-How does monitoring cerebral oxygenation help in managing patients with acute severe closed head trauma?,"Continuous monitoring of cerebral oxygenation in acute brain injury: injection of mannitol during hyperventilation. Global cerebral oxygenation, perfusion pressure, and expired pCO2 were continuously monitored in 10 adults with acute severe closed head trauma. Cerebral oxygenation was monitored by fiberoptic catheter oximetry, which allowed simultaneous measurements of arterial and jugular bulb oxyhemoglobin saturation. Intracranial pressure levels over 20 mm Hg were recorded several times in all patients, in spite of sedation, muscle paralysis, and profound hyperventilation. Intracranial hypertension was frequently associated with oligemic cerebral hypoxia, identified as abnormally low jugular oxygen saturation in the presence of normal arterial oxygenation. Intracranial hypertension was then managed with intravenous administration of mannitol boluses, which yielded simultaneous decreases in intracranial pressure and increases in cerebral oxygenation to highly statistically significant levels. Monitoring cerebral oxygenation was clinically useful because it allowed identification of impaired cerebral oxygenation even when cerebral perfusion pressure was normal. It is therefore proposed as a new monitoring technique, to supplement conventional monitoring of cerebral perfusion pressure."
-What were the key findings of the study on chronic neurological effects of acute organophosphate pesticide intoxication in Nicaraguan agricultural workers?,"Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group. Acute organophosphate pesticide poisonings cause substantial morbidity and mortality world wide; however, whether organophosphates cause chronic neurological sequelae has not been established. To see whether single episodes of acute unintentional organophosphate intoxication lead to chronic neuropsychological dysfunction, we carried out a retrospective study of agricultural workers in Nicaragua who had been admitted to hospital between July 1, 1986, and July 31, 1988, for occupationally related organophosphate intoxication. This ""poisoned"" group (36 men) was tested on average about two years after the episode of pesticide poisoning and compared with a matched control group. The poisoned group did much worse than the control group on all neuropsychological subtests, with significantly worse performance on five of six subtests of a World Health Organisation neuropsychological test battery and on 3 of 6 additional tests that assessed verbal and visual attention, visual memory, visuomotor speed, sequencing and problem solving, and motor steadiness and dexterity. Differences in neuropsychological performance could not be explained by other factors. The findings of a persistent decrease in neuropsychological performance among individuals with previous intoxication emphasise the importance of prevention of even single episodes of organophosphate poisoning."
-What was the accuracy of fine needle aspiration (FNA) cytology in differentiating between benign and malignant pancreatic lesions in this study?,"Preoperative and intraoperative fine needle aspiration cytology of pancreatic lesions. The aim of the present study was to describe our experience from 1976 through 1988 with fine needle aspiration (FNA) cytology of pancreatic lesions in 90 patients. Fine needle aspirations were performed preoperatively under ultrasound guidance (USG) in 46 patients, under computed tomographic guidance (CTG) in seven patients, and intraoperatively in 37 patients. Based on histologic, cytologic, and clinical findings, final diagnoses were reached in 80 patients, of whom 62 had malignant pancreatic disease (MPD) and 18 had benign pancreatic disease (BPD). The accuracy of cytologic diagnoses was verified by histologic, cytologic, and clinical findings. In 62 patients with MPD, the cytologic findings suggested malignancy in 54 patients, suspected malignancy in five, and did not reveal malignancy in three patients. Among 18 patients with BPD, all of the cytologic findings were reported as benign. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy for intraoperative FNA cytologic results were 96%, 100%, 100%, 91%, and 97%, respectively, and for USG FNA cytologic results were 94%, 100%, 100%, 78%, and 95%, respectively. No complications followed the procedure. Conclusions: Both transabdominal percutaneous imaging-guided and intraoperative FNA cytology of pancreatic lesions are simple, safe, and highly accurate methods in differentiation of benign from malignant pancreatic lesions."
-What measures have been used to reduce the incidence of stress erosive gastritis in critically ill patients?,"Stress erosive gastritis. Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention."
-What were the key findings of autonomic function studies in patients with Friedreich's ataxia?,"Autonomic function in Friedreich's ataxia. Autonomic function studies were performed on 15 patients with Friedreich's ataxia, and the results compared with those of 76 healthy subjects. There was an increase in resting supine heart rate, attributed to cardiac abnormalities. Other tests of sympathetic and parasympathetic function were normal. The normal autonomic function studies are consistent with the pathological findings of degeneration predominantly of large diameter myelinated fibres with sparing of small myelinated and unmyelinated fibres."
-What was the incidence of tracheostomal stenosis in patients who underwent total laryngectomy with immediate tracheoesophageal puncture compared to the control group?,"Tracheostomal stenosis after immediate tracheoesophageal puncture. The incidence of tracheostomal stenosis in a group of patients after total laryngectomy with or without pharyngectomy plus immediate tracheoesophageal or tracheogastric puncture was compared with that of a control group without puncture. The stenosis rate of the puncture group was significantly higher than that of the control group (19% vs 6%). The other probable etiologic factors for stomal stricture were similar in both groups. Analysis of the risk factors in the puncture group suggested a higher tendency of stenosis in females (43% vs 16%) and in patients receiving postoperative radiotherapy (29% vs 14%), although the difference failed to reach statistical significance."
-What was the primary objective of the Systolic Hypertension in the Elderly Program (SHEP) study?,"Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group OBJECTIVE.--To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal (total) stroke in isolated systolic hypertension. DESIGN.--Multicenter, randomized, double-blind, placebo-controlled. SETTING.--Community-based ambulatory population in tertiary care centers. PARTICIPANTS.--4736 persons (1.06%) from 447,921 screenees aged 60 years and above were randomized (2365 to active treatment, 2371 to placebo). Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg. Of the participants, 3161 were not receiving antihypertensive medication at initial contact, and 1575 were. The average systolic blood pressure was 170 mm Hg; average diastolic blood pressure, 77 mm Hg. The mean age was 72 years, 57% were women, and 14% were black. INTERVENTIONS.--Participants were stratified by clinical center and by antihypertensive medication status at initial contact. For step 1 of the trial, dose 1 was chlorthalidone, 12.5 mg/d, or matching placebo; dose 2 was 25 mg/d. For step 2, dose 1 was atenolol, 25 mg/d, or matching placebo; dose 2 was 50 mg/d. MAIN OUTCOME MEASURES.--Primary.--Nonfatal and fatal (total) stroke. Secondary.--Cardiovascular and coronary morbidity and mortality, all-cause mortality, and quality of life measures. RESULTS.--Average follow-up was 4.5 years. The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group, and the 5-year average diastolic blood pressure was 72 and 68 mm Hg, respectively. The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo. The relative risk by proportional hazards regression analysis was 0.64 (P = .0003). For the secondary end point of clinical nonfatal myocardial infarction plus coronary death, the relative risk was 0.73. Major cardiovascular events were reduced (relative risk, 0.68). For deaths from all causes, the relative risk was 0.87. CONCLUSION.--In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%, with 5-year absolute benefit of 30 events per 1000 participants. Major cardiovascular events were reduced, with 5-year absolute benefit of 55 events per 1000."
-What were the two antibiotic regimens compared in this clinical trial for treating children with ruptured appendicitis?,"A randomized clinical trial of ampicillin, gentamicin and clindamycin versus cefotaxime and clindamycin in children with ruptured appendicitis. This prospective, randomized, double-blind study compares the efficacy, safety and cost-effectiveness of ampicillin, gentamicin and clindamycin (AGC) or cefotaxime and clindamycin (CC) for the treatment of children with complicated appendicitis. Ninety-seven children were randomized. Forty-seven were assigned to the AGC regimen and 50 received CC. Forty-two patients in the AGC group had an appropriate therapeutic outcome, whereas 48 of 50 children who received CC completed the trial successfully (p = NS). There were no differences between the groups with reference to the duration of antibiotic administration, fever, leukocytosis or length of hospitalization. Complications of therapy were uncommon and neither regimen demonstrated a significant advantage from an economic standpoint. We concluded that, in childhood, complicated appendicitis can be treated with either CC or AGC with equal efficacy."
-What are the limitations of physical examination techniques in diagnosing splenomegaly according to the context?,"The clinical diagnosis of splenomegaly. Assessing for the presence of splenomegaly is an important component of the physical examination. Although several methods of palpation and percussion of the spleen have been described, until recently they have not been validated by noninvasive imaging techniques such as ultrasonography, radionuclide scanning, and computed tomography that offer objective means to assess splenomegaly. We review the literature comparing various physical examination techniques with noninvasive imaging modalities and conclude that palpation and percussion of the spleen are complementary but frequently insensitive and that further studies are needed to evaluate the efficacy of specific diagnostic methods."
-What are the various surgical procedures recommended for treating cubital tunnel syndrome?,"The failed ulnar nerve transposition. Etiology and treatment. Various procedures have been recommended for the treatment of cubital tunnel syndrome. Simple decompression in situ, medial epicondylectomy, subcutaneous transposition, intramuscular transposition, and submuscular transposition all have their advocates. The results of the surgical treatment for cubital tunnel syndrome are related to the severity of the compressive neuropathy at the time of diagnosis and to the adequate decompression of the nerve at all sites of potential compression at the time of surgical treatment. Fourteen patients who had previously undergone surgical treatment for cubital tunnel syndrome were evaluated because of persistent pain, paresthesia, numbness, and motor weakness. All patients had documented persistent compression of the ulnar nerve on clinical and electromyographic evaluation. The indication for repeat surgical exploration in all patients was unremitting pain despite nonoperative treatment. All patients had been treated by neurolysis and submuscular transposition of the ulnar nerve as described by Learmonth. The causes of continued pain after initial surgery included retention of the medial intermuscular septum, dense perineural fibrosis of the nerve after intramuscular and subcutaneous transposition, adhesions of the nerve to the medial epicondylectomy site, and recurrent subluxation of the nerve over the medial epicondyle after subcutaneous transposition. Revision surgery was found to be highly successful for relief of pain and paresthesias; however, the recovery of motor function and return of sensibility were variable and unpredictable."
-How does verapamil help protect against renal injury at the cellular level?,"Role of calcium channel blockers in protection against experimental renal injury. The available evidence indicates that the first generation calcium channel blocker verapamil has a protective effect against both acute and chronic renal failure. At the cell membrane, verapamil helps minimize the effects of excess calcium influx after ischemic injury, evidenced by reduced uptake of 45Ca, thus lessening tubular injury from both calcium-activated phospholipases and mitochondrial calcium overload. In experimental chronic renal failure, the long-term administration of verapamil protects against renal dysfunction and damage, independent of any effect on systemic mean arterial pressure. Protective effects of verapamil are delineated in several models, supporting the presented hypothesis of the pathogenesis of renal failure."
-What was the clinical significance of microsporidia detection in HIV-1-infected patients with chronic diarrhoea?,"Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals To assess the importance of microsporidiosis of the small intestine in the pathogenesis of chronic diarrhoea in HIV-1-infected individuals, duodenal biopsy samples from the following three patient groups were prospectively evaluated for bacterial, viral, and parasitic pathogens by standard methods, and for microsporidia by light microscopy: 55 consecutive HIV-1-antibody-positive subjects with unexplained diarrhoea of at least 3 weeks duration (group A); 38 HIV-1-seropositive subjects without diarrhoea (group B) who consecutively underwent upper gastrointestinal endoscopy for various reasons; and 7 patients without known risk factors for HIV infection with chronic unexplained diarrhoea (group C). In groups A and B most subjects had had previous AIDS-defining opportunistic infections and the median peripheral blood CD4 lymphocyte count was less than 0.1 x 10(9)/l. Microsporidia were detected as the single pathogen in 15 of the group A compared with 1 (in whom diarrhoea subsequently developed) of the group B patients (p = 0.001) and none of the group C patients. With the exception of 4 of the group A patients, no other intestinal pathogens were identified in any of the patients. The median peripheral blood CD4 count was significantly lower in patients with detectable microsporidia than in those without microsporidiosis (0.03 x 10(9)/l vs 0.06 x 10(9)/l; p = 0.03); in all patients with microsporidiosis, the CD4 count was equal to or less than 0.1 x 10(9)/l. 13 patients with microsporidiosis were treated with metronidazole, in 10 of whom treatment led to a substantial improvement or disappearance of diarrhoea within days of starting therapy, but did not result in eradication of the parasite in the 5 patients who underwent repeat biopsy. The findings suggest that small-intestinal microsporidiosis is an important cause of chronic unexplained diarrhoea in HIV-1-infected individuals with pronounced cellular immune deficiency. This infection should therefore be added to the list of AIDS-defining opportunistic infections."
-What are the key differences in vascular reactivity between norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure?,"Differences in vascular reactivity in models of ischemic acute renal failure. To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded."
-What is the significance of S100-positive sustentacular cells in determining the malignancy of pheochromocytomas?,"S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas. The absence or presence of S100-positive sustentacular cells has been previously shown to be correlated with benign and malignant pheochromocytomas and paragangliomas. We evaluated a total of 17 malignant and recurrent or locally aggressive adrenal pheochromocytomas for their quantity of sustentacular cells. An absence of sustentacular cells was demonstrated in the majority of malignant cases, while the locally aggressive or recurrent group usually contained an abundance of these cells. However, in one malignant case a constant moderate number of sustentacular cells in the primary site and in two sequential metastases was found. We conclude that the absence of sustentacular cells in pheochromocytomas may indicate a lesion with a greater potential for metastasis and that sustentacular cells, when they are present in a malignant pheochromocytoma, are an integral part of the tumor."
-What is the proposed solution for facilitating Nd-YAG laser hyaloidotomy in eyes prone to developing malignant glaucoma after surgery?,"Nd-YAG laser hyaloidotomy for malignant glaucoma following one-piece 7 mm intraocular lens implantation. Three cases of malignant glaucoma following extracapsular cataract extraction with 7 mm one-piece posterior chamber intraocular lens implantation are presented. Nd-YAG laser hyaloidotomy was successfully performed in all eyes, but was difficult and required several sessions in two eyes. In the third eye, which had a sector iridectomy, laser hyaloidotomy applied over the edge of the lens optic through the iridectomy resulted in brisk deepening of the anterior chamber and reduction of intraocular pressure. We propose that the one-piece 7 mm optic posterior chamber intraocular lens may constitute an obstacle to successful hyaloidotomy, mainly owing to its large size, as it may block aqueous percolation from the vitreous into the anterior chamber. Eyes prone to develop malignant glaucoma after surgery should have a sector or large peripheral iridectomy to facilitate postoperative Nd-YAG laser hyaloidotomy if required."
-What were the main indications for emergency pulmonary resection in the patients described in this context?,"Emergency pulmonary resection for pneumonia. High morbidity and mortality. Emergency pulmonary resection was performed because of complicated pneumonia in eight patients (5 pneumonectomies, 2 lobectomies, 1 bilobectomy) over a 2-year period. The patients' age range was 5 months to 43 years. The indications were rapid aggravation of respiratory insufficiency in children with staphylococcal pneumonia and enlarging pneumatoceles, and massive hemoptysis in patients with chronic destructive pneumonia. Two patients died after pneumonectomy, one from contralateral aspiration and one from cardiogenic shock. Postoperative complications occurred in four cases--bronchopleural fistula and pyopneumothorax in three and thoracic empyema with massive chest-wall infection in one. Only two patients had an uneventful postoperative course. Complications of pulmonary necrosis in pneumonia may dictate urgent pulmonary resection, often pneumonectomy. Surgery will be life-saving in most cases, but high morbidity is to be expected."
-What are the key risk factors for myocardial rupture after acute myocardial infarction?,"Myocardial rupture. Your patient's survival may depend on you. Myocardial rupture is the second leading cause of in-hospital death from acute myocardial infarction. It is most likely to occur in the elderly, women, and patients with transmural infarction and no previous history of angina. A high index of suspicion is critical to the diagnosis. Myocardial rupture should be suspected when recurrent chest pain or hemodynamic instability develops after myocardial infarction. Rapid intervention and appropriate infarct-limiting therapy may reduce the mortality rate of this catastrophic complication."
-What are the key contributing factors for developing an abdominal wall Actinomyces abscess associated with an intrauterine device?,"Abdominal wall Actinomyces abscess associated with an intrauterine device. A case report. An abdominal wall Actinomyces abscess occurred in a woman with an intrauterine device. Contributing factors were local trauma, spread from surrounding colonized body sites and symbiotic growth of other anaerobes. The diagnosis was based on the histologic finding of the sulfur granule. Special studies may be needed to distinguish this condition from other, similar ones (Nocardia, botryomycosis)."
-How does radionuclide ventriculography help in assessing prognosis after acute myocardial infarction?,"Radionuclide assessment of ventricular function and risk stratification after myocardial infarction. Prognosis after acute myocardial infarction is determined primarily by left ventricular function and by the extent to which additional coronary obstructions jeopardize viable myocardium. Radionuclide ventriculography is well suited for noninvasive assessments of resting and exercise ventricular function after acute myocardial infarction. The prognostic importance of resting left ventricular function after acute myocardial infarction is well established. Several studies have reported the prognostic utility of submaximal exercise radionuclide ventriculography at the time of hospital discharge. Patients with globally depressed left ventricular function after acute myocardial infarction are at increased risk for cardiac death, while patients with normal resting ventricular function but abnormal function during exercise appear to be at risk for nonfatal ischemic events. The development of gated tomographic techniques and new radiopharmaceuticals will make available more accurate and detailed assessments of ventricular function and combined assessments of function and perfusion. These new developments require further investigation but appear to be promising new techniques with the potential for providing improved assessments of prognosis after acute myocardial infarction."
-What uncommon complication occurred in a 38-year-old woman 7 days after lumbar myelography with iohexol?,"Intracerebral hemorrhage after lumbar myelography with iohexol: report of a case and review of the literature. Intracranial hemorrhage is an uncommon complication of dural puncture. In most instances, hematomas are subdural; they may be unilateral or bilateral. Rarely are intraparenchymal cerebral hemorrhages related to dural puncture. This report describes a delayed occurrence of bilateral intraparenchymal hemorrhages in a 38-year-old woman 7 days after lumbar myelography with iohexol. A review of the literature is presented."
-How does activity level modify the relationship between serum cholesterol level and coronary heart disease risk in older persons?,"Is the serum cholesterol-coronary heart disease relationship modified by activity level in older persons? Although coronary heart disease remains a leading cause of death and disability in old age, the relationship of serum cholesterol level to risk of coronary heart disease in old age is controversial. Data for 2,388 white persons aged 65-74 who participated in the National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-up Study (NHEFS) were examined to determine the relationship of serum cholesterol level to coronary heart disease incidence and whether activity level would modify this relationship. While there was no overall relationship between serum cholesterol level and coronary heart disease risk in either men or women, the relationship between serum cholesterol level and coronary heart disease differed within activity groups. For persons who were more active, serum cholesterol level was associated with a graded increase in risk of coronary heart disease, from 1.3 (95% CI 0.7, 2.3) in those with serum cholesterol level of 4.7-5.1 to 1.7 in those with serum cholesterol level of 6.2 mmol/L or more (95% CI 1.0, 2.7), when compared with those with serum cholesterol level below 4.7. For the least active persons, all levels of cholesterol were associated with a significant inverse relative risk, including cholesterol of 6.2 mmol/L or more (Relative risk = 0.4 (95% CI 0.2, 0.7]. These data suggest that factors such as activity level may modify the serum cholesterol-coronary heart disease association in old age. The serum cholesterol-coronary heart disease association in more active older persons resembles that seen in younger populations, whereas the association in less active persons is that of serum cholesterol level and risk of cancer or death. The modification of the serum cholesterol-coronary heart disease association by activity level may have implications for appropriate clinical management as well as appropriate design of research studies of this association."
-What evidence suggests an increase in GABA-ergic neurotransmission in patients with hepatic encephalopathy due to fulminant hepatic failure?,"Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure BACKGROUND. Increased gamma-aminobutyric acid (GABA) neurotransmission has been implicated in the pathogenesis of hepatic encephalopathy. The mechanism by which GABA-ergic activity is increased in hepatic failure is unclear, but recent studies in animals with encephalopathy due to fulminant hepatic failure suggest that GABA-ergic neurotransmission may be increased by the presence of elevated concentrations of benzodiazepine agonists such as diazepam and N-desmethyldiazepam. METHODS AND RESULTS. Samples of frontal cortex were obtained at autopsy from 11 patients with hepatic encephalopathy who died of acetaminophen-induced fulminant hepatic failure and 8 patients who died of cardiovascular disease or trauma. None of the 19 patients had received benzodiazepines while hospitalized. Chromatographic analyses of extracts of these samples revealed 4 to 19 peaks representing substances that inhibited the binding of a radiolabeled imidazobenzodiazepine ([3H]flumazenil) to its receptors. Several of these peaks had retention times corresponding to those of known 1,4-benzodiazepines. Ultraviolet- and mass-spectroscopic analysis confirmed that two of these peaks represented diazepam and N-desmethyldiazepam. The patients who died of fulminant hepatic failure could be divided into two groups: six who had had significantly elevated brain concentrations (2-fold to 10-fold higher than normal) of substances inhibiting the binding of [3H]flumazenil and five who had normal concentrations. CONCLUSIONS. Brain concentrations of substances inhibiting the binding of [3H]flumazenil to its receptors are increased in some patients with hepatic encephalopathy due to fulminant hepatic failure. The origin of these substances is unknown, but these findings provide a rational basis for trials of benzodiazepine-receptor antagonists in the management of this disorder."
-What method did the researchers use to detect hepatitis B virus DNA in liver tissue samples?,"Detection of hepatitis B virus DNA in paraffin-embedded liver tissues in chronic hepatitis B or non-A, non-B, hepatitis using the polymerase chain reaction. We developed a polymerase chain reaction assay for the direct detection of hepatitis B virus in paraffin-embedded liver tissue and applied this assay to determine whether hepatitis B virus DNA exists in livers with chronic hepatitis non-A, non-B. Fifty five liver biopsy samples were studied: 11 from patients with HBeAg-positive chronic hepatitis (paraffin-embedded) and 44 from patients with chronic hepatitis non-A, non-B (21 paraffin-embedded; 25 fresh frozen). Thirty three (75%) of the non-A, non-B cases were positive for hepatitis C virus antibodies. Approximately 1 to 10 ng of DNA was extracted from the paraffin-embedded tissue and amplified using oligonucleotide (23-mer) primers specific for the S gene (positions 261 to 692). The beta-globin gene was used as an internal control for sensitivity because this is a single copy gene and allows for relative quantification. In each of the chronic hepatitis B livers, the expected 432-base-pair amplification product for hepatitis B virus DNA and beta-globin gene product were both detected. On the other hand, in the 21 paraffin-embedded chronic hepatitis non-A, non-B livers, no hepatitis B virus DNA was detected, although beta-globin gene was observed in all. Furthermore, in all 25 frozen non-A, non-B livers, beta-globin gene was observed, but no hepatitis B virus band was seen. The limit of detection of hepatitis B virus DNA by this method was estimated to be one genomic copy of hepatitis B virus DNA per cell."
-What is the potential advantage of the step-down method of FSH administration for ovulation induction in women with polycystic ovarian syndrome (PCOS)?,Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome. The step-down method can be an alternative method of ovulation induction in women with PCOS. This protocol can induce ovulation with a smaller dose of FSH and with lower incidence of excessive ovarian enlargement in comparison with the traditional fixed-dose administration method.
-What were the key findings of the 12-week trial of fluoxetine in patients with borderline or schizotypal personality disorders?,"Fluoxetine in the treatment of borderline and schizotypal personality disorders. Twenty-two patients meeting the criteria for borderline or schizotypal personality disorder or both participated in a prospective, nonblind 12-week trial of fluoxetine. There were significant reductions in self-injury and in scores on the Hopkins Symptom Checklist regardless of diagnosis. The results suggest that controlled trials of fluoxetine and investigations of the serotonergic system in these disorders would be useful."
-What is the proposed term for the special variant of dermatofibroma described in the case report?,"Atypical polypoid dermatofibroma: report of two cases. Two cases of a hitherto undescribed special variant of dermatofibroma are reported. A man and a woman, aged 57 and 52 years, respectively, had slowly growing cutaneous tumors on the lower extremities. The tumors were exophytic and polypoid, 10 and 6 cm in maximal diameters, respectively; they were covered by rough nonulcerated skin and were joined by a short pedicle to an indurated base. Histologic examination showed some features of an otherwise conventional dermatofibroma, whereas the polypoid component was hypercellular and showed striking atypia and scattered mitotic figures. After 32 and 28 months' follow-up, the lesions did not recur after surgical excision. We suggest the term atypical polypoid dermatofibroma to summarize the special clinicopathologic features of these tumors."
-What was the average hospital stay for patients with pelvic fractures in this study?,"Pelvic fracture from major blunt trauma. Outcome is determined by associated injuries. Pelvic hemorrhage has been implicated as the cause of death in 50% of patients who die following pelvic fractures. To establish correlates of morbidity and mortality from pelvic fractures due to blunt trauma, we reviewed 236 patients treated during 4 years. The average age of the 144 men and 92 women was 31.5 years, the average Injury Severity Score was 21.3, the average blood requirement was 5 units, and the average hospital stay was 16.8 days. One hundred fifty-two patients (64.4%) were injured in motor vehicle accidents, 33 (14%) had motor vehicle-pedestrian accidents, 16 (6.8%) had crush injuries, 12 (5.1%) each had either motorcycle accidents or falls, and 11 (4.6%) had miscellaneous accidents. Eighteen patients (7.6%) died, with seven (38.9%) deaths due to hemorrhage. Only one death was caused by pelvic hemorrhage. Other deaths were due to hemorrhage from other sites (6), head injury (5), sepsis or multiple-organ failure (4), pulmonary injury (1), and pulmonary embolus (1). None of the septic deaths was related to a pelvic hematoma. Multivariate multiple regression analysis showed that the severity of injury was correlated with indices of severity of pelvic fractures such as fracture site (p less than 0.0001), fracture displacement (p less than 0.005), pelvic stability (p less than 0.0001), and vector of injury (p less than 0.01). However death could not be predicted on the basis of these indices of severity (p greater than 0.28). Of the nine patients who underwent pelvic arteriography, three required embolization of actively bleeding pelvic vessels, but seven had intra-abdominal hemorrhage that required laparotomy, and eight developed a coagulopathy. Massive bleeding from pelvic fractures was uncommon, and the major threat of hemorrhage was from nonpelvic sites. Furthermore, although injury severity was correlated with the severity of the pelvic fracture, hospital outcome was determined by associated injuries and not by the pelvic fracture."
-What is the estimated yearly risk of Giardia infection for water systems using polluted waters compared to pristine waters?,"Risk assessment and control of waterborne giardiasis. BACKGROUND: Waterborne giardiasis has been increasing in the United States with 95 outbreaks reported over the last 25 years. The Safe Drinking Water Act has mandated control of this pathogen. METHODS: A risk assessment model was developed to estimate risk of infection after exposure to treated waters containing varying levels of Giardia cysts. The model was defined by a dose-response curve developed from human feeding studies for Giardia and assumed 2L of water consumption per day. Data on concentrations and distribution of the organism in source waters were used to assess exposure after varying reductions achieved through treatment. RESULTS: In surveys reporting prevalence and levels of Giardia cyst contamination, average levels of cysts in surface waters ranged from 0.33 to 104/100L; from pristine watersheds (protected from all human activity) 0.6 to 5/100L. Yearly risks were 4.8 x 10(-3) for systems using polluted waters and 1.3 x 10(-4) for pristine waters with a 10(-3) treatment reduction. CONCLUSION: Public Health officials will need to work with the water industry to ensure a risk of less than 1/10,000 for source waters with 0.7 to 70 cysts per 100 liters through treatment achieving reduction of 10(-3) to 10(-5), respectively, of Giardia cysts."
-What rare medical condition is described in this case report involving the cauda equina?,Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis.
-What unique mitochondrial DNA characteristics were found in the muscle biopsy specimens of the two children with combined Kearns-Sayre and MELAS syndrome features?,"Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. A 9-year-old girl and an 11-year-old boy had ptosis, progressive external ophthalmoplegia, pigmentary retinopathy, and sensorineural hearing loss. The girl had diabetes mellitus and the boy had hypoparathyroidism. Both children also developed recurrent vomiting and cerebral infarcts with lactic acidosis. Muscle biopsy specimens showed ragged-red fibers and Southern analysis demonstrated a distinct heteroplasmic deletion of muscle mitochondrial DNA in each patient but no evidence of the point mutation in the transfer RNALeu(UUR) gene recently identified in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). These 2 children had combined features of Kearns-Sayre syndrome and MELAS, suggesting that mitochondrial DNA deletions occasionally can have pleomorphic clinical expression."
-What were the key psychiatric disorders found to be more prevalent in men with chronic low back pain compared to the control group?,"Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study. This study used structured diagnostic interviews and DSM-III criteria to assess lifetime prevalence and pre-morbid risk of psychiatric disorder in a sample of men with long-standing chronic back pain (CLPB) attending a primary care clinic. A control group of age and demographically matched men without history of back pain was also studied. Compared to controls, men with CLBP had significantly higher lifetime rates of major depression (32% vs. 16%), alcohol use disorder (64.9% vs. 38.8%), and a major anxiety disorder (30.9% vs. 14.3%). Almost all CLBP men ever experiencing a mood disorder reported recurrent, not single, episodes. The 6 month point prevalence of major depression, but not other disorders, was also significantly elevated for men with CLBP. In CLBP, the first episode of major depression generally (58.1%) followed pain onset. While the initial major depressive episode usually commenced within the first 2 years of established pain, late onset mood disorder was also common. By comparison in most cases (81%) onset of alcohol use disorders considerably preceded pain. When an age-matching procedure was used to gauge relative vulnerability to psychiatric illness in patients and controls, CLBP patients had significantly higher pre-pain rates of alcohol use disorder but not depression. After age of pain onset, CLBP subjects had over 9 times the risk of developing major depression, but had similar rates of developing alcoholism. We conclude that (1) alcohol use disorders rather than depression may increase risk of developing CLBP, and (2) risk of new onset and recurrent major depression remains high for men throughout their pain career. This suggests that psychological adaptation to long-standing pain may be less successful than previously thought, especially with regard to recurrent mood disorder."
-What are the two conflicting views regarding the nature of the transmissible agent in spongiform encephalopathies like scrapie?,"A 'unified theory' of prion propagation. There is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein PrPc, devoid of any nucleic acid. On the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the PrPc gene, it has been suggested that a nucleic acid must be a component of the agent. Can the two views be reconciled?."
-How do the regulatory elements within the 475-base-pair fragment of the sevenless gene contribute to its specific expression pattern during Drosophila eye development?,"Analysis of the enhancer element that controls expression of sevenless in the developing Drosophila eye. The sevenless gene encodes a protein-tyrosine kinase receptor expressed in a complex pattern during the development of the Drosophila melanogaster eye. We have previously shown that this pattern is regulated transcriptionally by an enhancer located in the body of the sevenless gene. Here we extend our analysis of the sevenless enhancer, defining a 475-base-pair fragment that contains elements necessary for the correct qualitative and quantitative expression of the sevenless gene. Within this fragment are sequence elements conserved in the sevenless gene of a distantly related Drosophila species and protected from DNase I digestion by nuclear extracts isolated from adult heads and imaginal discs. Partial deletions of the 475-base-pair fragment result in preferential loss of expression in different subsets of cells. These results suggest that the normal pattern of expression is generated by the combined action of separate cell-specific regulatory elements."
-What were the two major patterns of severe Helicobacter pylori infection identified in the CT scans?,"Helicobacter pylori gastritis mimicking gastric carcinoma at CT evaluation. The abdominal computed tomographic (CT) scans from 61 patients with biopsy-proved Helicobacter (formerly Campylobacter) pylori gastritis were retrospectively reviewed. The CT scans were interpreted on the basis of the original report of the findings at CT examination and without knowledge of the results of biopsy. Of 19 patients (31%) with gastric abnormalities at CT, 14 (74%) had inflammatory changes initially reported as suspicious for gastric malignancy; malignancy was entertained as the primary diagnosis in four of those patients. In five of the 19 abnormal cases (26%), the diagnosis with CT was gastritis. The two major patterns of severe H pylori infection identified were (a) circumferential antral wall thickening and (b) thickening of the posterior gastric wall along the greater curvature, with or without evidence of ulceration. Thickening averaged 1.5-2.0 cm in cases suspicious for malignancy. The majority of abnormalities involved the gastric antrum (68%). No cases demonstrated significant adenopathy, obliteration of fat planes, or invasion of adjacent organs."
-How do micrometastases of gastric cancer impact patient survival rates after node dissection?,"Non-ominous micrometastases of gastric cancer. So-called R2 or wider meticulous node dissection was performed in 1368 patients with resected gastric cancer invading beyond the submucosa but without distant metastases. Survival rates were similar in subsets of patients with or without microscopic node metastases and macroscopically normal lymph nodes. The extent of node metastases has previously been shown to be one of the two most important prognostic factors in gastric cancer without distant metastases, and its lack of impact in these patient groups was not explained by the imbalance of other prognostic factors. The findings indicate that micrometastases of gastric cancer are curable by a wide node dissection made in the absence of palpable abnormality. They also offer the possibility that an extensive node dissection may yield good stage-specific survival rates, in part because of upstaging of patients. The findings should influence the recording of node metastases for evaluation of stage-specific treatment results and for research purposes."
-What was the main finding regarding cardiovascular mortality in diabetic patients treated with diuretics for hypertension?,"Excess mortality associated with diuretic therapy in diabetes mellitus OBJECTIVE. To determine whether the high mortality among diabetic patients receiving treatment for hypertension can be explained by associated risk factors or must be attributed to a deleterious effect of antihypertensive treatment. DESIGN. Cohort analytic study with a median follow-up of 4.5 years. SETTING. Outpatients with diabetes and severe retinopathy who were enrolled in a multicenter, randomized clinical trial of laser treatment to prevent blindness had ophthalmologic examinations every 4 months and annual medical examinations that included measurement of blood pressure and recording of anti-hypertensive treatment. Only 5.5% of the patients were unavailable for follow-up. When a patient died, the circumstances surrounding the death were reviewed and classified by a mortality review committee. PARTICIPANTS.--There were 759 participants in the study; they were white, were aged 35 to 69 years, and had normal serum creatinine levels at the baseline examination. MEASUREMENTS AND MAIN RESULTS.--Patients were classified into five groups according to information recorded at the baseline and first annual follow-up examinations: normotensive (diastolic blood pressure less than 90 mm Hg), untreated hypertensive, hypertensive treated by diuretics alone, hypertensive treated by other agents alone, and hypertensive treated by both agents. Cardiovascular mortality was higher in patients treated for hypertension than in patients with untreated hypertension. The excess was primarily found in patients treated with diuretics alone, although that group had the lowest blood pressure with treatment. After adjusting for differences in risk factors, cardiovascular mortality was 3.8 times higher in patients treated with diuretics alone than in patients with untreated hypertension (P less than .001). CONCLUSIONS.--In individuals with diabetes, intervention with diuretics to reduce hypertension is associated with excess mortality. Until there is a clinical trial showing a beneficial effect of diuretic treatment in diabetic patients, there is urgent need to reconsider its continued usage in this population."
-What are the key differences between radiation and pagetic osteogenic sarcomas compared to classical osteogenic sarcoma?,"Radiation and pagetic osteogenic sarcomas. Radiation and pagetic osteogenic sarcomas should be distinguished from classical osteogenic sarcoma. Both occur in older patients with significantly greater comorbidity. Roentgenographically, radiation osteogenic sarcoma is typically sclerotic, whereas pagetic osteogenic sarcoma is lytic and associated with pathologic fracture. Radical resections give the best result, local control, and survival. Chemotherapy has not proven effective to date. Improvements in tumor imaging and more intensive chemotherapy regimens may permit limb-sparing surgery. Overall results remain poor, with approximately 15% five-year survival in each condition."
-What was the response rate and overall survival of patients with refractory lymphomas and cutaneous T-cell lymphoma treated with pentostatin in this Phase II trial?,"Phase II trial of pentostatin in refractory lymphomas and cutaneous T-cell disease. Thirty-seven patients with refractory lymphoma or cutaneous T-cell lymphoma were treated with 2'-deoxycoformycin (pentostatin; dCF), 5 mg/m2 intravenous (IV) bolus for 3 consecutive days of every 3-week cycle in this Eastern Cooperative Oncology Group (ECOG) trial. Included were 25 with the diagnosis of non-Hodgkin's lymphoma, three with Hodgkin's disease, eight with cutaneous T-cell lymphoma (CTCL), and one with unknown subtype, of whom 31 were considered eligible. The majority had failed at least two, but no more, conventional chemotherapy regimens. Ten (32%) of the eligible patients had a partial response (PR), including patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed (NM), diffuse poorly differentiated lymphocytic (DPDL), or diffuse histiocytic (DH), lymphoma mixed-cellularity (MC), Hodgkin's disease, and unknown subtype, and in four patients with CTCL. The overall median time to treatment failure (TTF) was only 1.3 months, but the range extended to 57.3 months. The overall response duration was 16.0 months, and the range extended to 53.4 months. Overall median survival was 2.7 months, with the range extending to 63.2 months. The majority of patients had no toxicity, but there were some instances of severe or life-threatening events. Four fatal toxicities occurred, in two patients with underlying pulmonary conditions and two with prior cardiac histories. From this study, we conclude that dCF is active in refractory lymphomas and CTCLs, should be avoided in patients with a history of serious pulmonary or cardiac diseases, and warrants consideration for incorporation of a low-dosage schedule into conventional combination chemotherapy regimens, including its use with biologic response modifiers."
-What were the main causes of bilateral blindness in the Central African Republic according to the study conducted between 1985 and 1989?,"Causes of blindness and visual handicap in the Central African Republic. The causes of bilateral blindness (best visual acuity less than 3/60) in 1371 people in the Central African Republic seen between 1985 and 1989 who attended eye clinics in 10 out of the 16 prefectures across the country are given. The main causes of bilateral blindness were cataract (51%), glaucoma (12.7%), and onchocerciasis (8.1%). In 710 patients with unilateral blindness the main causes were cataract (38%), glaucoma (10%), iritis (7.5%), and trauma (6.3%). Bilateral blindness in children was rarely seen. The causes of visual impairment (vision between 6/18 and 3/60) in 424 patients were cataract, including aphakia (38%), maculopathy (14%), and onchocerciasis (7%)."
-How does sucralfate enhance gastroduodenal protection and mucosal defense mechanisms?,"Mechanisms of gastroduodenal protection by sucralfate. Over the past 5-10 years, a number of studies have shown that topical sucralfate enhances a number of gastric and duodenal mechanisms, e.g., the ""mucus-bicarbonate barrier,"" mucosal hydrophobicity, mucosal blood flow, cell viability, and local production of prostaglandins, as well as endogenous mediators of tissue injury and repair. It seems likely that the complex actions of sucralfate are in part related to direct interaction between the drug or its components (aluminum, sucrose, and sulfate) and gastric mucosal tissues, and in part related to effects of the drug on the various mucosal mediators of tissue injury and repair. Local actions may play a role in accelerating healing of ulcer-damaged mucosa, but this does not explain the protective actions of sucralfate on normal mucosa. Thus sucralfate appears to enhance the protective function of the ""mucus-bicarbonate"" barrier by actions on both components. This may depend in part on an interaction with the unstirred layer overlying gastric epithelium. Sucralfate has also been shown to increase the hydrophobicity of mucus gel. There is little doubt that sucralfate increases local production and release of protective prostaglandins (PGs), but the precise role played by these agents in mediating mucosal protection and in chronic ulcer healing remains uncertain. Currently, the mechanism of action of sucralfate on vascular integrity remains unknown and the role of PGs in this protective function is unclear. There is little evidence that epidermal growth factor plays any role in mediating mucosal protection by sucralfate, but it may be important in its ulcer-healing action. Sucralfate has been shown to be truly ""cytoprotective"" in that it protects isolated epithelial cells from damage by noxious agents. In animals treated with sucralfate, the surface epithelial cells were disrupted, but necrotic lesions in the deep proliferative zone were virtually absent. It seems likely that investigations of the actions of sucralfate and its components will move ever closer to defining the target cells, the intracellular events, and the mediators that bring about its protective and ulcer-healing activity."
-What is the correlation between histological grade and bromodeoxyuridine (BUdR) labeling index in astrocytomas?,"Histological grading and bromodeoxyuridine labeling index of astrocytomas. Comparative study in a series of 60 cases. The histological grade and the bromodeoxyuridine (BUdR) labeling index of 60 astrocytomas of ""ordinary"" cell types (fibrillary, protoplasmic, gemistocytic, and anaplastic astrocytomas and glioblastomas) were compared to determine whether the grading system reflects the proliferative potential of the tumors. The tumor grade was based on the presence or absence of four criteria (nuclear abnormalities, mitosis, necrosis, and vascular endothelial proliferation): Grade 1, no criterion, Grade 2, one criterion, Grade 3, two criteria; and Grade 4, three or four criteria. The BUdR labeling index, or percentage of S-phase cells, was calculated in paraffin-embedded tumor sections after in situ labeling by intraoperative intravenous infusion of BUdR, 200 mg/sq m. Exponential regression analyses showed a positive correlation between the histological grade and labeling index (r = 0.88, p less than 0.001) that was stronger than the correlations between log labeling index and age (r = 0.55, p less than 0.001) and between grade and age (r = 0.55, p less than 0.001). These results indicate that the histological grading system reflects the proliferative potential of ""ordinary"" astrocytomas."
-What are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease?,"Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the ""symptom index."" Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain."
-What percentage of infectious agents were identified in the study of acute infectious erythemas in children?,"Acute infectious erythemas in children: a clinico-microbiological study. One-hundred children with an acute illness comprising fever and widespread erythematous rash were prospectively studied to determine whether clinical presentations are helpful in defining the causative agent and to identify the most appropriate microbiological specimens. An infectious agent was identified in 65 children; 72% were viruses, 20% were bacteria, 5% were Mycoplasma pneumoniae and in 3% both viruses and bacteria were detected. The most common infectious agents were picornaviruses, an atypical presentation of measles and Group A beta-haemolytic Streptococcus. Different patterns of rash occurred with each of these infections. The clinical presentation of a child with an acute febrile illness and rash was unhelpful in defining the causative agent. Routine management should include a throat swab for bacterial investigation and in selected cases a blood sample for IgM viral titres."
-What was the relationship between serum cholesterol concentration and mortality from coronary heart disease in the Shanghai population studied?,"Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. OBJECTIVE--To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE--Death from coronary heart disease and other causes. RESULTS--The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION--Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a ""low"" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death."
-What was the primary aim of the study on renovascular hypertension?,"The value of tests predicting renovascular hypertension in patients with renal artery stenosis treated by angioplasty. The aim of this study was to evaluate tests predicting renovascular hypertension. This was done by relating the results of renal vein renin tests, the captopril test, and renal scintigraphic tests to the blood pressure outcome 12 months after relief of renal artery stenosis by percutaneous transluminal renal angioplasty in 31 patients. Cure was seen in eight (26%). Improved blood pressure was obtained in 12 patients (39%), and in 11 patients (35%), the result for blood pressure was a failure. The accuracies of the two mathematical models used to analyze the renal vein renin assays were 44% and 60%. The captopril test showed a sensitivity of 36% and an accuracy of 43%. Renal captopril technetium Tc 99m-labeled pentetic acid scintigraphy gave a sensitivity of 60%. Stepwise logistic regression analysis of clinical variables in relation to blood pressure response revealed age as the only factor significantly related to blood pressure outcome. We conclude that the tests used are unfit for helping select patients for percutaneous transluminal renal angioplasty and that age may have an important influence on outcome."
-What are the two surgical approaches used for treating congenital atresia of the external auditory canal in this study?,"Surgical approaches to congenital atresia of the external auditory canal. During the past 4 years, 22 patients with congenital atresia of the external auditory canal underwent 24 initial operations by either an anterior or transmastoid approach. No attempt at randomization was made, but the two groups were similar in number and pathology (in 14 cases approach was anterior and in 10 cases approach was transmastoid). Followup ranged from 6 months to 4 years. Hearing results were similar in the two groups (71% with air-bone gap less than 30 dB). There were no instances of facial nerve injury or sensorineural hearing loss. Facial nerve monitoring was used. Complications of stenosis and drainage were more common with the transmastoid approach. In both groups, hearing results were accomplished with the patients' intact ossicles or prosthetic reconstructions. Meticulous soft-tissue technique, with split-thickness grafts covering all exposed bone, is the key to preventing stenosis. For the three cases of patients with thick, acellular atresia plates, a different approach was developed. Maintaining proper orientation during the medial dissection is more difficult in these cases. By opening the antrum primarily and identifying the lateral canal, ossicles, and facial nerve, an ear canal can then be created anteriorly with these landmarks in view. An intact canal wall-like procedure is carried out. Although hearing results are similar, the anterior approach, because of fewer postoperative complications, is now our procedure of choice. Proper orientation and soft-tissue technique are the keys to successful correction of the congenitally atretic ear canal."
-How does brief hypoxia affect the afterdischarge mechanism in conscious humans?,"Hypoxic exposure and activation of the afterdischarge mechanism in conscious humans. After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the ""afterdischarge."" Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing."
-What potential surgical complication occurred during the left radical nephrectomy for renal cell carcinoma?,"Celiac axis and superior mesenteric artery injury associated with left radical nephrectomy for locally advanced renal cell carcinoma. The superior mesenteric artery and celiac axis were inadvertently ligated during left radical nephrectomy for a large upper pole renal carcinoma with massive perihilar and periaortic adenopathy. Computer-generated 3-dimensional illustrations created from the computerized tomography scan demonstrated the close proximity between these visceral branches and the adenopathy mass complex, and showed how this bulky disease may interfere with surgical anatomy. When left radical nephrectomy is performed for locally advanced and/or bulky node-positive renal neoplasms, surgeons must be cognizant of the location of the major visceral arterial branches and possible anatomical distortions."
-Can moderately mentally retarded adults improve their cardiovascular fitness through a minimally supervised exercise program?,"Effects of a minimally supervised exercise program for mentally retarded adults. Previous exercise studies that attempted to improve the cardiovascular fitness (CVF) of mentally retarded (MR) adults were flawed with methodological shortcomings that prevented conclusive results. At issue in these training studies were fitness test validity and reliability, exactness of duration and intensity of training, and an inordinate amount of supervision. Therefore, we sought to determine whether moderately MR adults (seven males, five females; IQ = 61 +/- 3, age = 25 +/- 3 yr) could improve their CVF through a minimally supervised 16-wk training program. Each subject repeated exercise tests twice on two different modes of exercise, the treadmill (TM) and Schwinn Air-Dyne ergometer (SAE), before training to ensure validity and reliability of initial CVF levels. Intensity and frequency of exercise were closely monitored. An observer was present during the training bouts, but, following initial instructions, no additional encouragement or instructions were given. Although the training program significantly increased peak VO2 (29.2 +/- 8 to 33.5 +/- 9 ml.kg-1.min-1) and peak ventilation (73 +/- 26 to 81 +/- 231.min-1) when assessed on the TM, significant changes in these same parameters were not seen when assessed on the SAE. The importance of these results was discussed."
-What was the overall 30-day postoperative cardiac mortality rate for patients aged 80 years and older undergoing cardiac surgery during the study period?,"Cardiac surgery in the octogenarian: perioperative outcome and clinical follow-up The perioperative and follow-up results of cardiac operations employing extracorporeal circulation and cold cardioplegic arrest were examined in 191 consecutive patients greater than or equal to 80 years of age having surgery over a 5 year period (1982 to 1986). Most patients had severe preoperative symptoms with functional class III (39.8%) or IV (57.1%) limitation. The overall 30 day postoperative cardiac mortality rate was 15.7%. The total in-hospital mortality rate was 18.8%; the mean postoperative hospital stay was 16.4 +/- 13.3 days. The perioperative mortality rate for elective operations was as follows: coronary artery bypass (5.6%), aortic valve replacement (9.6%), aortic valve replacement with coronary bypass (17.9%) and mitral valve surgery with or without coronary bypass (21.4%). Urgent operations were performed in 39 patients (20.4%) with a total perioperative mortality rate of 35.9%; urgent coronary artery bypass was performed in 26 patients (67%) with an in-hospital mortality rate of 23.1%. Clinical evidence of left ventricular failure, functional class IV symptoms, left ventricular ejection fraction less than 50%, mitral valve repair or replacement for severe mitral regurgitation and urgent operation were associated with an increased perioperative mortality rate. Follow-up study in all 155 patients surviving postoperative hospitalization at 22.6 +/- 14.8 months showed significant improvement in symptom status in all surgical subgroups. There were 18 follow-up deaths (11.6%); 10 were noncardiac. The actuarial survival rate of the entire study group was significantly better than that in age- and gender-matched control subjects (p = 0.037)."
-What did the study reveal about the relationship between ethnic identity and pain perception?,"Interethnic differences in pain perception. While several investigators have reported relationships between ethnic background and expression of pain, such relationships are in fact highly problematical. Few studies of pain and ethnicity have used quantitative measures of pain combined with multivariate methods of data analysis. Most have focussed on populations which, unlike many in the United States today, are characterized by highly distinct ethnic groups. The study reported here interviewed 536 persons recently treated for forms of cancer known to cause significant pain. Pain was assessed using standard, well validated instruments, including Graphic Rating Scales anchored in several alternative time-frames and the McGill Pain Questionnaire. The study took place in an area with a low proportion of recent immigrants and only small concentrations of distinct ethnic minorities. No statistically significant relationships were observed between ethnic identity and measures of pain sensation. However, pain described in affective terms according to the McGill Pain Questionnaire did vary among ethnicities. This observation suggests that cultures associated with specific ethnic identities still condition individual expression of pain despite the high degree of assimilation that has occurred among ethnic groups in the United States."
-"What is the role of platelet activating factor (PAF) in shock, sepsis, and multiple organ failure?","The role of platelet activating factor and its antagonists in shock, sepsis and multiple organ failure. PAF has been implicated as a mediator of shock, sepsis and MOF. The results of experimental data demonstrate that PAF induces changes characteristic of endotoxemia and sepsis, including systemic hypotension and diffuse microvascular leakage. These effects are prevented by PAF antagonists. PAF induces many of the characteristic changes of MOF, including functional impairment in the lung, kidney, gastrointestinal tract and heart. PAF antagonists will inhibit these adverse effects. PAF antagonists are now being manufactured by a number of pharmaceutical companies studying the beneficial effects of PAF antagonists in human disease. Data from these studies promise valuable information with significant clinical relevance to the practicing surgeon."
-What were the effects of tocopherol and tocotrienol on rat mammary tumors induced by DMBA and NMU?,"A comparison of tocopherol and tocotrienol for the chemoprevention of chemically induced rat mammary tumors. Two forms of vitamin E, tocopherol and tocotrienol, were tested for chemopreventive activity in two chemically induced rat mammary-tumor models. When mammary tumors were induced by 7,12-dimethylbenz(a)anthracene (DMBA, 50 mg/kg), only the tocotrienol group had a statistically significant increase in tumor latency. There was no effect of either compound on tumor multiplicity. When tumors were induced by N-nitrosomethylurea (NMU, 30 mg/kg), neither analogue of vitamin E modified latency, whereas tocotrienol increased tumor multiplicity. In summary, neither vitamin analog had a major impact on mammary-tumor development after tumor induction with either DMBA or NMU."
-How do calcium-channel blockers like verapamil and diltiazem affect ventricular function differently in control hearts versus failing hearts?,"Increased negative inotropic effect of calcium-channel blockers in hypertrophied and failing rabbit heart. The effects on ventricular function of calcium channel blockers and isoproterenol were studied in isovolumically beating perfused control rabbit hearts and in hearts subjected to a double pressure plus volume overload studied at the early phase of heart failure. In control hearts, isoproterenol produced an increase of systolic ventricular function and relaxation that was maximal at 10(-7) M. In failing hearts, inotropic state increase in response to isoproterenol was significantly smaller (P less than .01) with no observed lusitropic effect. In control hearts, verapamil and diltiazem produced dose-dependent decreases of ventricular function which were larger with verapamil than with diltiazem (median drug concentration50 of developed pressure was, respectively, 1163 +/- 131 nM and 4524 +/- 451 nM, P less than .001). In failing hearts, contractility decrease was larger than in control hearts (median drug concentration50 of developed pressure was 604 +/- 69 nM and 2691 +/- 580 nM with verapamil and diltiazem, respectively). In contrast, Ro 40-5967, a new calcium-channel blocker, did not produce reductions of inotropic state with concentrations up to 10(-5) M. All three calcium-channel blockers produced a 2-fold increase of coronary flow at 10(-6) M. We conclude that the deleterious effect of verapamil and diltiazem in heart failure is due, at least in part, to a direct depressant effect of these drugs on contractility, which is larger than in control hearts. Additionally, the in vivo sympathetic compensation is probably reduced, as indicated by the decreased ventricular responsiveness to isoproterenol."
-What were the actuarial survival rates for children who underwent heart transplantation according to the international survey?,"Heart transplantation in children: an international survey. A survey of cardiac transplantation in children provided data from 381 transplantations in 362 patients from 32 centers in the United States and ten international centers. The number of transplantations continues to increase, in part because of transplantations in infants with hypoplastic left heart syndrome and patients with congenital defects. The immunosuppression regimens were more uniform than in the 1985 survey, and triple therapy was most common. Actuarial survival rates were 85% at 1 month, 72% at 1 year, 64% at 3 years, and 60% at 5 years. However, these improved rates are still not equal to the survival of the overall cardiac transplant population, in part because of lower survival rates in neonates. Ventricular dysfunction and rejection, rather than infection, were the leading causes of death. Rejection and infection were the most frequent complications. Also common were hypertension (39%) and seizures (25%), whereas coronary artery disease (8%) was unusual. Functional results were excellent in 85%, and only 7% were disabled. Questions concerning growth rates and many other aspects cannot yet be answered. However, it is apparent that cardiac transplantation in the pediatric population is a very worthwhile endeavor."
-What is sclerotherapy and how is it used in the treatment of large varicose veins?,"Practical phlebology. Sclerotherapy of large veins. A practical, step-by-step guide for the sclerotherapy of large varicose veins is offered. First, an orientation regarding the place of sclerotherapy and surgery in the total treatment of varicose veins is given, with a practical clinical classification of varicose veins. This is followed by a detailed discussion of patient education before sclerotherapy, material to be used with recommended concentrations, injection technique, compression after sclerotherapy, instructions to the patient after injection, and procedures at subsequent visits."
-What did the nuclear magnetic resonance spectroscopy reveal about brain pH in patients after cardiac resuscitation?,"Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation. We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining."
-What is the significance of this case report regarding intraocular hemangiopericytoma?,"Supraciliary hemangiopericytoma. A 10-year-old black girl complaining of pain and decreased vision in the left eye was found to have a smoothly elevated ciliochoroidal mass involving the superonasal quadrant of the left eye. The mass appeared circumscribed and uniformly dense by computed tomography. The tumor was hyperintense to vitreous and cerebral white matter on T1-weighted magnetic resonance imaging but was hypointense to vitreous and hyperintense to white matter on T2-weighted magnetic resonance imaging. Results of gross examination of the enucleated eye showed a sharply circumscribed, tan, intraocular mass arising equatorially. Results of histopathologic examination showed a well-vascularized spindle cell proliferation with a sinusoidal pattern characteristic of hemangiopericytoma. This is the third reported case of intraocular hemangiopericytoma and the first in a pediatric patient."
-What is the proposed modification to the definition of early gastric cancer according to the study?,"Problems in the definition and treatment of early gastric cancer. Radical operation with extensive dissection of lymph nodes (R1, 48 patients; R2, 196 patients; R3, one patient) was performed in 245 out of 247 patients with early gastric cancer. The 5-year survival rate was only 73.2 per cent in the 34 patients with lymph node metastases (31.8 per cent). Analysis of factors influencing recurrence revealed that not only lymph node metastases but also the depth of cancer invasion could affect prognosis in early gastric cancer. This study suggests that radical operation with complete dissection of the first and second group of lymph nodes (R2 resection) is a safe and appropriate treatment even for early gastric cancer. We propose that the definition of early gastric cancer be modified to 'carcinoma with invasion confined to the mucosa or submucosa and without evidence of lymph node metastases'."
-What is the purpose of using the Cavitron ultrasonic surgical aspirator in resecting residual mediastinal germ cell masses?,"Resection of residual mediastinal germ cell masses with the Cavitron ultrasonic surgical aspirator. Residual mediastinal masses after chemotherapy for germ cell tumors should be resected. Complete excision of bulky residual masses may sometimes be difficult because of problems with exposure in the region of the great vessels and important nerves. Two cases are presented in which the Cavitron ultrasonic surgical aspirator (Valleylab Inc., Surgical Systems Division, Stamford, Conn.) facilitated excision of large masses after intensive chemotherapy. We found that the collapsed pseudocapsule remaining after aspiration of tumor mass allowed early improved exposure and safer dissection from neighboring vessels and neural structures. Complete excisions were accomplished and no viable tumor was found, so that the patients were spared the immediate need for further therapy. Both had uneventful recoveries."
-What relationship did the study find between platelet membrane fluidity and stroke risk factors in Alzheimer's disease patients?,"Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease. We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease."
-What were the key findings of the study on total knee arthroplasty using the posterior stabilized condylar prosthesis?,"Results of total knee arthroplasty using the posterior stabilized condylar prosthesis. A report of 137 consecutive cases. One hundred thirty-seven consecutive posterior stabilized total knee arthroplasties (TKAs) were reviewed. Average age of the patient was 61.1 years and length of postoperative follow-up period was 29.2 months. Patients were evaluated using the Hospital for Special Surgery (HSS) knee rating scores. Average preoperative scores improved from 52 to 92, postoperatively. Ninety-eight percent of patients had no pain or mild occasional pain postoperatively compared with 99% of patients experiencing severe to disabling pain preoperatively. Complications included one myocardial infarction, two deep venous thrombosis, one urinary tract infection, one patellar dislocation, and four wound problems. There were two incidences of seroma, one hematoma, and one deep infection requiring revision after joint debridement and systemic antibiotics. Also noted was one incidence of ligamentous laxity and one patella fracture."
-How does precordial ST segment depression impact the prognosis of patients with inferior myocardial infarction?,"Precordial ST segment depression predicts a worse prognosis in inferior infarction despite reperfusion therapy. The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. The impact of associated precordial ST segment depression in inferior myocardial infarction on angiographic and clinical outcomes after thrombolytic therapy and selective coronary angioplasty was studied in 583 patients with acute myocardial infarction. Anterior infarction (Group I), inferior infarction with precordial ST segment depression (Group II) and inferior infarction without precordial ST segment depression (Group III) were present in 289, 135 and 159 patients, respectively. Precordial ST segment depression was more frequent in circumflex than right coronary infarct-related arteries (44 [71%] of 62 versus 91 [40%] of 230; p = 0.000). Although acute patency rates were not statistically different, there was a trend toward different patency rates at day 7 (Group I 88%, Group II 84%, Group III 80%; p = 0.089) partly because of insignificantly higher reocclusion rates in inferior infarction without precordial ST segment depression (Group I 11%, Group II 10%, Group III 18%, p = 0.104). Infarct zone regional wall motion (standard deviations/chord) in inferior infarction was lower with precordial ST segment depression, both acutely (Group I -2.8 +/- 0.9, Group II -2.5 +/- 1.2, Group III 2.0 +/- 1.1; p = 0.000) and at day 7 (Group I -2.2 +/- 1.1, Group II -2.3 +/- 1.1, Group III -1.9 +/- 1.3; p = 0.011). Precordial ST segment depression was associated with a lower ejection fraction in inferior infarction both acutely (Group I 47 +/- 11%, Group II 53 +/- 11%, Group III 58 +/- 9%; p = 0.000) and at day 7 (Group I 49 +/- 12%, Group II 53 +/- 10%, Group III 58 +/- 8%; p = 0.000). Complication rates tended to be higher in inferior infarction when precordial ST segment depression was present. Mortality rates for Groups I, II and III were 8%, 6% and 5%, respectively. These results suggest that precordial ST segment depression in inferior infarction predicts a worse ventriculographic and clinical outcome despite reperfusion therapy."
-What was the primary finding of the study regarding the combination of verapamil and recombinant tissue plasminogen activator in preventing postoperative adhesions?,"Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model. Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route."
-What are the key muscle-related complications observed in patients with sickle cell anemia?,"Myonecrosis and myofibrosis as complications of sickle cell anemia. Painful crises in sickle cell anemia are associated with infarction and subsequent fibrosis of many different organs. Myonecrosis secondary to muscle infarction during a crisis and subsequent fibrosis are often not recognized as complications of sickle cell anemia. We describe four patients, all of whom had recurrent episodes of symmetric proximal muscle pain and swelling as prominent features of their crises. Muscle biopsies showed acute myonecrosis with a minimal inflammatory reaction as well as myofibrosis with abundant collagen deposition. Chronic sequelae consisted of muscle induration, atrophy, and contractures."
-How does chronic ethanol feeding affect the composition of high-density lipoprotein (HDL) subfractions in rats?,"Effect of chronic ethanol feeding on high density lipoprotein subfractions in rats. We have reported previously that chronic alcohol consumption in the rat produced elevated total serum high density lipoprotein (HDL) fraction, but HDL particles of the alcohol-fed rat were deficient in apolipoprotein (apo) E. In that report, serum HDL particles were prepared by successive ultracentrifugation method and there were concerns that the apo E deficiency in HDL particles was artificially produced by centrifugal forces. In the present report, apo Al affinity column chromatography was used instead of successive ultracentrifugation and it likewise yielded HDL particles from alcohol-fed rats that exhibited lower apo E: apo Al ratio than HDL from control rats (0.185 +/- 0.016 vs. 0.303 +/- 0.017, respectively). When the total serum lipoprotein fraction (d less than 1.21) was analyzed by high performance liquid chromatography (HPLC), both HDL and VLDL peaks were higher in alcohol-fed rats than controls. The size of apo E deficient HDL particles from alcohol-fed rats determined by HPLC did not differ from that of normal HDL particles. When HDL (1.063 less than d less than 1.21) was subfractionated into HDL2 (1.063 less than d less than 1.125) and HDL3 (1.125 less than d less than 1.21), only HDL2 of alcohol-fed rats showed lowered apo E: apo Al ratio when compared with same HDL subfraction of control animals. Therefore, the molecular structure of only HDL2 (but not HDL3) was affected by alcohol-feeding. Another HDL subpopulation which is enriched with apo E, i.e. HDL1 (1.054 less than d less than 1.063), was also prepared."
-How does echocardiography help in managing patients with chronic ischemic heart disease?,"Use of echocardiography for patient management in chronic ischemic heart disease. Myocardial ischemia causes regional myocardial contractile and relaxation abnormalities. The extent of ischemia is determined by the distribution and severity of coronary artery stenoses. In coronary heart disease, two powerful predictors of prognosis are the coronary anatomy and ventricular function. Management in coronary heart disease is directed by accurate diagnosis and individualized objectives. Echocardiography at rest and exercise, combined with Doppler and color flow imaging, are properly applied to the differential diagnosis of common clinical syndromes in ischemic heart disease, the identification of the proximal coronary arteries, and the effects of ischemia and prior infarction. Subsequent use of coronary arteriography partially depends on the philosophy regarding the applicability of coronary surgery or angioplasty in an individual patient. Prediction of multivessel, left main, or proximal left anterior descending coronary artery disease by extensive wall motion abnormalities or an abnormal left ventricular ejection fraction may direct the clinician to coronary arteriography to select among coronary surgery, angioplasty, or medical management."
-What were the key findings of the study comparing MOPP and MOPP/CABS treatment for advanced-stage Hodgkin's disease?,"Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP. One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival."
-What is the significance of HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension (IPH)?,"HLA-DR expression on the microvasculature of portal tracts in idiopathic portal hypertension. Immunohistochemical characteristics and relation to portal phlebosclerosis. We recently reported that HLA-DR antigen was expressed on the microvasculature of portal tracts more frequently in idiopathic portal hypertension (IPH) than in normal livers or in other hepatic diseases, and that this HLA-DR expression may be involved in the development of the portal venopathy characteristic of IPH. The present study was performed to evaluate the relationship between the HLA-DR expression and portal tract lesions, as well as to investigate the immunohistochemical characteristics of the HLA-DR-positive microvasculature using liver wedge biopsy specimens obtained from 32 patients with IPH. According to the degree of phlebosclerosis of the portal veins, the portal tracts were divided into three groups: mild, moderate, and severe. The microvasculature in portal tracts was positive for HLA-DR in 21 (66%) of the 32 specimens and in 133 (44%) of 302 portal tracts. In the 21 specimens, there was no significant difference in the prevalence of HLA-DR-positive microvasculature among the three groups: it occurred in 57 (66%) of 86 portal tracts in the mild group, 53 (61%) of 87 portal tracts in the moderate group, and 23 (49%) of 47 portal tracts in the severe group. The HLA-DR-positive microvasculature was positive for type IV collagen and receptors of Ulex europaeus lectin I, suggesting that HLA-DR-positive microvessels are blood vessels. These findings suggest that HLA-DR antigen is already expressed on portal microvessels in the incipient stage of IPH, and that HLA-DR expression persists during the progression of portal phlebosclerosis. The HLA-DR expression may be an initiating factor leading to immunologic assault on portal microvessels in IPH."
-What methods were used to prevent thromboembolic complications in urological surgery in this study?,"A prospective comparison of thromboembolic stockings, external sequential pneumatic compression stockings and heparin sodium/dihydroergotamine mesylate for the prevention of thromboembolic complications in urological surgery. Deep venous thrombosis and pulmonary emboli are reported to occur in up to 66% of the patients undergoing a major urological operation. Thromboembolic stockings, external sequential pneumatic compression stockings and anticoagulant agents, such as heparin sodium plus dihydroergotamine mesylate, have been suggested to decrease the risk of deep venous thrombosis and pulmonary emboli. A total of 74 evaluable patients undergoing a major urological operation was randomized to receive either thromboembolic stockings, external sequential pneumatic compression stockings, or heparin plus dihydroergotamine as prophylaxis against deep venous thrombosis and pulmonary emboli. 111Indium-labeled platelet scans, performed preoperatively and on days 1, 3 and 6 postoperatively, were used to diagnose deep venous thrombosis and pulmonary emboli. Mean patient age was 63 years and all but 1 operation was performed for neoplastic disease. Deep venous thrombosis was detected in 5 of 25 patients (20%) with thromboembolic stockings, 3 of 24 (12.5%) with external sequential pneumatic compression stockings and 2 of 25 (8%) with heparin plus dihydroergotamine. There was no difference in blood loss or complications among the groups. Although statistical significance among the treatment groups was not reached in this study, the trend to a decrease in deep venous thrombosis and pulmonary emboli with external sequential pneumatic compression stockings and heparin plus dihydroergotamine, and an absence of an increase in morbidity in these groups supports the use of these modalities to decrease the morbidity and mortality of deep venous thrombosis and pulmonary emboli."
-What distinguishes patients with obstructive sleep apnea (OSA) from heavy snorers in terms of upper airway morphology?,"Why don't all heavy snorers have obstructive sleep apnea? Patients with obstructive sleep apnea (OSA) and heavy snorers without apnea both show intrathoracic suction pressures during sleep that exceed their static upper airway closing pressures. Complete airway occlusion, however, occurs only in the former patient group. We hypothesized that the kinetic properties of the airflow would be different in these two types of patients because of differences in upper airway morphology. The pharyngeal computed tomography (CT) was used to measure the cross-sectional areas of the upper airways in 15 patients with OSA, 25 nonapneic heavy snorers, and 14 control subjects while they were awake. Nocturnal breathing was monitored with the static charge-sensitive bed (SCSB). The patients with OSA had a narrower airspace at the velopharyngeal (VP) level than the controls (p less than 0.01); the nonapneic snorers did not differ from the other groups. At the tongue base (TB) and the hyoid bone (HB) levels there was no difference between the OSA and the control groups, but the nonapneic snorers had narrower airways at both of these levels compared with control subjects (p less than 0.01) and at the hyoid bone level compared with the OSA group (p less than 0.05). The VP/HB ratio was the parameter that best distinguished the patients with OSA from the nonapneic snorers (lower in the OSA group, p less than 0.001). We suggest that airway collapse during sleep is favored by a narrow velopharynx associated with large hypopharynx. Some heavy snorers may not have an oropharyngeal collapse because the peak inspiratory suction pressure could already be damped down at the level of the relatively narrow hypopharyngeal airways."
-What rare complication did the patient develop after internal jugular vein catheterization?,"Internal mammary artery subclavian vein fistula following internal jugular vein catheterization. A case report and review of the literature. We have recently treated a patient with an arteriovenous fistula that developed after a right internal jugular vein catheterization. The patient was found to have a pulsatile hematoma and a bruit five days after removal of a temporary pacemaker catheter. Digital subtraction arteriography documented a fistula between the right internal mammary artery and subclavian vein. The fistula was surgically repaired via the cervical route. To our knowledge, an arteriovenous fistula between the internal mammary artery and subclavian vein has not been previously described as a complication of a percutaneous internal jugular vein catheterization."
-What was the aim of the experiments in this animal model study of gluten-induced enteropathy?,"Animal model of gluten induced enteropathy in mice. The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy."
-What potential complications can arise from intralesional corticosteroid therapy for periocular capillary hemangiomas?,"Adrenal suppression and growth retardation after injection of periocular capillary hemangioma with corticosteroids. Adrenal suppression and/or growth retardation were noted in two patients after injection of periocular capillary hemangiomas with corticosteroids. Parents should be warned of these two potential complications of intralesional corticosteroid therapy. Baseline and posttreatment adrenal function should be monitored. If iatrogenic adrenal suppression occurs, supplemental systemic corticosteroids may be necessary in situations involving systemic stress such as infection or surgery."
-What is idiopathic myointimal hyperplasia of mesenteric veins and what are its key clinical characteristics?,"Idiopathic myointimal hyperplasia of mesenteric veins. Nonthrombotic occlusion or stenosis of the mesenteric veins is a rare cause of intestinal ischemia that usually occurs in association with systemic vasculitis. The current report includes four male patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins and their intramural branches; neither vasculitis nor arterial involvement were present. Three of the four patients were less than or equal to 38 years of age; the fourth was 67. All four patients were previously healthy and had no history of drug use of any kind. Clinical findings included abdominal pain, diarrhea, bloody stools, and colonic strictures discovered by barium enema. The intima of the mesenteric and intestinal mural veins was focally thickened by a marked increase in cells and matrix between the endothelium and internal elastic lamina, whereas the vessel walls external to the thickened intima appeared normal. Histochemistry and immunoreactivity with antibodies to muscle-specific actins (HHF-35) disclosed that the intimal thickening was caused by proliferation of smooth muscle cells in a proteoglycan matrix. All patients recovered completely after segmental resection of the ischemic portion of the colon and had no recurrence of intestinal symptoms on follow-up of up to 7 years. These unusual venous lesions do not appear to have been previously described; their etiology and pathogenesis remain unknown."
-What were the long-term outcomes of menstrual cycles and fertility for patients with different types of secondary amenorrhea after a 10-year follow-up?,"Ten-year follow-up of patients with secondary amenorrhea and normal prolactin. A group of 46 patients with secondary amenorrhea without galactorrhea or hyperprolactinemia were studied retrospectively after being clinically categorized into four groups with the use of progesterone-induced uterine bleeding and measurement of serum gonadotropins and prolactin levels. The ability to have regular spontaneous menstrual cycles and to conceive was assessed after a follow-up period of 10 years. Patients who had been classified as having hypothalamic pituitary ""failure"" (hypoestrogenic amenorrhea) with low levels of circulating estradiol had a greater rate of recovery of spontaneous ovulation and menses when compared with patients who had been classified as having only hypothalamic pituitary dysfunction (euestrogenic amenorrhea). The patients with diagnosis of hyperandrogenic chronic anovulation or polycystic ovary syndrome generally required clomiphene citrate for induction of ovulation and almost all the patients with premature ovarian failure (hypergonadotropic amenorrhea) remained estrogen-deficient and unable to ovulate. Hyperprolactinemia or an identifiable pituitary adenoma has not developed in any of the patients to date."
-What motor abnormalities were observed in the second patient that could potentially promote bacterial overgrowth in the Roux limb?,"Could recurrent cholangitis after Roux-en-Y hepaticojejunostomy be explained by motor intestinal anomalies? A manometric study. The aim of this study was to describe the motor patterns found in two patients with recurrent cholangitis episodes after Roux-en-Y hepaticojejunostomy. In one patient, cholangitis was due to a stenosis of the anastomosis between the limb and the left intrahepatic bile duct, while motility of the limb, duodenum, and distal jejunum was normal. In the second patient, no anatomical explanation was found for cholangitis attacks. However, although the duodenal motor activity was normal, the motility of the limb and of the jejunum below the jejunojejunal anastomosis was grossly abnormal: permanent minute rhythm, phase IIIs absent or rare and slowly propagated, all motor abnormalities that could promote bacterial overgrowth in the limb. This stresses the interest in performing motor studies of the Roux-limb when cholangitis remains unexplained after Roux-en-Y hepaticojejunostomy."
-What did the study reveal about eosinophil infiltration in orbital pseudotumor compared to control specimens?,"Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. To investigate the participation of the eosinophil in orbital pseudotumor, the authors studied surgical biopsy specimens from nine patients with pseudotumor. Surgical biopsy specimens of orbital tissue from four patients with Graves' ophthalmopathy and autopsy specimens of orbital tissue from six patients without orbital diseases served as controls. Eosinophil infiltration and degranulation were assessed by immunofluorescence staining of formalin-fixed, paraffin-embedded tissues for the cytotoxic eosinophil granule major basic protein. Eosinophil infiltration and extracellular major basic protein deposition were evident in all orbital pseudotumor specimens. In contrast, no eosinophil infiltration or extracellular major basic protein deposition was present in any of the ten control specimens. These findings indicate that eosinophil degranulation is found in orbital pseudotumor, and they also identify yet another clinical entity where eosinophil infiltration and degranulation are associated with fibrosis."
-What is the primary purpose of using superselective embolization in treating arteriovenous fistulas in renal transplant patients?,"Arteriovenous fistulas complicating biopsy of renal allografts: treatment of bleeding with superselective embolization. The use of superselective embolization was assessed as a treatment for bleeding from postbiopsy arteriovenous fistulas (AVFs) in renal transplants. AVFs commonly occur after biopsy procedures in renal transplants, but severe bleeding is rare. Transcatheter embolization can be used to control bleeding, but unless it is sufficiently selective, the procedure results in loss of significant amounts of renal parenchyma. During a 4-year period, embolization procedures were attempted in seven patients 30-65 years old. All had AVFs shown on arteriography. Five patients underwent embolization; occlusion occurred only in the branch supplying the AVF. In one patient with three large AVFs, two were found to have occluded the day after embolization was attempted. In another, an AVF occluded when superselective catheter position was achieved but before embolization. Catheter manipulation in these cases may have precipitated occlusion. In five cases, coaxial embolization techniques were used. Embolization materials consisted of coils in three cases: 0.038 in. (0.97 mm) in one case, 0.025 in. (0.64 mm) in one case, 0.018 in. (0.46 mm) in one case; 0.038 in. (0.97 mm) coils and gelatin foam particles in one case; and localized contrast extravasation in one case. Serum creatinine level was measured before and after embolization in all patients, and radionuclide studies were undertaken in three cases. In all patients, bleeding was effectively controlled. None of the patients showed an increase in serum creatinine level after embolization, and in four, significant improvement was seen. Nuclear medicine studies showed no loss of renal function and a dramatic improvement in one patient. No complications due to the procedure were seen. Our experience suggests that superselective embolization with coaxial catheter techniques is an effective method of treating bleeding from postbiopsy AVFs in renal transplants with minimal loss of renal parenchyma."
-How does preexisting cerebral ischemia affect the sympathetic nervous system's response to increased intracranial pressure?,"Effect of preexisting brain ischemia on sympathetic nerve response to intracranial hypertension. The performance of the sympathetic nervous system during sustained moderate cerebral ischemia (CI) was examined in the present study. For this purpose, a Cushing response was elicited repeatedly during incomplete global CI in anesthetized artificially ventilated cats after vagotomy and baroreceptor denervation. In control animals without CI, sympathetic activity in response to brief elevation of intracranial pressure (ICP) showed a well-repeatable two-phase reaction. During CI there was a progressive deterioration of background sympathetic nerve discharge (SND) over a period of 30 min. SND response to repeated elevation of ICP was initially similar to control response but later with progression of CI was seriously changed. 1) Instead of the usual hyperactivation, sympathetic nerve activity was depressed during intracranial hypertension. 2) The characteristic desynchronized activity either appeared later during the reperfusion period or remained absent. The progressive loss of SND response to raised ICP in developed CI was compared with the changes seen in experiments in which repeated ICP elevations were superimposed on asphyxia. These findings suggest that the sympathetic component of the Cushing reaction strongly depends on the actual state of brain stem autonomic circuits and may be seriously altered in pathological situations involving ischemic brain injury."
-How does the intracellular free magnesium concentration differ between normal brain tissue and brain tumor tissue?,"Free magnesium levels in normal human brain and brain tumors: 31P chemical-shift imaging measurements at 1.5 T. We have studied a series of normal subjects and patients with brain tumors, by using 31P three-dimensional chemical shift imaging to obtain localized 31P spectra of the brain. A significant proportion of brain cytosolic ATP in normal brain is not complexed to Mg2+, as indicated by the chemical shift delta of the beta-P resonance of ATP. The ATP beta-P resonance position in brain thus is sensitive to changes in intracellular free Mg2+ concentration and in the proportion of ATP complexed with Mg because this shift lies on the rising portion of the delta vs. Mg2+ titration curve for ATP. We have measured the ATP beta-P shift and compared intracellular free Mg2+ concentration and fractions of free ATP for normal individuals (n = 6) and a limited series of patients with brain tumors (n = 5). In four of the five spectra obtained from brain tissue containing a substantial proportion of tumor, intracellular free Mg2+ was increased, and the fraction of free ATP was decreased, compared with normal brain."
-What are the potential otolaryngologic symptoms associated with gastroesophageal reflux (GER)?,"Otolaryngologic manifestations of gastroesophageal reflux. The exact incidence of gastroesophageal reflux (GER) is unknown, although it is estimated that at least 25% of patients with GER have head and neck symptoms alone. These symptoms may consist of one or more of the following: excess salivation, hoarseness, ""post-nasal drip,"" voice change, persistent coughing, food sticking in the throat, globus hystericus, otalgia, throat clearing, neck pain, sore throats, the sensation of a lump in the throat, choking spells, and bronchospasm. Carcinoma of the larynx and upper aerodigestive tract may be a consequence of chronic reflux. GER, especially when the classic symptoms of reflux are absent, is frequently overlooked as a cause of these problems. This article reviews the symptoms and pathophysiology of these conditions. The diagnostic and therapeutic modalities available to us in managing these patients are also discussed."
-What are the current limitations of using blood flow velocimetry in obstetric practice?,"The current status of maternal and fetal blood flow velocimetry. Significant progress has been achieved in regard to normative data for uteroplacental and fetal blood flow velocity and the factors which may affect these observations. Associations have been demonstrated between abnormal indices of maternal and fetal blood flow velocity and pregnancy-induced hypertension, fetal growth retardation, fetal blood gas measures, and intrapartum clinical fetal distress. However, in general, the predictive power is modest and no evidence has yet been provided to indicate that these measures can be used as a screening test in the general obstetric population. Continuing research is highly desirable. At the present time, the use of Doppler assessment of blood flow in pregnancy should be limited to the investigational setting."
-What is the relationship between drusen of the optic disc and central retinal vein occlusion in this case study?,"Central retinal vein occlusion associated with drusen of the optic disc. A 43-year-old man had gradual visual changes OD. Funduscopic examination revealed central retinal vein occlusion OD. Complete ocular examination revealed bilateral drusen of the optic disc, confirmed by b-scan ultrasonography. Complete systemic evaluation showed no other etiology for the central retinal vein occlusion. Over a ten-year follow-up, in the absence of systemic disease or other local ocular anomalies, we concluded that central retinal vein occlusion can arise from external compression secondary to drusen of the optic disc."
-What are the key differences observed in the clinical outcomes of the two girls with congenital sideroblastic anaemia?,"Congenital sideroblastic anaemia in two girls. Transfusion dependent congenital sideroblastic anaemia occurred in infancy in two unrelated girls. One girl developed early organ failure which was not prevented by standard chelation treatment. The combination of modest iron burden and putative intrinsic mitochondrial dysfunction could have accounted for the clinical picture. The other girl remained well, receiving regular transfusion and standard chelation treatment. She had normal liver function and no other evidence of organ damage. The syndrome is unlikely to be due to extreme lyonisation in carriers of the usual X-linked condition. The contrasting clinical patterns seen in these two patients suggest that transfusion dependent congenital sideroblastic anaemia may comprise a heterogeneous group of disorders. It is suggested that such children be carefully monitored for evidence of increasing iron overload so that organ damage can be prevented."
-What novel cell line and experimental model did the researchers establish for studying human pancreatic carcinoid tumors?,"Novel therapy for the treatment of human carcinoid. Development of effective treatment for patients with carcinoid tumors has been hampered by lack of an experimental model. The authors have established the only long-term cell line of a functioning human pancreatic carcinoid tumor (BON) that produces tumors in nude mice. In this study the authors examined the effect of three agents, alpha-interferon (IFN), a somatostatin analog, SMS 201-995 (SMS), and an inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), on the growth of BON tumors. BON was implanted bilaterally as 3-mm2 pieces (subcutaneously [sc]) into male BALB/c nude mice. In the first study, 23 mice were randomized to four groups: control, IFN (1 x 10(6) units, sc, four times a day), IFN + SMS (300 micrograms/kg, intraperitoneally, three times a day), and IFN + 3% DFMO in drinking water. Treatments were initiated on day of tumor implantation. In the second study, mice were randomized to six groups: control, IFN, SMS, DFMO, IFN + SMS, IFN + DFMO, and IFN + SMS + DFMO. Treatments were started on day 15 after tumor implantation. Tumor area and body weights were measured weekly. In both studies mice were killed on day 28 after BON implantation and tumors removed, weighed, and analyzed for DNA and RNA content. In the first study, IFN either alone or in combination with SMS or DFMO suppressed BON tumor growth. When treatment was initiated after established tumor growth (study 2), however, the only effective treatments for suppression of growth of BON were IFN + DFMO and IFN + DFMO + SMS."
-What changes in magnetic resonance imaging can help diagnose spinal cord infarcts at different stages?,"Magnetic resonance imaging of human spinal cord infarction. Magnetic resonance images obtained in two cases of spinal cord infarction are described: one with hemorrhagic thoracic cord infarct, the other with ischemic cervical cord infarct with sequential magnetic resonance imagings. An enlarged cord with strand-shape or longitudinal hypointensity on both T1- and T2-weighted images was noticed in the hemorrhagic infarct; hypointensity on the T2-weighted image was thought to be due to hemosiderin, which shortens T2 relaxation. In the ischemic infarct, a small, round area of hypointensity on T1-weighted images, and of hyperintensity on T2-weighted images, noted 9 hours postictus (""early infarct"") changed on the 22nd day to a cephalocaudal strandlike hypointensity on T1-weighted image, which was enhanced by Gd-DTPA. The hypointensity suggested ""pencil-like softening"" in ""medium"" age infarct. On postictal day 49, it showed an extensive homogeneous hypointensity involving several segments of the cord on T1-weighted images and hyperintensity on T2-weighted images with negative Gd-DTPA enhancement suggesting ""late transverse infarct."" We considered that these changes are of value in diagnosing spinal cord infarcts on magnetic resonance imagings."
-What is the incidence of portal thrombosis after splenectomy in patients with idiopathic portal hypertension (IPH) compared to patients with cirrhosis of the liver?,"High rate of portal thrombosis after splenectomy in patients with esophageal varices and idiopathic portal hypertension. Data on 126 consecutive patients who were admitted to our clinics from January 1979 to May 1989 were scrutinized to assess changes in portal hemodynamics following splenectomy. Two groups were classified: (1) a group of 106 patients with cirrhosis of the liver and (2) a group of 20 patients with idiopathic portal hypertension (IPH). Portal thrombosis was present in five (25.0%) of the 20 patients with IPH and in two (1.8%) of the 106 patients with cirrhosis of the liver. As seen on celiac arteriography, the mean (+/- SD) diameter of the trunk of the splenic artery and vein was 8.99 +/- 1.55 and 16.2 +/- 3.6 mm, respectively, in patients with IPH, while it was 7.94 +/- 1.28 and 14.2 +/- 3.1 mm, respectively, in patients with cirrhosis of the liver. Changes in portal venous pressure were 78.4 +/- 59.4 mm H2O in patients with IPH and 43.5 +/- 38.7 mm H2O in patients with cirrhosis of the liver. There were no significant differences in the maximum level of thrombocytes in patients with IPH or in those patients with cirrhosis of the liver. These events suggest that portal thrombosis can occur with a significantly higher incidence in patients with IPH than in those patients with cirrhosis of the liver after splenectomy, and a decrease in blood flow in the portal vein may be closely linked to the formation of portal thrombosis after splenectomy in patients with IPH. Preoperative examination of portal hemodynamics must be thorough."
-What was the overall occurrence rate of gastroduodenal mucosal damage in this study of critically ill patients receiving total parenteral nutrition?,"Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study. OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients."
-What is the effectiveness of intraperitoneal thrombolytic agents like urokinase or streptokinase in treating relapsing or persistent peritonitis in CAPD patients?,"Intraperitoneal thrombolytic agents in relapsing or persistent peritonitis of patients on continuous ambulatory peritoneal dialysis. Urokinase or streptokinase was instilled intraperitoneally as an adjunct to the antibiotic therapy in 16 episodes of relapsing or persistent peritonitis in CAPD patients. In eight patients the combination of antibiotics and intraperitoneal thrombolytic agents resulted in clearing of the infection with no recurrences. The treatment failed in eight other patients, who had their peritoneal catheters removed. Six of the last eight patients had either abdominal wall abscesses or persistence of the bacteria on the wall of the peritoneal catheter. Elevated post-intraperitoneal instillation peritoneal fluid neutrophil counts and positive post-instillation peritoneal fluid cultures predicted failure of the intraperitoneal instillation of thrombolytic agents in most instances. Intraperitoneal instillation of urokinase or streptokinase may help cure approximately 50% of the episodes of relapsing for persistent peritonitis. Post-instillation peritoneal fluid cell counts and cultures should be monitored. Radiologic investigation for abdominal wall or intraabdominal abscesses is indicated if intraperitoneal instillation of urokinase or streptokinase fails to eradicate peritonitis."
-"How do the expression levels of c-jun, jun-B, and c-fos RNA transcripts differ between primary melanocytes and metastatic melanoma cell strains?","Expression of c-jun, jun-B, and c-fos proto-oncogenes in human primary melanocytes and metastatic melanomas. Analysis of the regulation of c-jun, jun-B, and c-fos RNA transcript expression was performed in human primary melanocytes and metastatic melanoma cell strains. The medium requirements for human melanocyte in vitro growth are phorbol esters, agents that elevate intracellular cAMP levels, hormones, and growth factors. Cellular jun, jun-B, and c-fos gene expression are known to be affected by growth promoting agents. In primary melanocytes, the expression of c-jun, jun-B, and c-fos RNA transcripts was dependent on the growth-promoting agents present in the medium. Uniformly high c-jun, jun-B, and c-fos RNA transcript levels were observed in melanocytes cultivated in complete medium. Higher levels of c-jun RNA transcripts and low levels of c-fos RNA transcripts were observed in melanocytes cultivated in plain medium. In contrast, a range of c-jun, jun-B, and c-fos RNA transcript levels was detected in metastatic melanoma cell strains cultivated in medium with or without serum. In general, an increase in jun-B and c-fos RNA transcript expression and a decrease in c-jun RNA transcript expression was observed in metastatic melanomas compared to neonatal melanocytes. These data suggest a potential role for c-jun, jun-B, and c-fos genes in the transformation of melanocytes to malignant melanoma."
-What was the primary objective of the study on pain characterization in cancer patients?,"Pain characterization in cancer patients and the analgetic response to epidural morphine. In 48 patients with pain related to malignancy, a pain characterization was performed during oral opioid therapy. After an optimal epidural morphine regimen had been established, the alteration in pain relief was evaluated by means of a visual analogue scale. The CSF and plasma morphine concentrations at minimum steady state were then analysed in 28 patients and related to the degree of pain relief. The efficacy of the spinal treatment ranked in the following order: somatic greater than visceral greater than radiating = 0, but the difference was only significant between the somatic and radiating pain groups. There was a tendency for continuous pain to be better relieved than intermittent pain. No correlations were found between the CSF or plasma morphine concentrations and the degree of pain relief, suggesting that not all pain impulses are modulated in a dose-dependent manner by morphine at the spinal level. Pain characterization may be instrumental in providing an optimal spinal opioid analgesia in malignancy. Moreover, there is a need for better defined diagnostic criteria for clinical pain characterization."
-How can small DNA alterations or abnormalities be detected in genetic diseases using restriction endonuclease techniques?,"Diagnosis of genetic disease by primer-specified restriction map modification, with application to cystic fibrosis and retinitis pigmentosa Detection of small alterations or abnormalities in genomic DNA (eg, point mutations or small deletions) has become increasingly important in the diagnosis of genetic disease and polymorphism. When a mutation or polymorphism creates a new restriction endonuclease site, it can easily be identified by polymerase chain reaction (PCR) amplification of the DNA region of interest, followed by digestion with the restriction endonuclease. However, useful restriction sites are the exception, and a variety of specialised techniques have been developed to identify subtle DNA abnormalities. We have shown that where a DNA mutation does not create a useful novel restriction site, such a site can be introduced by PCR and specially chosen primers. The approach is simple and inexpensive and should be broadly applicable in the diagnosis of genetic polymorphism and mutation. The technique is illustrated here by the three base-pair deletion responsible for most cases of cystic fibrosis and by detection of the point mutation in the rhodopsin gene that has been associated with some cases of autosomal dominant retinitis pigmentosa."
-What is the significance of the mitral valvuloplasty performed 5 years after the repair of a sinus venosus atrial septal defect?,"Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty."
-What quantitative nucleolar features were found to be most useful in distinguishing between follicular adenoma and follicular carcinoma of the thyroid?,"Value of quantitative nucleolar features in the preoperative cytological diagnosis of follicular neoplasias of the thyroid. Nucleolar prevalence, size, and outline were investigated on cytological material from cold thyroid nodules obtained by fine needle aspiration. The percentage of nucleolated nuclei in follicular adenoma (32 cases) was less than in follicular carcinoma (26 cases). In adenoma most nuclei contained one nucleolus, and nuclei with two or more nucleoli were less common than in carcinoma where most cases showed the highest nucleolar diameter values. There was some overlap between adenomas and carcinomas, however, when the mean of the 10 largest values of the major nucleolar diameter was considered. In follicular carcinoma the percentage of marginated nucleoli--that is, those touching the nuclear membrane--was, in general, greater than 20%; in adenoma the values were equal to or lower than 16%. The overlap index showed that the percentages of marginated nucleoli and nucleolated nuclei are the two best discriminatory features between adenoma and carcinoma."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-How does the masseter muscle respond to respiratory stimuli like hypercapnia and inspiratory loading?,"Respiratory-related recruitment of the masseter: response to hypercapnia and loading. To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway."
-What are the key characteristics of acute pandysautonomic neuropathy according to the given context?,"Acute pandysautonomic neuropathy. Acute pandysautonomic neuropathy is characterized by severe postganglionic sympathetic and parasympathetic dysfunction, with relative or complete sparing of motor and sensory function. Of four reported cases with sural nerve biopsies, two were normal and two abnormal, revealing loss of small myelinated and unmyelinated fibers. We present a patient with pandysautonomic neuropathy and elevated CSF protein whose sural nerve biopsy showed active axonal degeneration."
-What are the most prominent clinical signs of aseptic meningitis syndrome observed in cardiac transplant patients?,"Aseptic meningitis following cardiac transplantation: clinical characteristics and relationship to immunosuppressive regimen. Neurologic disorders are uncommon but alarming complications of cardiac transplantation. Of 29 patients from the Utah Cardiac Transplant Program (UCTP) who had lumbar puncture because of change in neurologic function, or to assess fever of uncertain etiology, CSF pleocytosis was present in 14 patients, 4 of whom had an active infectious process involving the nervous system. In 10 other patients, CSF pleocytosis with negative cultures appeared following treatment with OKT3 monoclonal antibody. The most prominent clinical signs of this aseptic meningitis syndrome are fever and transient cognitive dysfunction."
-What criteria were used to determine when patients could be weaned from mechanical ventilation and extubated after transsternal thymectomy for myasthenia gravis?,"Extubation after transsternal thymectomy for myasthenia gravis: a prospective analysis. Recommendations concerning postoperative extubation after thymectomy for myasthenia gravis are presently based upon retrospective chart reviews. We present the results of a prospective investigation of time to extubation after thymectomy for 14 patients over a 12-month period based upon a protocol that included preoperative immunologic therapy, combined epidural and general anesthesia, postoperative epidural narcotic analgesia, and a standardized approach to discontinuation of ventilatory support. After a neurologist took measures to optimize preoperative neuromuscular function, all 14 patients received agents to produce lumbar epidural anesthesia and light general anesthesia. Muscle relaxants were avoided in all but one patient. Postoperative analgesia was initially maintained with epidural hydromorphone, then therapy was switched to patient-controlled intravenous morphine sulfate. Criteria for weaning from mechanical ventilation, first measured at the end of anesthesia, were partial pressure of oxygen (arterial) greater than or equal to 90 mm Hg (fraction of inspired oxygen = 0.40), partial pressure of carbon dioxide (arterial) less than or equal to 50 mm Hg, pH greater than or equal to 7.30, and respiratory rate less than or equal to 30 breaths/min. If these criteria were not met, ventilatory support was continued postoperatively with intermittent mandatory ventilation, and the patient was weaned gradually from this support. Criteria for extubation included meeting the criteria for weaning, vital capacity greater than or equal to 10 mL/kg, and inspiratory pressure better than -30 cm H2O. Criteria for reintubation included tachypnea (respiratory rate greater than 40 breaths/min), respiratory acidosis not due to narcotics, or vital capacity less than or equal to 8 mL/kg. The mean time to extubation was 9 hours (range, 0.75 to 25 hours). Mean preoperative vital capacity was 2.59 +/- 0.64 L (range, 1.90 to 4.20), which decreased approximately 50% to 1.19 +/- 0.39 L (range, 0.70 to 2.0) at the time of extubation. No patient required reintubation. Half of the patients required postoperative anticholinesterase therapy based upon serial neurologic examinations; there were no instances of cholinergic crisis. Thirteen patients returned to the ward on the first postoperative day, and one on the second day. Thirteen patients preferred epidural analgesia to patient-controlled analgesia. The time to extubation and average length of stay in an intensive care setting were markedly reduced compared to those reported in previous retrospective studies. We conclude that a multidisciplinary approach that optimizes neuromuscular function and decreases poststernotomy pulmonary insult will shorten the time to extubation and decrease the length of stay in the intensive care or recovery room after thymectomy."
-What was the laser technique used for treating ovarian endometriomas in this study?,"The use of potassium-titanyl-phosphate laser for laparoscopic removal of ovarian endometrioma. From January 1989 through January 1990, 31 patients thought to have ovarian endometrioma at ultrasonography were treated by operative laparoscopy and potassium-titanyl-phosphate laser. The endometriomas ranged from 2 to 9.2 cm in diameter by preoperative transvaginal ultrasonography. The operative procedure used was a three-puncture technique with a 600 micron fiber attached to a potassium-titanyl-phosphate laser. The power setting was 10 W with a continuous pulse. In all cases endometriomas were opened, drained, and irrigated, and the potassium-titanyl-phosphate laser was used to vaporize or remove the entire cyst lining. The ovarian edges were inverted with the laser at the end of the procedure. With one exception, there was no recurrence of endometrioma at 1, 3, and 6 months after the procedure, on the basis of transvaginal ultrasonography or laparoscopy. In one case, 4 months after the initial laparoscopic procedure, exploratory laparotomy was performed for resection of a large, recurrent endometrioma. The use of the potassium-titanyl-phosphate laser allows the laparoscopic surgeon an aggressive approach to ovarian endometriomas that in the past necessitated exploratory laparotomy."
-What percentage of patients experienced vasovagal reactions during breast-imaging procedures in this study?,"Localization and needle aspiration of breast lesions: complications in 370 cases. A prospective study of the immediate complications of 370 consecutive breast-imaging procedures (203 wire localizations and 167 radiographically or sonographically guided fine-needle aspirations) is reported. Vasovagal reactions occurred in 27 (7%) of 370 cases, ranging in severity from syncope (four of 370, 1%) to mild light-headedness. These vasovagal reactions were independent of procedure type or use of local anesthesia, but were more common in younger patients. Other complications included prolonged (5 min or longer) bleeding (three of 370, 1%) and extreme pain (two of 370, 1%). One patient was found to have malignant hypertension. We conclude that wire localizations and imaging-guided aspirations are generally well tolerated procedures. However, vasovagal reactions are frequent enough to warrant close observation of patients. Radiologists and breast-imaging personnel should be able to recognize and treat vasovagal reactions."
-What imaging technique was crucial in identifying the pontine glioma in this patient with hemifacial spasm?,"Occult pontine glioma in a patient with hemifacial spasm. Hemifacial spasm due to an intracranial mass lesion is rare. We describe a 29-year-old man with hemifacial spasm successfully treated with botulinum A toxin injections for 2 years. The development of acquired diplopia secondary to acquired sixth cranial nerve palsy prompted investigation. Computed tomography done at the time of original diagnosis and on three other occasions (concentrating on the brain stem and cerebellopontine angle) failed to demonstrate an intracranial mass lesion. Magnetic resonance imaging (MRI) showed a large mass lesion in the pons presumed to be a glioma. Patients with hemifacial spasm who have atypical features, especially those with associated neurologic findings, should be screened for tumours. Our case illustrates the superiority of MRI in demonstrating pontine gliomas causing hemifacial spasm."
-How do monoclonal antibodies help in visualizing myocardial necrosis in dogs and humans?,"Imaging of myocardial infarction in dogs and humans using monoclonal antibodies specific for human myosin heavy chains. The use of three different monoclonal antibodies specific for human ventricular myosin heavy chains in the visualization of the location and extent of necrosis in dogs with experimental acute myocardial infarction and in humans is described. Using a classic immunohistochemical method or ex vivo analysis of heart slices in dogs with acute myocardial infarction subjected to intravenous injection of unlabeled antimyosin antibodies or antimyosin antibodies labeled with indium-111, it was observed that all antibody fragments specifically reached the targeted necrotic zone less than 2 h after antibody injection and remained bound for up to 24 h. In a limited but significant number of cases (5 of the 12 humans and 11 of 43 dogs), it was possible to image the necrotic zone in vivo as early as 2 to 4 h after antibody injection. In other cases, individual blood clearance variations retarded or even prevented in vivo necrosis detection. Higher antimyosin fixation values were obtained in the necrotic zones in dogs with a rapid blood clearance relative to that of the other dogs. It is concluded that antimyosin antibodies always reached necrotic areas within 2 h. If blood clearance was rapid, in vivo imaging of the necrotic area was possible 2 to 6 h after necrosis, even in humans. In some cases, however, uncontrolled individual variations in the timing required for sufficient blood clearance hampered this rapid in vivo detection of myocardial necrosis."
-What was the success rate of treating primary vesicoureteric reflux using subureteric injection of Polytef paste in this study?,"Primary vesicoureteric reflux: treatment with subureteric injection of Polytef paste. A series of 34 children with 40 primary refluxing ureters were treated endoscopically with a subureteric injection of polytetrafluoroethylene paste (Polytef). The amount injected ranged between 0.1 and 0.8 ml (mean 0.3). A single injection cured the reflux in 26 ureters (65%) and the grade of reflux improved in a further 9 ureters. Seven ureters required a second injection and reflux was cured in 6 of these. The overall cure rate was therefore 80% after the second injection. There was one complication due to self-limiting ureteric obstruction following injection. The procedure is quick, easy to perform and effective. We have some reservations about the long-term efficiency and safety of subureteric Polytef injection in children."
-What serum biomarkers were studied in patients with metastatic renal cell carcinoma and what were their key findings?,"Serum biomarkers in metastatic renal cell carcinoma. To identify possible clinically valuable markers of metastatic renal cell carcinoma, we measured the serum concentrations of several commercially available biomarkers in 117 patients with this disease. The alpha-fetoprotein level was measured in 75 patients and was elevated in 8 (11%); elevation did not correlate with the presence of liver metastasis. Beta subunit of human chorionic gonadotropin levels increased in 8 of 83 patients tested (10%). C-terminal parathyroid hormone levels were measured in 79 patients and were elevated in 15 (19%); their serum creatinine level was normal. Thirteen of this group had normal serum calcium levels, whereas 7 patients with hypercalcemia and no clinically evident bone metastasis had normal parathyroid hormone levels. In only 2 of 72 patients, serum lactate dehydrogenase and its isoenzyme 1 were elevated. Only 1 of 85 patients had mildly elevated serum carcinoembryonic antigen, in contrast to 3 of 7 patients with metastatic transitional cell carcinoma of the renal pelvis who had moderately elevated carcinoembryonic antigen. Elevations in alpha-fetoprotein, human chorionic gonadotropin, and parathyroid hormone correlated with the course of the disease in 13 patients for whom follow-up measurements were available; measurement of these markers, however, is only useful in a small proportion of patients with metastatic renal cell carcinoma."
-What was the purpose of the study comparing Trisdine bladder instillations and O'Neil catheters in patients with acute spinal cord trauma?,"Bladder instillations of trisdine compared with catheter introducer for reduction of bacteriuria during intermittent catheterisation of patients with acute spinal cord trauma. An open, prospective, randomised trial was conducted to compare the incidence of significant bacteriuria following 2 methods of intermittent urethral catheterisation in patients with acute spinal cord trauma. Twenty-two patients were catheterised with a Nelaton catheter and 50 ml of Trisdine were instilled into the bladder and left there immediately prior to withdrawal of the catheter. Fifteen patients were catheterised with a Nelaton catheter with a special introducer to improve asepsis (O'Neil catheter). The mean incidence of significant bacteriuria in males and females who received Trisdine bladder instillations was 0.58 and 0.48% per catheterisation respectively; in males and females catheterised with the O'Neil catheter it was 1.16 and 2.93% per catheterisation respectively. The instillation of Trisdine into the bladder after each passage of a catheter resulted in a significantly lower incidence of bacteriuria compared with that which resulted from the use of the O'Neil catheter. The former method is therefore to be preferred for aseptic intermittent urethral catheterisation in patients with acute spinal cord trauma."
-What percentage of patients survived long-term after receiving the Bio-Medicus ventricular assist device during cardiac surgery?,"Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients."
-What method did the researchers use to estimate the pressure difference between arms and legs in patients with suspected recoarctation of the aorta?,"Estimation of Doppler gradients at rest and during exercise in patients with recoarctation of the aorta. In patients with suspected recoarctation of the aorta the estimation of the pressure difference between the arms and legs is an important part of the examination. Because this difference is often augmented when the circulation is stressed by exercise, exercise tests are a useful part of the evaluation. Doppler echocardiography was used to estimate this pressure difference in 16 adult patients in whom simultaneous pressure and Doppler recordings were made both at rest and during exercise. There was a close correlation between the invasive peak instantaneous gradient and the Doppler gradient both at rest and during exercise. There was only a moderate correlation between the invasive peak to peak gradient and the Doppler gradient at rest and during exercise. Doppler echocardiography is recommended as an easy and accurate method of estimating the peak instantaneous gradient both at rest and during exercise in patients with suspected recoarctation."
-"How does abdominal surgery affect protein, RNA, and nucleotide synthesis in lymphocytes?","Stimulation of protein, RNA, and nucleotide synthesis in lymphocytes after abdominal surgery is not affected by postoperative amino acid supply. The effects of abdominal surgery on protein, RNA, and de novo purine nucleotide synthesis in lymphocytes, and modification of these changes by postoperative amino acid supply, were investigated in 24 patients undergoing cholecystectomy (n = 12) or removal of gastric cancer (n = 12). Mono-nuclear cells were isolated from the peripheral venous blood and incubated with radioactive tracers in vitro. Protein and RNA synthesis, as measured using [14C] glycine and [3H]uridine, respectively, increased postoperatively. Nucleotide synthesis determined by the incorporation of radioactivity from [14C] glycine into nucleotides increased simultaneously. The concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP) estimated by the incorporation of [14C]adenine into nucleotides also increased. These changes were greater and of longer duration in patients with cancer operation than in those with cholecystectomy. In neither case were they affected by the amount of amino acid intake, or increases in energy intake. These results suggest that abdominal surgery stimulates protein and ribonucleic acid (RNA) synthesis in lymphocytes. Increased RNA synthesis may be ensured by increased synthesis of nucleotides, and increased PRPP concentrations appear to regulate the rate of nucleotide synthesis. The responses are apparently dependent upon the severity of surgery, but unrelated to the amount of amino acid supplied postoperatively."
-Does intravenous aminophylline reduce the risk of relapse in patients with decompensated chronic obstructive pulmonary disease (COPD)?,"Aminophylline in the outpatient management of decompensated chronic obstructive pulmonary disease. The objective of this study was to determine if IV aminophylline reduces the risk of relapse after treatment of decompensated COPD in an ED. Forty-six visits in which IV aminophylline was given (T visits) were compared with an equal number of visits in which it was withheld (N visits) with respect to pretreatment serum theophylline level, number of treatments with nebulized bronchodilators and use of parenteral beta-adrenergic drugs, IV corticosteroids and prednisone. The difference in 48-h relapse rates for T and N visits was examined by McNemar's test. No differences were found between T and N visits with respect to vital signs, pretreatment FEV1, arterial blood gas values, hematocrit level or blood leukocyte count. The 48-h relapse rate for T visits (22.2 percent) was significantly higher than for N visits (6.7 percent; p = 0.035). Aminophylline does not appear to be beneficial for outpatients with decompensated COPD and may be harmful."
-How does the administration of estradiol and progesterone affect luteinizing hormone (LH) pulse frequency in women with polycystic ovarian disease?,"Reduction of gonadotropin-releasing hormone pulse frequency is associated with subsequent selective follicle-stimulating hormone secretion in women with polycystic ovarian disease. Polycystic ovarian disease (PCO) is characterized by hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. Mean plasma FSH concentrations are low, while LH is elevated in a majority of patients. LH pulsatile secretion has been shown to occur at rapid follicular phase frequencies (approximately one pulse per h) in PCO, suggesting persistent rapid frequency GnRH secretion in this disorder. Anovulatory women with PCO were given estradiol (E2; Estraderm skin patches) and progesterone (P; vaginal suppositories) to produce midluteal concentrations for 21 days. The aim was to determine if E2 and P would slow LH (GnRH) pulse frequency and if this would result in augmented FSH secretion and follicular development after withdrawal of E2 and P. Plasma LH was measured every 10 min for 8 h before, during (days 10 and 20), and 7 days after withdrawal of E2 and P (day 28). On each of these study days FSH was measured hourly, and E2 and P were measured every 2 h. After sampling, GnRH (25 and 250 ng/kg, iv) was given to assess pituitary responsiveness. Follicular development was monitored by vaginal ultrasound through day 34 of the study. Basal LH frequency was 8.5 +/- 0.5 pulses/8 h (mean +/- SEM). During E2 and P, LH pulse frequency fell to 3.3 +/- 1.0 (10 days) and 2.3 +/- 0.8 (20 days), 39% and 27% of the basal value, respectively, and subsequently increased to 5.6 +/- 0.7 (66% of basal) 7 days after withdrawal of E2 and P. LH pulse amplitude (basal, 7.2 +/- 1.5 IU/L) was not reduced until day 20, but remained suppressed (3.9 +/- 1.1 IU/L) on day 28. As a result, mean LH (basal, 21.0 +/- 3.5 IU/L) fell progressively during E2 and P, to 3.8 +/- 1.2 IU/L on day 20, and remained low (39% of basal) 7 days after steroid withdrawal. Mean plasma FSH (basal, 7.1 +/- 0.9 IU/L) also fell during steroid administration, but in contrast to LH, had risen to 93% of the basal value by 7 days after E2 and P. LH release in response to exogenous GnRH revealed marked initial responses which did not decrease until day 20, but remained suppressed (8% of basal) after withdrawal of E2 and P. FSH responses were also suppressed on day 20, but had increased to 75% of the basal value by day 28. Initiation of follicular development occurred in all patients, and the lead follicle measured 12.3 +/- 0.8 mm 13 days post-E2 and P. Ovulation occurred in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What is circumspinal decompression and how does it address thoracic myelopathy caused by ossification of the posterior longitudinal ligament and ligamentum flavum?,"Circumspinal decompression for thoracic myelopathy due to combined ossification of the posterior longitudinal ligament and ligamentum flavum. Ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the ligamentum flavum (OLF) in the thoracic spine can result in serious myelopathy, leading to circumferential compression of the spinal cord in advanced stages of the disease. The authors performed circumspinal decompression (circumferential decompression of the spinal cord) on these patients. This operation consists of two steps: posterior and lateral decompression of the spinal cord by removal of the OLF (first step) and anterior removal of the OPLL for anterior decompression (second step), followed by interbody fusion. In the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura to easily and safely remove the OPLL anteriorly at the second step. In the second step, the surgical approach varies according to the affected level; costotransversectomy in the upper thoracic spine and standard thoracotomy in the middle or lower thoracic spine. According to the authors, circumspinal decompression is not an easy procedure, but from their results in 10 patients, they identify it as a radical and promising surgical procedure."
-What percentage of patients with pulmonary embolism experienced dyspnea or tachypnea?,"Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. The history, physical examination, chest radiograph, electrocardiogram and blood gases were evaluated in patients with suspected acute pulmonary embolism (PE) and no history or evidence of pre-existing cardiac or pulmonary disease. The investigation focused upon patients with no previous cardiac or pulmonary disease in order to evaluate the clinical characteristics that were due only to PE. Acute PE was present in 117 patients and PE was excluded in 248 patients. Among the patients with PE, dyspnea or tachypnea (greater than or equal to 20/min) was present in 105 of 117 (90 percent). Dyspnea, hemoptysis, or pleuritic pain was present in 107 of 117 (91 percent). The partial pressure of oxygen in arterial blood on room air was less than 80 mm Hg in 65 of 88 (74 percent). The alveolar-arterial oxygen gradient was greater than 20 mm Hg in 76 of 88 (86 percent). The chest radiograph was abnormal in 98 of 117 (84 percent). Atelectasis and/or pulmonary parenchymal abnormalities were most common, 79 of 117 (68 percent). Nonspecific ST segment or T wave change was the most common electrocardiographic abnormality, in 44 of 89 (49 percent). Dyspnea, tachypnea, or signs of deep venous thrombosis was present in 107 of 117 (91 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain or atelectasis or a parenchymal abnormality on the chest radiograph was present in 115 of 117 (98 percent). In conclusion, among the patients with pulmonary embolism that were identified, only a small percentage did not have these important manifestations or combinations of manifestations. Clinical evaluation, though nonspecific, is of considerable value in the selection of patients in whom there is a need for further diagnostic studies."
-What are the key challenges in managing osteogenic sarcoma in children and adolescents?,"Management of osteogenic sarcoma in children and adolescents. The management of osteogenic sarcoma in children has made a fantastic step on the survival rate, but there still remains unexpected late metastatic recurrence even in initially good responders to chemotherapy and lower survival rate in the bad responder group. Therefore, the research on etiology and on the understanding and rating of oncologic power of the tumoral cells as well as other kinds of treatment (vaccine, immunotherapy, and other types of chemotherapy) must be increased. The initial function after replacement is good and is often excellent but increasing deterioration is noticed during each follow-up evaluation. A considerable effort is still to be done for bone and joint replacement. Biocompatible material with mechanical strength and resistance to wear will be used for a long time because of the young age of the patients. There must be better use and understanding of the allograft revascularization, as well as a better biologic connection between the bone host and replacement device. This will probably be used in the future with less cement and more of a modular system. The final prognosis will remain for a long time in the perfect cooperation between the various members of the teams (oncologist, surgeon, imager, pathologist, and research team) who treat the patients."
-What was the total morbidity rate for complications in the study of long-term seizure monitoring using subdural strip electrodes?,"The morbidity of long-term seizure monitoring using subdural strip electrodes. The authors report a prospective study of morbidity associated with long-term seizure monitoring using subdural strip electrodes. Three hundred fifty patients were divided into two groups: 175 patients received antibiotics intravenously during the entire period that the electrodes were implanted, and 175 patients received one dose of antibiotics on the morning of surgery. In the group given continuous antibiotic coverage there were two cases of meningitis, both treated without sequelae. In the group receiving one dose of antibiotics, one patient had a brain abscess and three had superficial wound infections. There were no other instances of major morbidity or mortality in either group of patients. The total morbidity rate for both serious and minor complications was 0.85%."
-What were the significant predictors of event-free survival after balloon aortic valvuloplasty?,"Predictors of event-free survival after balloon aortic valvuloplasty. BACKGROUND. Balloon aortic valvuloplasty was developed as an alternative to aortic-valve replacement in selected elderly patients with aortic stenosis. The use of this procedure is limited, however, by a high incidence of restenosis. METHODS. Between December 1985 and April 1989, valvuloplasty was performed in 205 patients. We evaluated 40 demographic and hemodynamic variables as univariate predictors of event-free survival by Cox regression analysis and identified independent predictors of event-free survival by stepwise multivariate analysis. RESULTS. Early hemodynamic results indicated a decrease in the peak transaortic-valve pressure gradient from 67 +/- 28 to 33 +/- 15 mm Hg after valvuloplasty and an increase in aortic-valve area from 0.6 +/- 0.2 to 0.9 +/- 0.3 cm2 (P less than 0.001 for both comparisons). The rate of event-free survival (defined as survival without recurrent symptoms, repeated valvuloplasty, or aortic-valve replacement) was 18 percent over the mean (+/- SD) follow-up period of 24 +/- 12 months (range, 1 to 47). Significant predictors of event-free survival included the left ventricular ejection fraction and the left ventricular and aortic systolic pressure before valvuloplasty, and the percent reduction in the aortic-valve pressure gradient; the pulmonary-capillary wedge pressure was inversely associated with event-free survival. Although the predicted event-free survival rate for the entire patient group was 50 percent at one year (95 percent confidence interval, 43 to 57 percent) and 25 percent at two years (95 percent confidence interval, 19 to 31 percent), the probability of event-free survival at one year varied between 23 and 65 percent when patients were stratified according to three independent predictors: the aortic systolic pressure, the pulmonary-capillary wedge pressure, and the percent reduction in the peak aortic-valve gradient. CONCLUSIONS. The most important predictors of event-free survival after balloon aortic valvuloplasty were related to base-line left ventricular performance. The best long-term results after valvuloplasty were observed among patients who would also have been expected to have excellent long-term results after aortic-valve replacement."
-"What medical condition did the pregnant young woman experience, and how was it treated?","Microangiopathy of the brain, retina, and ear: improvement without immunosuppressive therapy. We describe a pregnant young woman with branch retinal arteriolar occlusions, encephalopathy, and hearing loss in whom we demonstrated a patent foramen ovale. She improved while receiving anticoagulants and no immunosuppressive therapy. The microangiopathic syndrome of retinopathy, encephalopathy, and deafness may be due to a disturbance of coagulation and/or microembolism."
-What are the key characteristics of eosinophilic pustular folliculitis?,"Eosinophilic pustular folliculitis. Eosinophilic pustular folliculitis is characterized by the spontaneous development of recurrent, sterile papules, pustules, and plaques on the face, trunk, arms, and occasionally the palms and soles. Although the large majority of the reported cases have occurred in Eastern Asians, most patients in the United States have been infants or men seropositive for human immunodeficiency virus. We describe a North American woman with eosinophilic pustular folliculitis who was neither seropositive for human immunodeficiency virus nor of Asiatic descent."
-What medical condition did the 44-year-old male present with in the emergency department?,"Delirium and lactic acidosis caused by ethanol and niacin coingestion. A 44-year-old male presented to the emergency department with altered mental status. He was receiving niacin therapy for hypercholesterolemia, and 16 hours earlier had ingested a large quantity of wine. Past medical history was otherwise unremarkable; physical examination revealed paranoid ideation and asterixis. Laboratory evaluation was significant for metabolic acidosis with a calculated anion gap of 39. Liver enzymes were elevated, and lactic acid level was 9.5 mmol/L (normal: 0.5 to 2.2 mmol/L). White blood cell count was 23,100, but all cultures were negative, and all other diagnostic studies, including bilirubin, prothrombin time, and ammonia were normal. The patient recovered rapidly with hydration and administration of thiamine and magnesium. After psychiatric evaluation, a diagnosis of toxic delirium due to niacin and ethanol coingestion was made. This is the first case reporting toxic delirium and lactic acidosis due to niacin and ethanol coingestion. This occurred in the absence of significant hepatic impairment. Possible mechanisms for the observed derangements are discussed."
-What factors determine the severity and management of bacterial skin and soft tissue infections?,"Treatment of bacterial skin and soft tissue infections. Bacterial skin infections occur commonly and range in severity from mild to life threatening. The severity of skin infections, and their management and prognosis, can depend on the mechanism of infection, the skin structures involved and the infecting organism or organisms. Primary skin infections result from invasion of microorganisms through tiny breaks in the epidermis or from the spread of microorganisms through the bloodstream. Secondary infections arise from pre-existing trauma, burns or surgical wounds; infections involving the soft tissues underlying the skin are also discussed. These also frequently occur in areas of trauma, operation or ischemia. The cause, bacteriologic factors and management of skin infections were studied, with special attention to pyodermas, infections of the foot in diabetic patients and necrotizing soft tissue infections. Choice of appropriate antibiotic agents depends in large part on the infecting organism and patterns of antibiotic susceptibility. In necrotizing soft tissue infections, survival or limb salvage may depend on prompt surgical intervention. In these instances and in some of advanced primary skin infections in which bacteremia is involved, parenteral antibiotics are required. The available options are discussed and a report on the data with the combination agent ticarcillin disodium and clavulanate potassium is presented."
-What was the technical success rate of placing self-expandable stents in treating iliac artery obstruction or stenosis?,"Iliac artery stenosis or obstruction after unsuccessful balloon angioplasty: treatment with a self-expandable stent. Obstruction or stenosis of the iliac artery was treated by placement of a self-expandable stent in 91 patients. A total of 100 lesions was treated. All patients had had poor results of balloon angioplasty including residual stenosis, iliac occlusion, and dissection. The stent used in all cases was a self-expandable stainless steel endoprosthesis mounted on a 7- or 9-French catheter and covered by an invaginated tubular rolling membrane. The diameter of the expanded stent varied from 7 to 12 mm. A total of 129 stents was placed. Technical success was 97%. Thromboses occurred immediately after placement in two patients and within the first month in six; these were mainly due to residual obstruction. Eighty-two (93%) of 88 patients with a follow-up longer than 3 months had no recurrent symptoms. Restenosis caused by intimal hyperplasia inside the stent occurred in 10 patients; these required repeated intervention in only four cases. In the remaining six patients, no further complications occurred. Our results show that self-expanding endoprostheses are of value for improving the results of inadequate percutaneous transluminal angioplasty."
-How does ulinastatin affect polymorphonuclear leukocyte elastase levels and pulmonary vascular resistance after esophageal cancer surgery?,"Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations. To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment."
-How does platelet angiotensin II binding differ between normotensive and hypertensive pregnant women?,"Platelet angiotensin II binding sites in normotensive and hypertensive women. Specific binding of angiotensin II (AII) to platelets was measured in 89 women, 25 nulliparous non-pregnant women and 64 primigravida in the third trimester of pregnancy. There was significantly lower binding in the 25 pregnant women who were normotensive (2.3 fmol/10(9) cells) when compared with the non-pregnant women (9.0 fmol/10(9) cells P less than 0.001). Significantly higher platelet AII binding levels were found in the 39 women who had pregnancy induced hypertension (PIH) (5.5 fmol/10(9) cells) when compared with the 25 normotensive pregnant women (P less than 0.001). Of the 39 women with PIH, platelet AII binding was higher in the 23 women who had pre-eclampsia (7.0 fmol/10(9) cells), when compared with the 16 who had non-proteinuric PIH, (4.6 fmol/10(9) cells) although the difference was not statistically significant (P less than 0.04). The pressor response to AII is also diminished in pregnancy, yet less so if pregnancy induced hypertension develops. Platelets may provide a readily accessible tissue with which to study AII responsiveness in pregnancy."
-What challenges do cytologists face when interpreting gastrointestinal cytology specimens?,"Gastrointestinal cytology. Since the development of the fiberoptic endoscope, laboratories have received cytologic specimens obtained from all segments of the gastrointestinal tract in increasing numbers to identify infectious agents and neoplasms. Adenocarcinomas generally are easily diagnosed and distinguished from reparative atypia, but their precursor lesions, dysplasia and adenomas, provide greater interpretive challenges. The same is true for such entities as malignant lymphomas. Most mesenchymal tumors remain outside the diagnostic capabilities of most cytologists."
-How do the expression patterns of alpha smooth muscle actin and desmin in perisinusoidal cells change between normal adult liver tissue and pathological liver conditions?,"Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. It has been suggested that perisinusoidal liver cells (PSC) play a pivotal role in the pathogenesis of fibrocontractive changes. Using light and electron microscopic immunolocalization techniques, a series of 207 normal and pathologic human liver specimens were evaluated for the expression of alpha smooth muscle (SM) actin and desmin in this and other nonparenchymal cell types. In normal adult liver tissue, PSCs were practically devoid of desmin and exceptionally stained for alpha-SM actin, whereas this actin isoform frequently was encountered in PSCs from the embryonic to the adolescent period. A broad spectrum of pathologic conditions was accompanied by the presence of alpha-SM actin containing PSCs; these were detected preferentially in periportal or perivenular zones according to the predominant location of the underlying hepatocellular damage. The occurrence of this PSC phenotype generally was associated with fibrogenesis and was in some cases detected earlier than overt collagen accumulation. Fibrous bands subdividing liver tissue in cirrhosis and focal nodular hyperplasia, as well as desmoplastic reaction to malignant tumors, contained alpha-SM actin-rich cells admixed with variable proportions of cells coexpressing desmin. In end stages, this population was less numerous than in active fibrotic or cirrhotic processes. Using immunogold electron microscopy, alpha-SM actin was localized in microfilament bundles of typical PSCs. Our results are compatible with the assumption that the appearance of alpha-SM actin and desmin-expressing myofibroblasts results at least in part from a phenotypic modulation of PSCs."
-What percentage of women in the Charleston tricounty area reported having a mammogram within the past year?,"Breast cancer screening in a biracial community: the Charleston tricounty experience. Breast cancer remains a major cause of death among women in South Carolina. Mammography, breast self-examination, and clinical breast examination are effective methods for early detection and subsequent mortality reduction. The Tricounty Breast Cancer Screening Survey assessed knowledge of these methods and recommendations among 503 women in the Charleston area. While 57% of all respondents reported performing breast self-examination at least once per month, 13% of blacks and 6% of whites reported that they do not know how to perform the procedure. Clinical breast examinations within the past year were reported by 69%, yet 11% of blacks and 4% of whites reported that they had never had the examination. More than one third (40%) of all 503 women reported ever having had a mammogram, and 22% reported having had one within the past year. However, 18% of the blacks and 5% of whites reported never having heard of the procedure. The major barriers to mammography appear to be the belief that women do not need regular mammograms and the lack of recommendations by their physicians. Survey results support the need for educating women about what the procedures are, the importance of using them regularly, and the means to comply with them."
-What was the primary objective of the study examining skin test reactivity in patients with lung and breast cancer?,"Skin test reactivity in patients suffering from lung and breast cancer. Mast cells and histamine-mediated reactions may be altered in patients with cancer. In an attempt to characterize the possible skin defects in patients with cancer, we tested 22 patients suffering from lung cancers, 30 from breast cancers, and 30 age-matched normal individuals, using several compounds, in investigating the pathophysiology of the skin response. Histamine hydrochloride (10 and 100 mg/ml) and codeine phosphate (9%) were tested by prick test. Substance P (50 and 500 ng per injection site), phentolamine (20 micrograms per injection site), and carbachol (1 microgram per injection site) were tested by intradermal skin tests. Skin mast cells were also microscopically examined in 10 patients with lung cancer, five with breast cancer, and 10 normal subjects. The mean wheal sizes induced by all the tested substances were similar in patients with cancer and chronic bronchitis and in normal individuals. The flare to histamine, codeine phosphate, and substance P was completely abolished in 7/22 patients with lung cancer, but the lack of flare was not related to the age of the patients, nor to the staging of cancer, nor to metastasis. The mean numbers of alcian blue-stained or toluidine blue-stained positive mast cells were similar in normal subjects and in subjects with cancer. This study does not confirm the skin hyporeactivity of patients with cancer."
-How does isradipine potentially protect against thromboembolic diseases in patients with mild hypertension?,"Decreased fibrinolytic activity and increased platelet function in hypertension. Possible influence of calcium antagonism. Twelve patients with mild hypertension were compared, after 14 days of placebo, with an age- and gender-matched group of 12 healthy volunteers for platelet aggregability and fibrinolytic activity. Following this, 10 of the 12 hypertensives were treated with the calcium antagonist isradipine for 12 months. Blood was drawn for determinations of platelet aggregation and fibrinolytic activity after two weeks and 12 months of treatment. Platelet aggregation tended to increase in the hypertensives compared with controls, indicated by a lowering of the adenosine diphosphate (ADP) threshold value for irreversible aggregation. Tissue-plasminogen activator (t-PA) activity was significantly decreased in hypertensives compared to controls (P less than .05). During therapy, platelet aggregation decreased and t-PA activity increased (P less than .05). The present data suggest that fibrinolytic activity is decreased and platelet aggregation increased in mild hypertension. Besides the blood pressure-lowering effect, isradipine may protect against thromboembolic diseases by modifying platelet function and fibrinolytic activity."
-How do mothers adjust their babies' clothing and bedding in response to different temperatures and seasons?,"How mothers keep their babies warm. Details of room temperature, clothing, and bedding used by night and by day and in winter and in summer were recorded for 649 babies aged 8 to 26 weeks. Room temperature at night was significantly related to outside temperature and duration of heating. Total insulation was significantly related to outside temperature and to minimum room temperature, but there was wide variation in insulation at the same room temperature. High levels of insulation for a given room temperature were found particularly at night and in winter, and were associated with the use of thick or doubled duvets and with swaddling. At least half the babies threw off some or all of their bedding at night, and at least a quarter sweated. Younger mothers and mothers in the lower social groups put more bedclothes over their babies, and the latter also kept their rooms warmer. Many mothers kept their babies warmer during infections."
-What percentage of patients with a closed mastoid cavity were satisfied with their hearing aid?,"Use of hearing aids by patients with closed mastoid cavity. Twenty-five patients who had undergone a closed-cavity tympanomastoidectomy in our Unit and wore a hearing aid in the operated ear were reviewed, and information was recorded on the use of the aid, and the patients' impression about it. The information obtained was analysed and compared with similar data from 39 hearing aid users of similar age with no history of ear surgery. Eighty per cent of the patients with a closed mastoid cavity were satisfied with the aid, and no significant difference was found between the two groups regarding the impression about the aid (chi square 3.06, p = 0.08), or the problems with it, which, in most of the cases, were related to several changes of mould (chi square 2.19, p = 0.13). The various recorded parameters are discussed, and it is concluded that the patients with a closed mastoid cavity can tolerate a hearing aid in the operated ear at least as well as the control subjects with no ear surgery."
-What is the frequency of T-cell receptor delta gene recombination observed in acute lymphoblastic leukemias (ALL)?,"T-cell receptor delta gene recombination in common acute lymphoblastic leukemia: preferential usage of V delta 2 and frequent involvement of the J alpha cluster. A high frequency (greater than 80%) of acute lymphoblastic leukemias (ALL) exhibit a recombination of the T-cell receptor (TCR) delta chain locus. Interestingly, distinct TCR delta elements are preferentially used in immunologic subtypes. In a recent series of 201 children with common ALL (cALL) we observed a TCR delta rearrangement in 162 patients, 57% of the latter showing a hybridization pattern in Southern blots suggestive of a V delta 2 to D delta 3 recombination. To verify this interpretation and to elucidate in more detail the diversity of this common type of TCR delta recombination we amplified and sequenced the junctional region of nine cALL patients and cell line REH-6 by polymerase chain reaction (PCR). A V delta 2 D delta 3 recombination was confirmed in all cases; convincing evidence for the participation of D delta 1 or D delta 2 elements was not obtained. Eight of nine patients and REH-6 showed complete 5' D delta 3 boundaries within V delta 2 D delta 3 segments, a limitation of junctional diversity also detected in 50% of peripheral blood cell clones derived from two healthy probands. Notably, sequence identity at the V delta 2 D delta 3 junction was demonstrated for a cALL and one of the control clones. Another group of 35 of 162 cALL patients was characterized by V delta 2 rearrangements and biallelic deletion of J delta and C delta sequences. Using a J alpha consensus primer, PCR-directed sequence analysis demonstrated V delta 2 D delta 3 J alpha recombinations in all four cases analyzed by this approach. The J alpha segments of these patients differed, but were identical or homologous to published J alpha elements. Our data suggest a recombination pathway of the TCR delta/alpha locus leading to chimeric TCR alpha molecules, containing V delta and, remarkably, also D delta sequences."
-What were the antiproliferative effects of cytokines on squamous cell carcinoma of the head and neck cell lines in this study?,"Antiproliferative effects of cytokines on squamous cell carcinoma. A panel of 12 squamous cell carcinoma of the head and neck (SCCHN) cell lines has been used to determine sensitivity of tumor cells to cytokines, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interferon alfa (IFN-alpha) in vitro. Antiproliferative activity of these cytokines on squamous cell carcinoma of the head and neck monolayers was measured in a colorimetric MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide]-based assay. All 12 cell lines tested were sensitive to IFN-gamma, with the 50% inhibitory dose (ID50) ranging from 0.07 +/- 0.001 to 104 +/- 4.6 U/mL. The TNF-alpha showed antiproliferative activity on three cell lines at relatively high doses (ID50 from 55 +/- 4.1 to 847.10 +/- 10 U/mL), and IFN-alpha was growth inhibitory in only one line (ID50 = 1211 +/- 46.2 U/mL). The combination of IFN-gamma and TNF-alpha had a synergistic antiproliferative effect on eight cell lines and an additive effect on two cell lines. In two cell lines, the effect of the combination was equal to that of IFN-gamma alone. A combination of IFN-alpha and TNF-alpha resulted in cell growth inhibition in six of the seven lines tested, and this effect was synergistic. These in vitro studies indicate that combinations of IFN-gamma and TNF-alpha or IFN-alpha and TNF-alpha may be more growth inhibitory against squamous cell carcinoma of the head and neck and at lower doses than each of these cytokines used singly."
-What are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease?,"Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity. The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux--the ""symptom index."" Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6-100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83-94%), the acid perfusion test had poor sensitivity (32-46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52-67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain."
-What were the response rates and median survival times for patients in the chemotherapy arm (arm A) and the best supportive care arm (arm B) in this randomized trial of advanced non-small-cell lung cancer?,"A randomized trial of alternating chemotherapy versus best supportive care in advanced non-small-cell lung cancer. From April 1985 to September 1988, 128 patients with advanced non-small-cell lung cancer (NSCLC) were enrolled in a prospective randomized trial evaluating chemotherapy (arm A) versus best supportive care (arm B). Chemotherapy consisted of cyclophosphamide 500 mg/m2 intravenously (IV) day 1, epirubicin 50 mg/m2 IV day 1, and cisplatin 80 mg/m2 IV day 1 (CE'P regimen) alternating every 4 weeks with methotrexate 30 mg/m2 IV day 1, etoposide 200 mg/m2 IV day 1, and lomustine (CCNU) 70 mg/m2 orally day 1 (MEC' regimen) until progression. Of the 123 patients (62 treated and 61 controls) eligible for survival, 115 were fully evaluable for response (58 treated and 57 controls). Response rates were 21% partial response, 53% stable disease, and 26% progressive disease in arm A, and 47% stable disease and 53% progressive disease in arm B. Median survival was 34.3 weeks (range, 4.3 to 218.6+ weeks) in arm A versus 21.1 weeks (range, 4.3 to 188.6 weeks) in arm B; the difference was not significant at P = .153 (Mantel-Cox). Subgroups of patients retrospectively analyzed by age, performance status, stage M0/M1, and weight loss or not showed no significant difference in survival. Poor-risk patients (at least two of the following: poor performance status, stage M1, weight loss) of arm A survived significantly longer than poor-risk patients of arm B (23.6 weeks v 12.4 weeks, Mantel-Cox P = .008); a significant difference in survival was also observed between nonsquamous cell patients of arm A and those of arm B (median survival, 38.6 weeks v 16.7 weeks; Mantel-Cox P = .041). Toxicity on the chemotherapy arm was hematologic (World Health Organization [WHO] grade greater than 3) in 12% of CE'P and in 13% of MEC' courses and gastroenteric (WHO grade greater than 3) in 24% of CE'P courses and in 8% of MEC' courses. Our alternating treatment was not significantly superior to supportive care. It is likely that certain subgroups of the NSCLC category may have an advantage with chemotherapy."
-How do tocotrienols affect liver cell damage and enzyme activities in rats treated with 2-acetylaminofluorene (AAF)?,"Effect of tocotrienols on hepatocarcinogenesis induced by 2-acetylaminofluorene in rats. The effects of tocotrienols on hepatocarcinogenesis in rats fed with 2-acetylaminofluorene (AAF) were followed morphologically and histologically for a period of 20 wk. No differences between treated and control rats in the morphology and histology of their livers was observed. Cell damage was extensive in the livers of AAF-treated rats but less extensive in the AAF-tocotrienols-treated rats when compared with normal and tocotrienols-treated rats. 2-Acetylaminofluorene significantly increases the activities of both plasma and liver microsomal gamma-glutamyltranspeptidase (GGT) and liver microsomal UDP-glucuronyltransferase (UDP-GT). Tocotrienols administered together with AAF significantly decrease the activities of plasma GGT after 12 and 20 wk (P less than 0.01, P less than 0.002, respectively) and liver microsomal UDP-GT after 20 wk (P less than 0.02) when compared with the controls and with rats treated only with tocotrienols. Liver microsomal GGT also showed a similar pattern to liver microsomal UDP-GT but the decrease was not significant. These results suggest that tocotrienols administered to AAF-treated rats reduce the severity of hepatocarcinogenesis."
-How does thrombolysis affect the incidence of late potentials in patients within 10 days of acute myocardial infarction?,"Effect of thrombolysis on the evolution of late potentials within 10 days of infarction. Patients with late potentials in the signal averaged electrocardiogram are more at risk of lethal arrhythmias in the period after acute myocardial infarction. To test the effects of thrombolysis on the incidence and evolution of late potentials, 158 consecutive patients were prospectively studied during the first 10 days after acute myocardial infarction. The study population consisted of two groups: 93 control patients treated conservatively and 65 patients treated with intravenous thrombolysis. Recordings of signal averaged electrocardiogram were obtained within two days and 7-10 days after infarction. The incidence of late potentials in the first two days after infarction was not significantly different in the thrombolytic and control groups (14% v 11.8%). By 7-10 days the incidence of late potentials among patients who underwent thrombolysis remained unchanged (14%); however, it increased significantly in the control group (11.8% to 22.5%). Thus thrombolysis seems to reduce the evolution of late potentials within 10 days of infarction. Because the risk of fatal arrhythmias is higher in patients with late potentials this study may partly explain the reduced mortality after thrombolysis."
-What is the rare condition described in this case report involving a patient with Sjogren's disease and a choroid plexus mass?,"Inflammatory pseudotumor of the choroid plexus in Sjogren's disease. We report an unusual case of inflammatory pseudotumor of the choroid plexus of the right lateral ventricle, manifesting as an intraventricular mass and causing unilateral hydrocephalus in a 48-year-old man who suffered from Sjogren's disease and subacute cutaneous lupus erythematosus. The lesion obliterated the normal choroidal architecture by a mixed chronic inflammatory process that was associated with reactive connective tissue changes. Immunohistochemical studies showed no light-chain restriction in the cells, and residual islands of transthyretin-positive epithelial cells were identified, implicating the choroid plexus origin of the mass."
-What potential risks were associated with the colic medication mixture given to the eight infants in the study?,"Colic medication and apparent life-threatening events. Eight infants with histories of apnea and cyanosis were referred to the Southwest SIDS Research Institute for evaluation of apparent life threatening events (ALTE). All of the infants had been treated for colic with a 1:1 concentration of dimenhydrinate (Dramamine) and phenobarbital, hyoscyamine sulfate, atropine sulfate and scopolamine hydrobromide (Donnatal). The medication was pre-mixed by local pharmacists. A comprehensive work-up failed to reveal a cause for the ALTE in any infant. The Dramamine/Donnatal mixture was withdrawn and polygraphic evaluation was conducted. Cardiorespiratory abnormalities were identified in all eight infants and significant gastroesophageal reflux (GER) was documented in four. The possibility that colic medication contributes to cardiorespiratory instability and GER in vulnerable infants requires serious consideration and further evaluation."
-How did acetazolamide therapy impact the visual acuity and macular edema in this pseudophakic patient?,"A direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy. We report the case of a patient with pseudophakic cystoid macular edema whose visual acuity improved promptly with oral administration of 500 mg of acetazolamide extended-release capsules BID for two weeks. However, vision worsened again within two weeks of discontinuation of the treatment. On resumption of acetazolamide therapy for three weeks, and its slow withdrawal during the following three weeks, the macular edema eventually resolved, and vision returned to normal. Our observation provides a direct correlation of the resolution of pseudophakic cystoid macular edema with acetazolamide therapy and shows the importance of tapering the doses of this regimen."
-"What was the prevalence of headache with migrainous features among low-tension glaucoma, primary open-angle glaucoma, and normal subjects in this Japanese study?","Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese. We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients."
-How does high-resolution ultrasound help in evaluating cervical esophageal motility in patients with progressive systemic sclerosis?,"Cervical esophageal motility: evaluation with US in progressive systemic sclerosis. High-resolution ultrasound (US) showed that initial peristalsis propelled ingested soda smoothly and rapidly in 20 volunteers without symptoms who met both manometric and radionuclide esophageal scintigraphic (RES) criteria for normal motility. Twenty-eight patients with progressive systemic sclerosis were classified according to results of RES as follows: group 1, normal esophageal motility (three patients [11%]); group 2, hypomotility of the esophagus, excluding the cervical esophagus (18 patients [64%]); and group 3, hypomotility of the cervical esophagus (seven patients [25%]). In the seven patients of group 3, US demonstrated that an incomplete peristalsis sequence or a feeble peristalsis propelled the soda in a slow and/or to-and-fro motion with low velocities. In the other 21 patients (75%), the soda passed through the esophagus smoothly and rapidly. Retention of soda in the cervical esophagus was not limited to patients with hypomotility of the cervical esophagus. It is concluded that US is useful in evaluation of cervical esophageal motility."
-How does tumor-bearing affect albumin synthesis and degradation in mice compared to non-tumor-bearing animals?,"Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition. Hepatic albumin synthesis, serum albumin turnover, and hepatic albumin messenger RNA (mRNA) content were evaluated in mice bearing a transplantable low differentiated tumor (MCG 101). Results obtained on tumor-bearing mice were compared with results obtained from non-tumor-bearing animals that were either freely fed, food restricted so that their body composition was similar to tumor-bearing animals (pair-weighed), fed a protein-free diet for 5 days, or fasted for 48 hours. Tumor-bearing animals became hypoalbuminemic (33 +/- 5 vs. 44 +/- 3 g/L in freely fed mice), which could be explained by both depressed albumin synthesis (1.95% +/- 0.20% vs. 2.67% +/- 0.27%/h in freely fed mice) and increased albumin degradation. Pair-weighed and protein-calorie malnourished controls had reductions in albumin synthesis (1.81% +/- 0.18% and 1.67% +/- 0.17%/h, respectively) similar to tumor-bearing animals, and the starved controls had the lowest synthetic rates (1.07% +/- 0.10%/h). Albumin degradation was increased only in tumor-bearing animals. Hepatic albumin mRNA in undernourished animals was less (tumor bearing, 32% +/- 5%; pair weighed, 47% +/- 4%; 48 hours fasted, 18% +/- 2%; and protein-calorie malnourished, 26% +/- 3%) than 50% of the mRNA content in the livers of freely fed control mice. Messenger RNA-directed synthesis of albumin in vitro was also depressed to a variable degree in tumor-bearing and malnourished non-tumor-bearing controls. The hypoalbuminemia in tumor-bearing animals could not be prevented by daily injections of a prostaglandin synthesis inhibitor (indomethacin, 1 microgram/g body wt), but the hepatic acute phase protein serum amyloid P decreased from 157 +/- 12 to 103 +/- 9 micrograms/mL in indomethacin-treated tumor-bearing mice (P less than 0.01). It is concluded that increased albumin degradation seen in tumor-bearing animals cannot be explained by associated malnutrition, whereas tumor-associated malnutrition can explain to a large extent the depressed albumin synthesis. Decreased albumin synthesis in tumor-bearing animals correlated in part with a decreased quantity of liver albumin mRNA. The results of the current study are consistent with either a reduced transcription of the albumin gene or a change in albumin mRNA processing and stability communicated by anorexia and malnutrition."
-What is Cogan's syndrome and what are its potential neurological complications?,"Cogan's syndrome complicated by lacunar brain infarcts. Cogan's syndrome, nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction, is an uncommon disease of young adults, probably a manifestation of vasculitis. A 32 year old woman with this syndrome developed a thalamic syndrome with amnesia and dysphasia due to lacunar infarcts."
-"How does autologous bone marrow (ABM) infusion impact neutrophil count recovery in patients receiving high-dose cyclophosphamide, etoposide, and cisplatin?","Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin. Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients."
-What were the main findings of the endoscopic and histological examination in people with and without dyspepsia in this Norwegian population-based study?,"Prevalences of endoscopic and histological findings in subjects with and without dyspepsia OBJECTIVE--To examine the association between dyspeptic symptoms and endoscopic and histological diagnoses. DESIGN--Cross sectional study of people with dyspepsia and controls matched for age and sex identified by questionnaire survey of all inhabitants aged 20 to 69. Endoscopy and histological examination was performed with the examiner blind to whether or not the patient had dyspepsia. SETTING--Population based survey in Sorreisa, Norway. SUBJECTS--All people with dyspepsia and age and sex matched people without dyspepsia were offered endoscopy. A total of 309 people with dyspepsia and 310 without dyspepsia underwent endoscopy, giving 273 matched pairs. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses made according to internationally accepted standards. RESULTS--In all, 1802 of 2027 (88.9%) people returned the questionnaire. Of the 163 subjects who refused endoscopy, 114 were controls. Of five endoscopic and four histological diagnoses only peptic ulcer disease, endoscopic duodenitis, and active chronic gastritis were diagnosed significantly more often in people with dyspepsia. In all, 30% to 50% of the diagnoses of mucosal inflammation and peptic ulcer disease were made among subjects without dyspepsia, and only 10% of both those with and those without dyspepsia had normal endoscopic findings. CONCLUSIONS--The diagnostic findings, with possible exceptions of peptic ulcer disease and endoscopic duodenitis, showed no association of clinical value with dyspeptic symptoms. The small number of ""normal"" endoscopic findings in both those with and those without dyspepsia challenge well accepted endoscopic and histological diagnostic criteria with relation to the upper gastrointestinal tract."
-How are atrial natriuretic factor mRNA levels correlated with plasma concentrations and heart pressures in patients with heart failure?,"Transcription, storage and release of atrial natriuretic factor in the failing human heart. 1. In this study the relationship between the synthesis of atrial natriuretic factor at the level of atrial natriuretic factor mRNA and the atrial storage and circulating plasma levels of atrial natriuretic factor were investigated in 15 patients with heart failure. The patients underwent right and left heart catheterization before cardiac surgery for valve replacement or coronary artery bypass grafting. 2. Plasma concentrations of atrial natriuretic factor were correlated to atrial levels of atrial natriuretic factor mRNA. Atrial levels of atrial natriuretic factor mRNA and plasma concentrations of atrial natriuretic factor exhibited a close correlation to both pulmonary artery pressure and left atrial pressure. No relationship, however, could be found between the right atrial content of atrial natriuretic factor and both the expression of atrial natriuretic factor mRNA in the atria and the plasma levels of atrial natriuretic factor. 3. From these data it may be concluded that increased plasma levels of atrial natriuretic factor in the pressure- and/or volume-overloaded heart are associated with an elevated level of atrial natriuretic factor mRNA. We suggest that not only plasma levels of atrial natriuretic factor but also the expression of atrial natriuretic factor in the atrial are related to left ventricular filling pressures in the failing human heart."
-What makes this case of Hodgkin's disease unique in the context of HIV-seropositive patients?,"Intracerebral Hodgkin's disease in a human immunodeficiency virus-seropositive patient. Intracerebral involvement of Hodgkin's disease (HD) is rarely described, with only 42 cases in the literature. Since the outbreak of the acquired immune deficiency syndrome (AIDS) epidemic, there has been an increasing number of human immunodeficiency virus (HIV)-infected (HIV+) persons who have diffuse non-Hodgkin's lymphoma and, more recently, atypical aggressive HD. The authors report the case of a patient with a history of intravenous drug abuse (IVDA) and Stage IVB HD who, after a drug-induced clinical remission, had intracerebral mixed-cellularity HD. This appears to be the first report of intracerebral HD in a person who is HIV+."
-How do enterocytes from patients with inflammatory bowel disease (IBD) differ from normal enterocytes in their interaction with T cells?,"Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. The mechanisms underlying the chronic unrelenting inflammatory response seen in inflammatory bowel disease (IBD) are poorly understood. We have recently proposed a novel role for the normal intestinal enterocyte, that of antigen presenting cell. However, in contrast to conventional antigen presenting cells, normal enterocytes appear to selectively activate CD8+ antigen nonspecific suppressor T cells. To determine whether failure of this process may be occurring in inflammatory bowel disease, freshly isolated enterocytes from small and large bowel from normal patients, patients with Crohn's disease, ulcerative colitis, and inflammatory (diverticulitis, ischemic colitis, and gold induced colitis) controls were co-cultured with allogeneic T cells in a modified mixed lymphocyte reaction. In contrast to normal enterocytes, 42/42 Crohn's and 35/38 ulcerative colitis-derived epithelial cells stimulated CD4+ T cells, whereas 65/66 and 9/9 normal and inflammatory control enterocytes, respectively, stimulated CD8+ T cells (as previously described), suggesting that the results seen were not just a reflection of underlying inflammation. Furthermore, IBD enterocytes from both histologically involved and uninvolved tissue were similar in their ability to selectively activate CD4+ T cells, speaking for a more global defect in epithelial cells in IBD. Finally, activated T cells from IBD epithelial cell-stimulated mixed lymphocyte cultures displayed potent T helper activity in an antigen nonspecific fashion. Taken together, these data suggest that there may be an intrinsic defect in epithelial cells from patients with IBD, resulting in the inability to normally stimulate suppressor T cells in an antigen overloaded environment."
-What is the relationship between leukoaraiosis and ventricular size in patients with ischemic stroke?,"Leukoaraiosis and ventricular enlargement in patients with ischemic stroke. We studied the relationship between ventricular size and nonspecific periventricular lucency on computed tomograms (leukoaraiosis) in 192 patients with ischemic stroke. Leukoaraiosis did not occur in 21 patients less than 50 years of age; ventricular size could not be measured in an additional 29. Leukoaraiosis was graded from 0 to 4 on a semiquantitative scale; bicaudate, frontal horn, and posterior horn indices were used as measures of ventricular size. Patients with leukoaraiosis were older (difference between means 7 years, t = 5.3, df = 140, p less than 0.0001) and had larger bicaudate indices (difference between means 0.023, t = 3.54, df = 140, p = 0.0007) than patients without leukoaraiosis. Multiple regression analysis demonstrated that the effects of age and leukoaraiosis were independent. No effect of lesion type (cortical or lacunar infarct, or both) on bicaudate index could be demonstrated. Larger values for the bicaudate index were associated with a predominantly anterior location of leukoaraiosis. The frontal horn and occipital horn indices increased with age, but we could not find an effect of leukoaraiosis on these indices."
-What was the primary objective of the Canadian Atrial Fibrillation Anticoagulation (CAFA) Study?,"Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. The Canadian Atrial Fibrillation Anticoagulation Study was a randomized double-blind placebo-controlled trial to assess the potential of warfarin to reduce systemic thromboembolism and its inherent risk of hemorrhage. As a result of the publication of two other ""positive"" studies of similar design and objective, this study was stopped early before completion of its planned recruitment of 630 patients. There were 187 patients randomized to warfarin and 191 to placebo. Permanent discontinuation of study medication occurred in 26% of warfarin-treated and 23% of placebo-treated patients. The target range of the international normalized ratio was 2 to 3. For the warfarin-treated patients, the international normalized ratio was in the target range 43.7% of the study days, above it 16.6% of the study days and below it 39.6% of the study days. Fatal or major bleeding occurred at annual rates of 2.5% in warfarin-treated and 0.5% in placebo-treated patients. Minor bleeding occurred in 16% of patients receiving warfarin and 9% receiving placebo. The primary outcome event cluster was nonlacunar stroke, noncentral nervous systemic embolism and fatal or intracranial hemorrhage. Events were included in the primary analysis of efficacy if they occurred within 28 days of permanent discontinuation of the study medication. The annual rates of the primary outcome event cluster were 3.5% in warfarin-treated and 5.2% in placebo-treated patients, with a relative risk reduction of 37% (95% confidence limits, -63.5%, 75.5%, p = 0.17)."
-What is the importance of anticoagulation therapy after stent implantation in venous bypass grafts?,"The importance of adequate anticoagulation to prevent early thrombosis after stenting of stenosed venous bypass grafts. Stent implantation in native coronary arteries may be complicated by acute thrombosis, despite the use of stringent anticoagulation. Thrombotic occlusion of stented venous grafts may occur less frequently, possibly because of the larger caliber of these grafts. We report our experience with 46 stents (Wallstent, Medinvent, Lausanne, Switzerland) implanted in 35 lesions of 24 consecutive patients (mean age 64 years, range 43 to 75). Two overlapping stents were implanted in seven patients, and three overlapping stents were positioned in two. After implantation, activated partial thromboplastin time was maintained at two to three times the control level by intravenous administration of heparin (160 to 550 mg daily) until thrombotest values were reduced 5% to 10% by acenocoumarol. Impending thrombotic occlusion was recognized in two suboptimally anticoagulated patients: patient A after implantation of four stents and patient B after anticoagulation therapy was discontinued because of acute upper gastrointestinal bleeding. Coronary artery bypass grafting was performed successfully in both patients. A third patient had a myocardial infarction on day 7 after stent implantation, in spite of adequate anticoagulation and optimal medical drug therapy. It is concluded that stringent anticoagulation therapy appears mandatory to maintain graft patency after stent implantation."
-How does the consumption of fish and sea mammals relate to blood pressure during pregnancy among Inuit women in the Keewatin region?,"Blood pressure during pregnancy in Canadian Inuit: community differences related to diet. OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted."
-Can early anti-pseudomonas chemotherapy prevent chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis patients?,"Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable, 26 patients who had never received anti-pseudomonas chemotherapy were randomly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks, whenever Ps aeruginosa was isolated from routine sputum cultures. During the 27 months of the trial, infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects (2 [14%] vs 7 [58%]; p less than 0.05) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group (49/214 [23%] vs 64/158 [41%]; p = 0.0006). Thus, chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy."
-What is the relationship between the severity of primary biliary cirrhosis and pulmonary function in non-smoking patients?,"Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked. We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjogren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity."
-What are the major barriers that impede access to health care for millions of residents in the United States?,"Access to health care. One neurologist's perspective. Millions of residents of the United States have difficulty obtaining health care. Barriers impeding access to care include poverty, physical unavailability of health care services, absence of health insurance, and physicians unwilling to care for uninsured patients. Many patients do not successfully use health services because of educational, cultural, and language barriers. A major access barrier is lack of health insurance. Over 30 million people in the United States have none, the so-called medically indigent. Among them are over 3 million people with neurologic disorders. They have additional barriers to overcome because often they cannot work, cannot drive, have difficulty using public transportation, and have major cognitive and communication impairments. Medical and governmental bodies are debating solutions to the health care access crisis. Physicians should actively participate in this national debate. Neurologists should address the special needs of patients with neurological disorders."
-How did enflurane anesthesia affect the inducibility of ventricular tachycardia in patients undergoing cardiac ablation?,"Effects of enflurane on inducibility of ventricular tachycardia. The effects of enflurane on cardiac electrophysiologic parameters and on inducibility of ventricular tachycardia (VT) by programmed stimulation were studied in 12 patients (11 men, 1 woman, mean age +/- standard deviation 55 +/- 8 years) with drug refractory sustained monomorphic VT who underwent transcatheter ablation with high-energy direct-current shocks. One catheter ablation procedure was performed in 10 patients, whereas 2 ablation sessions were necessary in 2 patients. Programmed ventricular stimulation was performed on 2 separate days (mean interval 19). There were 2 baseline studies, 1 several days before (""baseline study I"") and the second at the beginning of the ablation procedure (""baseline study II"") while the patient was awake and nonsedated. The third programmed stimulation study was done 15 to 30 minutes after administration of anesthesia with enflurane, oxygen and nitrous oxide (""enflurane study""). Rate of sinus rhythm, QRS duration, PQ interval and ventricular effective refractory period were unaltered, whereas QTc interval increased significantly after initiation of anesthesia. Before and after induction of general anesthesia, clinical VT was inducible in all patients. However, in 1 patient, induction of VT was only possible by pacing in the left ventricle after enflurane administration. Based on these data, it is concluded that general anesthesia with enflurane, oxygen and nitrous oxide has no marked influence on inducibility of clinical VTs. Therefore, this type of anesthesia may be useful for nonpharmacologic, ablative procedures requiring general anesthesia."
-What was the mean age of patients diagnosed with endometrial adenocarcinoma in this Norwegian study?,"Endometrial adenocarcinoma in Norway. A study of a total population. Fifteen hundred sixty-six patients with adenocarcinoma of the endometrioid type (AC) were studied. These accounted for 78.9% of all 1985 patients with confirmed endometrial carcinoma diagnosed in Norway in the period 1970 through 1978. Four hundred and sixty-nine patients (29.9%) had well-differentiated tumors, 677 (43.2%) were moderately and 420 (26.8%) poorly differentiated. Eighty-one percent of the patients had surgicopathologic Stage I disease, 11% Stage II, 6% Stage III, and 2% Stage IV. Mean age at diagnosis was 62.1 years (range, 36 to 91). The crude 5-year and 10-year survival rates for all patients were 74.1% and 62.2%, respectively. Five-year crude survival was 86.8% for Grade 1 and 58.3% for Grade 3 tumors. The 5-year crude survival for patients with intramucosal tumors was 88.7% as opposed to 46.9% for patients with tumors infiltrating to the serosa. Sixty-six percent of the patients with vessel invasion survived for 5 years in contrast to 88.6% for patients without vessel invasion. Histologic grade, myometrial infiltration, vessel invasion, and lymphocyte reaction surrounding the tumor were strongly interrelated. Multivariate analysis showed that the age of the patient at the time of diagnosis was the most important single prognostic factor. Disregarding age, survival in operated patients was more dependent on the depth of myometrial invasion than on grade and stage of disease."
-What are the key characteristics of pain perception and coping strategies in patients with noncardiac chest pain (NCCP)?,"Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain."
-What problem can occur following craniofacial procedures involving periosteum stripping over the zygomatic maxillary complex?,"Periosteal suspension of the lower eyelid and cheek following subciliary exposure of facial fractures. Following craniofacial procedures that involve stripping of the periosteum and soft tissue over the zygomatic maxillary complex, descent of soft tissue with a decrease in anterior projection over the malar area and increase in fullness in the nasolabial fold have been seen to be a problem by these authors. Simple repositioning of the soft tissues to their normal anatomic position may be used to alleviate this problem."
-What is the primary advantage of using an uncemented porous-coated anatomic (PCA) hip system in total hip arthroplasty?,"Noncemented porous-coated anatomic total hip arthroplasty. In 1984, as an alternate to the acrylic fixation of the components of total hip arthroplasty, the use of an uncemented porous-coated anatomic (PCA) hip system with a beaded porous coating to achieve biologic fixation was initiated. Since then, 44 patients with cementless acetabular components and 35 patients with cementless femoral components have been followed for a minimum of 24 months and an average of 37 months. Harris hip scores averaged 90.5 at most recent follow-up intervals. No reoperations were necessary for failures of fixation or change in position of the acetabular component. Ominous roentgenographic signs such as progressive bead shedding, progressive radiolucencies, or progressive component migration have not occurred. Two femoral component revisions have been necessary: one for intractable pain and one for pain and roentgenographic loosening. Although thigh pain has been prevalent (20%), all patients have been accommodated and have retained stable hip scores. Progressive radiolucencies and progressive implant subsidence have been rare occurrences. The authors continue to use the cementless acetabular component in all cases of total hip arthroplasty in which initial stability can be obtained. It is their preference to cement the femoral component in patients over 65 or when initial stability cannot be achieved."
-What are interferons and how do they modulate the immune response?,"Immunologic effects of interferon. Interferons can be defined as a family of induced proteins sharing the capacity to exert pleiotropic effects on cell functions and to render cells resistant to virus infection. They are activating genes coding for a number of enzymes, most of which have not yet been characterized, and also by enhancing the synthesis of cell surface components. This enables interferons to modulate the immune response at different levels. This article will focus on the effects of interferon on antigen presentation, regulation of the immune response, activation of macrophage functions, and on its role in the pathogenesis of some diseases."
-What percentage of patients with neurosarcoidosis experienced seizures as the first manifestation of the disease?,"Clinical implications of seizures in neurosarcoidosis. Seizures are a recognized manifestation of neurosarcoidosis, but their clinical relevance is not well established. We reviewed the characteristics, clinical correlations, and prognosis of seizures in 79 patients with neurosarcoidosis. Thirteen (15%) of the 79 patients had seizures, and in eight patients (10%) a seizure was the first manifestation of neurosarcoidosis. These seizures were generalized tonic-clonic seizures in 12 patients (92%) and partial seizures in four patients (31%). The patients with neurosarcoidosis with seizures were more likely to have a progressive or relapsing clinical course and intracranial mass lesions (four patients [31%]), encephalopathy or vasculopathy (eight patients [62%]), or hydrocephalus (five patients [38%]). These central nervous system disorders, rather than the seizures per se, were responsible for most of the serious morbidity and the two deaths (15%) among our patients with seizures. Indeed seizure control was good in 11 (85%) of 13 patients treated with combinations of steroids and antiepileptic medications. Seizures are an important sign in neurosarcoidosis because they are associated with more severe and progressive or relapsing forms of central nervous system sarcoidosis and may be an early manifestation of such disorders."
-What were the MR imaging findings for hepatocellular carcinoma lesions before and after percutaneous ethanol injection (PEI)?,"Small hepatocellular carcinoma treated with percutaneous ethanol injection: MR imaging findings. Fifty-seven magnetic resonance (MR) imaging examinations were obtained at 0.5 T in 19 patients before and after percutaneous ethanol injection (PEI) for 23 hepatocellular carcinoma (HCC) lesions less than 3.5 cm in diameter. Seventeen patients also underwent MR imaging 6 months after completion of therapy. In 11 patients, computed tomography was performed before and after treatment. After PEI, fine-needle biopsy specimens were obtained in all cases. Before treatment, HCC lesions had low signal intensity on T1-weighted images in 13 cases, had the same signal intensity as normal liver parenchyma in six, and had high signal intensity in four; all 23 tumors had high signal intensity on T2-weighted images. After treatment and at 6-month follow-up, all 21 lesions that contained no malignant cells at fine-needle biopsy had high signal intensity on T1-weighted images and had low signal intensity on T2-weighted images. The remaining two HCC lesions in which tumor necrosis was not achieved with PEI displayed a different MR pattern, since the residual neoplastic tissue showed no change in signal intensity on either T1- or T2-weighted images. The authors conclude that MR imaging may be useful for evaluating the effectiveness of PEI in achieving tumor regression."
-"How does nicotine affect gastric mucosal damage, and what protective measures were found to reduce its harmful effects?","Nicotine induced gastric injury. A quantitative macroscopic and microscopic analysis of the protective effects of sucralfate and feeding. Nicotine, while an important component of cigarettes, does not cause gross gastric mucosal damage, although its microscopic effect remains unknown. We have evaluated the histology and the microvascular permeability of (a) the effect of nicotine alone or in combination with ethanol on the gastric mucosa of rats and (b) the effect of feeding and sucralfate on the mucosa of rats treated with nicotine and ethanol. Mucosal injury was assessed histologically by the depth of injury and microvascular permeability by the leakage of fluorescein isothiocyanate-labelled albumin. Our results show that nicotine induced microscopic mucosal damage and accentuated the damage induced by alcohol. The damaging effects on mucosa of nicotine and ethanol, alone or in combination, were reduced by pretreatment with sucralfate. Similarly, feeding reduced the degree of mucosal injury. Nicotine and ethanol increased leakage of albumin into the interstitium and the leakage was reduced after sucralfate pretreatment. This study substantiates the adverse effect of smoking on mucosal damage. Vascular factors are probably involved in the pathogenesis."
-How do fibroblasts from kidneys with interstitial fibrosis (FKIF cells) differ from normal kidney fibroblasts (NKF cells) in terms of growth and collagen synthesis?,"Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. Fibroblast cultures from normal human kidneys (NKF cells) and kidneys affected with interstitial fibrosis (FKIF cells) were analyzed for in vitro growth, differentiation dynamics, and collagen synthesis. FKIF cells are characterized by hyperproliferative growth, resulting in a prolonged mitotic lifespan, by an altered differentiation pattern, and by the expression of the FKIF cell-specific protein ""fibrosin"" (molecular weight 53 kd, isoelectric point [pi] 6.1). Furthermore, FKIF cells synthesize four to five times more total collagen per cell as compared with NKF cells, and the relative amounts of the collagen types produced (type I, III, and V) are significantly different from controls. Thus, the in vitro cell system of FKIF cells may help to elucidate the underlying mechanisms triggering the induction and progression of renal interstitial fibrosis in vivo."
-What is iniencephaly and how was the infant in this case report treated?,"Deformity correction and long-term survival in an infant with iniencephaly. Case report. The authors describe the case of a male infant who was diagnosed prenatally as having iniencephaly. Since birth, the child has grown, thrived, and undergone two successful operations to correct his cervical deformity. This case demonstrates that the iniencephaly defect is not uniformly fatal and that neurosurgical intervention may offer significant improvement in the cervical deformity."
-What did the statistical analysis reveal about the timing of chest pain onset in patients with myocardial infarction?,Circadian variation in the frequency of onset of chest pain in acute myocardial infarction. The time of onset of chest pain was studied prospectively in 1154 consecutive patients admitted to a coronary care unit with myocardial infarction during a five year period. Statistical analysis confirmed a previous finding in a retrospective study of a bimodal frequency distribution with peaks in the time of onset of chest pain between 2330 and 0030 hours and between 0630 and 0830 hours.
-How do angiotensin converting enzyme inhibitors like perindopril affect vascular resistance in spontaneously hypertensive rats (SHR)?,"Angiotensin converting enzyme inhibitors, regional vascular hemodynamics, and the development and prevention of experimental genetic hypertension. During the development of hypertension in young spontaneously hypertensive rats (SHR) vascular resistance is increased, particularly in the renal circulation, and, to a lesser extent, in the splanchnic bed. Treatment with angiotensin converting enzyme inhibitors in young SHR reverses the renovascular abnormalities more effectively than simple vasodilators, suggesting that the resistance changes may depend on angiotensin II. Perindopril treatment during the development of hypertension causes a reduction in blood pressure as a result of a fall in total peripheral resistance, which persists long after treatment is stopped. These long-term effects can be prevented by replacing angiotensin during perindopril treatment. Not all organs share the long-term resistance changes following perindopril treatment, which are most marked in the renal, splanchnic, and cerebral circulations. The heterogeneous patterns of regional vascular resistance during the development and after prevention of hypertension with angiotensin converting enzyme inhibitors in SHR suggest that local factors, for example, angiotensin II related to the tissue renin-angiotensin system or local adrenergic activity, may be important in the genesis of high blood pressure in this genetic model."
-How do oral glycopyrrolate and oral atropine compare in preventing cardiovascular depression during halothane anesthesia induction in infants?,"Is premedication with oral glycopyrrolate as effective as oral atropine in attenuating cardiovascular depression in infants receiving halothane for induction of anesthesia? The authors conducted a double-blind study to compare premedication with oral glycopyrrolate and oral atropine in prevention of bradycardia and hypotension during induction of anesthesia with halothane-N2O in 90 outpatient infants and children aged 1-18 mo who were randomized into three groups to receive either an oral placebo, oral atropine (0.02 mg/kg), or oral glycopyrrolate (0.05 mg/kg) approximately 1 h before induction of anesthesia. Heart rate and mean arterial pressure were measured before drug administration, just before induction of anesthesia, and every minute until surgical stimulation occurred. Glycopyrrolate, at the dose used, was significantly less effective than atropine in attenuating bradycardia during induction; neither glycopyrrolate nor atropine altered the incidence or degree of hypotension. Antisialagogic activity and side effects were comparable, except for significantly more flushing with atropine."
-What unusual hemorrhagic manifestations did the 19-year-old man with sickle cell anemia develop during a painful crisis?,"Case report: epidural and bilateral retroorbital hematomas complicating sickle cell anemia. Early in the course of a painful crisis, a 19-year-old man with known sickle cell anemia (SCA) developed a clinical picture that resembled either early cavernous sinus thrombosis or retroorbital and bifrontal microinfarcts. A brain computer tomography scan demonstrated bilateral retroorbital hemorrhages along with a left frontal epidural hematoma. In the absence of trauma, thrombocytopenia, or any other detectable hemostatic defect, this type of hemorrhagic manifestation in the setting of SCA has not, to our knowledge, been previously reported in the literature."
-What are the key differences between vigorous and classic achalasia according to the study?,"Classic and vigorous achalasia: a comparison of manometric, radiographic, and clinical findings. Compared with classic achalasia, vigorous achalasia has been defined as achalasia with relatively high esophageal contraction amplitudes, often with minimal esophageal dilation and prominent tertiary contractions on radiographs, and with the presence of chest pain. However, no study using current manometric techniques has compared manometric, radiographic, and clinical findings in vigorous and classic achalasia or questioned the usefulness of making this distinction. Fifty-four cases involving patients with achalasia whose radiographic and manometric studies were performed within 6 months of each other were available for review. Patients with vigorous achalasia (n = 17), defined by amplitude greater than or equal to 37 mm Hg, and patients with classic achalasia (n = 37), defined as amplitude less than 37 mm Hg, had substantial overlap in radiographic parameters of esophageal dilation, tortuosity, and tertiary contractions. Manometric properties of repetitive waves and lower esophageal sphincter pressure and clinical aspects of chest pain, dysphagia, heartburn, and satisfactory responses to pneumatic dilation were similar in both forms of achalasia. A separate analysis of patients with mean contraction amplitude greater than 60 mm Hg revealed similar findings. It is concluded that use of amplitude as a criterion for classifying achalasia is arbitrary and of dubious value."
-What was the prevalence of obesity among American Indian adults according to the 1987 National Medical Expenditure Survey?,"Prevalence of obesity in American Indians and Alaska Natives. Obesity is an important risk factor for cardiovascular diseases and non-insulin-dependent diabetes, which are chronic diseases that afflict American Indians and Alaska Natives today. Because American Indians are not represented in most national health and nutrition surveys, there is a paucity of data on actual prevalence of obesity in American Indians. We estimated prevalence of overweight and obesity for American Indian adults, school-age children, and preschool children from existing data. The prevalence of obesity in adults was estimated from self-reported weights and heights obtained from a special survey of American Indians performed as part of the 1987 National Medical Expenditure Survey. Prevalence of obesity in American Indians was 13.7% for men and 16.5% for women, which was higher than the US rates of 9.1% and 8.2%, respectively. Obesity rates in American Indian adolescents and preschool children were higher than the respective rates for US all-races combined."
-How does dipyridamole echocardiography test (DET) help in detecting jeopardized myocardium after thrombolytic therapy?,"Dipyridamole echocardiography test. A new tool for detecting jeopardized myocardium after thrombolytic therapy. BACKGROUND. We wished to assess whether dipyridamole echocardiography test (DET) can detect jeopardized myocardium after thrombolytic therapy. METHODS AND RESULTS. Seventy-six consecutive patients with a first acute myocardial infarction (AMI) were treated with 2 million IU urokinase i.v. within 4 hours of the onset of AMI and underwent high-dose (as much as 0.84 mg/kg over 10 minutes) DET 8-10 days after AMI. The results were correlated to the anatomy of the infarct-related vessel (IRV). In patients with positive DET, we evaluated the wall motion score index (WMSI; a semiquantitative integrated estimation of extent and severity of the stress-induced dyssynergy). WMSI was derived by summation of individual segment scores divided by the number of interpreted segments. In a 13-segment model, each segment was assigned a score ranging from 1 (normal) to 4 (dyskinetic). Fifty-three patients had positive results on DET. Of these, 42 had dipyridamole-induced new wall motion abnormalities (WMAs) confined to the infarct zone or adjacent segments. In these patients, mean WMSI increased from 1.46 +/- 0.26 (at resting conditions) to 1.73 +/- 0.35 (at peak dipyridamole) (p less than 0.01), whereas no significant change was detected in negative patients (1.6 +/- 0.34 versus 1.57 +/- 0.34, p = NS). Coronary angiography showed a patent IRV (TIMI grade 2 or 3) in 53 patients and no or minimal reperfusion (TIMI grade 0 or 1) in 23 patients. A patent IRV with critical residual stenosis was found in 35 of 42 patients with dipyridamole-induced WMAs in the infarct zone and in 18 of 34 patients without WMAs (p less than 0.05). Among the 23 patients with occluded IRVs, nine had collateral flow to the distal vessel; six of these had a positive DET. Thus, the sensitivity and specificity for identifying a critically stenotic but patent IRV or the presence of a collateral-dependent zone were 66% and 93%, respectively. In a subset of nine patients with a positive DET in the infarct zone or adjacent segments, DET and a control coronary angiography were repeated 1-3 months after an angiographically successful (residual stenosis, 50% or less) coronary angioplasty in the IRV. The repeat DET was negative in eight patients (all with patent IRV at control angiography) and again positive in one patient, who showed restenosis at angiography. The WMSI, at resting conditions was similar before and after angioplasty, whereas it differed significantly at peak dipyridamole (1.7 +/- 0.2 versus 1.4 +/- 0.2, p less than 0.01). CONCLUSIONS. DET can identify the anatomy of the IRV, and dipyridamole-induced WMAs within the infarct zone detect regions with jeopardized myocardium that may benefit from intervention."
-What percentage of postmenopausal women experienced persistent side effects from tamoxifen treatment in this study?,"Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance."
-What were the significant risk factors related to an obstructing tumor in Japanese patients with colorectal cancer?,"Prognostic factors in Japanese patients with colorectal cancer: the significance of large bowel obstruction--univariate and multivariate analyses. In order to define prognostic factors in colorectal carcinoma, univariate and multivariate analyses were carried out on data from 113 Japanese patients treated in a typical general hospital in Japan. In the univariate analysis, a poor prognosis was seen in those with poorly differentiated adenocarcinoma, in tumors that perforated the visceral peritoneum or that invaded directly other organs or structures (T4), in metastasis to the nodes along the main vascular pedicle (N3), in lymphatic permeation, in blood vessel invasion, in peritoneal dissemination, in Dukes C stage, and in those with lesions presenting with large bowel obstruction. Of these, only lymph node metastasis and peritoneal dissemination had an independent prognostic significance when a multivariate Cox analysis was performed. The significant risk factors related to an obstructing tumor were determined by multivariate logistic regression analysis. The significant variables were patient's age, nodal involvement and peritoneal dissemination. Since lymph node metastasis and peritoneal dissemination proved significant in both multivariate analyses, we propose that the presence of large bowel obstruction is not an independent prognostic factor in patients with colorectal carcinoma. In poor-risk patients who have an obstructing tumor, a staged operation should be attempted for definitive curative surgery."
-How do the clinical manifestations of loiasis differ between endemic and non-endemic populations?,"Loiasis in endemic and nonendemic populations: immunologically mediated differences in clinical presentation. To define the clinical spectrum of loiasis more precisely and to begin to assess the immunologic basis for the difference in clinical manifestations between visitors to endemic areas and natives of these areas, 51 West African patients with loiasis were evaluated and compared with 42 infected expatriates. Microfilaremia was present in 90% and Calabar swellings in only 16% of the endemic patients. Conversely, only 10% of the expatriates were microfilaremic while 95% complained of Calabar swellings. The endemic population showed significantly decreased levels of peripheral blood eosinophils, parasite-specific IgG, and lymphocyte proliferation to parasite antigens compared with the nonendemic population. These findings support the hypothesis that differences in the modulation of the immune response to parasite antigen are responsible for the observed differences in clinical presentation between expatriate and endemic populations with loiasis."
-What percentage of elderly patients in the primary care setting reported having at least weekly heartburn?,"Prevalence of gastroesophageal reflux in elderly patients in a primary care setting. Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER--none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed."
-What percentage of laboratory and nursing training programs made the hepatitis B vaccine available to their students?,"Availability and use of hepatitis B vaccine in laboratory and nursing schools in the United States. Hepatitis B is a well-documented occupational hazard for health care workers, including both laboratory and nursing personnel. Since the development of effective hepatitis B vaccines, the Immunization Practices Advisory Committee (ACIP) has recommended that health care workers receive the vaccine. In this study, 78 laboratory training programs and 83 nursing training programs were surveyed regarding availability and usage of hepatitis B vaccine. The hepatitis B vaccine was made available to students in 81 percent of the laboratory programs and 23 percent of the nursing programs. In those programs making the vaccine available, only 59 percent of the laboratory programs and 5 percent of the nursing programs reported a high (greater than 75 percent) use by students. Concern about cost and payment for the vaccine was the most common reason (80 percent) noted by laboratory schools that did not have hepatitis B vaccination programs for students. Of the nursing schools that did not have vaccine programs, 58 percent had not yet considered a program. At laboratory schools with vaccination programs, who paid for the vaccine (hospital or school versus student) was among the most important determinants for vaccine usage by students. These findings point out that some laboratory schools and many nursing schools have not applied the ACIP recommendations to their own programs. Educational efforts and creative payment plans for the vaccine are needed to increase the availability and use of hepatitis B vaccine among laboratory and nursing students."
-What was the purpose of using polymerase chain reaction in this study of multiple sclerosis patients?,"Analysis of retroviral sequences in the spinal form of multiple sclerosis. The polymerase chain reaction was used, in a blind study, to look for retroviral sequences in DNA extracted from the peripheral blood mononuclear cells of 11 patients with the spinal form of multiple sclerosis (MS). Control subjects consisted of 7 patients with other neurological diseases and 5 healthy blood donors. Three sets of oligonucleotides were used. They could detect all known human oncoretroviruses, lentiviruses, or spumaretroviruses. The primers recognized conserved sequences in the long terminal repeats of the proviral DNA. Control experiments showed that the primers crossreacted within the human immunodeficiency virus or human T-cell lymphotropic virus group and that they provided the expected level of sensitivity. Therefore the assay could have detected not only known human retroviruses but also new related members. In spite of this, no retroviral sequences were detected in either the MS or the control specimen."
-What was the main objective of the clinical trial involving the E5 murine monoclonal IgM antibody?,"A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated."
-How does complete Freund's adjuvant (CFA) treatment affect diabetes onset and insulitis in NOD mice?,"Prevention of insulitis and diabetes onset by treatment with complete Freund's adjuvant in NOD mice. In studies of immune cell defects in autoimmune diabetes mellitus, we observed that complete Freund's adjuvant (CFA) prevented the onset of diabetes when injected into 8- to 10-wk-old prediabetic nonobese diabetic (NOD) mice. The prevalence of the onset of diabetes in the CFA-injected versus uninjected NOD mice was 2 of 81 (2.5%) vs. 231 of 379 (61%) among females and 2 of 44 (4.5%) vs. 83 of 336 (25%) among males, respectively. The incidence of histologically identifiable insulitis was significantly reduced in CFA-treated prediabetic female NOD mice (18%) compared with the incidence in female age-matched controls (70%). Splenocytes or Mac-(1+)-enriched splenocytes from CFA-treated NOD mice, when cotransferred with splenocytes from diabetic mice, reduced the incidence of diabetes provoked by diabetic splenocytes in vivo. In the spleen, CFA injection induced sustained increases in cell proliferation and an associated major increase in the numbers of an immature cell type that expressed the Mac-1 surface antigen. In CFA-treated NOD mice, lymphocytes derived from the spleen failed to respond in vitro to stimulation by the mitogen concanavalin A or by anti-CD3. When cocultured, Mac-1+ cells, enriched from the splenocytes of CFA-treated mice, suppressed concanavalin A- or anti-CD3-induced proliferation of T lymphocytes derived from either the spleen or thymus of untreated NOD mice. Therefore, treatment with CFA prevents the development of diabetes, and concomitantly, insulitis while stimulating the generation of splenic suppressor cells that are capable of suppressing diabetogenic T-lymphocyte function in vivo and in vitro."
-What was the purpose of the study comparing intermittent intravenous injections and patient-controlled analgesia for sickle cell crisis pain in the emergency department?,"Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department. BACKGROUND.--The purpose of this study is a prospective assessment of morphine sulfate administration by intermittent intravenous (IV) injections (Int-IV) vs patient-controlled analgesia (PCA) in patients in the emergency department (ED) with sickle cell crisis pain. METHODS.--Patients were at bed rest and received intravenous hydration. Linear analog scale for pain intensity and verbal pain scale, level of alertness, and vital signs were assessed prior to therapy, every 60 minutes thereafter, and at the time of discharge from the ED. Patients were randomized to Int-IV or PCA. During phase 1, patients in the Int-IV group received morphine sulfate 4 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 2 mg bolus then 1.0 mg with a 6-minute lockout. During phase 2, patients in the Int-IV group received morphine sulfate 8 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 5 mg bolus then 2.7 mg with a 10-minute lockout. Data were analyzed by unpaired t test, general linear modeling, Mann-Whitney U test, and chi 2 test. RESULTS.--During phase 1, 10 patients (28.3 +/- 7.3 years) received Int-IV and 10 patients (33.9 +/- 12.5 years) received PCA. Treatment groups did not differ significantly regarding duration of pain, amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, level of alertness, or vital signs except for a significantly lower final respiratory rate with Int-IV. In phase 2, 12 patients (28.4 +/- 5.6 years) received Int-IV and 13 patients (26.8 +/- 8.1 years) received PCA. The PCA groups had a significantly shorter elapsed time between onset of pain and treatment (7.3 +/- 6.5 hours) when compared with the Int-IV group (18 +/- 16.9 hours). Treatment groups did not differ significantly with respect to total amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, vital signs, or level of alertness. The PCA group had a significant reduction in length of stay in the ED during phase 2 when compared with phase 1. The ED discharge rate and the incidence of side effects did not differ significantly between groups. CONCLUSION.--At both the low- and high-dose regimens, PCA is equally safe and effective and may be used in place of Int-IV administration of morphine in the ED treatment of sickle cell crisis pain."
-What was the main finding of the study regarding alcohol consumption and supraventricular tachyarrhythmias?,"Alcohol consumption of patients with supraventricular tachyarrhythmias other than atrial fibrillation. We studied the recent alcohol consumption and other possible precipitating factors in 99 consecutive patients (53 men and 46 women) all under 65 years of age with sustained re-entry and automatic supraventricular tachyarrhythmias and compared them with those of two groups of controls. One control group was derived from the Emergency Room patients and matched for age and sex; the other group (44 men, 22 women, mean age 48.7 years) was randomly selected from the general out-of-hospital population. There were 50 patients with supraventricular tachycardia, 30 with atrial flutter, and 19 with paroxysmal atrial tachycardia. Coronary heart disease (14% of patients), hypertension (10%), and dilated cardiomyopathy (6%) were the most prevalent cardiovascular diseases associated with the arrhythmias. The self-reported alcohol consumption of patients with arrhythmias during the week preceding the arrhythmia did not differ significantly from that of hospital or population controls, although significantly more patients than controls had liver enzyme levels above normal; neither were there any significant differences between the groups regarding prevalence for alcoholism as judged by the CAGE questionnaire. The results were essentially similar when patients with supraventricular tachycardia and those with intra-atrial tachyarrhythmias (flutter and paroxysmal tachycardia) were separately compared with the controls. We conclude that alcohol consumption, although a risk factor for atrial fibrillation, is not associated with the induction of other supraventricular tachyarrhythmias in patients of working age."
-What are the potential health risks associated with prolonged inhalation of mineral spirits?,"Mineral spirits inhalation associated with hemolysis, pulmonary edema, and ventricular fibrillation. A previously healthy 42-year-old woman developed severe dyspnea, chest discomfort, and malaise several hours after prolonged exposure to concentrated vapors from mineral spirits. On the way to the hospital, she sustained a cardiopulmonary arrest; on arrival several minutes later, she was found to be in ventricular fibrillation and was resuscitated. Her hospital course included slowly resolving cardiac abnormalities, amnesia, noncardiogenic pulmonary edema, abrupt hemolytic anemia, sustained rhabdomyolysis, and other metabolic abnormalities. It is highly probable that this syndrome represented acute and near-lethal toxicity caused by the inhalational exposure to the petroleum distillate known as mineral spirits. It is important that physicians be aware of this syndrome in order to recognize it on presentation and to warn patients of the risk of such toxic exposure."
-What was the outcome of ciprofloxacin treatment for patients with refractory chronic bacterial prostatitis caused by Escherichia coli?,Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months. A total of 16 men suffering from refractory chronic bacterial prostatitis caused by Escherichia coli was treated with ciprofloxacin for 4 weeks. After a median followup of 30 months (range 21 to 36 months) 10 of the 16 patients were considered cured as judged by bacteriological results and clinical symptoms. In 2 men a second ciprofloxacin regimen obviously showed success also. In 2 patients ciprofloxacin therapy failed and in 2 therapy had to be discontinued due to side effects of the central nervous system.
-What are the four categories of hypertension in pregnancy?,"Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years? High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive."
-What are the key characteristics of desmoplastic small cell tumors based on microscopic and immunohistochemical findings?,"Desmoplastic small cell tumors of the peritoneum coexpressing mesenchymal and epithelial markers. Desmoplastic small cell tumors arising diffusely within the abdomen and lacking an apparent organ of origin are rare. Most previously reported cases occurred in children, but young adult patients also have been described. Light microscopic examination shows the tumors to be composed of nests of small cells surrounded by an abundant desmoplastic stroma. Immunohistochemical findings reveal multidirectional differentiation with coexpression of cytokeratin, milk fat globule, neuron-specific enolase, Leu-7, desmin, and vimentin. Electron microscopic examination demonstrates paranuclear condensations of intermediate filaments. The authors describe two patients who died of their disease, despite aggressive chemotherapy and surgical intervention."
-What were the mortality rates for ischaemic heart disease and cerebrovascular disease among different ethnic groups in England and Wales during the 1970s and 1980s?,"Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade."
-What was the average peak effect of botulinum toxin treatment for tremors in this study?,"Botulinum toxin treatment of tremors. We report the results of an open trial of botulinum toxin (Botox) in the treatment of 51 patients with disabling tremors, classified as dystonic (14), essential (12), combination of dystonic and essential (22), parkinsonian (1), peripherally induced (1), and midbrain (1). The average age of the patients was 55.8 years, and duration of symptoms was 13.9 years. During a total of 160 treatment visits, an average of 242 +/- 75 units of Botox was injected per visit in cervical muscles of 42 patients with head tremor and 95 +/- 38 in forearm muscles of 10 patients with hand tremor; one patient was injected in both. The average peak effect for all patients was rated as 3.0 (0 to 4 scale). Thirty-five (67%) patients improved (peak effect greater than or equal to 1). The average latency from injection to response was 6.8 days, and the average duration of maximum improvement was 10.5 weeks. Local complications, lasting an average of 20.6 days, were noted in 17 (40%) patients injected for head tremor, consisting chiefly of dysphagia in 12 (29%), transient neck weakness in four (10%), and local pain in two (5%). Six (60%) patients with hand tremor had transient focal weakness. EMG recordings showed decreased amplitude of EMG bursts after Botox treatment. The results of this pilot study indicate that Botox injections can be used to control tremor in patients in whom other forms of therapy have failed."
-What complications did the patients with chickenpox pneumonia experience in this case report?,"Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation."
-How does tumor cell DNA content (ploidy) relate to recurrence rates in colorectal cancer patients?,"A prospective evaluation of the effect of tumor cell DNA content on recurrence in colorectal cancer. Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy."
-What are the key challenges emergency physicians face when treating patients with headaches?,"Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache."
-What genetic modifications cause the nonsecretory alpha-chain disease plasma cells to produce only membrane-form alpha-chain?,"Gene deletions force nonsecretory alpha-chain disease plasma cells to produce membrane-form alpha-chain only. We studied a case of nonsecretory alpha-chain disease. The proliferating plasma cells contained a short transcript coding for a truncated membrane-form alpha 1-chain. The productive alpha-gene bore several noncontiguous deletions affecting the VHDJH and CH1 regions. Two deletions were accompanied with peculiar insertions containing duplications. The first insertion contained an acceptor splice site and was present in part in the mature transcript, thus coding for an abnormal aminoterminal peptide. Another deletion located 3' to CH3 eliminated the polyadenylation site of secreted-form alpha-mRNA. As a result, only membrane-form alpha mRNA was present in the tumoral plasma cells, thus explaining the nonsecretory phenotype of the disease. Comparison of cDNA and genomic sequences showed that the previously undescribed human alpha membrane region is encoded by a single exon, beginning with two alternate acceptor splice sites, and comprises either 65 or 71 amino acids."
-What is the purpose of the anterior sternal retraction technique in reoperative median sternotomy?,Anterior sternal retraction for reoperative median sternotomy. The incidence of reoperative median sternotomy for repeat cardiac surgery is increasing. Reoperative median sternotomy is associated with a higher morbidity and mortality than first-time cardiac surgery. A portion of this morbidity and mortality may be due to direct injury to the heart and great vessels in the process of reopening the sternum. We report a new technique utilizing anterior sternal retraction that allows division of adhesions between the undersurface of the sternum and the heart and great vessels under direct vision. This technique enables the surgeon to minimize the risk of serious injury to these underlying structures during reoperative cardiac surgery.
-How does physical overdistension of the ventricular wall affect the production of atrial natriuretic peptide (ANP) in cardiomyocytes?,"Physical overdistension converts ventricular cardiomyocytes to acquire endocrine property and regulate ventricular atrial natriuretic peptide production. Atrial natriuretic peptide (ANP) is present in adult atria but at very low concentrations in normal adult mammalian ventricles. In the atria, the production of ANP is regulated by physical distension of the atrial wall. The same phenomenon was investigated in the ventricles of rats and men. Cardiac tissues from human ventricular aneurysm (n = 5), spontaneously hypertensive rats (n = 30), and rats that had overloaded left ventricles induced by surgery (n = 84) were studied with the methods of light microscopic immunocytochemistry, electron microscopic immunogold staining, and RNA-RNA tissue in situ hybridization. It was found that the levels of ANP gene expression, ANP immunoreactivity, and ANP-containing specific granules in the overburdened ventricles were elevated and their degrees of fluctuation were directly proportional to the force of physical distension applied to the ventricular cardiomyocytes. In rats, ANP mRNA and ANP immunoreactivity returned to the control level seven days after the ventricular overload was surgically released. The changes of ANP and its mRNA in the ventricles were related more closely to the changes of intraventricular pressure than to cardiocytic hypertrophy. In addition, ANP immunoreactivity was demonstrated in Purkinje cells and periarteriolar cardiomyocytes in the ventricles of normotensive rats. In conclusion, physical overstretch of the ventricle wall is likely to be the triggering factor affecting ventricular cardiomyocytes to acquire endocrine property, and also to regulate the production of ventricular ANP, thereby contributing to the control of the blood volume and the blood pressure."
-What were the key functional outcomes observed in children with sickle-cell disease who had experienced strokes?,"Functional outcomes of children with sickle-cell disease affected by stroke. The nature and degree of functional recovery after stroke in children with sickle-cell disease (SCD) has not been extensively investigated. The purpose of this study was to evaluate retrospectively the functional status of 14 SCD children who had had strokes and to compare them with age-matched and gender-matched SCD children who had not had strokes. By doing so, we would be able to quantify the eventual physical and cognitive functional outcomes of survivors of stroke secondary to SCD and assess the impact of stroke on these patients. These children (five boys and nine girls) with SCD and stroke(s) were 11.6 +/- 4.3 years of age (range five to 18 years). They experienced one to three strokes at a mean age of 6.1 +/- 5.2 years (range one to 17 years). A series of tests were administered to these subjects to evaluate physical and psychosocial functions. These tests were performed at least one year after the latest stroke. This study showed that all of the SCD-stroke children were physically independent. Only a few had impairments of hand functions and mild difficulties in self-care activities. However, most of these children demonstrated intellectual deficits ranging from borderline to moderate mental retardation, reduced language functions ranging from low normal to retarded range, and problems in adjustment. Intelligence quotient of the children with SCD-stroke(s) was significantly lower than those of age-matched and gender-matched nonstroke SCD children, suggesting that stroke caused an adverse effect on the cognitive functioning of these children. The results indicate that in the SCD-stroke children psychosocial deficits outweighed physical disabilities."
-What percentage of appendicitis cases were perforated during the 5-year review at the Guthrie Medical Center?,"Acute appendicitis. A 5-year review. A startling 31 per cent rate of perforated appendicitis in 1984 prompted a 5-year review at the Guthrie Medical Center. An increase over previous rates of 13 per cent and 0 per cent in 1964 and 1944 was confirmed in this study. Perforation accompanied 44 of 240 cases of appendicitis (18.3%); diagnostic accuracy in 295 cases undergoing operation was 81.4 per cent. Groups at risk for perforation were patients in the first decade of life (34.3% with perforations) and those over 50 years of age (48% perforated). Perforation rates were generally inversely related to accuracy. Accuracy was poorest in women in the second to fourth decade or those in the mid-portion of the menstrual cycle. When the appendix was not perforated, complications occurred in 8.7 per cent of patients while 29.5 per cent with a perforation had a complication. The mean hospital stay was prolonged by 2.5 days if the appendix was perforated. An increased awareness of the risk by both the public and physicians is essential to reduce the number of perforations."
-What method did the study suggest for determining the optimal time to remove a nephrostomy tube?,Intrarenal pressure following pyeloplasty or percutaneous surgery. In a study of 37 patients it was shown that recording the intrapelvic pressure is a safe and reliable means of judging the best time to remove a nephrostomy tube. No post-operative complications were encountered and the procedure has the added advantage of avoiding the use of X-rays.
-What is oncocytic metaplasia of the pharynx and how was it typically discovered in the reviewed cases?,"Oncocytic metaplasia of the pharynx. Oncocytic metaplasia of the pharynx has been infrequently described, with only two previous cases in the literature. With the advent of panendoscopy during the last decade, however, a better understanding of this histopathologic diagnosis is desirable. Thirty-three cases are reviewed, with thirty occurring in the nasopharynx. This was most commonly discovered as an unrelated finding during endoscopic evaluation of a head and neck mass or malignancy in twenty-two patients, either histologically after random biopsy or after biopsy of small but visible lesions. An additional eight cases manifested otitis media or eustachian tube dysfunction. The histology, terminology, and benign clinical nature of these lesions are discussed."
-How did the researchers use a cholera toxin transgene to study the effects of cAMP on pituitary growth hormone-producing cells?,"Pituitary hyperplasia and gigantism in mice caused by a cholera toxin transgene. Cyclic AMP is thought to act as an intracellular second messenger, mediating the physiological response of many cell types to extracellular signals. In the pituitary, growth hormone (GH)-producing cells (somatotrophs) proliferate and produce GH in response to hypothalamic GH-releasing factor, which binds a receptor that stimulates Gs protein activation of adenylyl cyclase. We have now determined whether somatotroph proliferation and GH production are stimulated by cAMP alone, or require concurrent, non-Gs-mediated induction of other regulatory molecules by designing a transgene to induce chronic supraphysiological concentrations of cAMP in somatotrophs. The rat GH promoter was used to express an intracellular form of cholera toxin, a non-cytotoxic and irreversible activator of Gs. Introduction of this transgene into mice caused gigantism, elevated serum GH levels, somatotroph proliferation and pituitary hyperplasia. These results support the direct triggering of these events by cAMP, and illustrate the utility of cholera toxin transgenes as a tool for physiological engineering."
-What was the outcome of the balloon dilatation attempts on fetuses with critical aortic stenosis?,"Balloon dilatation of the aortic valve in the fetus: a report of two cases. Because they had irreversible damage to the left ventricular myocardium none of 12 patients with critical aortic stenosis diagnosed prenatally survived after postnatal treatment. This experience prompted three attempts at intrauterine balloon dilatation of the aortic valve in two fetuses with this condition. On each attempt the balloon catheter was successfully delivered to the left ventricle. In the first fetus the aortic valve was not crossed and the fetus died the next day. In the second fetus the balloon was correctly positioned across the aortic valve and inflated in the valve ring. After delivery, a further balloon angioplasty was performed; this relieved the stenosis but the patient died five weeks later from persisting left ventricular dysfunction related to endocardial fibroelastosis. Balloon angioplasty is feasible in fetal life but the prognosis depends on the ability of the relief of stenosis to limit, prevent, or allow regression of left ventricular damage before delivery."
-What is the new method described for dealing with late-presenting spontaneous esophageal ruptures?,"New method for dealing with late-presenting spontaneous esophageal ruptures. A new technique is described for dealing with late-presenting spontaneous esophageal ruptures. This method requires only a short period of general anesthesia to drain the periesophageal abscess by a drainage tube inserted into the abscess cavity from the esophagus with the aid of a gastroscope and fluoroscopy. Gastric fluids are diverted from the esophageal rupture with a gastrostomy, and a jejunostomy is used for enteral feeding. The esophagus is retained, and closure of the fistula with resumption of normal swallowing is documented with serial sinograms."
-What anaesthetic technique was used for a parturient with severe mitral stenosis and pulmonary hypertension during an urgent Caesarean section?,"Alfentanil for urgent caesarean section in a patient with severe mitral stenosis and pulmonary hypertension. We present the case of a parturient with severe mitral stenosis and pulmonary hypertension who received general anaesthesia using alfentanil for urgent Caesarean section. Alfentanil promoted haemodynamic stability and allowed immediate postoperative extubation. Epidural morphine provided postoperative analgesia. This combination permitted early ambulation and prevention of thromboembolism. A disadvantage of this technique, neonatal respiratory depression, was promptly reversed with a single dose of naloxone. The anaesthetic management of mitral stenosis in pregnancy is discussed and the neonatal pharmacokinetics of maternally administered alfentanil are presented."
-What is the specific genetic mutation identified in the patient with adenosine deaminase deficiency (ADA-SCID)?,"Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). We have identified a previously unrecognized missense mutation in a patient with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The mutation is a G646-to-A transition at a CG dinucleotide and predicts a glycine-to-arginine substitution at codon 216. Computer analysis of secondary structure predicts a major alteration with loss of a beta-pleated sheet in a highly conserved region of the protein. The basepair substitution also generates a new site for the restriction enzyme BstXI in exon 7 of the genomic DNA. Digestion of genomic DNA from the patient and from his parents revealed that he was homozygous for the mutation and that his mother and father were carriers. This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase. Analysis of DNA from 21 additional patients with ADA-SCID and from 19 unrelated normals revealed that, while none of the normal individuals showed the abnormal restriction fragment, two of the 21 patients studied were heterozygous for the G646-to-A mutation."
-What are the key factors for survival in cases of spontaneous abdominal arteriovenous fistulae?,"Spontaneous abdominal arteriovenous fistulae: report of eight cases and review of the literature. The spontaneous rupture of an abdominal aneurysm into an adjacent major vein results in a profound and rapidly worsening haemodynamic disturbance. Survival depends on prompt diagnosis and closure of the fistula at operation. Eight cases are reported and modes of presentation, diagnostic criteria and management principles are reviewed in a detailed analysis of 148 cases in the English literature."
-How does the acidity of nebulized salbutamol solution affect oxygen levels in wheezy infants?,"Hypoxaemia after nebulised salbutamol in wheezy infants: the importance of aerosol acidity. The effect of nebulised iso-osmolar, preservative free, but acidic salbutamol solution was studied in 34 acutely wheezing infants aged 1-17 months. Transcutaneous oxygen pressure (TcPO2) and oxygen saturation (SO2) fell significantly during the first five minutes after nebulisation with further deterioration at 15-20 minutes. Ten of these infants were followed up for another two hours and showed slight improvement. Even after the second hour TcPO2 had not reached baseline values. Three months later the response to salbutamol and a placebo of equal acidity (pH 3.9) was studied in 11 infants from the same group, now free of symptoms. Lung function tests were included and showed no significant changes in specific conductance and volume corrected maximum expiratory flows (Vmax at functional residual capacity/thoracic gas volume). However, hypoxaemia occurred after the acidic placebo with a significant drop of TcPO2 (mean 0.9 kPa); SO2 decreased similarly but this did not reach significance. After salbutamol there was a further significant deterioration of mean TcPO2 (1.4 kPa) and of SO2. These results show that beside a possible pharmacological effect of salbutamol the acidity of the aerosol also induces hypoxaemia in infants."
-How does the study validate the technique for quantifying myocardial blood flow using oxygen-15-labeled carbon dioxide and positron emission tomography?,"Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography. BACKGROUND. Oxygen-15-labeled water is a diffusible, metabolically inert myocardial blood flow tracer with a short half-life (2 minutes) that can be used quantitatively with positron emission tomography (PET). The purpose of this study was to validate a new technique to quantify myocardial blood flow (MBF) in animals and to assess its application in patients. METHODS AND RESULTS. The technique involves the administration of 15O-labeled carbon dioxide (C15O2) and rapid dynamic scanning. Arterial and myocardial time activity curves were fitted to a single tissue compartment tracer kinetic model to estimate MBF in each myocardial region. Validation studies consisted of 52 simultaneous measurements of MBF with PET and gamma-labeled microspheres in nine closed-chest dogs over a flow range of 0.5-6.1 ml/g/min. A good correlation between the two methods was obtained (y = 0.36 + 1.0x, r = 0.91). Human studies consisted of 11 normal volunteers and eight patients with chronic stable angina and single-vessel disease, before and after intravenous dipyridamole infusion. In the normal group, MBF was homogeneous throughout the left ventricle both at rest and after administration of dipyridamole (0.88 +/- 0.08 ml/g/min and 3.52 +/- 1.12 ml/g/min, respectively; p less than or equal to 0.001). In patients, resting MBF was similar in the distribution of the normal and stenotic arteries (1.03 +/- 0.23 and 0.93 +/- 0.21 ml/g/min, respectively). After dipyridamole infusion, MBF in normally perfused areas increased to 2.86 +/- 0.83 ml/g/min, whereas in the regions supplied by stenotic arteries it increased to only 1.32 +/- 0.27 ml/g/min (p less than or equal to 0.001). CONCLUSIONS. PET with C15O2 inhalation provides an accurate noninvasive quantitative method for measuring regional myocardial blood flow in patients."
-What was the average cost of averting death or severe disability through neurosurgical intervention in this study?,"Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community."
-What morphological abnormalities were observed in the sural nerves of patients with inherited tendency to pressure palsy (ITPP)?,"Uncompacted inner myelin lamellae in inherited tendency to pressure palsy. Nerves in patients with inherited tendency to pressure palsy (ITPP) are susceptible to degrees of traction or compression which in nonaffected persons do not induce neuropathic symptoms or deficits, conduction block of fibers, or electromyographic changes characteristic of the disorder. Two observations suggest a widespread asymptomatic abnormality of nerves: 1) low conduction velocity of clinically unaffected nerves, and 2) focal thickenings (tomacula) on teased myelinated fibers of clinically unaffected sural nerves. Sural nerves from five patients and five healthy subjects were assessed for morphologic abnormality in ITPP that might account for the susceptibility of nerves to compression. Teased nerve fibers showed a higher frequency of segmental demyelination or remyelination, or both (p less than 0.003). The mean frequency of fibers showing focal myelin thickenings was 57 +/- 10% in ITPP and 0% in controls. In electron micrographs, regions of uncompacted myelin lamellae, usually affecting the innermost lamellae and extending for a variable distance averaging 9 +/- 4 microns were seen in 11 +/- 4% of fibers in ITPP. None were found in the control nerves. The finding of uncompacted myelin lamellae may suggest an abnormality of myelin composition or of interaction of Schwann cells and axons accounting for the increased susceptibility to pressure palsy, tomaculous formation, or demyelination. From electron microscopic evaluation of serial skip sections we infer that myelin of tomaculae is in continuity with internodal myelin and is reduplicated (full-thickness or cleaved layers are longitudinally or circumferentially folded-back on themselves)."
-What are the key characteristics of mouse mannose-binding proteins A and C based on their molecular characterization?,"Molecular characterization of the mouse mannose-binding proteins. The mannose-binding protein A but not C is an acute phase reactant. Mannose-binding proteins play a role in first line host defense against a variety of pathogens. We report the molecular cloning of two mouse mannose-binding proteins designated A and C based on their close identity with their rat homologues. The deduced amino acid sequence of the mouse mannose-binding proteins, as with rat and the human forms, have an NH2 terminus that is rich in cysteine that stabilizes a collagen alpha helix followed by a carboxyl- terminal carbohydrate binding domain. We further show that the mouse mannose-binding protein A mRNA, as with the human, is induced like the acute phase reactant serum amyloid P protein, yet the expression of mouse mannose-binding protein C mRNA is not regulated above its low baseline level. The expression of both mannose-binding proteins A and C mRNA is restricted to the liver under basal and stress conditions."
-What is the purpose of the clinical trial involving Cronassial in patients with Chagas' disease?,"Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo."
-What is the clinical significance of nonvisualization in HIDA scans after endoscopic retrograde sphincterotomy in patients with and without cholelithiasis?,"Biliary patency imaging after endoscopic retrograde sphincterotomy with gallbladder in situ. Clinical impact of nonvisualization. We prospectively performed nuclear biliary patency imaging (HIDA scanning) in 62 patients who had undergone endoscopic retrograde sphincterotomy for management of pancreaticobiliary disease with their gallbladders in situ. Elective cholecystectomy was not recommended because of advanced age, comorbidity, or absence of gallstones. All patients had patent cystic ducts at endoscopic retrograde cholangiopancreatography balloon cholangiography. Eighteen (29.1%) of 62 patients had nonvisualizing HIDA scans, and in 44 (70.9%) of 62 visualization was normal or delayed. Six cholecystectomies were required for colic (n = 1), acute cholecystitis (n = 4), and acute cholecystocholedochal fistula with cholangitis (n = 1). Among the patients with cholelithiasis and nonvisualization (n = 13), five (38.5%) required surgery, whereas only one (4.8%) of 21 patients with cholelithiasis and visualization required surgery. Nonvisualizing HIDA scans are frequent (30%) after endoscopic retrograde sphincterotomy and have no clinical relevance in patients without cholelithiasis but predict the need for cholecystectomy within 16 months in 38.5% of patients with cholelithiasis."
-How did damage to the fornix affect memory function in the two patients after colloid cyst removal?,"Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans."
-What was the outcome of autologous bone marrow transplantation (ABMT) for patients with neuroblastoma in this study?,"High-dose melphalan with 6-hydroxydopamine-purged autologous bone marrow transplantation for poor-risk neuroblastoma. Long-term results are presented of 28 patients who were diagnosed with neuroblastoma at more than 12 months of age and who received melphalan 180 mg/m2 (n = 6) or 240 mg/m2 (n = 22) to consolidate remissions of Stage IV disease or to control refractory disease. Twenty-four patients also received dianhydrogalactitol 180 to 240 mg/m2, and 11 received total body irradiation 450 to 600 cGy. Autologous bone marrow transplantation (ABMT) was performed with marrow that was unpurged (n = 2) or purged ex vivo (n = 26) with 6-hydroxydopamine (6-OHDA) 20 micrograms/ml plus ascorbate 200 micrograms/ml. The median time to an absolute neutrophil count of 500/microliters was 21 days and to self-sustaining platelet counts more than 20,000/microliters, 28 days. One patient required infusion of unpurged reserve marrow. Two groups of patients underwent ABMT: (1) 17 patients (Group I) who were in first remission a median of 7 months after diagnosis; and (2) 11 patients (Group II) who had refractory disease or were in second remission. For Group I, event-free survival was 29% at 12 months and 6% at 24 months post-ABMT. All Group II patients died of disease or ABMT-related toxicity. Overall, of the 28 patients, one is a long-term relapse-free survivor; five died of ABMT-related toxicity; ten patients with tumors present at ABMT had progressive disease within 6 months of ABMT; and 12 patients with no measurable disease at ABMT relapsed 4 to 32 months (median, 12) post-ABMT. Among the latter, six relapses involved the primary site, and six were restricted to distant sites. These results--in accord with the long-term outcome in other series--suggest that for neuroblastoma high-dose melphalan cannot be relied on to ablate residual disease or to salvage patients with refractory tumors. In addition, the pattern of relapse in several patients could be explained by infusion of incompletely purged autografts; this would support recent laboratory evidence that 6-OHDA/ascorbate is a suboptimal purging method."
-What innovative approach was used to place a stent in a patient with malignant biliary obstruction complicated by ascites?,"Malignant biliary obstruction complicated by ascites: transjugular insertion of an expandable metallic endoprosthesis. Although the transjugular approach has long been used to provide safe access to the liver, it has not been used for placement of stents in biliary obstruction. The recent development of an expandable metallic endoprosthesis now makes this method more feasible. The case of a patient with malignant biliary obstruction complicated by ascites is presented herein. Palliation was achieved with an expandable biliary endoprosthesis placed by the transjugular-hepatic vein approach."
-How do spousal caregivers and adult children differ in their caregiving responsibilities and support received for brain-impaired adults?,"Time spent caregiving and help received by spouses and adult children of brain-impaired adults. Caregivers for brain-impaired adults differ in living arrangements, amount of time spent giving care, and assistance received from family and friends and from paid help depending on their kin relationship and employment status. Spousal caregivers devote large amounts of time to caregiving, and husbands spend no less time than wives. Most caregivers receive little assistance from other family members and friends, but husbands receive more than others. Employed spouses receive more paid help than those without jobs, but employment does not affect the amount of paid help received by adult daughters."
-How can surgical interventions help manage epilepsy in patients with brain tumors?,Epilepsy and brain tumors: implications for treatment. Primary intraparenchymal tumors of the brain are important etiologic factors in partial or focal epilepsy. Indolent low-grade gliomas may be associated with a long-standing seizure disorder refractory to medical treatment. Surgical resection of the neoplasm and the epileptogenic area may render patients seizure-free. Removal of the tumor alone may also be associated with an excellent survival rate and surgical outcome. Conventional neurosurgical procedures are restricted in patients with tumors that are deep-seated lesions or involve functional cerebral cortex. Computer-assisted stereotactic surgical procedures have been developed for biopsy and resection of intra-axial brain-mass lesions. Stereotactic tumor resection may allow pathological determination of intracranial lesions and produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.
-What is labyrinthitis ossificans and how does it potentially impact cochlear implantation?,"Labyrinthitis ossificans: histopathologic consideration for cochlear implantation. Labyrinthitis ossificans may be a hindrance to cochlear implantation by making electrode insertion difficult. We performed a histopathologic study of 24 temporal bones with labyrinthitis ossificans from multiple causes. The organ of Corti was graphically reconstructed and the degree of obstruction was estimated for each millimeter of the cochlea. Correlations were calculated between the degree of new bone formation and the cause, patient's age and sex, and time from the original temporal bone insult. Our results demonstrate that complete cochlear ossification is rare. The scala tympani in the basal turn of the cochlea is the most frequent area of ossification, regardless of the cause of the labyrinthitis ossificans. Meningogenic labyrinthitis, usually a childhood disease, was associated with the greatest amount of ossification. When ossification resulted from tympanogenic labyrinthitis, the scala tympani was completely ossified near the round window niche in all temporal bones. Neo-ossification of the basal turn associated with otosclerosis was limited to the proximal 6 mm of the scala tympani in all cases. Three temporal bones had a patent round window niche and basal turn, but significant apical and middle-turn ossification. Peripheral sensorineural elements were severely degenerated in the region of the ossification in all specimens, and spiral ganglion cell counts were decreased."
-What health risks can welding pose to workers according to the given context?,Fume fever and reactive airways dysfunction syndrome in a welder. I have reported a case of fume fever and concurrent reactive airways dysfunction syndrome (RADS) after welding. The RADS should be added to the list of potential hazards associated with welding.
-What are the key immunohistochemical findings in carcinosarcomas of the uterus and ovary?,"Carcinoma (malignant mixed mullerian [mesodermal] tumor) of the uterus and ovary. Correlation of clinical, pathologic, and immunohistochemical features in 29 cases. We examined the histologic, immunohistochemical, and clinical features of a series of 23 endometrial, five cervical, and one ovarian carcinosarcomas (malignant mixed mullerian [mesodermal] tumors) and nine associated distant peritoneal metastases. The primary tumors all showed epithelial differentiation (cytokeratin and/or epithelial membrane antigen expression) of the carcinomatous component, while sarcomatous areas showed epithelial differentiation in all but one case. The metastases showed uniform staining for cytokeratin (eight of eight cases) and epithelial membrane antigen (eight of eight cases), including the spindle cell component that was present in four of nine cases. Desmin significantly changed the interpretation of rhabdomyosarcoma differentiation by refuting putative rhabdomyoblasts in two cases and identifying rhabdomyoblasts in two other cases where they were unrecognized on hematoxylineosin staining. S100 protein was positive in all five cases with chondrosarcoma differentiation. Muscle-specific actin and vimentin were positive in the sarcomatous component of all cases and in the carcinomatous component of seven and 10 cases, respectively. After immunostaining, heterologous elements were present in 18 of 29 cases (11 cases of rhabdomyosarcoma, three cases of chondrosarcoma, three cases of mixed rhabdomyosarcoma and chondrosarcoma, and one case of liposarcoma). Only six of 27 patients with follow-up were disease free for 12 months or longer (associated with stage I or II disease, smaller size, no lymphatic invasion in the resection specimen, and no invasion of the outer two thirds of myometrium). Presence and type of heterologous elements, grade of sarcomatous or carcinomatous components, histologic type of carcinomatous component, gross appearance, presence of necrosis, or use of chemotherapy or radiotherapy did not affect outcome. Carcinosarcomas are clinically aggressive distinctive mixed epithelial-stromal neoplasms with histologic and immunohistochemical features that overlap with metaplastic carcinoma in many cases."
-How does Borrelia burgdorferi stimulate glioma cells to secrete interleukin-6 in the context of neuroborreliosis?,"Cytokines and the pathogenesis of neuroborreliosis: Borrelia burgdorferi induces glioma cells to secrete interleukin-6. Lyme disease is a multisystemic disease caused by a tickborne spirochete, Borrelia burgdorferi. Neuroborreliosis is characterized by intrathecal production of antibodies specific for the spirochete. This suggests that spirochetal infection of the central nervous system produces conditions that support the maturation of B lymphocytes to immunoglobulin-secreting cells. Interleukin 6 (IL-6) stimulates B cell differentiation into antibody-secreting cells. The present study was undertaken to determine whether B. burgdorferi can stimulate cells of central nervous system origin to secrete IL-6. C6 rat glioma cells cultured with spirochetes induced secretion of IL-6 activity. Peak stimulation was achieved at 24 h with 25 spirochetes per glioma cell. Glioma cells were also stimulated to produce IL-6 by interleukin 1 and tumor necrosis factor. That very few spirochetes are found in Lyme disease patients suggests that biologic amplification factors derived from the organism or the host, or both, are responsible for the pathogenesis of this disease. IL-6 can now be added to the growing list of such factors."
-What percentage of eyes maintained visual acuity at 20/60 or better after cataract extraction following brachytherapy for choroidal malignant melanoma?,"Cataract extraction after brachytherapy for malignant melanoma of the choroid. Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid."
-What unique finding was observed in the cardiac examination of a 29-year-old man and his 4-year-old son?,"Familial aneurysms of the interventricular septum. Congenital aneurysms of the interventricular septum were found in a 29 year old man and his four year old son. Both were symptom free. In both, M mode and cross sectional echocardiography showed an aneurysm in the mid-muscular trabecular portion of the ventricular septum with considerable paradoxical motion of the aneurysmal segment. Otherwise the chamber dimensions, intracardiac structures, and cardiac function were normal for age. Congenital aneurysm of the interventricular septum is rare and these familial cases may be unique."
-What was the mean increase in graft diameter observed in the ultrasound measurements compared to the manufacturer's recorded box size?,"Clinical significance of aortic graft dilation. To determine if there is a relationship between aortic graft dilation and graft complications, 443 serial ultrasound studies performed on 106 patients were analyzed. Of 443 studies, 243 were done retrospectively on 59 patients from 3 to 144 months (mean, 38 months) after graft implantation. Forty-seven additional patients were studied prospectively, with direct measurement of external graft diameter after aortic clamp release. Subsequent ultrasound examinations at 3, 6, 9, and 12 months and then annually (n = 200) were routinely performed. Mean follow-up was 12 months (range, 3 to 48). Knitted double velour Dacron prostheses were used in all cases reported in this study. This cohort was culled from our ongoing graft surveillance program, which includes grafts of other materials and manufacturers. Comparison of the manufacturer's recorded box size with follow-up ultrasound measurements in all cases demonstrated a mean increase in graft diameter of 3.7 mm (23%). Little dilation occurred after 1 year. In 47 patients with direct graft diameter measurements taken after declamping, an immediate mean increase of 1.7 mm (11%) was noted. Dilation was not related to surgical indication (aneurysm vs occlusive disease) or hypertension. Analysis of the 10% segment of the series with the greatest dilation (mean, 39%) did not demonstrate a predilection for graft complications. No significant dilation was noted in the single cases encountered of femoral and iliac anastomotic aneurysms and perigraft seroma. Although dilation of knitted Dacron grafts is to be anticipated, no association between graft dilation and graft complications was found in this series."
-How can quantitative motor performance tests help in early detection of Parkinson's disease?,"Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are ""at risk for"" Parkinson's disease and other related disorders."
-What were the independent prognostic factors identified in the multivariate analysis of primary sclerosing cholangitis patients?,"Natural history and prognostic variables in primary sclerosing cholangitis. The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation."
-What were the two major psychological insights about orthognathic surgery patients that emerged from this research?,"Psychological aspects of orthognathic surgery: how people respond to facial change. This study was undertaken to explore the motivations and problems shared by adult orthognathic surgical patients over the age of 25. Objective findings included demographic information and reasons for seeking surgery. The majority of 65 respondents cited functional problems as their primary reason for seeking treatment. Eighty-nine percent were pleased with esthetic changes, and 83% responded that the functional problem had been corrected. For most, the greatest discomfort related to the surgery was the postoperative intensive care unit. Two of the most common side effects of the surgery were the loss of sensation in the lips and chin area and a short period of depression. Women had depression more often than men but were more enthusiastic about the final results of the procedure. Two major areas of interest to surgeons emerged from the research. First, although women have functional problems, the majority seem to have a desire for cosmetic improvement. Having a functional problem seemed to provide the psychological permission necessary to spend the time and money for a cosmetic change. The second point focused on the need for good communication between surgeon and patient. The patients who were more positive toward the procedure and more satisfied with the results were those who were better informed and who thought they had a good system of communication with the orthodontist, surgeon, and their respective staffs."
-How does partial ischaemia affect free-radical damage compared to total ischaemia in rabbit skin flaps?,"Secondary ischaemia in rabbit skin flaps: the roles played by thromboxane and free radicals. 1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485. 2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase. 3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels. 4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter. 5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia. 6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-"How does the volume of low-grade, latent prostate cancer tissue relate to the incidence of high-grade clinical cancer?","Low-grade, latent prostate cancer volume: predictor of clinical cancer incidence? We hypothesize that each cell in low-grade (Gleason grade 1-3) prostate cancer tissue is at risk of transformation into a cell which produces a high-grade (Gleason grade 4-5) clinical cancer after a short period of growth. As a consequence, the volume of low-grade, latent cancer tissue in the prostate glands of men at any age determines their incidence rate for high-grade, clinical cancer a few years later. Autopsy and incidence data for both white men and black men support this conclusion, with a tumor growth period of about 7 years. The transformation rate is similar for black men and for white men, about 0.024 high-grade cancers per year per cm3 of low-grade, latent cancer volume. Our hypothesis explains the infrequent occurrence of clinical cancer despite the high prevalence of latent cancer, the steep rise of clinical cancer incidence with age despite the slow rise of latent cancer prevalence with age, and the disparities in clinical cancer incidence among some populations despite their similar latent cancer prevalence. This hypothesis suggests that low-grade cancer volume is a critical determinant of clinical cancer risk."
-"What were the electrophysiologic effects of UK-68,798 in a canine model of sudden coronary death?","The antifibrillatory actions of UK-68,798, a class III antiarrhythmic agent. The electrophysiologic and antifibrillatory properties of UK-68,798 were studied in vivo in a conscious canine model of sudden coronary death. Electrophysiologic testing was performed on conscious male mongrel dogs (14.5-21.5 kg) 3 to 5 days after surgical induction of an anterior myocardial infarction by occlusion (2 h)-reperfusion of the left anterior descending coronary artery. Compared to saline-treated control animals, UK-68,798 at a dose of 0.9 mg/kg i.v. did not (P = .083) suppress the induction of ventricular tachycardia by programmed electrical stimulation. Six of 12 UK-68,798-treated dogs remained inducible, whereas 10 of 12 vehicle-treated dogs responded to electrical induction of arrhythmia. When compared to predrug inducibility, UK-68,798 significantly (P = .007) reduced the incidence of programmed electrical stimulation-induced ventricular tachycardia. In five of the six dogs inducible after UK-68,798 administration, the cycle length of the induced ventricular tachycardia was prolonged (P = .007) compared to the predrug cycle length. Heart rate, PR interval and QRS duration were not affected by UK-68,798 administration. The rate-corrected QT interval was prolonged (P less than .05) by UK-68,798. The ventricular effective refractory period was increased by UK-68,798 (158 +/- 7 msec, predrug vs. 185 +/- 7 msec, postdrug). Subsequent to programmed electrical stimulation, a 150 microA anodal current was applied to the luminal surface of the left circumflex coronary artery to induce transient episodes of posterolateral ischemia in response to electrolytic injury of the vessel wall."
-What is the significance of the leucocyte alkaline phosphatase (LAP) score in differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS)?,"Use of leucocyte alkaline phosphatase (LAP) score in differentiating malignant from benign paraproteinaemias. The leucocyte alkaline phosphatase (LAP) score of peripheral blood neutrophils was examined in 20 patients with multiple myeloma and compared with the score in 18 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean (95% confidence limit) LAP score in those with multiple myeloma was 186 (169-218) compared with 92 (64-120) in the MGUS group. In the multiple myeloma group all but one patient had a high LAP score, irrespective of disease. No cause for raised LAP, such as infection, was present in any of the patients with multiple myeloma. In the MGUS group six patients had a raised LAP score; in two of them another cause for such a rise was present (autoimmune haemolytic anaemia and primary thrombocythaemia). In neither group did the LAP score correlate with duration of the disease, bone marrow plasma cell count, paraprotein concentration, haemoglobin, total white cell or neutrophil count. It is concluded that a normal LAP count in patients with paraproteinaemia suggests a benign condition, but a raised count does not indicate a malignant condition."
-How do ATP-dependent K+ channels modulate pulmonary vascular responses during severe hypoxia in ferret lungs?,"ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. In normo- and hypoglycemic ferret lungs, the pulmonary vascular response to severe hypoxia (PiO2 less than or equal to 10 mmHg) is characterized by an initial intense vasoconstriction followed by marked vasodilation, whereas in hyperglycemic lungs, vasodilation is minimal, causing vasoconstriction to be sustained. In contrast, the response to moderate hypoxia is characterized by a slowly developing sustained vasoconstriction which is unaffected by glucose concentration. To determine the role of ATP-dependent K+ (KATP) channels in these responses, we examined the effects of cromakalim, which opens KATP channels, and glibenclamide, which closes them. During steady-state vasoconstriction induced in isolated ferret lungs by moderate hypoxia, cromakalim caused dose-dependent vasodilation (EC50 = 7 x 10(-7) M) which was reversed by glibenclamide (IC50 = 8 x 10(-7) M), indicating that KATP channels were present and capable of modulating vascular tone. During severe hypoxia in hypoglycemic lungs [( glucose] less than 1 mM), glibenclamide markedly inhibited the secondary vasodilation. Raising perfusate glucose concentration to 14 +/- 0.4 mM had the same effect. As a result, initial vasoconstrictor responses were well sustained. However, neither glibenclamide nor hyperglycemia affected vasoconstrictor responses to moderate hypoxia or KCl, indicating that effects during severe hypoxia were not due to nonspecific potentiation of vasoconstriction. These findings suggest that in the ferret lung (a) severe hypoxia decreased ATP concentration and thereby opened KATP channels, resulting in increased K+ efflux, hyperpolarization, vasodilation, and reversal of the initial vasoconstrictor response; and (b) hyperglycemia prevented this sequence of events."
-What is the cost-effectiveness of periodic colonoscopic surveillance after the removal of an adenomatous colon polyp?,"Colonoscopic surveillance after polypectomy: considerations of cost effectiveness. OBJECTIVE: To assess the cost effectiveness of the current recommendation that persons who have had an adenomatous colon polyp removed have periodic colonoscopic surveillance at fixed and regular intervals. DESIGN: Cost-effectiveness analysis using data from the medical literature in a simulation model to estimate the costs of and the risk for perforation associated with periodic colonoscopic surveillance for a 50-year-old man followed for 30 years. MAIN RESULTS: A program of colonoscopy every 3 years would incur cumulatively a 1.4% risk for colon perforation, a 0.11% risk for perforation-related death, and direct physician costs of $2071 for colonoscopy (discounted at 5%). If a 50-year-old man's cumulative remaining risk for death from cancer is 2.5% after the removal of a single small adenoma and if effectiveness of colonoscopic surveillance every 3 years is 100%, then one death from cancer could be prevented by doing 283 colonoscopies, incurring 0.6 perforations, 0.04 perforation-related deaths, and direct physician costs of $82,000. If surveillance were 50% effective and the cumulative remaining risk for death from cancer were 1.25%--a plausible scenario--1131 colonoscopies would be required to prevent one death from cancer, incurring 2.3 perforations, 0.17 perforation-related deaths, and physician costs of $331,000. CONCLUSIONS: The cost effectiveness of colonoscopic surveillance is very sensitive to estimates of the cumulative remaining risk for death from cancer after polypectomy as well as to surveillance efficacy. For persons whose remaining risk for death from cancer may be low, such as persons with a single small adenoma, recommendations for colonoscopic surveillance at fixed and regular intervals may be excessively costly."
-What was the purpose of asking donors questions about gastrointestinal symptoms during blood donation screening?,"Screening blood donors for gastrointestinal illness: a strategy to eliminate carriers of Yersinia enterocolitica. Recent reports of fatal transfusion-associated Yersinia enterocolitica sepsis prompted a study of the feasibility of adding a question to the routine donor health history as a method of reducing this risk. In three American Red Cross blood centers, 11,323 donors were asked one of two questions about gastrointestinal symptoms during their health history screenings. Affirmative responses were obtained from 0.6 or 4.0 percent of the donors, depending on how the question was asked. In one center, more than 6 percent of donors gave affirmative answers. The efficacy of asking a relatively simple question about gastrointestinal symptoms as a way of preventing Y. enterocolitica should be evaluated further, because relatively large numbers of donors may respond affirmatively. Other methods of reducing the risk of transfusion-associated Y. enterocolitica infection should be pursued."
-What were the key findings of the study comparing chorionic villus sampling and amniocentesis as prenatal genetic diagnostic procedures?,"Single-center comparison of results of 1000 prenatal diagnoses with chorionic villus sampling and 1000 diagnoses with amniocentesis. Large multicenter studies have confirmed the safety and accuracy of chorionic villus sampling as a prenatal genetic diagnostic procedure, but there have been few single-center evaluations. We report our experience with 1000 consecutive chorionic villus sampling procedures compared with 1000 consecutive amniocentesis procedures during the same period. The procedures were performed by the same genetic counselors, sonographers, obstetricians, and laboratory personnel. Indications for referral, demographic characteristics of patients, numbers of attempts per patient, fetal loss rates, laboratory results, and evaluation of accuracy are included. Analysis of all data suggests that chorionic villus sampling is a safe and accurate alternative to amniocentesis in our community-based teaching hospital."
-How can an immunocytochemical (ICC) panel help improve the diagnostic accuracy of cytologic examination in serous effusions?,"Immunocytochemical panel for the identification of malignant cells in serous effusions. The cytologic diagnosis of malignancy in serous effusions can be challenging. An immunocytochemical (ICC) panel using commercially available antibodies (to carcinoembryonic antigen [CEA], epithelial membrane antigen [EMA], B72.3, Leu-M1, cytokeratin [CK], leukocyte common antigen [LCA], S-100 protein, and vimentin) was applied to cell blocks fixed in methyl Carnoy's solution that were from 55 consecutive pleural, peritoneal, and pericardial fluid specimens. The results were correlated with data from clinical records and routine cytologic studies. Final cytologic diagnoses included 26 of adenocarcinoma and 1 of mesothelioma. The remaining 28 cases were considered to be benign (reactive) proliferations. EMA, CEA, B72.3, and Leu-M1 were present in 96%, 77%, 58%, and 42% of adenocarcinomas, respectively. These determinants were absent in the mesothelioma and the reactive effusions, although anti-CEA yielded strong background staining of inflammatory cells. The CK markers identified malignant cells in 93% of cases, but consistently stained mesothelial cells as well. Antivimentin strongly labeled mesothelial cells in all cases, with weak to absent staining of malignant cells. In 3 of 26 carcinoma cases (12%), the ICC panel identified malignant cells that were not recognized initially on routine cytologic examination. In 1 of 26 cases (4%), the panel was falsely negative. Use of this approach can improve the diagnostic accuracy of cytologic examination of serous fluids. The ICC panel is especially helpful when atypical mesothelial proliferation is present, or in cases that are clinically suspect for malignancy, but cytologically negative because there are only a few malignant cells, or those that are cytologically bland."
-What was the cause of the patient's failure to regain consciousness after a total hip replacement surgery?,"Failure to awaken after general anaesthesia secondary to paradoxical venous embolus. A patient is presented who failed to regain consciousness after an apparently uneventful nine-hour revision of a total hip replacement. There were no clinically important haemodynamic changes during the operation, and oxygen saturation, capnography and acid base balance were normal throughout. Postop CT of the head showed a large left MCA infarct with midline shift. At autopsy, the patient was found to have a previously unsuspected patent foramen ovale, and a venous embolus in the left internal carotid artery, which probably had originated from the periprostatic venous plexus with a large infarct in the distribution of the left anterior and middle cerebral arteries. The authors conclude that massive paradoxical venous emboli can occur during surgery with minimal haemodynamic changes."
-How did the healing rates of gastric ulcers compare between enprostil and ranitidine in this clinical study?,"Gastric ulcer healing: a comparison of enprostil versus ranitidine. Enprostil is a synthetic prostaglandin E2 analogue with gastric antisecretory and mucosal protective properties. We compared the effects of enprostil and ranitidine on the healing of gastric ulcers and the subsequent relapse rates over 6 months. Patients (N = 156) were recruited for a double-blind study from 12 centers in Europe; 71 were randomly assigned to oral treatment with 35 micrograms enprostil twice daily and 85 to 150 mg ranitidine twice daily for up to 8 weeks. Both groups were of similar demography; their healing rates were also similar. Cumulative intent-to-treat healing rates were at 4 weeks enprostil 48%, ranitidine 41%: at 6 weeks enprostil 65%, ranitidine 68%; and at 8 weeks enprostil 72%, ranitidine 80%. Of those patients who met all protocol criteria and completed treatment, and were endoscoped at the prescribed times, healing rates were at 4 weeks enprostil 55%, ranitidine 54%, at 6 weeks enprostil 75%, ranitidine 84%; and at 8 weeks enprostil 80%, ranitidine 90%. Relief of pain was rapid and similar in both groups. The incidence of adverse events was low and similar in the two groups. The treatment-free relapse rate at 6 months was enprostil 64%, ranitidine 49%; the median times to relapse were 169 and 203 days, respectively. Enprostil and ranitidine appear to be equally effective in healing gastric ulcers."
-How does the Fos-Jun protein complex potentially suppress osteocalcin gene transcription during osteoblast proliferation?,"Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the proliferation period of osteoblast phenotype development. We present evidence that AP-1 (HeLa cell-activating protein 1) sites residing within two promoter elements of the osteocalcin gene bind the Fos-Jun protein complex: the osteocalcin box (OC box; nucleotides -99 to -76), which contains a CCAAT motif as a central element and influences tissue-specific basal levels of osteocalcin gene transcription, and the vitamin D-responsive element (VDRE; nucleotides -462 to -440), which mediates enhancement of osteocalcin gene transcription. Gel electrophoretic mobility-shift analysis demonstrated high AP-1 binding activity in proliferating osteoblasts and dramatic changes in this activity after the down-regulation of proliferation and the initiation of extracellular-matrix mineralization in primary cultures of normal diploid osteoblasts. Methylation interference analysis established at single nucleotide resolution that purified recombinant Fos and Jun proteins bind in a sequence-specific manner to the AP-1 sites within the VDRE and OC box. Similarly, an AP-1 motif within a putative VDRE of the alkaline phosphatase gene, which is also expressed after the completion of proliferation, binds the Fos-Jun complex. These results support a model in which coordinate occupancy of the AP-1 sites in the VDRE and OC box in proliferating osteoblasts may suppress both basal level and vitamin D-enhanced osteocalcin gene transcription as well as transcription of other genes associated with osteoblast differentiation--a phenomenon we describe as phenotype suppression. This model is further supported by binding of the Fos-Jun complex at an AP-1 site in the type alpha I collagen promoter that is contiguous with, but not overlapping, the VDRE. Such a sequence organization in the collagen VDRE motif is compatible with vitamin D modulation of collagen but not with osteocalcin and alkaline phosphatase expression in proliferating osteoblasts."
-What potential therapeutic effect of pentoxifylline was observed in patients being treated for claudication of the lower extremities?,Pentoxifylline in the treatment of vascular impotence--case reports. Vascular impotence is a common medical problem for which available therapies are limited. Three impotent patients observed in the authors' practice who were receiving pentoxifylline for treatment of claudication of the lower extremities spontaneously reported improved sexual function. A controlled trial of pentoxifylline for vascular impotence may be warranted.
-How can gonadotropin-releasing hormone analogs help improve ovulation and pregnancy rates in patients with polycystic ovary syndrome?,"Polycystic ovary syndrome: abnormalities and management with pulsatile gonadotropin-releasing hormone and gonadotropin-releasing hormone analogs. Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The administration of a gonadotropin-releasing hormone analog for 4 to 8 weeks before the initiation of pulsatile gonadotropin-releasing hormone ovulation induction can temporarily correct endocrine abnormalities of polycystic ovary syndrome, such as excessive luteinizing hormone and androgen secretion, and improve ovulatory and pregnancy rates in these patients. For optimal results, this pretreatment should probably be repeated before each pulsatile gonadotropin-releasing hormone ovulation induction cycle. Obesity is associated with a lower success rate, and spontaneous abortion remains a prominent complication in polycystic ovary syndrome even after gonadotropin-releasing hormone analog suppression. With this regimen the risks of ovarian hyperstimulation and multiple pregnancy are virtually abolished. Thus, pulsatile gonadotropin-releasing hormone appears to be highly effective and safe for ovulation induction in patients with polycystic ovary syndrome also, provided that this treatment is preceded by pituitary-ovarian suppression with a gonadotropin-releasing hormone analog."
-What are the common pathologic features shared by ANCA-associated vasculitides?,"Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. Antineutrophil cytoplasmic autoantibodies (ANCA) are a useful diagnostic serologic marker for the most common forms of necrotizing vasculitis, provide a means of categorizing vasculitides so that diagnostically useful shared pathologic and clinical characteristics can be recognized, and offer insight into the pathogenesis of previously idiopathic diseases. ANCA-associated vasculitides can be categorized into a number of distinctive clinicopathologic categories, eg, Wegener's granulomatosis, Churg-Strauss syndrome, pulmonary renal syndrome, microscopic polyarteritis nodosa, leukocytoclastic angiitis, and necrotizing and crescentic glomerulonephritis. At least the latter four syndromes can also be caused by other ANCA-negative immunopathogenic mechanisms, eg, immune complex deposition. Therefore, thorough diagnostic classification requires both an assessment of clinicopathologic category, as well as an assessment of immunopathologic category. Although different ANCA-associated vasculitic syndromes have distinctive clinical and pathologic features, all ANCA-associated vasculitides share a number of common pathologic features, ie, focal distribution, necrosis, and neutrophil infiltration. ANCA assays have very good sensitivity and specificity for ANCA-associated diseases, but the prevalence of these diseases in the patient population being analyzed must be taken into consideration when determining the predictive value of a test result. As with all serologic tests, ANCA results must be integrated with other clinical and pathologic data in order to reach the most accurate diagnostic conclusion."
-How does chronic xerostomia affect esophageal acid exposure and potential injury?,"Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency."
-What immunohistochemical markers were used to distinguish sarcomatoid liver carcinomas from true sarcomas?,"An immunohistochemical study of sarcomatoid liver carcinomas. Six cases of primary hepatic carcinomas with a significant amount of sarcomatoid elements were examined by using immunohistochemical stainings. Four of the six cases were associated with ordinary hepatocellular carcinoma (HCC), one with cholangiocellular carcinoma (CCC), and one with mixed HCC and CCC. Alpha-fetoprotein and alpha-1-antitrypsin were negative in sarcomatoid cells of all cases; vimentin stained positively in sarcomatoid tumor cells in two of the six cases; and cytokeratin (CK8) was detected in five cases. The CK8 was not detected in tumor cells of two cases of hepatic angiosarcoma, two of metastatic leiomyosarcomas, and one of metastatic fibrosarcoma, although vimentin stained positively in all these true sarcomas. It was concluded that sarcomatoid dedifferentiation of liver carcinomas might derive from both HCC and CCC. In addition CK8 might be an excellent marker to make a differential diagnosis of sarcomatoid cancers from true metastatic or primary sarcomas of the liver."
-What were the main causes of death in patients who underwent emergency surgery for colorectal cancer?,"Outcome after emergency surgery for cancer of the large intestine. The data for 77 patients with colorectal cancer who underwent emergency surgery for acute intestinal obstruction (57 patients) or perforation (20 patients) within 24 h of admission were evaluated. The patients were older and had more advanced disease than patients undergoing elective surgery for colorectal cancer. Emergency surgery for carcinoma of the right colon consisted of primary resection in 95 per cent of cases and was followed by a 28 per cent mortality rate. Perforated tumours of the left colon and rectum were managed by primary resection in 82 per cent of cases with a 22 per cent mortality rate. In contrast, obstructing tumours of the left colon and rectum were treated by primary resection in 38 per cent of cases with a 6 per cent mortality rate, and by primary decompression in 62 per cent of cases with a 25 per cent mortality rate. The overall postoperative mortality rate was 23 per cent and increased with advanced tumour disease, perforation and peritonitis. Cardiac decompensation and intraabdominal sepsis were the major causes of death. Although the long-term survival rate following emergency surgery was worse than after elective surgery, improvements in outcome should be achieved by better management of the initial emergency situation."
-What are the key characteristics of pain perception and coping strategies in patients with noncardiac chest pain (NCCP)?,"Pain threshold levels and coping strategies among patients who have chest pain and normal coronary arteries. Patients with noncardiac chest pain (NCCP) tend to show lower pain threshold levels for esophageal balloon distention than do patients with other painful gastrointestinal disorders and healthy controls. The NCCP patients also report greater usage of negative pain-coping strategies, less ability to perform specific behaviors to decrease pain, and higher levels of clinical pain than do other patient and healthy control groups. Behavioral treatments produce significant decreases in pain and disruption of daily activities. Further effort is needed, however, to develop treatments for NCCP that are based on knowledge of the behavioral manifestations of this disorder and the afferent mechanisms involved in perception of visceral pain."
-What are the key diagnostic features of superficial thrombophlebitis?,"Acute venous thrombosis. Therapeutic choices for superficial and deep veins. Superficial thrombophlebitis is common in varicose veins or veins that have undergone trauma from catheters or intravenous medications. Pain and tenderness, warmth, and erythema are diagnostic features. A compression bandage and nonsteroidal antiinflammatory agent are often all that is required for treatment. Deep vein thrombosis occurs in veins beneath the deep fascia of the leg or in the pelvis or abdomen. It is often asymptomatic but must be treated to prevent pulmonary embolization and postthrombotic syndrome. Standard therapy is administration of heparin sodium for 5 days, followed by tapering and discontinuation. Warfarin sodium (Coumadin, Panwarfin, Sofarin) is sometimes given simultaneously. Longer courses of anti-coagulation therapy are necessary in patients with an ongoing risk of recurrence."
-What were the key findings of the decision-analysis study on prophylactic intravenous immune globulin in chronic lymphocytic leukemia patients?,"Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia [see comment] BACKGROUND. A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS. We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality-adjusted life expectancy. RESULTS. Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS. Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective."
-What was the key finding regarding pain perception during gastric distension in patients with chronic idiopathic dyspepsia?,"Abnormal perception of visceral pain in response to gastric distension in chronic idiopathic dyspepsia. The irritable stomach syndrome. Sensory and pressure responses to gastric distension were evaluated in 24 consecutive patients suffering from chronic idiopathic dyspepsia and 20 healthy subjects. A latex balloon was placed in the proximal stomach and inflated by increments of 100 ml of air up to a maximal volume of 800 ml. Symptom response and intragastric pressure-volume curve were recorded during the gradual balloon distension. Thirteen of the 24 patients experienced pain at a distension volume less than or equal to 400 ml of air, but only one of the 20 controls (P less than 0.001). Intragastric pressure-volume curves were similar in patients and controls, and in patients with and without abnormal pain threshold, suggesting that a compliance defect was not the cause of the sensory anomaly. Gastric emptying of solids and liquids was measured in 20 of the 24 patients using a dual isotopic technique; psychological status was also evaluated in 18 patients using the Mini-Mult test. The frequency of the sensory anomaly was not different in patients with (7/14) or without (4/6) gastric stasis, but was lower in patients with (5/13) than in those without psychological disturbances (5/5, P less than 0.01). Thus, a primary visceral sensory anomaly, either alone or in conjunction with motility disturbances, can play an important role in chronic idiopathic dyspepsia and must be taken in account for further therapeutic research."
-What percentage of lower respiratory tract infections in Thai children were associated with viral infections and Chlamydia trachomatis during the study period?,"A study of nonbacterial agents of acute lower respiratory tract infection in Thai children. From January 1986 to December 1987, 596 children less than 5 years of age with lower respiratory tract infection (LRI)--manifested as laryngitis, croup, bronchitis, bronchiolitis, and pneumonia--were studied for evidence of infection with respiratory tract viruses Mycoplasma pneumoniae, and Chlamydia trachomatis. Of the 596 children in the study, 315 were ambulatory and 281 were hospitalized. Virologic studies included isolation and rapid diagnosis of virus from specimens of nasopharyngeal aspirate (NPA) and serologic studies of blood samples. Cultures of NPA for C. trachomatis were performed for children less than 6 months of age who had pneumonia. Of the LRI cases, 45% were associated with viral infections of the respiratory tract and 12.1% were associated with C. trachomatis. Respiratory syncytial virus (RSV) accounted for 45.2% of infections with viral agents and was associated with acute bronchitis, acute bronchiolitis, and pneumonia. Parainfluenza type 3 virus was the most common virus found in conjunction with laryngitis and croup. The incidence of infections due to RSV peaked in July and August, while that of infections due to parainfluenza viruses peaked in February and March; influenza viruses and adenoviruses were isolated throughout the year."
-What are the key considerations for physicians when managing febrile seizures and counseling parents?,Febrile seizure. Caring for patients--and their parents. Management of febrile seizure involves diagnosis and treatment of the underlying cause and assessment of risk factors for recurrence. What should physicians tell anxious parents about this frightening occurrence? Is prophylaxis with anticonvulsant agents appropriate? The authors address these questions and discuss the changing approach to management of febrile seizure.
-What was the miss-rate of large colorectal polyps found in this prospective blinded trial of tandem colonoscopy?,Prospective blinded trial of the colonoscopic miss-rate of large colorectal polyps. We prospectively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring tandem colonoscopy. Sixty-three lesions greater than or equal to 1 cm in size were discovered and none were missed. Confidence intervals of 95% are a miss-rate of 0 to 4.6%. We conclude that less than 5% of large colorectal polyps are missed during the index colonoscopic examination in a well-prepared colon.
-What was the outcome of the six-year-old boy with symptomatic cerebral swelling complicating diabetic ketoacidosis?,"Symptomatic cerebral swelling complicating diabetic ketoacidosis documented by intraventricular pressure monitoring: survival without neurologic sequela. A six-year-old boy developed symptomatic cerebral swelling four hours after the initiation of treatment for newly diagnosed diabetes mellitus complicated by ketoacidosis. Ventriculostomy documented intracranial pressure over a two-day period. Increased intracranial pressure unresponsive to controlled hyperventilation and sedation was treated by administering a diuretic and by drainage via a ventriculostomy. Intracranial pressure monitoring was a useful adjunct in management of this rare, but often lethal, complication of diabetes mellitus. One year later, both school performance and the results of a neurologic examination were normal."
-What were the independent predictors of heart failure identified in the study using multivariant stepwise logistic regression analysis?,"Predicting left heart failure after a myocardial infarction: a preliminary study of the value of echocardiographic measures of left ventricular filling and wall motion. Heart failure occurs from both systolic and diastolic dysfunction. To determine whether simple Doppler echocardiographic measures of left ventricular filling could improve upon the ability of systolic function to predict heart failure after infarction, patients with acute myocardial infarction were studied within the first 36 hours by Doppler and two-dimensional echocardiography. Forty-eight patients who did not have heart failure before the Doppler echocardiographic study and who did not have myocardial revascularization, moderate or severe mitral regurgitation, or other complications during recovery were monitored for 6 months or to the onset of heart failure (n = 10). The univariate predictors of heart failure were age (p less than 0.05), anterior infarction (p less than 0.05), early diastolic peak filling velocity (p = 0.05), filling velocity with atrial systole (p less than 0.05), the ratio of these velocities (p less than 0.001), the percentage of filling with atrial systole (p less than 0.001), and the wall motion score index (p less than 0.001). However, the only independent predictors of heart failure by use of multivariant stepwise logistic regression analysis were the wall motion score index (p less than 0.05) and either the ratio of early and late peak filling velocities (p less than 0.001) or the percentage of filling with atrial systole (p less than 0.001). The combined use of a measure of systolic function and measures of the relative contribution of atrial systole to ventricular filling were useful predictors in identifying patients likely to develop subsequent heart failure after myocardial infarction."
-What were the key clinical patterns observed in paediatric urolithiasis across different stone types in this retrospective study?,"Clinical patterns of paediatric urolithiasis. A series of 270 paediatric stone patients was studied retrospectively according to the clinical pattern of urolithiasis (age and sex, stone location, stone analysis, recurrence rate) and aetiology of stone disease (infection, anatomical, metabolic or idiopathic). Infection stones occurred earliest and more commonly in males and were usually upper tract struvite calculi related to Proteus infection. Anatomical stones were most commonly associated with pelviureteric junction (PUJ) obstruction and had a high recurrence rate, despite surgical correction of obstruction. Idiopathic stones most resembled those found in adult urolithiasis by virtue of occurring latest, being sited in the ureter more often and being more frequently composed of calcium oxalate. Metabolic stones were most frequently calcium phosphate or cystine and virtually all were renal. They comprised the smallest group but had the highest recurrence rate."
-How did the response to desflurane differ between normal and malignant hyperthermia-susceptible swine in the study?,"Desflurane is a trigger of malignant hyperthermia in susceptible swine. Desflurane (difluoromethyl 1-fluoro 2,2,2-trifluoroethyl ether: CF2-H-O-CFH-CF3) is a potent inhalation anesthetic agent being investigated for possible clinical use. The authors examined the effects of this agent on normal swine and those from a special breeding program that were considered purebred for susceptibility to malignant hyperthermia (MH). Animals were exposed to 1 or 2 MAC or both doses of desflurane and observed for changes in end-tidal CO2, arterial blood gases, lactate, catecholamines, core temperature, blood pressure, and heart rate. All normal swine tolerated exposure to desflurane without clinical signs of MH, but significant changes in heart rate and blood pressure were noted. In contrast, of six MH susceptible swine tested, two had unequivocal MH reactions to deflurane, defined by significant increases of end-tidal CO2 (greater than 50 mmHg), an increase in PaCO2 (greater than 70 mmHg), a decrease in blood pH (less than 7.30), an increase in blood lactate concentration, and an increase in core temperature. Two other susceptible swine showed equivocal signs of MH but not until desflurane had been administered for 40-60 min. Finally, two other susceptible swine showed no signs of MH after 60 min of exposure to 2 MAC desflurane. These latter four animals all developed episodes of MH immediately after intravenous succinylcholine (2 mg/kg). The increased PaCO2, blood lactate concentrations, and temperature, and the decrease in pH induced by desflurane, were successfully treated with dantrolene and supportive measures. All surviving animals were biopsied 1 to 2 weeks after the exposure to desflurane for in vitro contracture testing to confirm MH susceptibility."
-How does dipyridamole improve the specificity of thallium-201 single-photon emission computed tomography in detecting coronary artery disease in patients with left bundle branch block?,"Improved specificity of myocardial thallium-201 single-photon emission computed tomography in patients with left bundle branch block by dipyridamole. Reduced septal uptake of thallium-201 during exercise is frequently observed in patients with left bundle branch block (LBBB) and normal coronary arteries. This may reflect normal coronary autoregulation in response to lower septal oxygen demand; thus, dipyridamole, which uniformly exploits flow reserve, would be more accurate for diagnosis of coronary artery disease (CAD). Sixteen patients with LBBB underwent exercise and dipyridamole thallium-201 single-photon emission computed tomography and coronary angiography within 3 months. Sensitivity for detection of left anterior descending CAD (greater than 50% stenosis) was 0.83 for exercise and 1.00 for dipyridamole. Specificity was 0.30 (visual) or 0.20 (quantitative analysis) for exercise and 0.80 (visual) or 0.90 (quantitative) for dipyridamole (p less than 0.05). Dipyridamole combined with quantitative analysis also improved specificity of CAD detection overall (p less than 0.01). These data demonstrate that pharmacologic vasodilation is more accurate than exercise when diagnosing CAD by myocardial perfusion scintigraphy in patients with LBBB."
-"How are depression, chronic fatigue, and chronic pain interconnected in terms of their psychological and neurobiological factors?","Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery."
-What prognostic factors were found to be associated with a higher recurrence rate in papillary carcinoma of the thyroid in this retrospective study?,"Prognostic factors in papillary carcinoma of the thyroid. In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hurthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men."
-How does local thrombin synthesis contribute to platelet recruitment and thrombus stabilization in heparinized blood?,"Local thrombin synthesis and fibrin formation in an in vitro thrombosis model result in platelet recruitment and thrombus stabilization on collagen in heparinized blood The role of the local synthesis of thrombin in platelet recruitment and thrombus stabilization in heparinized blood was examined in vitro. Mural thrombosis was visualized and measured in a thin, rectangular, collagen-coated capillary under controlled rheological conditions by using fluorescence digital videomicroscopy and fluorescence microphotometry. Thrombin activity was inhibited in heparinized blood by the synthetic competitive inhibitor, D-phenylalanyl-L-prolyl-L-arginyl chloromethylketone (FPRCH2Cl), resulting in a marked reduction in the rate of platelet accumulation on collagen surfaces, indicating a role for thrombin in platelet recruitment. Similar although lesser effects were observed by reducing thrombin synthesis with antibodies to factors II and X. To decouple the role of thrombin in platelet recruitment by direct stimulation of platelet activity from its role in thrombus stabilization via fibrin formation, thrombosis was measured in heparinized blood treated with the tetrapeptide glycyl-prolyl-arginyl-proline, which inhibits fibrin monomer assembly into fibrin. The ultimate level but not the initial rate of platelet accumulation was reduced markedly, indicating a role for fibrin in thrombus stabilization against hemodynamic forces. Scanning electron micrographs demonstrated fibrin stands in the heparinized control samples but not in the heparinized samples with glycyl-prolyl-arginyl-proline. These results demonstrate a role for the local action of thrombin synthesized on the surfaces of thrombi even under conditions when the thrombin exerts no bulk effect, such as under heparin anticoagulation. Furthermore, this role appears to be a result of both platelet recruitment and thrombus stabilization."
-How does the p53 gene mutation correlate with the progression of chronic myelocytic leukemia (CML) in this patient's case study?,Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
-What is the relationship between silent myocardial ischemia and autonomic dysfunction in diabetic patients?,"Detection of silent myocardial ischemia in diabetes mellitus. The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as greater than or equal to 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as greater than or equal to 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia."
-What was the purpose of the study comparing the use of dexapolyspectran drops in one ear versus the control ear after tympanostomy tube insertion?,"Use of prophylactic otic drops after tympanostomy tube insertion. In a 1-year prospective study, 60 patients with chronic serous otitis media underwent bilateral tympanocentesis with tube insertion. The right ear was treated with dexapolyspectran (a solution consisting of polymyxin B sulfate, neomycin sulfate, sulfonamide, and hydrocortisone) intraoperatively and for 72 hours afterward, and the left ear served as the control. All patients were followed up at weekly intervals for the first month. Five (8.3%) out of 60 experimental ears had purulent otorrhea within the first 14 days after surgery, compared with eight (13.3%) out of 60 control ears. Statistical analysis showed no difference between the two groups."
-What was the treatment approach for the patient with pancreatic islet cell carcinoma and how long did the remission last?,"Pancreatic islet cell carcinoma with hypercalcemia: complete remission 5 years after surgical excision and chemotherapy. A 45-yr-old man who presented with hypercalcemia was found to have an abdominal mass that was a pancreatic islet cell carcinoma. Although clinical features were suggestive of primary hyperparathyroidism, his parathyroid hormone level was not elevated. The patient underwent a radical resection of the pancreatic neoplasm which was situated in the tail of the gland. After surgery, the serum calcium fell within the normal range, suggesting that the tumor was responsible for production of a parathyroid hormone-like substance. Because of malignant histologic features of the lesion, a chemotherapeutic regimen including 5-fluorouracil and streptozotocin was indicated. Five years later, the tumor has remained in total remission."
-What specific mitochondrial DNA mutation was found to be associated with myoclonus epilepsy and ragged-red fibers (MERRF) in this study?,"Rapid detection of the A----G(8344) mutation of mtDNA in Italian families with myoclonus epilepsy and ragged-red fibers (MERRF). We devised a rapid PCR-based method to screen for an A----G transition at nucleotide 8344 of the human mitochondrial tRNA(Lys) gene, which was recently reported, by Shoffner and co-workers, to be associated with myoclonus epilepsy and ragged-red fibers (MERRF), a maternally transmitted mitochondrial encephalomyopathy (Shoffner et al. 1990). We confirmed this association in five of seven Italian MERRF pedigrees. The mutation was specific for the MERRF trait, because it was never found in mtDNA of non-MERRF individuals, including 14 normal and 110 diseased controls. Our study corroborates the idea that the A----G(8344) mutation is the most frequent and widespread genetic cause of MERRF."
-What is the relationship between arachidonic acid metabolism and brain edema in different types of brain pathologies?,"""Ex vivo"" release of eicosanoid from human brain tissue: its relevance in the development of brain edema. The specific mechanism underlying the genesis of vasogenic brain edema is still debated: the role of arachidonic acid is considered extremely important, as it is a possible activator of self-maintaining reactions enhancing the release of vasoactive and cytotoxic compounds. The relationship between arachidonic acid metabolism and brain edema has been studied primarily in brain tissue samples or in the extracellular fluid, whereas the residual capacity of perilesional tissue to synthesize and release eicosanoids has not been investigated. In the present study, perilesional samples of brain tissue were available from 4 patients operated on for brain metastasis, from 8 patients who had malignant neuroepithelial tumors, from 4 with meningiomas, and from 5 with subarachnoid hemorrhage. A brain edema index was calculated from the preoperative computed tomographic scan. The ""ex vivo"" method allowed determination of the residual capacity of endogenous arachidonic acid metabolism. The edema index is significantly higher in patients with brain metastasis (6.5 +/- 0.8) and neuroepithelial tumors (3.6 +/- 0.2) than in those with meningiomas (1.5 +/- 0.06), subarachnoid hemorrhage (1.7 +/- 0.18), and in controls. In patients with metastatic and neuroepithelial tumors there is a significant correlation between peritumoral brain edema and the capacity to synthesize leukotriene C4 (P less than 0.05); the capacity to synthesize leukotriene C4 is also significantly elevated after subarachnoid hemorrhage (13.91 +/- 2.6 ng/ml of incubation medium) when compared with control cases (5.56 +/- 0.91). The capacity to synthesize prostacyclin is significantly higher in patients with brain metastasis than in those with neuroepithelial tumors and meningiomas (P less than 0.05)."
-How does pentoxifylline affect intestinal microvascular blood flow during resuscitation from hemorrhagic shock?,"Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock. We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow."
-What was the primary aim of the study investigating the antihypertensive effects of ketanserin?,"The acute and chronic antihypertensive effects of ketanserin cannot be explained by blockade of vascular serotonin, type 2, receptors or alpha 1-adrenergic receptors. The mechanism underlying the antihypertensive effect of acute and chronic administration of ketanserin was investigated in eight hypertensive patients. Intrabrachial artery infusions of serotonin and the selective alpha 1-adrenergic receptor agonist methoxamine were given before and 1 hour after a single oral dose of 20 mg ketanserin and after 4 weeks of treatment with 20 to 40 mg twice daily. Blood pressure was reduced by ketanserin both after the initial dose (p less than 0.01) and after 4 weeks of treatment (p less than 0.01). During placebo, serotonin, 1 ng/kg/min, increased forearm blood flow by 51% +/- 9% (p less than 0.01), whereas the highest dose induced a decrease in flow (-33% +/- 6%; p less than 0.01). Methoxamine elicited a vasoconstriction (p less than 0.001). These effects of serotonin and methoxamine were not influenced by either the initial dose of ketanserin or after 4 weeks of treatment. It is concluded that serotonin cannot be considered a general endogenous pressor agent in these patients. The antihypertensive effects of ketanserin cannot be attributed to either vascular alpha 1-receptor or serotonin, type 2, receptor blockade."
-What was the survival rate of patients with paracetamol overdose who underwent liver transplantation in this study?,"Liver transplantation after paracetamol overdose. OBJECTIVE--To evaluate the role of liver transplantation after paracetamol overdose. DESIGN--Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING--Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES--Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS--30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION--Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol."
-What medical condition did the 31-year-old alcoholic woman suffer from and how was it treated?,The perils of Pauline: visual loss in a tippler [clinical conference] A 31-year-old alcoholic woman who smoked had subacute visual loss. She was treated for tobacco-alcohol amblyopia with subsequent improvement in vision.
-Does delaying antibiotic therapy by 48 hours affect the recurrence rate of group A beta-hemolytic streptococcal (GABHS) pharyngitis?,"Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates. To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate."
-What are the endocrine and reproductive effects observed in patients after total body irradiation for haematological malignancy?,"Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. The endocrine and reproductive sequelae of total body irradiation for haematological malignancy have been studied in 21 patients (11 male) who were treated with 10 Gy in five fractions or 12 or 13.2 Gy in six fractions over 3 days. Eighteen patients (eight male) aged 16-49 years underwent dynamic tests of the hypothalamic-pituitary axis with insulin hypoglycaemia, thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone stimulation and basal measurement of prolactin, sex steroids and thyroid hormones. Growth hormone responses (mean peak 64 +/- 36 mU/l, range 21-146 mU/l) and cortisol responses (mean peak 831 +/- 122 nmol/l, range 626-1105 nmol/l) were all within the normal range. Two patients had minimally elevated serum prolactin levels (445 and 588 mU/l, normal less than 350 mU/l). Serum thyroxine levels (57-133 nmol/l) were normal but six patients had elevated basal thyrotrophin (TSH) levels (6-9 mU/l) and seven had an exaggerated TSH response to thyrotrophin releasing hormone, indicating radiation-induced damage to the thyroid. Amenorrhea developed within 3 months of irradiation in all females and oestradiol levels were low, at 37-108 pmol/l (mean 58 +/- 22 pmol/l). Severe oligospermia or azoospermia was noted in men tested 5-70 months after irradiation and testicular volume was below the normal adult range in five of seven men assessed. Serum testosterone levels (12.4-35 nmol/l) were normal. Gonadotrophin-releasing hormone-stimulated gonadotrophin levels were elevated in all patients. However, two men have fathered two children each; one has refused semen analysis, but the other has a sperm count of 7 x 10(6)/ml (60 per cent motile, 20 per cent abnormal forms) 70 months after irradiation. When given by the above fractionated regimens, the endocrine sequelae of total body irradiation are limited to gonadal failure requiring oestrogen replacement in women and severe impairment of fertility in men. Subclinical thyroid dysfunction has been seen in 39 per cent of patients there is no evidence of direct damage to the hypothalamic pituitary axis."
-What is the key treatment approach for the patient with steroid-responsive tubular aggregate myopathy described in this case report?,"Steroid-responsive tubular aggregate myopathy. We report a man with an acute myalgia/cramp syndrome and tubular aggregates on his muscle biopsy. He was placed on prednisone and was found to be exquisitely sensitive to the drug, with changes of only 5 mg precipitating recurrence of symptoms. He was eventually tapered off all steroids, without symptoms, and repeat biopsy showed no tubular aggregates. We recommend similar patients be given a trial of high-dose steroids."
-What did the study find about the relationship between racial differences and the incidence of hypertensive end-stage renal disease (HT-ESRD)?,"Does racial variation in risk factors explain black-white differences in the incidence of hypertensive end-stage renal disease? Prospectively collected data on the incidence of treated hypertensive end-stage renal disease (HT-ESRD) were analyzed to investigate whether the higher rate of HT-ESRD in blacks compared with whites is due to differences in putative ESRD risk factors. The overall age-adjusted relative risks of HT-ESRD for black compared with white residents in the Maryland Regional ESRD Registry (Network 31) Catchment Area were 7.4 (95% confidence interval, 5.9 to 9.4) and 9.9 (95% confidence interval, 7.4 to 13.1) for men and women, respectively. In a population level analysis, race-specific HT-ESRD incidence rates in the black and white populations of 13 regions in Network 31 were related to the prevalence of putative ESRD risk factors in those populations. The latter were estimated from the 1981-1982 Maryland Statewide Household Hypertension Survey. Black populations had a 5.6-fold (95% confidence interval, 3.9 to 8.1) higher unadjusted incidence of HT-ESRD than white populations. The HT-ESRD incidence in a population was also directly related to that population's prevalence of hypertension, severe hypertension, and diabetes mellitus and inversely related to measures of socioeconomic status and mean age at diagnosis of hypertension. When adjusted simultaneously for age, prevalence of hypertension, severe hypertension, diabetes, and level of education, the risk of HT-ESRD was still 4.5 (95% confidence interval, 3.2 to 6.2) times higher for black compared with white populations. Our findings failed to support the hypothesis that race-related differences in the prevalence, severity, or age at onset of hypertension, in the prevalence of diabetes or in socioeconomic status, explain the well-recognized black-white differences in the HT-ESRD incidence."
-What oral lesions were found to be more prevalent in HIV-infected homosexual and bisexual men compared to HIV-negative subjects?,"The prevalence of oral lesions in HIV-infected homosexual and bisexual men: three San Francisco epidemiological cohorts. To establish the prevalence of HIV-related oral lesions, we performed oral examinations of members of three San Francisco epidemiological cohorts of homosexual and bisexual men over a 3-year period. Hairy leukoplakia, pseudomembranous and erythematous candidiasis, angular cheilitis, Kaposi's sarcoma, and oral ulcers were more common in HIV-infected subjects than in HIV-negative subjects. Among HIV-infected individuals, hairy leukoplakia was the most common lesion [20.4%, 95% confidence interval (CI) 17.5-23.3%] and pseudomembranous candidiasis was the next most common (5.8%, 95% CI 4.1-7.5%). Hairy leukoplakia, pseudomembranous candidiasis, angular cheilitis and Kaposi's sarcoma were significantly more common in patients with lower CD4 lymphocyte counts (P less than 0.05). The prevalence of erythematous candidiasis and Kaposi's sarcoma increased during the 3-year period. Careful oral examinations may identify infected patients and provide suggestive information concerning their immune status."
-How does streptokinase treatment affect chest pain duration in patients with acute myocardial infarction?,"The effect of streptokinase on chest pain in acute myocardial infarction. Treatment with intravenous streptokinase is known to restore blood flow to the ischaemic myocardium in patients with acute myocardial infarction. However, little is known about its effect on chest pain. In a retrospective cohort study, 76 patients treated with streptokinase were compared to 76 patients not treated with streptokinase. All patients had acute myocardial infarction and less than 6 h of cardiac symptoms. Patients treated with streptokinase had a significantly lower need for nicomorphine (median 20 mg) than patients not treated with streptokinase (median 41 mg). Correspondingly, the median duration (3.5 h) of pain was reduced significantly in patients treated with streptokinase compared to patients not treated (24 h). We conclude that intravenous streptokinase given in the acute phase of myocardial infarction is effective in reducing the duration of cardiac chest pain."
-What was the disease-free survival rate for patients with Stage I and II Hodgkin's disease treated with subtotal nodal irradiation in this study?,"Cure of early-stage Hodgkin's disease with subtotal nodal irradiation. Ninety-four consecutive patients with Stage I or II Hodgkin's disease who presented supradiaphragmatically were treated with radiation therapy alone at the Mallinckrodt Institute of Radiology from January 1978 through December 1986. Fifty-two patients (55%) were staged pathologically, and 42 (45%) were staged clinically. The latter included lymphangiography and/or abdominal computed tomographic scan. Most patients with B symptoms and/or bulky disease were excluded from this series. Seventy-four patients were treated with subtotal nodal irradiation (mantle and periaortic fields). The spleen was treated if the patient had not undergone splenectomy. Twenty patients received mantle irradiation only. No patient received total nodal irradiation. All patients had an initial complete response. With a minimum follow-up of 7 months (median, 7.7 years; seven patients died before 3 years of follow-up, but all other patients had at least 3 years of follow-up), 81 patients (86%) remained disease-free. Six of 52 (12%) of the pathologically staged group had a relapse, as did seven of 42 (17%) of the clinically staged group (P = 0.68). Eight of 57 Stage I patients versus five of 37 Stage II patients had a relapse (P greater than 0.99). Analysis of disease-free survival by age, histologic findings, sex, and sites of involvement did not predict relapse. The pelvis was the most common site of failure (nine patients, 10%). However, only three patients (3%) failed in the pelvis alone. These results indicate that patients who, after adequate clinical staging with selective use of staging laparotomy, are found to have Stage I and II Hodgkin's disease may be treated with subtotal nodal irradiation with a high rate of cure."
-How does prolonged hemorrhagic shock affect the regeneration of plasma coagulant masses in rabbits?,"Prolonged hemorrhagic shock does not impair regeneration of plasma coagulant masses in the rabbit. BACKGROUND AND METHODS: Twelve adult male albino rabbits were assigned alternately to normotensive and hypotensive groups to assess the effect of hypovolemic shock on spontaneous correction of dilutional coagulopathy. All animals underwent dilutional exchange transfusion with 200 mL of rabbit RBCs and 5% human albumin. Half the animals were then acutely hemorrhaged and subsequent aliquots of blood removed as needed to maintain the mean arterial pressure at 40 mm Hg. RESULTS: By 6 hr after production of dilutional coagulopathy, masses and plasma concentrations of fibrinogen and Factor II had increased modestly but significantly, and Factor VII mass and concentration and in vitro coagulation had returned almost to normal; plasma volume was unchanged in the normotensive animals. In the hypovolemic shock animals, where coagulant mass regeneration was as rapid as in the normotensive animals, a doubling of total plasma volume (p less than .01) prevented the concentrations of fibrinogen and Factor II, and hence the coagulation times, from improving. CONCLUSIONS: Dilutional coagulopathy corrects spontaneously within hours. Normovolemic shock prolongs dilutional coagulopathy not by impairment of factor regeneration but because of further (internal) dilution due to plasma expansion. Rapid correction of dilutional coagulopathy is likely to necessitate cryoprecipitate administration."
-What specific genetic abnormalities have been identified as potentially important in the progression from normal to malignant colonic mucosa?,"Genetics of colon cancer. Strikingly rapid advances in the identification of genetic events that are important in colonic carcinogenesis have been made in the past several years. Specific inherited (adenomatous polyposis coli gene) and acquired (ras gene point mutations; c-myc gene amplification; allelic deletion at specific sites on chromosomes 5, 17, and 18) genetic abnormalities appear to be capable of mediating steps in the progression from normal to malignant colonic mucosa. Understanding these genetic factors and how they influence cellular function will have a profound effect on medical practice. High-risk populations will be (and are being) identified by genetic markers, thus allowing prevention and screening to be more precisely targeted to the population at risk; intervention strategies will be designed on the basis of the known cellular defects of neoplastic colonic mucosa; and new molecular preventive and therapeutic approaches can be developed."
-What rare intrathoracic complications can occur in acute pancreatitis according to the given context?,Rare intrathoracic complications in acute pancreatitis. Ascites and pleural effusions may complicate pancreatitis but pericarditis with pericardial effusion and tamponade is rare and necrosis of mediastinal fat has not been described before. All these complications occurred in the case reported here.
-How does the expression of TNF receptors on neoplastic B-CLL cells change when cultured in vitro compared to their state in vivo?,"Receptors for tumor necrosis factor on neoplastic B cells from chronic lymphocytic leukemia are expressed in vitro but not in vivo. Recombinant tumor necrosis factor-alpha (TNF-alpha) is a cytokine that induces proliferation of neoplastic B cells from patients with chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms involved in regulating TNF responsiveness, we have examined TNF receptor expression on neoplastic B-CLL cells. We have demonstrated that freshly isolated neoplastic B cells from patients with CLL did not express TNF receptors. After 1 day of incubation in culture medium, TNF receptors were detectable in the range of 540 to 1,500/cell. Kinetic experiments revealed that receptor expression was half-maximal after 3 hours of culturing and required de novo protein synthesis. The Scatchard plots of TNF-alpha binding indicated a single set of high-affinity TNF receptors with a dissociation constant of 70 pmol/L. TNF receptor expression in vitro was found in all examined cases. All cytokines tested, with the exception of IL-2, did not influence the expression of TNF receptors. The TNF receptor expression is enhanced in B-CLL cells cultured in the presence of interleukin-2 when compared with the receptor expression of cells cultured in medium alone. Our data suggest that neoplastic B-CLL cells in patients with stable disease do not express TNF receptors in vivo and that an unknown mechanism suppressing TNF receptor expression in vivo may play a role in growth regulation of neoplastic B cells."
-What were the initial surgical techniques used for patients before balloon angioplasty in this study?,"Balloon angioplasty for recurrent coarctation of aorta. Immediate and long-term results BACKGROUND. As angioplasty techniques have been refined and larger low-profile balloons developed, a nonsurgical approach to recoarctation has become available. Several reports have documented both the efficacy and safety of this procedure. However, there are little data available on the long-term follow-up of these patients. This report details the initial results and long-term evaluation of both the relief of obstruction and the presence of hypertension after balloon angioplasty for recurrent coarctation. METHODS AND RESULTS. Balloon angioplasty for recurrent coarctation of the aorta was performed 29 times in 26 patients at a median age of 4 years and 9 months (range, 4 months to 29 years), with eight patients less than 1 year old. Initial surgical techniques were end-to-end anastomosis in 11 patients, subclavian flap aortoplasty in 11 patients, and patch aortoplasty in four patients. Angioplasty was performed at a median interval of 2 years and 7 months (range, 4 months to 23 years) after surgery. Mean peak systolic pressure difference across the coarctation decreased from 40.0 +/- 16.8 to 10.3 +/- 9.5 mm Hg (p less than 0.05) after the initial angioplasty, and mean diameter of the aortic lumen at the coarctation site increased from 5.8 +/- 3.5 to 9.0 +/- 4.3 mm (p less than 0.05). There was no mortality, and only one patient developed an aneurysm (4%). Three patients underwent repeat angioplasty for a pressure difference of more than 20 mm Hg. Long-term follow-up is available on 24 of 26 patients with a mean follow-up of 42 +/- 24 months (range, 12-88 months). Mean peak systolic pressure difference across the area of coarctation decreased from 40.3 +/- 17.4 before angioplasty to 8.5 +/- 8.3 mm Hg after final angioplasty (p less than 0.05) and 7.5 +/- 7.5 mm Hg at follow-up. Mean peak systolic blood pressure in the upper extremities decreased from 133.1 +/- 14.9 before angioplasty to 111.1 +/- 14.1 mm Hg at long-term follow-up (p less than 0.05). CONCLUSIONS. Balloon angioplasty should be considered the treatment of choice for relief of recurrent aortic coarctation."
-What is the relationship between syringomyelia and congenital intraspinal lipoma in this case study?,Syringomyelia secondary to congenital intraspinal lipoma. Preoperative evaluation using serial magnetic resonance imaging was performed on an infant with lumbosacral lipoma. Syrinx formation arising just above the lipoma was observed in conjunction with rapid growth of the lipoma. Definite shrinkage of syringomyelia was obtained after radical excision of the lipoma. The syrinx formation was possibly caused by compression from the extramedullary lipoma.
-How does persistent measles virus infection affect endothelin 1 signaling in C6 rat glioma cells?,"Loss of the endothelin signal pathway in C6 rat glioma cells persistently infected with measles virus. Endothelin 1 causes a strong Ca2+ signal in C6 rat glioma cells as measured by fura-2 fluorescence. This endothelin 1-induced Ca2+ signal was not observed when the cells were persistently infected with a measles virus strain of subacute sclerosing panencephalitis (SSPE, strain Lec). Binding of 125I-labeled endothelin 1 to the C6/SSPE cells was less than 5% of the binding to the C6 control cells, suggesting that the impairment in signal transduction was due to a loss of binding sites for endothelin 1. Treatment of the C6/SSPE cells with measles antiserum resulted in the loss of expression of viral proteins located in the membrane as well as inside the cells (antigenic modulation), but it restored neither the endothelin 1-induced Ca2+ rise nor the 125I-endothelin 1 binding. Cocultivation of uninfected C6 cells with C6/SSPE cells (9:1 ratio) resulting in contact-mediated transmission of measles virus showed that the 125I-endothelin 1 binding activity was gradually lost as a consequence of persistent virus infection."
-What is the incidence of stroke during pregnancy according to the study conducted at Parkland Memorial Hospital?,"Cerebrovascular accidents complicating pregnancy and the puerperium. The decreasing incidence of direct causes of maternal death over the past half century has led to a heightened awareness of nonobstetric factors responsible for maternal mortality. For example, cerebrovascular accidents are an important nonobstetric cause of maternal morbidity and mortality. During the 6.5-year period from 1984 to mid-1990, we encountered 15 women in whom pregnancy or the puerperium was complicated by an acute cerebrovascular accident. Six of these women had hemorrhagic strokes and nine had ischemic strokes. During this same time, approximately 90,000 women were delivered at Parkland Memorial Hospital, and thus the incidence of stroke was about one in 6000 pregnancies. Chronic hypertension or preeclampsia was causative in three cases of hemorrhagic stroke. It is important that 20% of the women died as a result of stroke, and of the 12 survivors, 40% have residual neurologic deficits. An aggressive work-up to define the etiology of stroke is necessary in order to implement cause-specific management, with subsequent reduction in morbidity and mortality."
-What were the key differences in clinical outcomes between patients who underwent mitral valve replacement with and without preservation of the posterior leaflet?,"Clinical results of mitral valve replacement with and without preservation of the posterior mitral valve leaflet and subvalvular apparatus. In this study we attempted to investigate the importance of posterior leaflet preservation during mitral valve replacement (MVR). One hundred and forty randomly selected patients with isolated mitral insufficiency were studied, half of whom had MVR with preservation of the posterior leaflet (Group I), whereas in the other half conventional MVR was performed, without preservation of the posterior leaflet (Group II). Within these two groups there were no in hospital deaths, but 5 patients in Group II were admitted to the hospital with congestive heart failure and 3 of them died after approximately 6 months. Long term mortality rate was 4.2% in Group II. Ejection fraction (EF) decreased postoperatively from 56% to 50% in Group I (p less than 0.05), and from 59% to 49% in Group II (p less than 0.05). Fifteen patients in each group and aged below 30 with sinus rhythm and in the first functional capacity according to the New York Heart Association classification (NYHA) were subjected to exercise study, 18 months after the operation. After exercise EF increased from 47% to 64% in Group I and decreased from 51% to 47% in Group II. These findings suggested that MVR with the preservation of the chordae tendineae can be done with a low morbidity and mortality rate in the early and late postoperative period."
-How does platelet-activating factor (PAF) contribute to complement activation and tissue injury in mice?,"Platelet-activating factor produces shock, in vivo complement activation, and tissue injury in mice. We previously showed that TNF and endotoxin (LPS) synergize to activate the complement system and produce shock and bowel injury in normal mice. However, C5-deficient mice were protected from these adverse effects. In this study, we show that in mice, platelet-activating factor (PAF) antagonist prevents TNF- and LPS-induced complement activation, bowel injury, and death, indicating that PAF mediates the actions of TNF and LPS. We then examined the role of the complement system in PAF-induced shock and tissue injury. We found that 1) PAF (3 micrograms/kg) induces shock, hemoconcentration, bowel necrosis, and death in normal mice, whereas C5-deficient mice are protected from these effects. (Protection was abrogated when the dose of PAF was raised to 5 micrograms/kg.) Furthermore, when C5-deficient mice were reconstituted with normal serum, they also developed shock, bowel injury, and death in response to PAF. Thus, C5 is required for PAF to induce injury. 2) PAF activates the complement system in vivo, but not in vitro. The mechanism of complement activation by PAF is unclear. Inasmuch as PAF stimulates neutrophils to release protease that may activate the complement system, we examined the effect of neutrophil depletion on PAF-induced injury and complement activation. We found that neutrophil depletion fails to prevent PAF-induced complement activation, although PAF-induced lethality is much reduced. We conclude that PAF causes complement activation, and acts in synergy with active complement fragments to produce shock and tissue injury. Neutrophils probably do not play the pivotal role in PAF-induced complement activation."
-What was the purpose of the study on the Graseby patient-controlled analgesia system?,Evaluation of the Graseby PCAS. A clinical and laboratory study. The Graseby patient-controlled analgesia system was evaluated in the laboratory and in clinical use. The problems encountered with eight examples used to treat 510 patients are reported. Laboratory performance revealed the unit to be accurate at infusion volumes of 1 and 2 ml.
-What is the purpose of the review by the Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee?,"Occupational and industrial toxin exposures and the gastrointestinal tract. Gastrointestinal Toxicology Subcommittee of the American College of Gastroenterology Patient Care Committee. The subcommittee on Gastrointestinal Toxicology of the Patient Care Committee of the American College of Gastroenterology has reviewed potential effects of exposures to occupational and industrial hazards on the gastrointestinal tract, liver and pancreas. This review is presented to 1) share clinical data concerning gastrointestinal toxicology, 2) emphasize the paucity of available information to the practicing clinician, and 3) stimulate basic research interest in this field."
-What is the recommended initial antibiotic combination for treating necrotizing fasciitis according to the review?,Necrotizing fasciitis. Ten cases of necrotizing fasciitis are reviewed. Three patients died but only two of these deaths were due to uncontrolled septicaemia. All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice. Prompt and aggressive surgical debridement remains the cornerstone of management.
-What was the total possible loss of calcium during the preparation of paraffin blocks and slide preparation in the study of breast specimen microcalcifications?,"Breast specimen microcalcifications: radiographic validation and pathologic-radiologic correlation. A prospective analysis of specimens from location and biopsy of mammographically suspect microcalcifications in 108 patients was carried out to determine if microcalcifications were lost during histopathologic processing and the clinical relevance of such loss. Nine hundred sixty-eight paraffin blocks were prepared from 425 gross tissue slices containing calcifications identified at radiography of the specimens. Calcium was apparently lost both during preparation of the blocks (13.6%) and after slide preparation (12.6%), for a total possible loss of 26.2%. All specimens demonstrated calcification histologically. One pathology report was amended because of information obtained after recuts, but all cancers were detected on original slides whether or not calcifications were identified initially. The results indicate that, by following the suggestions offered to ensure adequate histopathologic sampling of calcification seen at mammography, most if not all of the calcification present can be detected on the original slide."
-What is the significance of the zinc finger protein gene cluster deletion in the mouse embryonic lethal mutation tw18?,A cluster of related zinc finger protein genes is deleted in the mouse embryonic lethal mutation tw18. We report that a number of related zinc finger protein genes are closely linked on mouse chromosome 17. At least four of these genes are transcribed in the 8.5-day postcoitum embryo and are deleted in the t complex early acting embryonic lethal mutation tw18. We have evidence that additional finger protein genes are located in this region. These findings demonstrate that related finger protein genes can be clustered in the murine genome and identify genes that may be considered as candidates for the tw18 mutation.
-How does regional cerebral blood flow differ between aphasic stroke patients and control subjects during a functional naming test?,"Remote cortical dysfunction in aphasic stroke patients. We studied the effect of deep-seated left hemispheric lesions on cortical blood flow in 18 right-handed aphasic stroke patients. Regional cerebral blood flow was measured at rest and during the performance of a functional naming test using the two-dimensional xenon-133 inhalation method. Compared with 10 controls, at rest the patients showed regional cortical hypoperfusion in the left frontoparietal region. In the controls, activation patterns from the rest to the test condition involved mainly the left hemisphere areas. In the patients, a lack of blood flow change was observed in several areas that were usually hypoperfused at rest. However, in patients with slight verbal expression disorders there were obvious blood flow increases in other brain regions in both hemispheres. Such cortical functional reorganization and the presence of a remote cortical dysfunction could play a role in the pathophysiology of language disorders."
-How did the researchers study the chemosensory responses of the carotid body in this in vitro preparation?,"In vitro perfused-superfused cat carotid body for physiological and pharmacological studies. An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible."
-What was the efficacy of different oral doses of ondansetron in preventing nausea and emesis in breast cancer patients receiving cyclophosphamide-doxorubicin chemotherapy?,"Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy. We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related."
-What challenges can arise when differentiating between germ cell tumors and central nervous system sarcoidosis?,"Germ cell tumors masquerading as central nervous system sarcoidosis. The diagnosis of central nervous system sarcoidosis is uncertain without typical multisystem involvement. We describe two patients with isolated central nervous system mass lesions whose biopsy results were consistent with sarcoidosis. After a progressive clinical course, they were found to have diencephalic germinomas. Germ cell tumors, in particular, should be considered in the differential diagnosis of central nervous system sarcoidosis as they are potentially treatable, occur in intracranial locations favored by sarcoidosis mass lesions, and may be surrounded by granulomatous inflammation that can be mistaken for the noncaseating granulomas of sarcoidosis."
-What did the researchers discover about circulating ICAM-1 isoforms in the study of healthy young volunteers?,"Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Intercellular adhesion molecule-1 (ICAM-1, CD54) is an important early marker of immune activation and response. Evidence on its role has come from immunohistological staining of tissues, since no free circulating ICAM-1 has been detected. By means of monoclonal antibodies against ICAM-1 and a sensitive chemiluminescence technique, free circulating ICAM-1 was detected in serum from sixteen healthy young volunteers. The concentrations varied among the subjects. Non-denaturing gel separation methods showed that ICAM-1 circulates in at least three isoforms, the proportions of which also varied. These findings have important implications for the investigation, diagnosis, and therapeutic monitoring of various inflammatory, neoplastic, and immune disorders."
-What makes pancreatic cancer a particularly challenging disease to treat?,"Biology of pancreatic cancer. Pancreatic cancer is the fifth leading cause of death from malignant disease in Western society. Apart from the fortunate few patients who present with a resectable small pancreatic adenocarcinoma, conventional treatment offers no hope of cure and has little palliative value. Over the past two decades major steps have been made in our understanding of the biology of pancreatic growth and neoplasia. This review sets out to explore these advances, firstly in the regulation of normal pancreatic growth, and secondly the mechanism which may be involved in malignant change of the exocrine pancreas. From an understanding of this new biology, new treatment strategies may be possible for patients with pancreatic cancer."
-How do the bile acid compositions differ between intrahepatic and extrahepatic brown pigment stones?,"Microanalysis of bile acid composition in intrahepatic calculi and its etiological significance. Brown pigment stones in the intrahepatic bile ducts were compared with those found in the extrahepatic bile ducts with special reference to the bile acids modified by bacterial intervention, that is, unconjugated, glucuronidated, secondary, and ketonic bile acid fractions. The former showed significantly lower amounts of total bile acids (P less than 0.01) and lower proportions of unconjugated bile acid fraction (P less than 0.01), secondary bile acid fraction (P less than 0.05), and ketonic bile acid fraction (P less than 0.05) to total bile acids than the latter. The discriminant analysis using these bile acid parameters led to complete separation between intrahepatic and extrahepatic stones in the case of brown pigment stones. In contrast, cholesterol stones in the intrahepatic bile ducts showed the bile acid composition close to those found in the extrahepatic ducts and gallbladder. The above data show that the bacterial infection plays a less important role in the formation and ensuing growth of most intrahepatic brown pigment stones than in extrahepatic stones, and that factors other than or in addition to bacterial infection are involved."
-What were the independent predictors of respiratory failure in patients undergoing thoracoabdominal aortic aneurysm repair?,"A prospective study of respiratory failure after high-risk surgery on the thoracoabdominal aorta. From June 1960 to September 1990, 1414 patients underwent repair of thoracoabdominal aortic aneurysms, of whom 112 (8%) had pulmonary complications requiring respiratory support with tracheostomy; subsequently 45 (40%) died in the hospital. We determined by stepwise logistic regression analysis, in a prospective study of high-risk type I and II thoracoabdominal aortic aneurysms repairs, the independent predictors of respiratory failure, defined as respiratory ventilation exceeding 48 hours after operation. In 98 patients studied, 38 (39%) were women, 60 (61%) were men, 54 (55%) had type II thoracoabdominal aortic aneurysms, 34 (35%) had aortic dissection, 19 (19%) were nonsmokers, 40 (41%) exsmokers, and 39 (40%) active smokers. Before operation, 55 (56%) had chronic pulmonary disease with respiratory failure developing in 58% (p = 0.0005 versus no chronic pulmonary disease, 10/43, 23%), and of the 26 patients in the lower quarter of forced expiratory volume (1 sec) (FEV1 less than or equal to 1.45 L) respiratory failure developed in 61% (p = 0.035). In-hospital survival was 98% and 83% (p = 0.008), respectively, and cumulative survival at 6 months by Kaplan-Meier analysis was 96% and 80% (p = 0.004, log-rank test), respectively, for patients without respiratory failure (N = 56/98, 57%) and with respiratory failure (N = 42/98, 43%). On univariate analysis, the following were associated with respiratory failure (p less than 0.05): FEV1, FEV1% predicted, FVC, FEF25, FEF25% predicted, FEF25-75, FEF25-75% predicted, PaCO2 Pao2, symptoms, smoking history, chronic pulmonary disease, cryoprecipitate volume, postoperative neuromuscular deficit, cardiac complications, reoperation for bleeding, renal complication, stress ulceration, postoperative creatinine level, postoperative dialysis, and postoperative encephalopathy. The independent predictors of respiratory failure were (p less than 0.05): chronic pulmonary disease, smoking history, cardiac and renal complications. In patients with chronic pulmonary disease, the only independent predictor was FEF25 (p = 0.030). These observations may be of value in selecting patients for elective operation."
-How did electrical muscle stimulation affect periodic leg movements in sleep for the patients in the study?,"Nonpharmacologic treatment of periodic leg movements in sleep. The effects of a 30-minute stimulation of the dorsiflexors of the feet and toes before bedtime were investigated in eight patients with periodic leg movements in sleep (PLMS). None were taking medications at the time of the investigation. All subjects were treated with the EMS-250 Neuromuscular Stimulator, which has a maximum output per channel of 1.5mA and a frequency of 47Hz. Stimuli were delivered via a pulse train (on for 1.5sec and off for 1.8sec). A single all-night polysomnogram after this stimulation showed that all patients responded to stimulation, with reduction of leg movements from an average pretreatment PLMS index of 44.6 per hour to a posttreatment PLMS index of 14 per hour (p less than .01). Nocturnal leg movements were primarily reduced during the non-REM sleep. Multiple indices of sleep continuity did not change significantly, although there was a trend toward better sleep consolidation."
-What is the relationship between absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery and the development of necrotising enterocolitis?,"Absent or reversed end diastolic flow velocity in the umbilical artery and necrotising enterocolitis. Absent or reversed end diastolic flow (AREDF) velocities in the umbilical artery were identified in 25 high risk pregnancies. In six pregnancies the fetus was abnormal and all but one of these ended in perinatal death. Of the 19 morphologically normal fetuses, three died in utero and there were four neonatal or infant deaths. The mortality rate was 48% for all pregnancies and 37% for those with morphologically normal fetuses. There was a highly significant increased risk for the development of necrotising enterocolitis in these morphologically normal fetuses with AREDF (53%) compared with controls (6%) who did have umbilical artery end diastolic flow velocities in fetal life. There were no significant differences between the matched pairs for parameters of neonatal outcome chosen to reflect neonatal morbidity. These findings demonstrate the close association between AREDF and necrotising enterocolitis that appears to be independent of other variables such as degree of growth retardation, prematurity, and perinatal asphyxia."
-How do interpersonal conflicts differ in their impact on chronic pain for patients with arthritis versus those with myofascial disorders?,"The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology. This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed."
-What makes the dislocation of an osseointegrated screw a rare event?,Total avulsion of an osseointegrated screw. The close union achieved between pure grade titanium and healthy bone makes dislocation a rare event. We report the case of the total avulsion of an apparently well-integrated implant from a healthy mastoid bone.
-What was the key finding regarding chromosome 14 inheritance in the patient with a Robertsonian translocation?,"Uniparental heterodisomy for chromosome 14 in a phenotypically abnormal familial balanced 13/14 Robertsonian translocation carrier. A 9-year-old mentally retarded girl with multiple congenital anomalies was found to carry a balanced 13/14 Robertsonian translocation [45,XX,t(13q14q)] which was also present in her father. Her mother carried a balanced reciprocal translocation between chromosomes 1 and 14 [46,XX,t(1;14) (q32;q32)]. Both of her parents were phenotypically normal. Molecular studies were carried out to determine the parental origin of chromosomes 1, 13, and 14 in the patient. Using probes for D14S13 and D14S22, we could show that the patient inherited both chromosomes 14 from her father and none from her mother. Similar studies using probes for chromosomes 1 (D1S76) and 13 (D13S37) loci showed the presence of both maternal and paternal alleles in the patient. Our findings indicate that paternal uniparental heterodisomy for chromosome 14 most likely accounts for the phenotypic abnormalities observed in our patient. It is suggested that uniparental disomy may be the basis for abnormal development in at least some phenotypically abnormal familial balanced-translocation carriers."
-What factors were found to be most strongly correlated with sleep problems in the South Australian community health survey?,"Sleep difficulties, pain and other correlates. A multiple regression analysis was used with variables relevant to sleeping problems from a large community health survey in South Australia. The variables that were found to be most strongly correlated with sleep problems were, in order of importance, pain, anxiety, age, somatic health and annual household income, all of which accounted for 22% of the variance. Weight problems, depression and sex of the respondent were not so important in this analysis. Arthritis, which often increases with age, appeared to be most strongly associated with pain, explaining in part why sleeping problems increase with age. Anxiety, pain and poor somatic health were most strongly associated with lying awake at night or sleeping badly, and anxiety and pain were most strongly correlated with taking longer to get to sleep. Poor somatic health and anxiety were most strongly associated with waking early, and age and pain were the most important variables in taking tablets to aid sleep."
-What are the key findings of the study regarding patient-controlled analgesia in children?,Long-term patient-controlled analgesia in children. Three children who received patient-controlled analgesia for periods of up to 41 days are described. In each case patient-controlled analgesia allowed pain control to be achieved in difficult situations. No patient developed tolerance or clinical signs of dependence. This use of long-term patient-controlled analgesia warrants further evaluation.
-What are the key findings of the study regarding infectious disease transmission in outpatient healthcare settings?,"Transmission of infectious diseases in outpatient health care settings. Increased provision of health care in outpatient settings and concerns about occupational transmission of infections have focused attention on the risk of transmission of infectious diseases in ambulatory health care settings. In contrast to inpatient nosocomial infections, infections transmitted in outpatient settings are neither systematically monitored nor likely to be detected by routine qi surveillance. To better define the spectrum of such events, we reviewed the literature to identify cases and clusters of infections associated with outpatient health care. In this review, we identified and epidemiologically characterized 53 such reports that occurred from 1961 through 1990. Transmission occurred in general medical offices, clinics, and emergency departments (23); ophthalmologists' offices and clinics (11); dental offices (13); and alternative-care settings (six). Our findings suggest that inpatient infection-control practices should be extended to outpatient health care settings by assigning specific responsibility for infection control and by adapting surveillance methods and prevention measures."
-How do Staphylococcus epidermidis and Escherichia coli compare in their ability to induce inflammatory responses and physiological changes in rabbits?,"Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli. Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism."
-"What complication occurred in the patient who underwent endoscopic variceal sclerotherapy, and how was it discovered?","Portal vein thrombosis complicating endoscopic variceal sclerotherapy. Convincing further evidence. Portal vein thrombosis occurred in a patient who bled from gastric varices that developed after obliteration of esophageal varices by endoscopic sclerotherapy. This complication was recognized only at surgery when thrombectomy and endovenectomy preceded the successful placement of an end-to-side portocaval shunt. At histopathology, the presence of an amorphous, eosinophilic material staining negatively for fibrin and similar to sclerosant injected at sclerotherapy was observed within the clot. This latter finding, previously unreported, provides convincing evidence for the causal relationship of portal vein thrombosis to endoscopic sclerotherapy."
-What were the three major inclusion criteria for patients in this deep vein thrombosis prevention study?,"Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of Logiparin and standard heparin. H.B.P.M. Research Group. A total of 1290 patients were enrolled in a randomized multicentre double blind study in order to investigate the use of two doses of a new low molecular weight heparin, Logiparin, in the prevention of deep vein thrombosis (DVT) in general surgery. Patients who were included had no contraindication to heparin therapy and had at least one of the recognized risk factors for DVT. Patients were randomized to receive unfractionated heparin (UH) 5000 units b.d., Logiparin 2500 units daily or Logiparin 3500 units daily. Each treatment was given subcutaneously 2 h before surgery and continued for 7-10 days. Daily 125I-labelled fibrinogen uptake tests (FUTs) were performed from day 2 to day 7 to detect DVT, and phleboangiography was used to confirm the diagnosis. The wound was examined on a daily basis to check for haematoma formation, and all patients were followed up for 1 month after operation. All three treatment arms were well matched for age, sex, weight, diagnosis and type of operation performed. The three major inclusion criteria in the trial were malignancy, age over 60 years and a history of varicose veins. Positive FUTs (UH = 4.2 per cent, Logiparin 2500 units daily = 7.9 per cent, Logiparin 3500 units daily = 3.7 per cent) and positive angiograms (UH = 3.0 per cent, Logiparin 2500 units daily = 5.6 per cent, Logiparin 3500 units daily = 2.3 per cent) were significantly more common in the Logiparin 2500 units daily group than in the UH and Logiparin 3500 units daily groups. The rates of major complications (severe haemorrhage, death, pulmonary embolism, reintervention) were similar in the three groups."
-What treatment was found to be effective for a 28-year-old woman with pulmonary endometriosis after surgical procedures and other treatments failed?,"Treatment of pulmonary endometriosis with a long-acting GnRH agonist. We report the case of a patient who was successfully treated with a long-acting GnRH agonist for pulmonary endometriosis. This 28-year-old woman had symptomatic pleural endometriosis, documented by biopsies, as well as symptomatic pelvic endometriosis. Two surgical procedures, consisting of excision of pleural endometriotic tissue and partial pleurectomies, failed to relieve her chest symptoms. Little relief was achieved with pseudopregnancy treatment. Satisfactory symptomatic improvement was obtained with danazol, but this medication had to be discontinued because of severe side effects. Trial of a GnRH agonist, leuprolide acetate, achieved complete remission of her chest symptoms; in addition, the patient became pregnant immediately after cessation of therapy. Gonadotropin-releasing hormone agonist therapy may be an important therapeutic alternative for women with pulmonary endometriosis who cannot tolerate danazol treatment and in whom surgical therapy fails to relieve the chest symptoms."
-What was the patient and graft survival rate in this study of primary liver transplants using FK 506?,"One hundred ten consecutive primary orthotopic liver transplants under FK 506 in adults. An account is given of the 6- to 12-month survival, and causes of failure in 110 consecutive patients who underwent primary liver transplantation under treatment from the outset with FK 506 and steroids. The patient survival is 92.7%, and the first graft survival is 87.3%. At a very high frequency, the patients achieved good graft function, and they had a relatively low morbidity that was partially ascribable to minimal use and early discontinuance (in 60% of cases) of steroids. Renal dysfunction and other adverse findings were largely confined to patients with poor initial graft function and consequent apparent alteration of the kinetics of FK 506 elimination, causing functional overdosage. Results compare very favorably with our past record using conventional immunosuppression, and support the belief that FK 506 is a superior immunosuppressive agent which is suitable for chronic administration."
-How did the hepatic perfusion index (HPI) change before and after mesenteric revascularization in this patient with mesenteric angina?,"Hepatic perfusion index (HPI) in mesenteric angina and following successful revascularization. This is a case report of a 45 year old man who had previously undergone a small bowel resection for acute mesenteric ischaemia. He subsequently suffered from mesenteric angina due to stenosis of the origin of the superior mesenteric artery and intermittent claudication due to aorto-iliac atheroma. The patient underwent a successful aorto-bifemoral Y graft and small bowel revascularization with a saphenous vein graft between the Y graft and the accessible proximal portion of the superior mesenteric artery. Before vascular reconstruction, the hepatic perfusion indices (HPI) in both the fasted and fed states were elevated; after mesenteric revascularization the HPI values were substantially lowered. The hepatic perfusion index may, by demonstrating functional abnormality, be useful in the diagnosis of mesenteric ischaemia and also in the assessment of treatment. Further evaluation of HPI in patients with suspected mesenteric ischaemia is therefore required."
-What are the key cardiac complications associated with Kawasaki disease?,"Diagnosis and management of Kawasaki disease. Kawasaki disease is an acute vasculitis characterized by mucosal inflammation, rash, cervical adenopathy, indurative edema of the hands and feet, and late membranous desquamation of the fingertips. Early cardiac effects include myocarditis (occasionally with congestive heart failure), pericardial inflammation, and, rarely, valve involvement. Coronary artery aneurysms are a long-term concern because coronary thrombosis with myocardial infarction can be a late manifestation. The origin of Kawasaki disease is unknown, but an infectious agent is most likely. Management consists of aspirin for control of fever and inflammatory manifestations and intravenous gamma globulin for the prevention of coronary aneurysm formation. Careful late follow-up is required, especially for patients with persistent coronary abnormalities. Giant aneurysms (greater than 8 mm) are more likely to progress to coronary obstructive disease, and coronary bypass grafts have been required for some patients. Late coronary artery manifestations in patients with mild early coronary dilatation have not been described. However, since long-term epidemiologic studies have not yet been performed, it is prudent to consider childhood Kawasaki disease to be a potential risk factor for coronary disease, especially in atherosclerosis-prone Western societies."
-What was the localization and pattern of HPV 16 E4 protein expression observed in cervical biopsy tissues?,"Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues. The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation."
-How did actigraphic monitoring help in understanding the potential risks of discontinuing lithium treatment in bipolar patients?,"Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep-wake cycles. In this preliminary report, we describe four patients in whom long-term lithium therapy was discontinued, combined with actigraphic monitoring to assess changes in motor activity and the sleep-wake cycle. Two patients experienced rapid relapse of manic symptomatology, while two remained stable throughout a 1-year follow-up. Actigraphic monitoring revealed disintegration of the sleep-wake cycle and increased motor activity in the relapsed patients only. It is suggested that actigraphic recordings can be used to monitor lithium discontinuation."
-What blood conservation techniques were used in this study of 500 consecutive coronary artery bypass operations?,"Conventional blood conservation techniques in 500 consecutive coronary artery bypass operations. With use of a nonpharmacological, simple, and inexpensive program for blood conservation, 500 consecutive patients underwent elective coronary artery bypass grafting without need of homologous red cell transfusions in 493 (98.6%). At least one internal mammary artery was grafted in all but 1 patient, with supplemental saphenous vein grafts. Intraoperatively, autologous heparinized blood was removed before bypass and retransfused at the conclusion of extracorporeal circulation. The volume remaining in the oxygenator and tubing set was returned without cell processing or hemofiltration. Using the hard-shell cardiotomy reservoir from the heart-lung machine, autotransfusion of the shed mediastinal blood was continued hourly up to 18 hours after operation. The mean postoperative mediastinal blood loss was 643 +/- 354 mL, whereas 624 +/- 296 mL was autotransfused. Thirteen patients (2.6%) needed reexploration for bleeding, of whom 7 (7/500, 1.4%) received homologous blood. No other patients required red cell transfusions. In addition, 9 patients were given a mean of 2.6 units of fresh frozen plasma because of suspected coagulopathy. No platelets were transfused, and no cryoprecipitate therapy was undertaken. Thus, in total, 484 patients (96.8%) were not exposed to any homologous blood products during the hospital stay. At discharge, the mean hemoglobin concentration was 121 +/- 14 g/L (12.1 +/- 1.4 g/dL) and the hematocrit, 0.36 +/- 0.04. Postoperative complications were few. There was one in-hospital death (0.2%)."
-What was the outcome of the study on patients with gastro-oesophageal reflux disease without oesophagitis?,"Natural history of gastro-oesophageal reflux disease without oesophagitis. This retrospective study was undertaken to characterise the clinical course and reflux pattern of patients with gastro-oesophageal reflux without evidence of oesophagitis. We investigated 33 patients (12 women, 21 men; mean age 36 years) with typical symptoms, a negative oesophagoscopy, and a 24 hour oesophageal pH-metry indicative of pathological gastro-oesophageal reflux. All patients received antacids or prokinetic drugs or both for three to six months. Nineteen of 33 patients still had symptoms at the end of treatment, of whom five had developed erosive changes of the oesophageal mucosa. The other 14 discontinued treatment and remained asymptomatic during a six month follow up period. Comparison of the pretreatment pH-metry data of the 19 symptomatic patients and the 14 asymptomatic patients showed no differences in the pattern of gastro-oesophageal reflux in the two groups. We conclude that in a substantial proportion of patients with pathological reflux without oesophagitis symptoms may persist and mucosal lesions may develop during conventional treatment without any apparent change in the reflux. Patients who developed endoscopic oesophagitis did not have a more severe pretreatment pattern of gastro-oesophageal reflux when compared with those who did not develop oesophageal mucosal damage."
-How does copper loading affect the recovery of heart function after ischemia and reperfusion in an isolated rat heart model?,"Copper loading of hearts increases postischemic reperfusion injury. We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal."
-What were the key findings regarding gastric cancer incidence and mortality in Scotland between 1978 and 1987?,"Gastric cancer in Scotland: changing epidemiology, unchanging workload. OBJECTIVE--To determine the changes in incidence of and mortality from gastric cancer in Scotland between 1978 and 1987 and in the operative workload in Lothian between 1979 and 1988. DESIGN--Analysis of national incidence statistics for gastric cancer derived from the Scottish national cancer registry, deaths from gastric cancer recorded by the registrar general for Scotland, and Lothian surgical audit data. SETTING--Scotland and Lothian Health Board area. PATIENTS--Patients in Scotland with gastric cancer during 1978 to 1987 inclusive; patients in Scotland with gastric cancer recorded on their death certificate as cause of death during 1978 to 1987; patients who had an operation in Lothian for gastric cancer during 1979 to 1988. MAIN OUTCOME MEASURES--Changes in incidence of and mortality from gastric cancer in Scotland from 1978 to 1987 and in the number of operations performed for gastric cancer in Lothian from 1979 to 1988. RESULTS--Mortality from gastric cancer in Scotland fell by about 25% over the 10 years. The incidence and standardised incidence of gastric cancer showed a marginal decline of about 9%. The differences in trends between incidence and mortality were significant (p less than 0.05). CONCLUSIONS--This study shows that the surgical workload associated with gastric cancer is not declining. This is because the incidence has remained almost static, which may be due to the relative increase in the numbers of older people in the population, who are at greater risk of developing gastric cancer. Gastric cancer should not be regarded as a disease in decline. Incidence and workload should determine resources allocated to this disease rather than mortality statistics."
-What is the definition of a mucin-hypersecreting tumor of the pancreas according to the study?,"Mucin-hypersecreting tumor of the pancreas with mucin extrusion through an enlarged papilla. Patient records, imaging films, macroscopic and microscopic features, and clinical follow-up data of seven Japanese patients with a mucin-hypersecreting tumor of the pancreas were reviewed. The mucin-hypersecreting tumor was defined as an enlarged major or minor papilla with a dilated orifice and visible mucin oozing on endoscopy. The series consisted of six men and one woman ranging from 47 to 79 yr old. The excretion of mucin through a patulous orifice of the enlarged ampulla of Vater was seen in six patients and of the enlarged minor papilla in the other patient with pancreas divisum. The main pancreatic duct was dilated in all patients. Amorphous mucin was seen in the dilated duct of five patients, and papillary nodules were present in two patients. Computed tomography and/or ultrasonography showed dilatation of the main pancreatic duct with multilocular cysts in six patients and with a solid tumor in the other patient. The tumor was located diffusely in the main pancreatic duct in one patient, whereas it was confined to branches in the head (four patients), body (one patient), or tail (one patient) of the pancreas in the six other patients. Histopathologic diagnosis was a cyst lined by hyperplastic mucus-secreting epithelium in one patient, mucinous cystadenoma in two, and mucinous cystadenocarcinoma in two. Five patients underwent resection and have survived for 1-46 months after the operation. The authors would like to emphasize this endoscopic syndrome because about half of mucin-hypersecreting tumors are malignant with a favorable prognosis."
-What was the correlation between immunological reactions and the time course of cerebral vasospasm in the primate model?,"The correlation between immunological reaction in the arterial wall and the time course of the development of cerebral vasospasm in a primate model. To investigate the role of immunological reactions in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH), the authors studied the correlation between immune/inflammatory reactions in the arterial wall and the time course of vasospasm in primates. Twenty monkeys were divided into four groups of 5 animals each: 1) a control group of sham-operated animals, 2) animals subjected to angiography 3 days after the induction of SAH (3-day SAH), 3) animals subjected to angiography 7 days after SAH (1-week SAH), and 4) animals subjected to angiography 7 and 14 days after SAH (2-week SAH). To induce SAH, the main cerebral arteries on the right were dissected free of the arachnoid, and an autologous blood clot was placed around the arteries. To evaluate vasospasm, all animals underwent a baseline angiogram before SAH; angiography was repeated at different intervals in each group, as outlined above. Histopathological changes and the deposition of the immunoglobulin IgG in the arterial wall were evaluated immunohistochemically in each group. The cerebral arteries on the side of the clot showed evidence of mild vasospasm (-24.6% reduction) on the angiogram performed on Day 3, severe vasospasm (-51.7%) on Day 7, and mild vasospasm (-12.8%) on Day 14. The infiltration of inflammatory cells was most marked in the spastic arterial wall in the 1-week SAH group. In the 2-week SAH group, severe myonecrosis and intimal disruption were observed, even in the vessels that showed only mild vasospasm, and the inflammatory reactions had almost abated."
-How does the length of the waiting list impact the survival benefit of cardiac transplantation for outpatients?,"Decreasing survival benefit from cardiac transplantation for outpatients as the waiting list lengthens. Many patients are accepted for cardiac transplantation during a period of clinical instability associated with a high risk of death, even though most can be discharged home to await transplantation. As the waiting lists lengthen, priority is awarded solely on the basis of the waiting time of outpatients, who now usually undergo transplantation after they have already survived a major period of jeopardy. To determine the impact of the current waiting times and priority system on the previously expected benefit offered by transplantation, 1-year actuarial survival without transplantation was recalculated after each month without transplantation for 214 potential candidates with an ejection fraction of 0.17 +/- 0.05 discharged on tailored medical therapy after evaluation. These data were compared with the 1-year survival data of 88 outpatients who underwent transplantation. Actuarial survival after 1 year was 67% on tailored therapy compared with 88% after transplantation (p = 0.009). Death without transplantation was sudden in 43 of 51 patients, resulting from hemodynamic decompensation in 8. For outpatients already surviving 6 months without transplantation, actuarial survival over the next 12 months was 83% without transplantation. Thus, the expected improvement in survival after transplantation would be only 5% over the subsequent year for patients waiting 6 months, which is the waiting time for many outpatients. Such patients should be reevaluated to determine whether transplantation remains indicated during the next year."
-How many cases of occipital meningoceles in patients with Dandy-Walker syndrome have been reported in this study?,"Occipital meningoceles in patients with the Dandy-Walker syndrome. Occipital cephaloceles in the Dandy-Walker syndrome are not rare. To date, 28 cases have been reported. We report on 8 cases of associated occipital meningocele, totalling 16% of all patients with the Dandy-Walker syndrome in our series. In all patients, communication existed between the posterior fossa cyst and the occipital meningocele. In 2 patients, the occipital meningocele disappeared after cerebrospinal fluid shunting and never required surgical repair. It appears that the cranial defect had ossified and resulted in self-closure. Poor intellectual development in persons with the Dandy-Walker syndrome is associated with the presence of other central nervous system and systemic abnormalities and not with occipital meningoceles alone."
-How do intermediate biomarkers help in understanding the predisposition to gastrointestinal cancer?,"Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: introduction and perspective. In this article, abnormalities in the proliferation and differentiation of gastrointestinal cells are described in diseases that increase predisposition to gastrointestinal cancer. Recent findings related to the effects of calcium on gastrointestinal cell proliferation, differentiation, and tumor occurrence in rodent models and in human subjects are summarized."
-What is the primary cause of malnutrition in patients with malignant disease?,"Nutritional support of patients with cancer of the gastrointestinal tract. Malnutrition is extremely common in patients with malignant disease. Whereas the causes are multifactorial, the predominant factor is the imbalance between nutrient intake and host nutrient requirements. Furthermore, the evidence suggests that cachexia is related to abnormal changes in host intermediary metabolism induced by host-tumor interactions, and endogenous peptides such as TNF may be important mediators. The role of nutritional therapy in cancer patients remains to be defined. Clearly, patients with severe malnutrition benefit from nutritional intervention. However, the benefit of nutritional therapy in less severe cases of malnutrition as an adjuvant to oncologic therapy has yet to be established."
-What percentage of subjects reported symptom relief after using a neutral-angle wrist splint for carpal tunnel syndrome?,"Carpal tunnel syndrome: objective measures and splint use. One hundred five adults with carpal tunnel syndrome (CTS) were studied to assess the efficacy of a neutral-angle wrist splint, and to identify criteria for splint referral. Ten observations before and after treatment were analyzed with descriptive and inferential statistics. After splint use, 67% of the subjects reported symptom relief. T-test comparison of sensory latency of values before and after treatment indicated improvement for the total group. Chi-square and t-tests failed to reveal significant differences between relief and no-relief groups for gender, affected hand, presence of concomitant conditions, duration of symptoms before treatment, age, length of time between pretreatment and posttreatment nerve conduction testing, initial nerve latency of motor and sensory fibers, or the difference between pretreatment and posttreatment sensory latencies. A significant difference was found for motor latency; the relief group improved and the no-relief group deteriorated. Data suggest that splinting is most effective if applied within three months of symptom onset. Those with damage to the wrist structures or median nerve were least responsive to splinting."
-What was the typical duration of antibiotic treatment for patients with Whipple's disease in this study?,"Short-term antibiotic treatment in Whipple's disease. We report the results of short-term antibiotic treatment in 19 patients with Whipple's disease (WD). The diagnosis was based on clinical features and on a characteristic small bowel biopsy. Patients received treatment for a mean of 7.9 weeks (range 4-20). Fourteen were treated with de-methyl-chlortetracycline (600 mg/day), and 1 also received chloramphenicol (1 g/day); 1 was treated with ampicillin (2 g/day), and 4 were treated with amoxicillin (1.5 g/day). In all patients, the clinical response was rapid and excellent, body weight increased significantly, diarrhea subsided, and fecal fat values returned to normal. Intestinal biopsies obtained after treatment was completed showed significant improvement based on a decrease in the number of macrophages staining positive with periodic acid-Schiff (PAS), normalization of villous structure, and decreased dilatation of lymphatic channels; free bacilli were absent, as shown both by light and electron microscopy. Seventeen patients have been followed for a mean of 99.4 months (range 6-300). Two died 30 and 72 months after diagnosis of Whipple's disease, 1 of laryngeal carcinoma and the other of colonic carcinoma. Fifteen patients are in excellent health. Three patients treated with tetracycline have had clinical and/or histologic relapses. In our experience, short-course antibiotic treatment with tetracycline or ampicillin and derivatives can be effective in WD, with few relapses and excellent outcome. No neurologic symptoms, either initially or during follow-up were observed."
-What was the overall prevalence rate of dementia among individuals aged 85 years and older in the Leiden community survey?,"Prevalence of dementia in the 'oldest old' of a Dutch community. OBJECTIVE: To estimate the prevalence rate of dementia in subjects 85 years of age and over. DESIGN: A two-phase design with the Mini-Mental State Examination (MMSE) in the screening phase and the Geriatric Mental State Schedule (GMS) in the diagnostic phase. SETTING: Community survey including subjects in residential care. SUBJECTS: All (n = 1,259) inhabitants of Leiden, The Netherlands, aged 85 years and over on December 1, 1986. First phase participation rate was 71% (17% dropout due to death); second phase participation rate was 82%. MAIN OUTCOME MEASURE: DSM-III diagnosis of dementia without further specification of the etiology of the dementia. RESULTS: An overall prevalence rate of 23% (95% C.I.: 19%-26%) was found. This included 12% mild dementia, 7% moderate and 4% severe dementia. The prevalence rate was higher among women (24%) than among men (18%). It increased with age from 19% (95% C.I.: 16%-22%) in the group of 85-89 years to 32% (95% C.I.: 26%-39%) in the group of 90-94 years to 41% (95% C.I.: 25%-58%) in the 95+ group. CONCLUSION: A fifth of the 85+ and a third of the 90+ population suffer from dementia with an indication that half of the 95+ population is affected. With the expected steep rise in the number of the oldest old, dementia will stay a major health problem in the near future."
-What was the purpose of the study on mastoid cavities and how was the symptom score determined?,"Mastoid misery: quantifying the distress in a radical cavity. Seventy-eight mastoid cavities were studied in 39 patients who required revision surgery for troublesome symptoms. A retrospective questionnaire was used to assign a symptom score to each patient in his pre and post-operative condition. The 5 leading symptoms of pain, wax, discharge, smell and giddiness were reviewed. A score of 15 points represented the worst case and zero the best. The average improvement after surgery was 4.7 points. Hearing was not considered in this study."
-What was the average lifetime benefit of chemotherapy for 45-year-old and 60-year-old women with node-negative breast cancer according to the decision-analysis model?,"Efficacy and cost effectiveness of adjuvant chemotherapy in women with node-negative breast cancer. A decision-analysis model. BACKGROUND. In 1988 the National Cancer Institute issued a Clinical Alert that has been widely interpreted as recommending that all women with node-negative breast cancer receive adjuvant chemotherapy. Acceptance of this recommendation is controversial, since many women who would not have a recurrence would be treated. METHODS. Using a decision-analysis model, we studied the cost effectiveness of chemotherapy in cohorts of 45-year-old and 60-year-old women with node-negative breast cancer by calculating life expectancy as adjusted for quality of life. The analysis evaluated different scenarios of the benefit of therapy: improved disease-free survival for five years, with a lesser effect on overall survival (base line); a lifelong benefit from chemotherapy; and a benefit in disease-free survival with no change in overall survival by year 10. The base-line analysis assumed a 30 percent reduction in the relative risk of recurrence for five years after treatment. RESULTS. For the 45-year-old woman, the base-line analysis found an average lifetime benefit from chemotherapy of 5.1 quality-months at a cost of $15,400 per quality-year. The 60-year-old women gained 4.0 quality-months at a cost of $18,800 per quality-year. Under the more and less optimistic scenarios, the benefit of chemotherapy varied from 1.4 to 14.0 quality-months for both groups. CONCLUSIONS. Chemotherapy substantially increases the quality-adjusted life expectancy of an average woman at a cost comparable to that of other widely accepted therapies. This benefit decreases markedly if the changes in long-term survival are less than in disease-free survival. Given its uncertain duration, the benefit may be too small for many women to choose chemotherapy. Selective use of chemotherapy to maximize the benefit to individual patients may be possible with refinements in risk stratification and explicit assessment of the patients' risk preferences."
-What percentage of patients with civilian craniocerebral gunshot wounds survived with a good outcome?,"Civilian craniocerebral gunshot wounds. Experience with 120 patients who incurred a gunshot wound to the head with dural penetration is presented. All of the patients were managed by a standard resuscitation protocol and assigned a clinical grade based on their level of consciousness both at the time of presentation and at 2 to 4 months after injury. Fifty patients (42%) underwent surgery. Twenty-eight patients (23%) had a good recovery, 19 (16%) were moderately disabled, 6 (5%) were severely disabled, and 67 (56%) died. All patients who were alert and awake with a normal or near normal neurological examination at the time of admission survived with a good outcome. All but 4 patients who were comatose at the time of admission died. Nine patients, however, who were not comatose at the time of admission died from potentially preventable causes. In 3 of these patients, a more aggressive diagnostic approach (including cerebral angiography) may have altered their ultimate outcome. An expeditious approach to the trauma victim with a comprehensive management scheme after injury may have altered the course in the remainder of these patients."
-What were the key findings of the study on total androgen ablation using Zoladex plus flutamide compared to orchiectomy in prostate cancer patients?,"Total androgen ablation: European experience. The EORTC GU Group. Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups."
-What percentage of nursing home residents in the study had a nutrient-modified diet prescription?,"Use of modified diets in nursing homes. Randomly chosen medical charts of 212 elderly subjects in 11 nursing homes were reviewed to determine which characteristics of the subjects were most closely associated with their diet prescriptions. The chart reviews indicated that 104 (49.0%) of the 212 subjects had some type of nutrient-modified diet prescription. Eight patients who were tube fed were not included in subsequent analyses. Sodium restriction was the most common modification (60 [29.4%] of the remaining 204 patients) and calorie-controlled diets were also common (52 [25.5%] of the patients). Of the 55 patients with hypertension, 31 (56.4%) had no sodium restriction. Only 10% of all low-sodium diets limited sodium to 2 g per day. Of the 38 patients with diabetes, 7 (18.4%) had no prescription for calorie control, and there was no indication that increased dietary fiber was encouraged for diabetic patients. Only one of the 121 subjects with a diagnosis of coronary heart disease or atherosclerosis had a prescription for a cholesterol-lowering diet. Characteristics of the subjects not specifically related to diet or diagnosis, such as age, sex, duration of stay, and level of care, had no significant relationship to diet prescription. These findings suggest that the practitioners in our sample were not convinced of the efficacy of modified diets to control disease for most nursing home residents."
-What improvements in lung function were observed in patients who underwent thoracoscopic carbon dioxide laser treatment for bullous emphysema?,"Thoracoscopic carbon dioxide laser treatment of bullous emphysema. A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation."
-What is the relationship between methotrexate cumulative dose and the progression of liver disease in patients with rheumatoid arthritis or psoriatic arthritis?,"Methotrexate and histologic hepatic abnormalities: a meta-analysis. STUDY OBJECTIVE: To determine the risk of liver toxicity from the long-term administration of methotrexate in patients with rheumatoid arthritis or psoriatic arthritis. DESIGN: A meta-analysis of 15 studies examining the relationship between long-term, low-dose methotrexate administration and biopsy evidence of liver fibrosis. PATIENTS: A total of 636 patients from 15 studies. RESULTS: The incidence of progression of liver disease (defined as worsening of at least one grade on the histologic classification of Roenigk) among 636 patients was 27.9% (95% confidence intervals 24.3 to 31.6). The rate of progression of liver disease in the 15 studies was associated with the cumulative dose of methotrexate (p = 0.01). Patients on average had a 6.7% (95% confidence intervals 2.1 to 11.4) chance of progressing at least one histologic grade on liver biopsy for each gram of methotrexate taken. The overall incidence of advanced pathologic changes on liver biopsy (grades IIIB or IV) among 636 patients was 5.0% (95% confidence intervals 3.5 to 7.0). The development of advanced histologic changes was not associated with the cumulative dose of methotrexate (p = 0.08). Patients who according to their history were heavy drinkers (at least 100 g of alcohol per week) were more likely to have advanced changes on liver biopsy (17.8% versus 4.5%, p = 0.0003) and to show histologic progression (73.3% versus 25.9%, p = 0.0002). Patients with psoriasis were more likely than patients with rheumatoid arthritis to have advanced changes (7.7% versus 2.7%, p = 0.003) and histologic progression (33.1% versus 24.3%, p = 0.02). CONCLUSIONS: The risk of liver toxicity in patients undergoing long-term, low-dose methotrexate therapy is substantial, and that risk increases with the total cumulative dose and with heavy consumption of alcohol. Heavy users of alcohol should not receive long-term methotrexate therapy. For most patients who are not heavy users of alcohol, liver biopsies should be done periodically to monitor for the occurrence of liver toxicity."
-What is the recommended strategy to manage nitrate tolerance in patients?,"A practical guide to nitrate use. Nitrate preparations are useful in the treatment of acute and chronic angina, acute and chronic congestive heart failure, and acute myocardial infarction. Development of tolerance is best managed by providing a nitrate-free interval, thus avoiding continuous drug levels. This interval probably should be 10 to 12 hours with use of a transdermal patch. Nitrate treatment of the elderly may require lower doses to avoid hypotension."
-What types of tumors were most commonly associated with radial nerve paralysis in this review?,"Radial nerve paralysis and tumor. This paper presents ten cases of radial nerve paralysis because of tumor and reviews 38 previously reported cases. The tumor distribution was 35 lipomas, four neurofibromas, four ganglions, three neuromas, one fibroma, and one neurilemoma. Malignant tumors are not discussed in this review. Electromyography is of value if diagnostic problems occur. Postoperative results are normally good."
-What was unusual about the ECG findings in this patient with fulminant hepatic failure?,"Massive ST-segment elevation without myocardial injury in a patient with fulminant hepatic failure and cerebral edema. A 49-year-old woman presented in fulminant hepatic failure. The ECG showed dramatic ST-segment elevation, suggesting diffuse myocardial injury. However, echocardiography, creatine phosphokinase enzyme determinations, and examination of the heart at autopsy (six days later) failed to demonstrate any physiologic, anatomic, or histologic evidence of abnormality. The appearance of ST-segment elevation in this setting should not prompt treatment for cardiac disease or limit the candidacy for liver transplantation of such critically ill patients."
-What is the proposed pathophysiological reason for the rarity of peripheral neuropathy in sickle cell disease?,Mononeuropathy in sickle cell anemia: anatomical and pathophysiological basis for its rarity. Peripheral neuropathy is a rare complication of sickle cell disease. We report a young black woman with sickle cell anemia who developed a proximal median mononeuropathy in the setting of sickle cell crisis. The clinical and electrodiagnostic features are consistent with an ischemic mechanism from the sickling process. The pathophysiological basis for the rarity of this complication may be related to the rich anastomotic microvasculature of peripheral nerve and the unique large size of the capillaries of this vascular network.
-What was the success rate of scleral buckling surgery for rhegmatogenous retinal detachments in patients with severe myopia during the study period?,"Scleral buckling for rhegmatogenous retinal detachment associated with severe myopia. From Jan. 1, 1980, to Dec. 31, 1989, we performed scleral buckling surgery on 48 eyes of 46 patients for rhegmatogenous retinal detachments associated with severe myopia (greater than 5.00 diopters). Forty eyes of 38 patients were observed for at least six months, and the mean follow-up period was 46 months. Intraoperative complications occurred in four of 48 eyes (8%) and included retinal incarceration (two eyes), choroidal hemorrhage (one eye), and choroidal detachment (one eye). Three of the 40 eyes (7.5%) followed up for more than six months developed a recurrent retinal detachment and underwent a revision of the scleral buckle. At the last follow-up examination, the retinas of all 40 eyes were totally reattached. Final visual acuity of 20/40 or better was attained in 26 of 40 eyes (65%). Because of the low rate of intraoperative complications and the high rate of success, scleral buckling is recommended for most patients with rhegmatogenous retinal detachments associated with severe myopia."
-What are the five breast cancer screening strategies compared in the cost-effectiveness analysis in Japan?,"Cost-effectiveness analysis of mass screening for breast cancer in Japan. The official Japanese recommendation for breast cancer screening is physical examination by a physician, in contrast to US recommendations of mammography. In this analysis of breast cancer screening, the authors used Japanese data in a cost-effectiveness model to compare the following five strategies: (1) no screening (N); (2) physical examination alone (PE); (3) mammography (MG); (4) PE followed by MG if PE findings were abnormal (PE----MG); and (5) PE combined with MG for all screened women (PE + MG). None of these programs would save medical expenditures. The total discounted net costs per patient (in US dollars) were as follows: N, +54; PE, +412; MG, +517; PE----MG, +340; and PE + MG, +731. The number of years of life saved per cohort of 100,000 asymptomatic Japanese women would range from 708 (PE----MG) to 3724 (PG + MG). The additional cost of each strategy (compared with N) per additional year of life would be +49,700 for PE, +40,400 for PE----MG, +14,300 for MG, and +18,000 for PE + MG. The least costly screening option (PE----MG) does not have the lowest cost per additional year of life saved (MG does). MG would be preferable to the current Japanese recommendation of PE alone."
-What was the key finding regarding c-erbB-2 gene product expression in lobular breast neoplasia?,"C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Lobular carcinoma in situ (LCIS) has uncertain malignant potential; biologic markers that will identify patients at risk for a poor clinical outcome have been sought actively. Amplification of the c-erbB-2 protooncogene has been correlated with poor prognosis in invasive mammary carcinoma, and immunohistochemical evaluation for expression of the oncogene protein has been correlated with gene amplification. The authors retrospectively evaluated 62 cases of lobular neoplasia for expression of the c-erbB-2 gene product on formalin-fixed, deparaffinized sections, using two monoclonal anti-erbB-2 (p185) antibodies (c-neu Ab3 and m-erb) and one polyclonal anti-erbB-2 antibody (pAb 1) by the avidin-biotin-peroxidase method. All 62 cases were negative with the pAb 1 antibody; one of 62 cases was weakly positive with the c-neu Ab3 in a membranous pattern. Expression of c-erbB-2 gene product was identified on adjacent invasive ductal carcinoma in one case and in adjacent ductal carcinoma in situ in another. None of 15 cases if infiltrating lobular carcinoma was positive with either of the two anti-c-erbB-2 antibodies. Strong positivity was found on benign epithelium in one case, demonstrating epitheliosis. In summary, evidence of expression of the c-erbB-2 gene product was found in one of 57 cases of LCIS and none of 15 cases of invasive lobular carcinoma. This suggests that, in contrast to reported data concerning intraductal and invasive ductal carcinoma, c-erbB-2 oncogene amplification and/or overexpression does not play a significant role in the progression of lobular breast neoplasia."
-What percentage of head and neck squamous cell carcinoma patients had elevated carcinoembryonic antigen (CEA) levels in this study?,"Carcinoembryonic antigen and head and neck cancer. Carcinoembryonic antigen (CEA) concentrations were determined in the sera of 45 patients with a head and neck squamous cell carcinoma and of 13 controls. In 13 patients serial CEA measurements were made during the follow-up period. In 38% of the patients the serum CEA level was slightly elevated (greater than or equal to 2.5 ng/ml). Only 13% of the patients had clearly elevated CEA levels (greater than 5 ng/ml). CEA levels were significantly higher in patients with advanced, e.g. stage IV, disease but a correlation between serum CEA concentration and prognosis was not found. Patients who smoked had significantly higher serum CEA levels than non-smoking patients. In the serial determinations slight CEA elevations could be found in only 50% of patients with tumour recurrence. Combined with the data from the literature we conclude that serum CEA determination is not useful in predicting the outcome in patients with a head and neck squamous carcinoma."
-What diagnostic imaging technique was used to identify the spinal cord herniation and intradural spinal arachnoid cyst?,"Spinal cord herniation associated with an intradural spinal arachnoid cyst diagnosed by magnetic resonance imaging. Two rare cases of spinal cord herniation associated with intradural spinal arachnoid cyst are reported. A preoperative magnetic resonance imaging scan demonstrated the presence of spinal cord herniation, identified as a protrusion continuous with the spinal cord. Surgery upon the intradural spinal arachnoid cyst improved progressive neurological dysfunction. The authors postulate that spinal cord herniation occurred for the following reason: The pressure of the intradural arachnoid cyst on the dorsal aspect of the spinal cord caused thinning of the dura, leading to a tear and, thus, the development of an extradural arachnoid cyst. Along with the enlargement of intradural arachnoid cyst, the spinal cord herniated through the tear in the dura into the extradural arachnoid cyst."
-How did the researchers use pulsed Doppler technique to evaluate blood flow velocity in the pulmonary artery of dogs with acute pulmonary hypertension?,"Intraluminal pulsed Doppler evaluation of the pulmonary artery velocity time curve in a canine model of acute pulmonary hypertension. The velocity pattern of the blood flow in the pulmonary artery was investigated in an animal model of acute pulmonary hypertension. Nine anesthetized, open-chest dogs were embolized with polystyrene microspheres, and the velocity pattern of the blood flow in the pulmonary artery was studied with use of an invasive pulsed Doppler technique. Phasic intraluminal velocity was recorded with use of a miniature piezoelectric crystal activated by 20-MHz Doppler pulses and mounted on the tip of a needle probe introduced into the pulmonary artery. The recorded Doppler quadrature signals were processed by spectral analysis. Significant increases occurred in mean, systolic, and diastolic pulmonary arterial pressures (p less than 0.0002), in pulmonary vascular resistance (p less than 0.005), and in negative velocity time (duration in milliseconds that the mean velocity was directed toward the pulmonic valve) (p less than 0.002). Significant decreases occurred in right ventricular ejection time (p less than 0.006) and in positive velocity time (duration in milliseconds that the mean velocity was directed away from the pulmonic valve) (p less than 0.005). A significant shortening in the time to peak velocity (acceleration time) was found (p less than 0.005). Second-order regression analyses demonstrated an inverse correlation between the ratio of positive velocity time to negative velocity time and the mean pulmonary artery pressure in all animals (r = 0.71). These findings should be compared with the velocity patterns of the blood flow in the pulmonary artery obtained under pulmonary hypertensive conditions due to various causes to facilitate interpretation and understanding of clinical investigations."
-How does the energy state of pig lungs change under different levels of oxygen and cyanide exposure?,"Energy state and vasomotor tone in hypoxic pig lungs. To evaluate the role of energy state in pulmonary vascular responses to hypoxia, we exposed isolated pig lungs to decreases in inspired PO2 or increases in perfusate NaCN concentration. Lung energy state was assessed by 31P nuclear magnetic resonance spectroscopy or measurement of adenine nucleotides by high-pressure liquid chromatography in freeze-clamped biopsies. In ventilated lungs, inspired PO2 of 200 (normoxia), 50 (hypoxia), and 0 Torr (anoxia) did not change adenine nucleotides but resulted in steady-state pulmonary arterial pressure (Ppa) values of 15.5 +/- 1.4, 30.3 +/- 1.8, and 17.2 +/- 1.9 mmHg, respectively, indicating vasoconstriction during hypoxia and reversal of vasoconstriction during anoxia. In degassed lungs, similar changes in Ppa were observed; however, energy state deteriorated during anoxia. An increase in perfusate NaCN concentration from 0 to 0.1 mM progressively increased Ppa and did not alter adenine nucleotides, whereas 1 mM reversed this vasoconstriction and caused deterioration of energy state. These results suggest that 1) pulmonary vasoconstrictor responses to hypoxia or cyanide occurred independently of whole lung energy state, 2) the inability of the pulmonary vasculature to sustain hypoxic vasoconstriction during anoxia might be associated with decreased energy state in some lung compartment, and 3) atelectasis was detrimental to whole lung energy state."
-Does aerobic exercise training provide significantly better physical performance improvements compared to light exercise for patients recovering from acute myocardial infarction?,"Effect of early programmes of high and low intensity exercise on physical performance after transmural acute myocardial infarction. Does a programme of light exercise training after acute myocardial infarction produce the same improvement in treadmill performance as aerobic exercise training? Three hundred and eight men from a consecutive series of 479 men with transmural (Q wave) acute myocardial infarction, admitted to a single coronary care unit, were randomly allocated to eight weeks of group aerobic exercise training or group light exercise. Groups were well matched for all characteristics other than site of infarction, which did not significantly affect results. Mean (SD) physical working capacity (metabolic equivalents) determined by treadmill testing at the start of the study (in the third week after infarction) was 6.8 (2.2) v 6.7 (2.5) METs, at the end (in the eleventh week after infarction) 10.8 (2.3) v 9.9 (2.4) METs, and at 12 month review 10.8 (2.4) v 10.7 (1.9) METs for the exercise training group and the light exercise group respectively. The difference of 0.9 METs at the end of the study was the only significant difference between groups. There were no significant intergroup differences at any stage in resting and maximal heart rate, resting and maximal systolic blood pressure, or rate-pressure product. Apart from a small temporarily greater physical working capacity, the physical benefits of aerobic exercise training were equally well achieved by group light exercise."
-What were the key findings regarding nocturnal body temperature in women with premenstrual syndrome (PMS) and late luteal phase dysphoric disorder (LLPDD)?,"High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder. OBJECTIVE: Because women with late luteal phase dysphoric disorder (LLPDD) experience symptomatic affective states predictably, they can be studied to determine whether there are biological findings related solely to the clinically symptomatic state. The authors sought to answer the question, Does body temperature change with affective state? METHOD: The core body temperature and motor activity patterns of 10 women with premenstrual syndrome (PMS), six of whom also met criteria for LLPDD, and no other psychological or medical illness were compared to those of six women with chronic, noncyclic dysphoria and six asymptomatic comparison women at four phases of the menstrual cycle. RESULTS: The nocturnal temperatures of the women with PMS/LLPDD were significantly higher than those of the comparison subjects across the entire menstrual cycle, but there were no differences in nocturnal activity levels. The women with noncyclic dysphoria had a mean nocturnal temperature in the follicular phase as high as that of the women with PMS/LLPDD. The temperatures of all women were higher in the luteal phase than in the follicular phase. CONCLUSIONS: These findings suggest that in the future investigators should document menstrual cycle phase in all female subjects and, when studying body temperature, should carefully monitor symptomatic state in comparison subjects."
-What specific HLA-DQ alleles were found to be associated with insulin-dependent diabetes mellitus (IDDM) susceptibility in Japanese and white populations?,"Particular HLA-DQ alpha beta heterodimer associated with IDDM susceptibility in both DR4-DQw4 Japanese and DR4-DQw8/DRw8-DQw4 whites. Insulin-dependent diabetes mellitus (IDDM) susceptibility is associated with the DR4-DQw4 haplotype in Japanese and the DR4-DQw8/-Drw8-DQw4 genotype (among others) in whites. We investigated whether these Japanese and white individuals encode the same or a similar DQ alpha beta heterodimer, which may be an IDDM-susceptibility molecule in both populations. First, we carried out genomic DQA1 and DQB1 typing with sequence-specific oligonucleotide probes. The results revealed that Japanese DR4-DQw4 and white DR4-DQw8/DRw8-DQw4 IDDM patients carried the DQA1*0301 allele and the DQB1*0401 or DQB1*0402 allele, either in the cis (Japanese DR4-DQw4 individuals) or trans (white DR4-DQw8/DRw8-DQw4 individuals) position. Because the DQB1*0401 and DQB1*0402 alleles differ only at residue 23, these DQB1 genes are very similar. We next tested cells from these individuals with a particular DQ-specific T-lymphocyte clone, HH58. The clone was only restimulated with cells from Japanese individuals who carried the DQA1*0301 and DQB1*0401 alleles in the cis position or white individuals who carried the DQA1*0301 and DQB1*0402 alleles in the trans position. Thus, particular cis- or trans-encoded DQ alpha beta heterodimers, which in both cases are recognized by T lymphocytes, may confer susceptibility to IDDM in both ethnic groups."
-What was the success rate of tumor destruction in patients with colorectal villous adenomas using endoscopic resection and Nd:YAG laser photocoagulation?,"Endoscopic treatment by snare electrocoagulation prior to Nd:YAG laser photocoagulation in 85 voluminous colorectal villous adenomas. The association of endoscopic resection with Nd:YAG laser photocoagulation was used to treat benign colorectal villous adenomas. Eight-five patients were included: 49 with surgical contraindications, 35 for whom surgical resection appeared to be too hazardous, and 1 who refused surgery. Forty-five tumors had an axial extension between 1 and 3 cm, and 40 tumors had an axial extension of at least 4 cm. Diathermic snare resection was performed to remove large tumoral fragments prior to laser photocoagulation of the residual flat lesions. Treatments were repeated every 15 days until total tumor destruction was achieved. A carcinoma was detected in biopsy specimens obtained during endoscopic treatment of five patients. Two patients were lost to follow-up. Treatment results could be analyzed in 78 patients. Successful treatment was achieved in 67 patients. Tumor destruction was complete in 77 percent of patients who had lesions of at least 4 cm diameter and in 93 percent of patients with smaller lesions. The axial extension of the tumor was the main factor affecting the results of treatment. No major complications occurred. During the average 103-week follow-up period, 21 percent of the patients with total tumor destruction had a recurrence. The risk of recurrence was correlated with the number of initial treatment sessions and previous surgery treatment. It would appear that the treatment with endoscopic resection prior to Nd:YAG laser photocoagulation is a safe and effective method in the destruction of colorectal villous adenomas."
-How do the fixed-reference and floating-reference systems differ in their assessment of wall motion abnormalities in patients with myocardial infarction?,"Reference systems in echocardiographic quantitative wall motion analysis with registration of respiration. Registration of respiration allows analysis at the end-expiratory phase and may thus favor the use of the fixed-reference system versus the floating-reference system in echocardiographic quantitative wall motion analysis. Analysis is performed on two-dimensional echocardiograms of 44 normal subjects, 38 patients with anterior myocardial infarction, and 17 patients with posterior myocardial infarction. Two different models for wall motion analysis are applied, each using the fixed-reference system and the floating-reference system, respectively. In patients with anterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the anterior, septal, and apical walls, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. In patients with posterior myocardial infarction, the fixed-reference system indicates severe wall motion abnormalities at the posterior wall, whereas the floating-reference system indicates less severe wall motion abnormalities almost equally at every wall. These findings indicate that the fixed-reference system is superior to the floating-reference system in quantification of wall motion of end-expiratory two-dimensional echocardiograms."
-"In the study comparing diamorphine and morphine, what was the overall finding regarding the speed of onset of analgesic effect?","Comparison of speed of onset of analgesic effect of diamorphine and morphine. In a random, double-blind crossover trial using an ischaemic limb pain model we have assessed the speed of onset of analgesia after an i.v. bolus of equipotent doses of diamorphine and morphine in 12 healthy male volunteers. Pain and its subsequent relief were assessed by means of a visual analogue scale. Two of the subjects found diamorphine acted quicker than morphine, one found no difference and nine found that morphine was quicker than diamorphine. The mean time to diamorphine effect was 53% greater than for morphine (P less than 0.005, Wilcoxon rank sum test). These findings suggest that, for rapid relief of pain, morphine is more suitable than diamorphine."
-What unique neurological condition was observed in the 30-year-old woman that suggested a potential loss of nerve growth factor (NGF) trophic action?,"New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides. A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF."
-How does left ventricular hypertrophy (LVH) relate to cardiovascular disease risk in patients with hypertension?,"Left ventricular hypertrophy in hypertension. Major advances in left ventricular hypertrophy (LVH) and hypertension have occurred in recent years. The ability to diagnose LVH has been improved by echocardiography, and with this technique it has been shown that evidence of LVH is an important independent risk factor for cardiovascular disease. The major cause of death in patients with hypertension and LVH is coronary artery disease. Therefore an understanding of the interrelationships between these two disorders is fundamental, and it is now clear that the hypertrophied ventricle is vulnerable to myocardial ischemia. Appreciation of the mechanisms of sudden death has also increased, although the exact situation in patients with LVH remains to be clarified. Regression of LVH is known to occur with the use of several different antihypertensive drugs. Recent studies indicate that the calcium blocking agent nicardipine, in addition to beta-blocking drugs and angiotensin-converting enzyme inhibitors, brings about LVH regression without any deterioration of left ventricular function. However, further studies are needed to assess the long-term benefits of this regression."
-What medical condition did the 27-year-old man with osteogenesis imperfecta develop after sustaining a femoral fracture?,Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.
-What treatment method was used to achieve tumor regression in patients with gastrointestinal leiomyosarcoma liver metastases?,Regression of hepatic metastases from gastrointestinal leiomyosarcoma after hepatic arterial chemoembolization. Two patients with gastrointestinal leiomyosarcoma metastatic to the liver were treated by hepatic chemoembolization with cisplatin and polyvinyl sponge followed by hepatic arterial infusion of vinblastine. Effective palliation in terms of durable tumor regression was achieved in both patients after two chemoembolization-infusion procedures. These results suggest that regional therapy may offer new hope for the subset of sarcoma patients who have liver metastases resistant to combination systemic chemotherapy.
-What is the Damus-Kaye-Stansel operation and what type of heart conditions is it used to treat?,"The Damus-Fontan procedure. The Damus-Kaye-Stansel operation is a useful technique for the treatment of complex cyanotic congenital heart disease when there is obstruction between the systemic ventricle and the aorta. Modifications of the technique include transection of the aorta and the pulmonary artery, anastomosis of the contiguous aortic and pulmonary walls, and connection of the distal aorta to the perimeter of the new bivalved proximal great artery. In addition, the bidirectional cavopulmonary shunt technique can be used with or without the Fontan procedure. Six patients underwent a Damus-Fontan operation, and all survived. Two patients underwent the Damus-cavopulmonary shunt (hemi-Fontan) procedure, and 1 survived. The postoperative status of the 7 survivors is good to excellent. Follow-up ranges from 2 months to 7 1/2 years."
-What is the proposed mechanism of anastomotic obstruction after stapled enteroanastomosis in this medical case report?,Anastomotic obstruction after stapled enteroanastomosis. We have recently treated two cases of anastomotic obstruction after side-to-side stapled enteroanastomosis. Complete obstruction of a stapled small-bowel anastomosis has not been reported to our knowledge. The mechanism of the obstruction appears to be the healing together of the cut edges of viable bowel beyond the inverted stapled lines. An alternative method of constructing the functional end-to-end enteroanastomosis that is offered is intended to prevent the occurrence of postoperative anastomotic obstruction.
-What percentage of children at the Children's Hospital in Bangkok were found to have bloody diarrhea?,"Epidemiologic aspects of shigellosis and other causes of dysentery in Thailand. Nearly 20% of children seen in the outpatient department of Children's Hospital in Bangkok, Thailand, for diarrheal disease had bloody diarrhea. Shigella species and enteroinvasive Escherichia coli--isolated from 13% and 2% of children with diarrhea, respectively--were the most frequent causes of bloody diarrhea. Campylobacter species and nontyphoidal Salmonella species were also isolated frequently but were much less often associated with bloody diarrhea. Shigella species were rarely isolated from patients who did not have diarrhea, while Campylobacter and Salmonella species were isolated frequently from well children. None of the species isolated always caused bloody diarrhea. Studies on infection with Campylobacter suggest that natural immunity may prevent bloody diarrhea and in fact may eventually prevent all disease due to this organism. Studies of endemic Shigella flexneri and epidemic Shigella dysenteriae 1 in Thailand have shown that immunity may also explain an age-related decrease in rates of S. flexneri infection but not in rates of S. dysenteriae 1 isolation."
-How does hypertension impact stroke risk in the black population?,"Cerebrovascular disease in hypertensive blacks. There is convincing evidence that all grades of persistent diastolic hypertension, especially in blacks, should be treated in order to prevent stroke and other cardiovascular complications. Studies are now in progress to gather additional information concerning isolated systolic hypertension, especially in the aged. Inasmuch as at least one half or more of stroke deaths in blacks develop as the result of hypertension, lowering blood pressure offers the perfect opportunity to reduce considerably the frequency of this devastating illness. The recent dramatic fall in U.S. stroke mortality, greatest in the black female, is a commendable achievement, but the flattening of the declining mortality curve over the past several years should be a cause for alarm and intensive investigation."
-What are gastrointestinal lipomas and how are they typically identified during radiologic examination?,"Gastrointestinal lipomas: a radiologic and pathologic review. Lipomas of the gastrointestinal tract are an infrequent finding on radiologic examination; however, they occur often enough to warrant consideration in the differential diagnosis of mass lesions of the gut. In many instances, their morphologic characteristics allow the specific diagnosis of a lipoma. In this report, we review gastrointestinal lipomas with an emphasis on their radiologic and pathologic correlation."
-How did the researchers classify patients with orthostatic disorders based on their blood pressure and heart rate responses when standing?,"Spectrum of orthostatic disorders: classification based on an analysis of the short-term circulatory response upon standing. 1. In 31 consecutively referred patients (20 females, 11 males) with overt or suspected orthostatic disorders, the changes in blood pressure and heart rate that occur in the first 2 min of standing were analysed. 2. Blood pressure was measured continuously by Finapres. The blood pressure and heart rate responses after 1-2 min of standing (early steady-state response) were used to classify the patients as follows: group I (n = 17, age 42 +/- 17 years), normal early steady-state blood pressure and heart rate responses; group II (n = 5, age 40 +/- 14 years), combination of normal early steady-state blood pressure and postural tachycardia; group III (n = 9, age 51 +/- 14 years), hypotensive orthostatic response with (4/9) or without (5/9) postural tachycardia. We examined whether additional information could be obtained by beat-to-beat analysis of the initial circulatory response (first 30 s). It was quantified by identifying the blood pressure trough and overshoot and the maximum heart rate and relative bradycardia. 3. The initial drop in systolic and diastolic blood pressures did not differ between the three groups. A recovery of blood pressure with a systolic and/or diastolic blood pressure overshoot was present in all group I and II patients, but was absent in all except two patients in group III. The initial maximum heart rate increase did not differ between the three groups. The relative bradycardia was less in groups II and III than in group I. 4. We conclude that analysis of the beat-to-beat blood pressure changes in the first 30 s after the onset of standing provides almost all the information that is necessary to determine abnormalities in orthostatic circulatory control."
-How does atrial appendectomy affect the secretion of atrial natriuretic polypeptide in dogs with high-output heart failure?,"Does atrial appendectomy aggravate secretory function of atrial natriuretic polypeptide? The present study was designed to clarify how atrial appendectomy affects hemodynamics and secretory function of atrial natriuretic polypeptide in the failing heart. Eleven mongrel dogs were prepared for the experimental model of high-output heart failure by creation of arteriovenous fistulas between femoral arteries and veins. Two months after the first operation, effects of bilateral atrial appendectomies on basal and pacing-induced secretions of atrial natriuretic polypeptide were investigated in five dogs with simultaneous measurement of various hemodynamic indices. In the remaining six dogs, used as a control group, pacing-induced secretion of atrial natriuretic polypeptide was examined in the same way as in the appendectomy group. After excision of the atrial appendages, neither systolic blood pressure nor either atrial pressure changed, but plasma atrial natriuretic polypeptide level was decreased (292 +/- 54 to 188 +/- 47 pg/ml, p less than 0.01) and cardiac output fell (3.7 +/- 0.9 to 3.0 +/- 0.8 L/min, p less than 0.01). During pacing-induced tachycardia, the peak level of plasma atrial natriuretic polypeptide was lower in the appendectomy group than in the control groups (593 +/- 213 versus 1170 +/- 324 pg/ml, p less than 0.05), despite similar left atrial pressures in the two groups. The excised appendages contained approximately 30% of the total amount of atrial natriuretic polypeptide. These results demonstrate that atrial appendectomy decreases secretory function of atrial natriuretic polypeptide and reduces cardiac output in dogs with experimental high-output heart failure."
-What type of adverse skin reaction did the patient experience when taking medications containing pseudoephedrine and norephedrine hydrochloride?,"Systemic contact dermatitis from pseudoephedrine. A patient with rhinitis developed systemic contact dermatitis when starting oral treatment with Rhinalair, containing pseudoephedrine hydrochloride. A few months later, another oral treatment Rinutan, containing norephedrine hydrochloride, provoked a more severe generalized eczema. Patch test reactions were strongly positive to ephedrine and pseudoephedrine, slightly positive to phenylephrine and negative to epinephrine. Norephedrine was not tested."
-What were the two antibiotic combinations compared in this study for prophylaxis of infection following colorectal surgery?,"Colorectal surgery: short-term prophylaxis with clindamycin plus aztreonam or gentamicin. A randomized study was conducted to compare the effectiveness of aztreonam plus clindamycin with that of gentamicin plus clindamycin for prophylaxis of infection following colorectal surgery. A total of 138 patients undergoing elective colorectal surgery were randomized to treatment with clindamycin (600 mg) plus either aztreonam (1 g) or gentamicin (80 mg) 30 minutes before and 8 and 16 hours after surgery. The study included 122 patients (88.4%) with colorectal carcinoma. Samples from the abdominal cavity and from the subcutaneous tissues were taken for bacteriologic study. All samples from the abdominal cavity yielded microorganisms; both aerobic and anaerobic bacteria were isolated. Wound infections occurred in eight patients (12.1%) in the aztreonam group and in 12 patients (16.7%) in the gentamicin group. Escherichia coli, Bacteroides species, enterococci, and staphylococci were isolated most frequently from wounds and were often isolated from bacteriologic samples from the abdominal cavity of the same patients. The incidence of septic complications reflected the extent of nutritional and immunologic impairment. No significant differences were found between groups in the rate of urinary tract or lower respiratory tract infections. Aztreonam/clindamycin appears to be a valid alternative to gentamicin/clindamycin for the prophylaxis of infections following colorectal surgery."
-What percentage of patients with CHARGE Association had upper airway abnormalities beyond choanal atresia and cleft lip and palate?,"Incidence and management of airway problems in the CHARGE Association. The airway problems associated with anaesthesia in patients with the CHARGE Association have been underreported. We undertook a retrospective review of 50 cases, of which anaesthetic records were available for 37 patients. Apart from choanal atresia and cleft lip and palate, 56% of patients has some other upper airway abnormality. There appeared to be greater difficulty in tracheal intubation with increase in age in four patients. The incidence and management of airway abnormalities are discussed."
-What potential complications can arise from overfeeding critically ill patients according to the context?,"Report of a hidden case of overfeeding. Nutritional support is essential to the care of the critically ill patient, but complications of overfeeding can occur. Precise metabolic measurement by indirect calorimetry can detect problems of nutrition and allow adjustment in caloric intake. This case study illustrates the complications of carbon dioxide retention and inability to wean from mechanical ventilation with subsequent prevention of further complications."
-Why was trimethoprim-sulfamethoxazole (TMP-SMX) ineffective in treating experimental enterococcal endocarditis in the rat model?,"Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis. To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection."
-What significant finding was made regarding the p53 gene in a patient with an intracranial ependymoma?,"Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma. We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited."
-What was the relationship between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram in patients with acute myocardial infarction?,"Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction. This study evaluated the relation between patency of the infarct-related artery and the presence of late potentials on the signal-averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergoing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71%; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among patients with an open or closed artery, respectively (p less than 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct-related artery. These data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery."
-How does insulin resistance affect inhibin levels in women with polycystic ovary syndrome (PCOS) compared to control subjects?,"Serum inhibin levels in polycystic ovary syndrome: effect of insulin resistance and insulin secretion. Insulin resistance is common in women with the polycystic ovary syndrome. We investigated the relationship between insulin resistance and the serum inhibin concentration in a group of 19 women with polycystic ovary syndrome and eight control subjects at different phases of the menstrual cycle. Insulin resistance was measured by the frequently sampled intravenous glucose tolerance test, and inhibin was measured by a specific radioimmunoassay. Insulin sensitivity (mean +/- SE) was significantly reduced in the polycystic ovary syndrome group compared with controls: reduced insulin sensitivity 46.7 +/- 5.0 min-1/(nmol/mL), normally insulin-sensitive 106.6 +/- 11.7 min-1/(nmol/mL) (P less than .01). The women with polycystic ovary syndrome had inhibin levels (126 +/- 15.2 microLEq/mL) comparable to those found during the early follicular phase of the control group (117 +/- 22.1 microLEq/mL), but significantly lower than late follicular phase (259 +/- 25.6 microLEq/mL) or luteal phase (448 +/- 91.8 microLEq/mL) levels in the control group. No association was found between the degree of insulin resistance and the inhibin concentration, which remained unaltered over a 3-hour period despite maximal stimulation of endogenous insulin secretion. The inhibin concentrations in polycystic ovary syndrome may reflect impaired follicular maturation. Inhibin secretion is not acutely affected by insulin secretion in normal or in hyperandrogenic women."
-What were the findings of the study regarding the presence of human papillomavirus (HPV) DNA in cervical adenocarcinoma?,"Absence of human papilloma virus in cervical adenocarcinoma determined by in situ hybridisation. A few studies using DNA technology have suggested that human papillomavirus (HPV) may be an aetiological factor for adenocarcinoma of the uterine cervix. Twenty one cases of cervical adenocarcinoma were studied by in situ hybridisation using biotinylated DNA probes for HPV types 6, 11, 16 and 18 and a streptavidin, biotinylated alkaline phosphatase detection system. Intranuclear HPV DNA was detected in none of the adenocarcinomas, while positive controls gave a clear intranuclear signal. Adjacent areas of normal, koilocytic, and dysplastic squamous epithelium also gave positive results. It may be that squamous epithelium contaminates adenocarcinomas reported as positive by Southern blotting. Our results showing absence of detectable HPV DNA within adenocarcinomas suggest that HPV infection may not have a major role in the aetiology of adenocarcinoma of the uterine cervix."
-How does combined treatment with pulsatile LH-RH and hMG affect follicular development in patients with polycystic ovaries?,"Treatment with pulsatile luteinizing hormone-releasing hormone modulates folliculogenesis in response to ovarian stimulation with exogenous gonadotropins in patients with polycystic ovaries. Combined treatment with pulsatile LH-RH and hMG, given to eight patients who had anovulation associated with PCO and resistant to CC, significantly reduced the number of large follicles induced by hMG alone. A direct effect of pulsatile LH-RH on the ovary is postulated. This combined treatment eased the problems of multifollicular development, thereby increasing efficiency and reducing complications in patients with PCO stimulated by gonadotropins."
-What were the initial findings of the clinical study on granisetron for treating migraine headaches?,"First clinical study of the selective 5-HT3 antagonist, granisetron (BRL 43694), in the acute treatment of migraine headache. Granisetron (BRL 43694), a selective 5-HT3 receptor antagonist, was assessed as acute therapy for the first time in migraine patients. In an open pilot study 7 migraine attacks were treated in 6 patients. All but 1 patient experienced marked and rapid relief from the headache, and nausea and vomiting were rapidly resolved in the 6 cases where these symptoms accompanied the attack. No side effects were recorded. Development of granisetron for migraine was suspended during the study for extraneous reasons."
-"What are the differences in the expression of Tn, sialosyl Tn, and T antigens across normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma?","Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis."
-How does QTc prolongation relate to the risk of sudden death in patients with and without cardiac dysfunction?,"QTc prolongation measured by standard 12-lead electrocardiography is an independent risk factor for sudden death due to cardiac arrest. BACKGROUND. QTc prolongation has been implicated as a risk factor for sudden death; however, a controversy exists over its significance. METHODS AND RESULTS. In the Rotterdam QT Project, 6,693 consecutive patients who underwent 24-hour ambulatory electrocardiography were followed up for 2 years; of these, 245 patients died suddenly. A standard 12-lead electrocardiogram and clinical data at the time of 24-hour ambulatory electrocardiography were collected for all patients who died suddenly and for a random sample of 467 patients from the study cohort. In all patients without an intraventricular conduction defect (176 patients who died suddenly and 390 patients from the sample), QT interval duration was measured in leads I, II, and III and corrected for heart rate with Bazett's formula (QTc). In patients without evidence of cardiac dysfunction (history of symptoms of pump failure or an ejection fraction less than 40%), QTc of more than 440 msec was associated with a 2.3 times higher risk for sudden death compared with a QTc of 440 msec or less (95% confidence interval: 1.4, 3.9). In contrast, in patients with evidence of cardiac dysfunction, the relative risk of QTc prolongation was 1.0 (0.5, 1.9). Adjustment for age, gender, history of myocardial infarction, heart rate, and the use of drugs did not alter these relative risks. CONCLUSIONS. These data indicate that in patients without intraventricular conduction defects and cardiac dysfunction, QTc prolongation measured from the standard electrocardiogram is a risk factor for sudden death independent of age, history of myocardial infarction, heart rate, and drug use. In patients with cardiac dysfunction, QTc duration is not related to the risk for sudden death."
-"What were the key findings regarding adverse events in children who completed treatment for acute lymphoblastic leukemia across studies VIII, IX, and X?","Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St. Jude Total Therapy studies VIII, IX, and X. We studied the frequency, causes, and predictors of adverse events in 624 patients who had completed treatment for acute lymphoblastic leukemia (ALL) in three consecutive total therapy studies (VII, IX, and X, 1972 to 1983). Event-free survival in study X was significantly better overall than that in studies VIII and IX (P less than .0001 by the log-rank test). In study X, 75% of the patients were electively taken off therapy, compared with 54% in studies VIII and IX. However, the risks of having an adverse event during the first 5 years after completion of therapy were remarkably similar: 22% (95% confidence interval, 17% to 29%) in study X versus 24% (20% to 29%) in studies VIII and IX. Bone marrow, testicular, and CNS relapses accounted for the majority of failures in both groups (85% in study X and 92% in studies VIII and IX). Late adverse events consisted largely of hematologic relapses and the development of solid tumors. Black race (P = .001) and leukemia without an anterior mediastinal mass (P = .05) were associated with an increased risk of failure after completion of treatment in the two earlier clinical trials, whereas a lower leukemic cell DNA content (DNA index less than 1.16) was the only predictor of late treatment failure in the more recent trial (P = .019). None of the other presenting features that were examined (eg, age, leukocyte count, and sex) had value as predictors of late failure. Thus, improved treatment altered the impact of specific prognostic factors and the distribution of sites of relapse, but it did not significantly affect the risk of delayed failure."
-What is the purpose of the educational device described in the context related to Mohs micrographic surgery?,An educational device for Mohs micrographic surgery. A three-dimensional model of basal cell carcinoma. Mohs micrographic surgery for skin cancer (fresh-tissue technique) involves the processing of tissue in a complex fashion. The advantages of this method relate to the asymmetric three-dimensional growth of basal cell carcinoma (BCC). A device is described here based on published knowledge about the growth of BCC. The model demonstrates the precise way in which Mohs surgery varies from other surgical approaches to yield higher cure rates in specific circumstances. This device may be helpful in educating residents and medical students about Mohs surgery and in preparing patients for this procedure.
-What was the incidence of ischemic injury to the spinal cord or lumbosacral plexus following abdominal aorta operations during the study period?,"Ischemic injury to the spinal cord or lumbosacral plexus after aorto-iliac reconstruction. Between January 1, 1980, and June 30, 1989, 9 patients (6 males and 3 females) developed ischemic injury to the spinal cord or lumbosacral plexus following 3,320 operations on the abdominal aorta (0.3%). The incidence of this complication was 0.1% (2 of 1,901) after elective and 1.4% (3 of 210) after emergency abdominal aortic aneurysm repair, and 0.3% (4 of 1,209) after repair for occlusive disease. Three of the latter had prior clinical evidence of distal embolization. Eight grafts were bifurcated (aorto-iliac:four, aorto-femoral: three, aorto-ilio-femoral:one). One patient underwent extra-anatomic revascularization. Only two patients had supraceliac aortic cross-clamping and one patient underwent exclusion of both internal iliac arteries. Four patients had hypotension. Early mortality was 22% (two of nine). Severe perioperative complications, mostly due to associated visceral and somatic ischemia and sepsis, were present in seven of the nine patients. The extent and type of the neurologic injury correlated with long-term outcome. Patients with ischemic injury of the lumbosacral roots or plexus had better recovery. Attention to the pelvic circulation and the collateral blood supply is important. Use of gentle technique to prevent embolization, avoidance of hypotension and prolonged supraceliac cross-clamping, revascularization of at least one internal iliac artery, and the use of heparin may decrease but not eliminate paraplegia. Once this unexpected complication occurs, careful neurologic evaluation should be done to localize the lesion and aid prognosis."
-What is the significance of Agrobacterium radiobacter peritonitis in the two patients on chronic peritoneal dialysis?,"Agrobacterium radiobacter peritonitis in two patients maintained on chronic peritoneal dialysis. We report two patients with end-stage renal disease maintained on chronic peritoneal dialysis who developed peritonitis in which the infecting organism was Agrobacterium radiobacter, normally a rare pathogen in humans. Both patients initially responded to antibiotics, but later relapsed and required catheter removal. Neither had been exposed to soil or plant material. A radiobacter is yet another of a growing list of unusual organisms that infect the peritoneal cavity of peritoneal dialysis patients."
-How does calcium potentially help in reducing the risk of colon cancer according to the given context?,"Modulating effects of calcium in animal models of colon carcinogenesis and short-term studies in subjects at increased risk for colon cancer. A substantive amount of evidence from animal models supports the hypothesis that dietary fat is an etiological factor in colon cancer. Although various theories account for possible mechanisms, it is clear that under the influence of a basic colonic pH, fatty acids and bile acids may become highly surfactant in the colon, causing cell loss and compensatory hyperproliferation. Calcium likely reduces lipid damage in the colon by complexing with fat to form mineral-fat complexes or soaps. It has been shown in an increasing number of animal experiments that calcium has the ability to inhibit colon cancer. In limited studies in man, the colonic hyperproliferation associated with increased risk for colon cancer has been reversed for short periods by administration of supplemental dietary calcium. Taken together the available evidence suggests that increases in the daily intake of calcium in the diet may provide a means of colorectal-cancer control."
-What is the recommended treatment approach for symptomatic cavernous malformations of the brain stem?,"Cavernous malformations of the brain stem. Once they become symptomatic, cavernous malformations of the brain stem appear to cause progressive morbidity from repetitive hemorrhage, and can even be fatal. Twenty-four patients with long-tract and/or cranial nerve findings from their cavernous malformations of the brain stem were seen for initial evaluation or surgical consultation and thereafter received either surgical or continued conservative treatment. The decision to operate was based on the proximity of the cavernous malformation to the pial surface of the brain stem, the patient's neurological status, and the number of symptomatic episodes. Sixteen patients were treated by definitive surgery directed at excision of their malformation. In four patients, associated venous malformations influenced the surgical approach and their recognition avoided the risk of inappropriate excision of the venous malformation. Although some of the 16 patients had transient, immediate, postoperative worsening of their neurological deficits, the outcome of all except one was the same or improved. Only one patient developed recurrent symptoms: a new deficit 2 1/2 years after surgery required reoperation after regrowth of the cavernous malformation. She has been neurologically stable since the second surgery. One patient died 6 months postoperatively from a shunt infection and sepsis. The eight conservatively treated patients are followed with annual magnetic resonance imaging studies. One has a dramatic associated venous malformation. Seven patients have either minor intermittent or no symptoms, and the eighth died from a hemorrhage 1 year after his initial presentation. Based on these results, surgical extirpation of symptomatic cavernous malformations of the brain stem appears to be the treatment of choice when a patient is symptomatic, the lesion is located superficially, and an operative approach can spare eloquent tissue. When cavernous malformations of the brain stem are completely excised, cure appears permanent."
-What chromosomal translocation was observed in the meningioma cells of patient MN32?,"A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene. Cytogenetic analysis of meningioma cells from one particular patient (MN32) displayed the stem-line karyo-type 45, XY, -1, 4p+, 22q-, 22q+, which thus had rearrangements of both chromosomes 22. The 22q+ marker appeared as a dicentric: 22 pter----q11::1p11----qter. The reciprocal product of this translocation has presumably been lost because it lacked a centromere. The 22q- chromosome also appeared to have lost sequences distal to band q11. We assumed that this marker could have been the result of a reciprocal translocation between chromosomes 4 and 22. To investigate the 4p+ and 22q- chromosomes in more detail, human-hamster somatic cell hybrids were constructed that segregated the 22q- and 4p+ chromosomes. Southern blot analysis with DNA from these hybrids showed that sequences from 22q were indeed translocated to 4p+ and that reciprocally sequences from 4p were translocated to 22q-, demonstrating a balanced t(4;22)(p16;q11). On the basis of these results we presume that in this tumor a tumor-suppressor gene is deleted in the case of the 22q+ marker and that the t(4;22) disrupts the second allele of this gene. The latter translocation was mapped between D22S1 and D22S15, a distance of 1 cM on the linkage map of this chromosome. The area in which we have located the translocation is within the region where the gene predisposing to neurofibromatosis 2 has been mapped."
-How does the activity of calcium-independent plasmalogen-selective phospholipase A2 change during myocardial ischemia?,"The rapid and reversible activation of a calcium-independent plasmalogen-selective phospholipase A2 during myocardial ischemia. Recent studies have demonstrated the existence of two members of a novel family of calcium-independent plasmalogen-selective phospholipases A2 in mammalian myocardium (Wolf, R. A., and R. W. Gross. 1985. J. Biol. Chem. 260:7295-7303; and Hazen, S. L., D. A. Ford, and R. W. Gross. 1991. J. Biol. Chem. 266:5629-5633). To examine the potential role of these calcium-independent phospholipases A2 in mediating membrane dysfunction during early myocardial ischemia, the temporal course of alterations in phospholipase A2 activity during global ischemia in Langendorf perfused rabbit hearts was quantified and compared with traditionally accepted markers of myocytic ischemic injury and anaerobic metabolism. We now report that membrane-associated calcium-independent plasmalogen-selective phospholipase A2 activity increased over 400% during 2 min of global ischemia (P less than 0.01), was near maximally activated (greater than 10-fold) after only 5 min of ischemia, and remained activated throughout the entire ischemic interval examined (2-60 min). Activation of membrane-associated plasmalogen-selective phospholipase A2 after 5 min of myocardial ischemia was rapidly reversible during reperfusion of ischemic tissue. Both the activation of phospholipase A2 and its reversibility during reperfusion were temporally correlated to alterations in myocytic anaerobic metabolism. Furthermore, activation of membrane-associated phospholipase A2 was essentially complete before electron microscopic evidence of cellular damage. Collectively, these results identify dynamic alterations in calcium-independent plasmalogen-selective phospholipase A2 activity during myocardial ischemia which precede irreversible cellular injury and demonstrate that activation of plasmalogen-selective phospholipase A2 is amongst the earliest biochemical alterations in ischemic myocardium."
-What was the purpose of the study on thallium-201 scintigraphy and how reproducible were the quantitative measurements?,"Reproducibility of quantitative planar thallium-201 scintigraphy: quantitative criteria for reversibility of myocardial perfusion defects. Fifty-two paired stress/delayed planar 201TI studies (27 exercise studies, 25 dipyridamole studies) were processed twice by seven technologists to assess inter- and intraobserver variability. The reproducibility was inversely related to the size of 201TI perfusion abnormalities. Intraobserver variability was not different between exercise and dipyridamole studies for lesions of similar size. Based upon intraobserver variability, objective quantitative criteria for reversibility of perfusion abnormalities were defined. These objective criteria were tested prospectively in a separate group of 35 201TI studies and compared with the subjective interpretation of quantitative circumferential profiles. Overall, exact agreement existed in 78% of images (kappa statistic k = 0.66). We conclude that quantification of planar 201TI scans is highly reproducible, with acceptable inter- and intraobserver variability. Objective criteria for lesion reversibility correlated well with analysis by experienced observers."
-What are the main components of delay in treatment for acute myocardial infarction?,"Delays in the treatment of acute myocardial infarction: an overview. Delays in treatment of acute myocardial infarction prevent a substantial portion of patients from receiving maximal benefit from reperfusion therapy. Median delay between onset of symptoms and arrival at the hospital is 2 to 4 hours. Average time between arrival at the hospital and initiation of thrombolytic therapy is 84 minutes. Approximately 50% of patients hospitalized for suspected acute myocardial infarction do not use the emergency medical service system. Delay before treatment can be divided into several components: patient delay, emergency medical service delay, and hospital delay. Factors contributing to delay in each component and possible approaches to decreasing these delays are discussed. The effects of treatment delay on prognosis and future care-seeking behavior of patients hospitalized with suspected acute myocardial infarction are also discussed."
-"How does Na,K-ATPase activity change in different nephron segments in rats with moderate heart failure compared to the control group?","Na,K-ATPase in isolated nephron segments in rats with experimental heart failure. To characterize renal transport of Na+ in heart failure, urinary Na+ excretion (UNaV), aldosterone levels, and Na,K-ATPase activity in isolated nephron segments were determined in three groups: control rats, rats with heart failure and moderate sodium retention, and rats with heart failure and severe sodium retention. Heart failure was induced by a fistula between the aorta and vena cava. For the control group, UNaV was 0.66 +/- 0.04 (mean +/- SEM) mueq/min, and aldosterone was 18.4 +/- 3.5 ng%. Na,K-ATPase activity (in 10(-11) mol/mm/min) was 28.4 +/- 1.1 in the proximal convoluted tubule, 23.3 +/- 1.0 in the proximal straight tubule, 37.4 +/- 1.9 in the medullary thick ascending limb, 40.2 +/- 1.9 in the cortical thick ascending limb, 43.2 +/- 2.2 in the distal convoluted tubule, and 20.5 +/- 0.9 in the cortical collecting duct. For the group with moderate heart failure, UNaV was 0.35 +/- 0.02 (p less than 0.001 versus control), and aldosterone was 15.9 +/- 4.4 (p = NS versus control). Na,K-ATPase activity was unchanged in the proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb, and cortical collecting duct, but it increased in the cortical thick ascending limb to 57.7 +/- 3.1 (p less than 0.001 versus control) and decreased in the distal convoluted tubule to 35.3 +/- 1.2 (p less than 0.005 versus control). For the group with severe heart failure, UNaV was 0.029 +/- 0.016 (p less than 0.001 versus control), and aldosterone was 186.0 +/- 14.8 (p less than 0.001 versus control)."
-What were the key findings regarding the prognosis of Hodgkin's disease in patients aged 60 to 79 years compared to patients aged 40 to 59 years?,"The prognosis of Hodgkin's disease in older adults. This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates."
-"How do the concentrations of somatostatin, gastrin-releasing peptide (GRP), and gastrin differ in the stomachs of rats with streptozotocin-induced diabetes and insulinoma compared to control rats?","Somatostatin, gastrin-releasing peptide and gastrin in the stomach of rats with streptozotocin-induced diabetes and insulinoma. Somatostatin, gastrin-releasing peptide (GRP) and gastrin were measured in the stomach of rats with streptozotocin-induced diabetes, insulinoma-bearing rats and their respective controls. Rats injected with streptozotocin exhibited hyperphagia, insulinopenia and severe hyperglycemia. Stomach weights, and the concentrations and total amounts of GRP and gastrin in the stomach, were similar to nondiabetic control rats. The concentration of somatostatin in the stomach of diabetic rats was 25% greater, but the total stomach content of somatostatin was similar to that of control rats. Insulinoma-bearing rats exhibited hyperphagia, hyperinsulinemia and hypoglycemia. Concentrations of GRP and gastrin in the stomach were 72% and 19% lower, respectively, than in control rats. Despite 45% greater stomach weight, the total stomach content of GRP was 61% lower. Stomach concentrations of somatostatin, and total stomach contents of somatostatin and gastrin, were similar in insulinoma-bearing and control rats. The results demonstrate abnormalities in the stomach concentrations of regulatory peptides in rats with diabetes and insulinoma. These abnormalities are not attributable to changes in food intake alone, suggesting specific effects of these metabolic diseases on gastric regulatory peptides and gastric function."
-"What rare condition was observed in the 4-year-old girl with sinusitis, and how was it diagnosed and treated?","Periorbital hematoma secondary to sinusitis in a child. Periorbital abscess secondary to sinusitis is a well-recognized entity in children. However, subperiosteal hematoma is extremely rare and has been reported in only four adult patients. This article presents the case of a 4-year-old girl with sinusitis, proptosis, and decreased visual acuity. Surgical exploration of the orbit revealed the presence of a large organizing subperiosteal hematoma that was drained. The presence of a periorbital hematoma should be suspected in patients with acute onset of proptosis and findings of a periorbital mass and sinusitis on computed tomographic scan."
-How does dopamine release in the nucleus tractus solitarii change during severe hypoxia in rabbits?,"Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits. A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures."
-What is gliomatosis peritonei and what unique transformation was observed in this case report?,"Gliomatosis peritonei with malignant transformation: a case report and review of the literature. Gliomatosis peritonei is the implantation of glial tissue within the peritoneal cavity associated with ovarian teratomas. Previous reports have emphasized improved outcomes when these implants are found to be mature, even if the ovarian component is immature. A 16-year-old female with grade 3 immature teratoma was found on two subsequent laparotomies to have extensive peritoneal implantation of mature glial tissue. More than 5 years after the original surgery she was found to have a malignant abdominal glial neoplasm. This case illustrates a rare finding of malignant transformation of previously mature gliomatosis peritonei."
-How does glucagon affect the serum total bile acid levels in patients with different stages of liver cirrhosis?,"Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis. Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Child's grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Child's grade B disease. On the other hand, only 2 of 10 cases with Child's grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver."
-How can PCR analysis of BCR-abl fusion transcripts help in detecting potential relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia patients after bone marrow transplantation?,"Chimeric BCR-abl messenger RNA as a marker for minimal residual disease in patients transplanted for Philadelphia chromosome-positive acute lymphoblastic leukemia. We correlated polymerase chain reaction (PCR)-detectable BCR-abl fusion transcripts with cytogenetic status in 24 patients with acute lymphocytic leukemia (ALL). Of 10 Philadelphia chromosome negative (Ph-) patients, only one was found to exhibit a BCR-abl fusion transcript. Fourteen patients with Ph+ ALL, including eight in clinical remission, exhibited PCR-detectable BCR-abl rearrangements. A detectable Ph chromosome was present in only five of the eight patients in clinical remission. Of the three cytogenetically negative, BCR-abl-positive patients, two eventually succumbed to post-bone marrow transplantation (BMT) relapse. The third died of early transplant complications. Serial PCR analyses were performed on four Ph+ ALL patients in clinical remission who underwent allogeneic BMT. One patient who was PCR negative on post-BMT days 21 and 75 became PCR-positive on day 116 and died in relapse on day 154. One patient was weakly positive for BCR-abl on day 23, negative on day 56, but died of transplant complications on day 124. Two patients exhibited no post-BMT BCR-abl rearrangements and remain well on days 279 and 371. Our findings suggest that PCR analysis may be useful in the early identification of relapse in patients transplanted for Ph+ ALL."
-What was the hospital mortality rate for patients undergoing coronary bypass reoperation with bilateral internal mammary artery grafts compared to those receiving primary revascularization?,"Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups."
-What was the purpose of the Rheumatoid Arthritis Azathioprine Registry (RAAR) established in 1982?,"Occurrence of neoplasia in patients with rheumatoid arthritis enrolled in a DMARD Registry. Rheumatoid Arthritis Azathioprine Registry Steering Committee. The Rheumatoid Arthritis Azathioprine Registry (RAAR) was established in 1982 to examine the safety of azathioprine (AZA) and other disease modifying agents (DMARD) in the treatment of RA. In yearly followup over the past 7 years, 20 malignant conditions have been reported in 530 DMARD treated adult patients with RA. Incidence density ratios (IDR) and standardized morbidity ratios (SMR) were calculated to assess cancer risk. For all cancers the SMR was 1.52 (95% CI 0.90-2.60). For men the SMR was 1.71 (95% CI 0.84-3.52); for women the SMR was 1.52 (95% CI 0.89-2.60). Adjusted for age, the IDR was highest in the 70-79-year-old study population (3.41). The age and sex adjusted SMR for lymphoproliferative disorders and myeloma was 8.05 (95% CI 3.30-20.81). The SMR for lung cancer (n = 6) was also increased (3.37; 95% CI 1.58-7.34). Compared with the general population, patients with RA requiring DMARD therapy may be at increased risk of malignancy, particularly lymphoproliferative disorders. The RAAR is an important prospective technique which will ultimately permit assessment of neoplasia risk by type and duration of DMARD therapy."
-What advantages does adenosine have over dipyridamole as a pharmacologic stress agent in positron emission tomography (PET) imaging?,"Adenosine in myocardial perfusion imaging using positron emission tomography. Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction."
-What are the precipitating factors for colovesical fistula in the described diabetic patient?,Colovesical fistula secondary to vesical gangrene in a diabetic patient. We present a case of colovesical fistula secondary to vesical gangrene. Precipitating factors were diabetes and vesical distension caused by the obstruction of an indwelling catheter. This complication is an exceptional outcome in gangrenous cystitis and it requires emergency surgical treatment.
-How did the atrial natriuretic factor analog A68828 affect glomerular filtration rate (GFR) in a postischemic acute renal failure model?,"Beneficial effect of the atrial natriuretic factor analog A68828 in postischemic acute renal failure. Short-term administration of atrial peptides has been reported to improve renal function in several animal models of acute renal failure. We designed experiments that determined the effect of a 13-amino acid analog of atrial natriuretic factor (ANF), A68828, on renal function in the postischemic model of acute renal failure. Experiments were conducted using euvolemic, male Sprague-Dawley rats (200-250 g) under Inactin anesthesia. Acute renal failure was induced by complete occlusion of both renal arteries for 30 min. After release of the clamp, vehicle (0.1% bovine serum albumin in saline), A68828 (3, 10 or 30 micrograms/kg/min), dopamine (10 micrograms/kg/min), A68828 (10 micrograms/kg/min) plus dopamine (10 micrograms/kg/min) or ANF (1-28) (0.5 micrograms/kg/min) were infused i.v. for a 2-h period. A68828 at 10 micrograms/kg/min produced a significant increase in glomerular filtration rate (GFR) compared with vehicle controls (0.39 +/- 0.08 vs. 0.19 +/- 0.04 ml/min/100 g; P less than .05) despite a lower arterial pressure (87 +/- 5 vs. 101 +/- 5 mm Hg; P less than .05). A subpressor dose of dopamine had no effect on GFR during the postischemic period (0.25 +/- 0.11 ml/min/100 g). Dopamine in combination with A68828 prevented the decrease in arterial pressure seen with A68828 alone but did not potentiate the beneficial effects on GFR (0.28 +/- 0.05 ml/min/100 g). ANF (1-28) at 0.5 micrograms/kg/min increased GFR to levels nearly identical to those induced by A68828 (0.40 +/- 0.04 ml/min/100 g). These results indicate that infusion of a reduced-size analog of ANF improves renal function in the immediate postischemic period. Furthermore, prevention of the hypotensive effects of the analog with dopamine provides no additional beneficial effect."
-What is clear cell cribriform hyperplasia (CCCH) of the prostate and what were the key findings of this study?,"Clear cell cribriform hyperplasia of the prostate. Immunohistochemical and DNA flow cytometric study. Clear cell cribriform hyperplasia (CCCH) of the prostate is an unusual form of benign prostatic hyperplasia characterized by a nodular proliferation of clear cells with small, uniform nuclei. The authors studied 15 cases of CCCH by immunohistochemistry and 13 of them by DNA flow cytometry to establish the immunohistochemical and DNA profile of this lesion. Patients ranged in age from 58 to 88 years (mean, 68 years). Follow-up of a mean of 22 months showed all patients alive with no evidence of malignant prostatic disease. All 13 CCCHs showed diploid DNA content; in contrast, among 4 papillary/cribriform carcinomas of the prostate used for comparison, 3 were aneuploid and 1 was diploid. A basal cell layer was demonstrated in all 15 CCCHs by the use of the 34 beta E12 anti-high-molecular-weight keratin antibody (EAB-903) that reacts with the basal cells but not with the acinar cells of the prostate. A continuous basal cell layer was not evident in the carcinomas. The blandness of the epithelium, the well-defined nodular configuration, the presence of a basal cell layer demonstrable by immunocytochemistry, and the lack of aneuploidy as determined by DNA flow cytometry together lend support to the concept that CCCH is a benign lesion."
-What is cramp-fasciculation syndrome and how was it treated in the reported patients?,"Cramp-fasciculation syndrome: a treatable hyperexcitable peripheral nerve disorder. We report nine patients with muscle aching, cramps, stiffness, exercise intolerance, and peripheral nerve hyperexcitability. Neurologic examination showed calf fasciculations in seven, quadriceps myokymia in two, and deltoid myokymia in one patient. Two patients had mild increase in serum creatine kinase. Muscle biopsy showed either no abnormality (three patients) or mild neurogenic changes (four patients). Fasciculations were the only abnormality on routine electrodiagnostic studies. Supramaximal stimulation of the median, ulnar, peroneal, and posterior tibial nerves at frequencies of 0.5, 1, 2, and 5 Hz produced showers of electrical potentials following the M response in at least one nerve. In three patients, the fasciculations and evoked electrical potentials were abolished by regional application of curare but not nerve block. Carbamazepine therapy caused moderate-to-marked reduction of symptoms and nerve hyperexcitability. We designate this hyperexcitable peripheral nerve disorder as the ""cramp-fasciculation syndrome.""."
-What diagnostic methods are recommended for identifying acid peptic disease in adolescents?,"Acid peptic disease in adolescents. How to avoid misdiagnosis and undertreatment. Acid peptic disease in adolescents may be more common than previously recognized. However, appropriate medical attention is often delayed because of misdiagnosis and undertreatment. Thorough questioning of adolescent patients is important to elicit a complete description of symptoms. Endoscopy or intraluminal pH monitoring may be necessary to establish a diagnosis of gastroesophageal reflux disease or peptic ulcer. Therapy with histamine receptor antagonists, especially ranitidine (Zantac), is recommended. Antireflux surgery may be needed to prevent potential long-term gastrointestinal damage. Patients with duodenal ulcer should also be advised to make life-style changes to avoid recurrence of disease later in life."
-How did the perceived beliefs of others and attitudes impact regimen compliance among myocardial infarction patients two years after the intervention?,"Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens."
-What was the incidence of allergic reactions in patients receiving long-term benzathine penicillin prophylaxis for rheumatic fever?,"Allergic reactions to long-term benzathine penicillin prophylaxis for rheumatic fever. International Rheumatic Fever Study Group. 1790 patients from 11 countries were enrolled in a prospective international study to determine the incidence of allergic reactions to monthly intramuscular benzathine penicillin (penicillin G benzathine) injections to prevent recurrences of rheumatic fever. After 32,430 injections during 2736 patient years of observation, 57 of the 1790 patients (3.2%) had an allergic reaction. 4 had anaphylaxis, an incidence of 0.2% (1.2/10,000 injections), all in patients over 12 years of age, and 1 patient died, a fatality incidence of 0.05% (0.31/10,000 injections). These rates are similar to those described for patients without rheumatic fever who receive short-term treatment with parenteral penicillin. Rheumatic fever recurred in 8 of 1790 patients (0.45%) who received benzathine penicillin prophylaxis compared with 11 of 96 (11.5%) who did not comply with treatment. Life-threatening allergic reactions are rare in patients on long-term parenteral benzathine penicillin to prevent recurrences of rheumatic fever; the long-term benefits of such prophylaxis by far outweigh the risk of a serious allergic reaction."
-How does the degree of carotid arterial stenosis affect cerebral blood flow reactivity to hypercapnia?,"Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results. To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia."
-How does protein kinase C (PK-C) contribute to parathyroid hormone (PTH)-induced desensitization in UMR-106 osteosarcoma cells?,"Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells. We have investigated mechanisms of PTH-induced homologous desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced desensitization. Thus, PK-C seemed to play a major role in rPTH-induced desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced homologous desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells."
-How did the use of the Hemonetics cell saver apparatus impact blood transfusion requirements during coronary artery bypass graft surgery?,"The benefit of the Hemonetics cell saver apparatus during cardiac surgery. This retrospective chart review of 155 patients having coronary artery bypass graft surgery (CABG) over a two-month period determined whether the use of a cell saver apparatus (CSA) (1) reduced or increased the requirements for homologous blood; (2) increased the incidence of post-surgical bleeding; (3) was cost-effective. Two groups of patients were identified. Group 1 (n = 99) received both CSA processed red blood cells and homologous blood components. Requirement for homologous blood products was reduced in the first 24 hr after surgery (0.5 +/- 1.0 vs 1.3 +/- 1.8 units; P less than 0.05) when compared with Group 2 (n = 56) in whom only homologous blood products were utilized. More patients in Group 1 had no transfusion requirements (45 vs 8; P less than 0.05) and there was no increased risk of major haemorrhage. When the capital costs are included, utilization of the CSA was not cost-effective. We conclude that utilisation of a CSA was safe, with no increased risk of bleeding, reduced requirements for homologous blood transfusions, but added to the cost of the procedure."
-What percentage of patients in the study had syncope produced by orthostatic testing?,"Abnormal responses to orthostatic testing in children and adolescents with recurrent unexplained syncope. Syncope in the pediatric age group is a frequent event. Most often the cause is readily apparent--i.e., orthostatic hypotension or a vasovagal event. However, there are a large number of children with frequent recurrent unexplained syncope. Neither history, physical examination, nor standard testing reveals a cause. One hundred four consecutive patients were evaluated by orthostatic testing after standard methods found no cause for the recurrent syncope. Forty-seven (44%) of these 104 patients had syncope produced by orthostatic testing. Twenty-six of the 47 (55%) became syncopal within 5 minutes of testing initiation and 21 of the 47 (45%) after 5 to 11 minutes of testing. These patients had an average decrease of 81.5 mm Hg in blood pressure and a 25 beat/min decrease in heart rate. Of 12 control subjects, none lost consciousness with standing times as long as 14 minutes. Pacing was ineffective in preventing syncope, as two patients with a previously implanted normally functioning pacemaker had recurrent syncope clinically. Syncope was also induced by orthostatic testing, with the pacemaker showing a normal response with pacing as the patient became bradycardic. The syncopal event produced by orthostatic testing occurred with a downward blood pressure trend and a narrowing of the pulse pressure without a significant increase in heart rate. This was followed by a sudden drop in blood pressure and then by bradycardia. There is a group of children and adolescents with recurrent unexplained syncope due to abnormal orthostatic control mechanisms. Orthostatic testing appears helpful in identifying these patients."
-What were the two methods of epidural diamorphine administration compared in this study?,"Lumbar epidural diamorphine following thoracic surgery. A comparison of infusion and bolus administration. Twenty-two patients received a single dose of diamorphine 5 mg through a lumbar epidural catheter before thoracic surgery. The patients were transferred after surgery to a high dependency unit where they were allocated randomly to receive either an infusion of epidural diamorphine at a rate of 1 mg/hour (group 1) or bolus doses of epidural diamorphine 5 mg on demand (group 2). There was no statistically significant difference between the groups in visual analogue pain scores in the first 18 postoperative hours. Arterial carbon dioxide tension was elevated in both groups and was consistently higher in group 1 than in group 2, with a statistically significant intergroup difference 12 hours after operation. Respiratory rate was not a useful index of respiratory depression. The commonest nonrespiratory side effect was urinary retention, but the incidences of this and other minor side effects were similar in the two groups."
-How accurate is MR imaging with a body coil in estimating prostate tumor volumes?,"Carcinoma of the prostate: MR images obtained with body coils do not accurately reflect tumor volume. MR imaging with a body coil is unreliable in directly demonstrating tumor spread through the prostatic capsule. However, the likelihood of extracapsular spread of prostatic cancer rises with increasing tumor volume. The aim of our study was to assess the accuracy of MR with a body coil in diagnosing capsular penetration indirectly via an estimation of prostatic tumor volumes. Twenty-six patients with proved prostatic cancer that was clinically confined to the gland underwent MR imaging before radical prostatectomy and whole-mount pathologic sectioning of the specimen. Twenty of 31 lesions prospectively outlined on the MR images corresponded to cancers outlined on the pathology slides, and tumor volumes were calculated by using a voxel summation technique. On MR, tumor volume was underestimated in 11 of 20 cases and overestimated in nine of 20 cases. Only two of 20 size estimates based on MR findings were within 10% of actual tumor volume. Overlap in MR tumor volumes was significant between lesions with and without capsular penetration at microscopy. Factors contributing to inaccuracies in measurements of tumor volume on MR images included the variable histologic make-up of the tumors. Our results show that, although knowledge of the size of a prostatic lesion is important in predicting the behavior of the tumor, MR imaging with a body coil is not reliable for accurate estimation of tumor volume."
-What is Parathyroid Hypertensive Factor (PHF) and in what percentage of North American essential hypertensive patients is it found?,"Purification of parathyroid hypertensive factor from plasma of spontaneously hypertensive rats. Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor that may be related to elevation of blood pressure in 30-40% of North American essential hypertensive patients. PHF is also found in several animal models of hypertension, including spontaneously hypertensive rats, and deoxycorticosterone acetate salt hypertensive rats. Plasma collected from spontaneously hypertensive rats (SHR) was used in the present study for purification of PHF. Plasma was dialyzed at a molecular mass cutoff of 1 kDa, and then ultrafiltered at a molecular mass cutoff of 5 kDa. PHF activity, as determined by bioassay (characteristic delayed hypertensive response in normotensive rat) was retained in the fraction that was greater than 1 kDa and less than 5 kDa. Dialyzed and ultrafiltered SHR plasma was fractionated by molecular-exclusion chromatography, either with Bio-Gel P-6 liquid chromatography, or TSK 2000 SW HPLC. The biological activity was detected in a discrete region corresponding to a molecular mass of 2.5-3 kDa. When the molecular-exclusion fraction was subsequently fractionated by reverse-phase HPLC, biological activity was located in a single discrete peak, which did not occur in plasma from normotensive rats prepared in a similar manner. The biologically active fraction of PHF was inactivated by trypsin; this and its UV spectrum indicate the presence of a peptide structure."
-What is a nasal schwannoma and what is the recommended treatment approach?,Nasal schwannoma. A 36-year-old man with a nasal septal mass is presented. The diagnosis of a benign neoplasm arising from peripheral nerve Schwann cells was made by excisional biopsy. A benign nerve sheath tumor may be either a schwannoma or neurofibroma. Schwannomas may be distinguished from neurofibroma by clinical and histologic criteria. Malignant degeneration and intracranial extension may complicate the course of a nasal schwannoma. Complete excision is the preferred therapy.
-What signs of essential fatty acid deficiency were observed in infants receiving a medium-chain-triglyceride (MCT) infant formula?,"Essential fatty acid deficiency associated with the use of a medium-chain-triglyceride infant formula in pediatric hepatobiliary disease. Serum phospholipid fatty acid patterns were determined by gas chromatography in four infants with hepatobiliary disease receiving a formula with a high content of medium-chain-triglyceride (MCT) oil. All four infants demonstrated signs of essential fatty acid deficiency, characterized by decreased arachidonic acid and increased palmitoleic and oleic acids. All had substantial concentrations of the pathologic triene 5,8,11-eicosatrienoic acid. Three of four had decreased linoleic acid concentrations and abnormal ratios of triene to tetraene (5,8,11-eicosatrienoic acid: arachidonic acid), greater than 0.38. One patient may have experienced growth failure due to abnormal essential fatty acid status. Infants with the potential for fat malabsorption should only receive MCT-oil feedings with well above the generally recommended requirements for linoleic acid (3% of total caloric intake)."
-What is the main purpose of the postoperative infusional continuous regional analgesia (PICRA) technique described in the context?,"Postoperative infusional continuous regional analgesia. A technique for relief of postoperative pain following major extremity surgery. A new technique using postoperative infusional continuous regional analgesia (PICRA) for postoperative pain relief was investigated in 23 surgical patients treated by amputation (12 patients) or by limb-salvage resection operations (11 patients). Bupivacaine was delivered into peripheral nerve sheaths via catheters placed therein at the time of surgery. Only patients in whom the nerves were easily accessible were treated. Catheters were placed in the axillary sheath, the lumbosacral trunk, and the femoral nerve sheaths of patients treated with shoulder girdle and pelvic procedures (resections and amputations), and within the sciatic nerve sheath of those treated with lower extremity procedures. The anesthetic agent was delivered at controllable rates. Regional analgesia was obtained in the operative site with minimal motor or sensory decrease. To assess the efficacy of this technique, the results of this study group were compared with those of a matched group of 11 patients treated with similar surgical procedures but who received epidural morphine. Eleven of the 23 patients on PICRA required no supplemental narcotic agents. The mean level of the narcotic agents required by the remaining 13 PICRA patients was approximately one third of that required by the matched group of 11 patients receiving epidural morphine. Overall, the patients on PICRA had an 80% reduction of narcotic requirements when compared to the historical controls. The technique is reliable and can be performed by the surgeon, requiring about a ten-minute increase in operating time. It has potentially wide application in orthopedics in procedures in which the major nerves are easily accessible (e.g., pelvic fractures and revision hip surgery) and for patients with intractable pain of the extremities."
-What are the key findings of the immunoelectronmicroscopic study regarding the binding sites of jejunal antibodies (JAB) in patients with dermatitis herpetiformis?,"Extracellular binding sites of IgA anti-jejunal antibodies on normal small bowel detected by indirect immunoelectronmicroscopy. Patients with dermatitis herpetiformis (DH) have IgA deposition in the papillary dermis and in the lamina propria of the small bowel. In addition, most of DH patients' sera contain IgA class anti-reticulin antibodies, anti-endomysium antibodies (EMA), and anti-jejunal antibodies (JAB) during times of gluten intake. In previous studies, JAB and EMA seemed to be identical and related to the group of anti-reticulin antibodies. In the present study, pre-embedding en bloc immunoelectronmicroscopic methods were applied for analysis of the ultrastructural binding sites of JAB on monkey and rabbit small bowels. These substrates were incubated with sera from DH patients strongly positive for JAB. Simultaneous investigations with the PAP technique and with 5 nm gold-labeled protein A or second antibodies visualized the bound IgA identically: it was associated with collagen fibrils underlying the epithelial and cryptal basement membranes and with collagen fibrils around capillaries. Staining was also detected along the endomysial collagen fibrils of smooth muscle layers, around elastica and smooth muscle cells of blood vessel walls, and along collagen fibrils near smooth muscle cells in the lamina propria. Neither the peroxidase product nor gold deposition was detected directly on the fibers, but was associated with amorphous material surrounding collagen fibers of different diameters. The distribution of JAB-stained structures corresponded to the localization of reticulin network of the small bowel. Our data indicate that JAB recognize an antigen or antigens associated with an amorphous component of the reticulin-collagen structure of jejunum and may have identical binding sites, as anti-reticulin antibodies and EMA."
-What are the key findings regarding amenorrhoea in women with non-alcoholic chronic liver disease?,"Amenorrhoea in women with non-alcoholic chronic liver disease. Amenorrhoea is common in women with non-alcoholic chronic liver disease, but little is known about its causes or consequences. We investigated 12 young women with non-alcoholic chronic liver disease and amenorrhoea and compared them with 11 healthy age matched controls studied in the follicular phase of the menstrual cycle. None of the patients had raised serum concentrations of follicle stimulating hormone suggesting primary gonadal failure, but the variance in serum concentrations of testosterone, oestradiol, prolactin, and luteinising hormone were significantly greater in chronic liver disease patients than control subjects (p less than 0.01). Seven of the 12 chronic liver disease patients had low serum luteinising hormone concentrations, and compared with controls these patients also had significantly reduced median values of oestradiol (64 pmol/l), testosterone (1.1 nmol/l), and follicle stimulating hormone, and were significantly underweight as assessed by skinfold thickness measurements (all comparisons p less than 0.025). In the group with chronic liver disease skinfold thickness was significantly correlated with serum luteinising hormone (p less than 0.02). The five patients with normal serum luteinising hormone had higher median values of both oestradiol (237 pmol/l) and testosterone (3.0 nmol/l) than the control subjects (oestradiol: 113 pmol/l, testosterone: 1.9 nmol/l) but were not more obese or hirsute. Amenorrhoea was unrelated to the duration or severity of liver disease. The metacarpal cortical bone area (an index of bone density) was inversely related to the duration of amenorrhoea (p less than 0.02). We conclude that amenorrhoea in women with non-alcoholic chronic liver disease arises from hypothalamic-pituitary dysfunction and can occur at any stage."
-What is the purpose of computer-assisted superimposition of magnetic resonance and high-resolution SPECT images in this study?,"Computer-assisted superimposition of magnetic resonance and high-resolution technetium-99m-HMPAO and thallium-201 SPECT images of the brain. A method for registering three-dimensional CT, MR, and PET data sets that require no special patient immobilization or other precise positioning measures was adapted to high-resolution SPECT and MRI and was applied in 14 subjects (five normal volunteers, four patients with dementia (Alzheimer's disease), two patients with recurrent glioblastoma, and three patients with focal lesions (stroke, arachnoid cyst and head trauma]. T2-weighted axial magnetic resonance images and transaxial 99mTc-HMPAO and 201Tl images acquired with an annular gamma camera were merged using an objective registration (translation, rotation and rescaling) program. In the normal subjects and patients with dementia and focal lesions, focal areas of high uptake corresponded to gray matter structures. Focal lesions observed on MRI corresponded to perfusion defects on SPECT. In the patients who had undergone surgical resection of glioblastoma followed by interstitial brachytherapy, increased 201Tl corresponding to recurrent tumor could be localized from the superimposed images. The method was evaluated by measuring the residuals in all subjects and translational errors due to superimposition of deep structures in the 12 subjects with normal thalamic anatomy and 99mTc-HMPAO uptake. This method for superimposing magnetic resonance and high-resolution SPECT images of the brain is a useful technique for correlating regional function with brain anatomy."
-What are the typical 2-year survival rates for dementia patients in outpatient clinics and nursing homes?,"Survival of patients with dementia. The evidence on survival in dementia is summarized. There are no reliable data on survival after onset of dementia or after first contact with medical services. People with dementia in outpatient clinics and nursing homes have 2-year survival rates of 75% (range 60%-95%) and 50% (range 30%-65%), respectively. Differences in survival between patients with senile dementia of the Alzheimer's type (SDAT) and multi infarct dementia (MID) are small. Women in nursing homes have a better prognosis than men (2-year survival rates, 60% vs 40%). Dementia patients have a considerable excess mortality when compared to the vital statistics. There is no evidence for improvement of survival rates during recent decades. Recommendations for future studies are made."
-What percentage of patients in the study had lesions not ideal for balloon angioplasty?,"Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty BACKGROUND. Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates. METHODS AND RESULTS. In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively. CONCLUSIONS. In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients."
-What percentage of postmenopausal women with adnexal masses were found to have malignant tumors in this study?,"The postmenopausal adnexal mass: correlation between ultrasonic and pathologic findings. One hundred two postmenopausal women underwent ultrasonographic evaluation of adnexal masses before surgery. Twenty-nine (28%) had malignant tumors and 73 (72%) had benign tumors. Two of 33 patients with a ""simple cyst"" smaller than 5 cm in diameter by ultrasound had malignant ovarian tumors. Twenty-two of the 52 women (42%) with ""complex masses"" by ultrasound and five of the 17 (29%) with solid tumors had ovarian cancer. For predicting malignancy in ovarian tumors, abdominal ultrasonography had a positive predictive value of 39% and a negative predictive value of 94%. If a negative sonogram had been relied upon, 6% of malignant ovarian tumors in postmenopausal women might have been missed."
-What were the key findings of the study comparing enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure?,"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination."
-What treatment was used for Pneumocystis carinii pneumonia in heart transplant patients and how effective was it?,"Pneumocystis carinii pneumonia after heart transplantation. Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation."
-What novel technique was developed for detecting Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections?,"Detection of single copies of Epstein-Barr virus in paraffin wax sections by non-radioactive in situ hybridisation. A highly sensitive non-isotopic in situ hybridisation technique was developed for the localisation of Epstein-Barr virus (EBV) in paraffin wax embedded tissue sections. The method uses a repeated sequence of the EBV genome as a probe, labelled with the novel reporter molecule, digoxigenin. The method can identify individual copies of EBV by detection of both EBV DNA and highly localised RNA transcripts. A combination of careful proteolytic digestion of tissue sections, high temperature denaturation of probe and target DNA, and sensitive immunocytochemical detection are used to attain single copy sensitivity. The technique is quicker and simpler to perform than some other methods used for the identification of EBV, and provides simultaneous morphological information which cannot be obtained by methods using tissue extracts. This method permits the investigation of the role of EBV in neoplastic conditions of lymphoid and epithelial cells, and may prove valuable in determining the sites of latent virus in healthy subjects."
-What imaging technique was used to locate the intrathoracic meningocele in the patient with neurofibromatosis?,"Intrathoracic meningocele associated with neurofibromatosis: case report. The authors present a case of intrathoracic meningocele associated with neurofibromatosis. Computed tomography with metrizamide myelography proved valuable in locating the lesion, thus facilitating surgical intervention. With the preoperative diagnosis established and the severity of the meningocele known, the surgeons safely employed a subpleural approach at thoracotomy."
-"What is cyclosporine, and how does it potentially cause hypertension in patients?",Mechanism of cyclosporine-induced hypertension. Cyclosporine is a common immunosuppressive agent used in solid organ and bone marrow transplants and the treatment of some immunological diseases. It has been established that treatment with cyclosporine can cause a patient to develop hypertension within a few weeks of treatment. This review will examine this effect and effective ways to treat it.
-"How do serum, salivary, and intestinal IgA anti-gliadin antibody levels differ in celiac disease patients compared to controls?","Mucosal and systemic IgA anti-gliadin antibody in celiac disease. Contrasting patterns of response in serum, saliva, and intestinal secretions. Serum IgA anti-gliadin antibody estimation is a recognized screening method for celiac disease. However, celiac disease is primarily a small intestinal mucosal disorder, and so we have examined the possibility that secreted, mucosal IgA anti-gliadin antibody might provide a more relevant measure of gluten sensitivity than that obtained from serum tests. Serum IgA anti-gliadin antibody and serum, salivary, and small intestinal aspirate IgA anti-gliadin antibody were measured by enzyme-linked immunosorbent assay. Serum IgA and IgG anti-gliadin antibody were markedly increased in untreated celiacs (N = 31) as compared to normals (N = 20) or disease controls (N = 39) (P less than 0.0001). Levels were lower in treated (N = 30) than untreated celiacs (P less than 0.001). In intestinal aspirates both untreated and treated patients had similar levels of IgA anti-gliadin antibody (P = 0.48), but both were significantly higher than in controls (P less than 0.01). Salivary IgA anti-gliadin antibody, by contrast, was not increased in celiac patients as compared to controls. Serum IgA anti-gliadin antibody was the most sensitive (84%) and specific (95%) test for detecting untreated celiac disease. It was also the most useful in patient follow-up where it provides an early objective indicator of adherence to a gluten-free diet. Mucosal IgA responses to gliadin in celiac disease appear to be compartmentalized, with different portions of the gastrointestinal tract functioning as separate immunological organs. Our results also demonstrate that serum and secretory IgA production are under independent control."
-How does intraaortic balloon pumping (IABP) affect reocclusion rates and left ventricular function in patients with acute myocardial infarction after successful percutaneous transluminal coronary angioplasty (PTCA)?,"Intraaortic balloon pumping as the postangioplasty strategy in acute myocardial infarction. To assess the usefulness of intraaortic balloon pumping (IABP) in acute myocardial infarction (AMI), 114 patients with anterior AMI undergoing emergency percutaneous transluminal coronary angioplasty (PTCA) for total occlusion of the left anterior descending artery were studied. After successful PTCA 66 patients were treated with conventional therapy (group I), and 48 patients were treated with IABP for 25 +/- 8 hours (group II). The reocclusion rate was significantly lower in group II (2.4% vs 17.7% p less than 0.05). An increase in ejection fraction in group II compared with group I was marginally significant (4.5 +/- 12.2% vs 9.2 +/- 13.0%, p = 0.08). Vascular complications occurred in two patients, but there were no deaths from IABP. These results suggest that after successful PTCA for acute myocardial infarction, IABP prevents reocclusion and may add strength to reperfusion in the improvement of left ventricular function."
-What were the five-year disease-free survival rates for different treatment stages of IIB osteosarcoma in this study?,"IIB osteosarcoma. Current management and survival statistics in the USSR. Three hundred and ninety-three patients with IIB osteosarcoma were treated at the author's institution between 1955 and 1986. In the first stage of the study, 88 patients were treated with surgery only. The five-year disease-free survival rate was 7%. In the second stage of the study, the efficacy of preventive chemotherapy after radical surgery was studied in 55 patients. The five-year disease-free survival rate was 34.4%. In the third stage of the study, the efficacy of combination therapy consisting of preoperative treatment, limb-saving surgery, and preventive chemotherapy was studied in 66 patients. The five-year disease-free survival rate was 35.5%. The authors examined results in 21 patients with Grade IV responses to evaluate the relationship between prognosis and morphogenic changes after preoperative radiotherapy and chemotherapy. The five-year disease-free survival rate was 57.9%. In the fourth stage of the study (conducted in 1986), two regimens of preoperative chemotherapy were initiated. The first regimen consists of intraarterial platinum infusions to patients with lower extremity bone damage. The second regimen consists of high-dose methotrexate infusions. The preliminary conclusion is that primary tumor damage is significantly more marked after intraarterial cisplatin infusion."
-How did the jitter and blocking characteristics of motor end-plates differ between patients with myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) at different stimulation rates?,"Single motor end-plates in myasthenia gravis and LEMS at different firing rates. The jitter and frequency of blocking was studied at single motor end-plates in 10 patients with myasthenia gravis (MG) and in a patient with Lambert-Eaton myasthenic syndrome (LEMS), using single fiber EMG (SFEMG) with axonal microstimulation at rates varying from 0.5 Hz to 20 Hz. While some myasthenic motor end-plates showed lowest degrees of transmission disturbance at the lowest rates and most pronounced abnormality at the highest rates of stimulation, over one-half were most abnormal at intermediate rates and improved at higher rates. In 1 patient, all end-plates behaved in this way. On the other hand, all end-plates in the LEMS patient showed the expected improvement of the abnormal jitter and blocking on increasing the stimulation rate. It is argued that improvement of jitter and blocking at higher rates, unless dramatic, does not necessarily suggest a presynaptic abnormality."
-What was the main finding of the study comparing low and high doses of ethanolamine oleate in treating esophageal varices?,"Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant."
-"What were the key findings regarding proarrhythmia, cardiac arrest, and death in young patients receiving encainide and flecainide?","Proarrhythmia, cardiac arrest and death in young patients receiving encainide and flecainide. The Pediatric Electrophysiology Group The potential for proarrhythmic responses to the class IC sodium channel-blocking drugs encainide and flecainide has not been well described in young patients. Therefore, data were retrospectively collected from 36 institutions regarding 579 young patients who were administered encainide or flecainide for treatment of supraventricular tachycardias (encainide 86 patients, flecainide 369 patients) or ventricular arrhythmias (encainide 21 patients, flecainide 103 patients) to assess the frequency of proarrhythmia, cardiac arrest and death during therapy (adverse events). The two drugs were similar in regard to efficacy (flecainide 71.4%, encainide 59.8%) and rate of proarrhythmic responses (flecainide 7.4%; encainide 7.5%). However, patients receiving encainide more frequently experienced cardiac arrest (encainide 7.5% vs. flecainide 2.3%, p less than 0.05) or died during treatment (encainide 7.5% vs. flecainide 2.1%, p less than 0.05). Detailed data were provided for 44 patients experiencing one or more adverse events. Patient age, previous drug trials, concomitant therapy and days of inpatient monitoring were similar for patients receiving encainide or flecainide. However, echocardiographic left ventricular shortening before treatment was lower among patients receiving encainide (0.23 +/- 0.09) than among those receiving flecainide (0.34 +/- 0.06, p less than 0.05). Plasma drug concentrations were rarely elevated. Cardiac arrest (12 patients) and deaths (13 patients) occurred predominantly among patients with underlying heart disease, particularly among patients receiving flecainide for supraventricular tachycardia (8.3% vs. 0.3%, p less than 0.001). Fifteen patients with an ostensibly normal heart and normal ventricular function experienced proarrhythmia during treatment for supraventricular tachycardia, but only 3 of the 15 had a cardiac arrest or died. The relatively high incidence of adverse events should be considered when contemplating treatment with encainide or flecainide, particularly among patients with underlying heart disease."
-How does plasma glucose level affect infarct size in focal cerebral ischemia-reperfusion?,"Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious."
-How does hypoalbuminemia impact various physiological processes in the human body?,"The role of albumin in human physiology and pathophysiology, Part III: Albumin and disease states. The serum albumin level is one of several clinical parameters of the status of general health. There is a marked correlation between low albumin levels and the incidence of morbidity and mortality in hospitalized patients. Therefore, it is not surprising to find that hypoalbuminemia is a common finding among hospitalized patients. This results from alterations in the catabolic or anabolic rates, losses of albumin, or redistribution between the various fluid compartments of the body. Somewhat less well defined than the role of albumin as a prognostic indicator is its role in compounding pathophysiology. Hypoalbuminemia is known to be associated with delayed wound healing. The hypoalbuminemic state interferes with the normal functioning of the gastrointestinal tract. Qualitative changes in the albumin molecule which occur in renal disease may damage the nephron. Low serum albumin levels may adversely affect the coagulation system. Further investigation into the role of albumin in pathophysiology is warranted."
-How does blood pressure serve as a predictor of cardiovascular diseases according to the Framingham Study?,"Blood pressure as a risk factor for cardiovascular disease. The Framingham Study--30 years of follow-up Data from 30 years of follow-up of the original Framingham Study cohort of 5,070 men and women aged 30-62 years who were first examined during the period 1948-1952 and who were free of cardiovascular disease reveal that blood pressure is a strong and consistent predictor of the development of coronary heart disease, stroke, transient ischemic attack, and congestive heart failure. Other factors related to blood pressure like obesity, left ventricular hypertrophy as demonstrated on electrocardiograms, and heart enlargement as shown by x-ray radiography made several selective additional independent contributions to risk; heart enlargement by x-ray radiography was the best predictor of congestive heart failure."
-What challenges do physicians face in distinguishing between Crohn's colitis and amebic colitis?,"Crohn's colitis complicated by superimposed invasive amebic colitis. The clinical characteristics and endoscopic appearance of inflammatory bowel disease (IBD) may be very similar to those of amebic colitis. Physicians, especially in areas in which amebiasis is endemic, are familiar with this difficulty. Moreover, in individual cases, it may even be impossible to distinguish between the two conditions, since stool specimens, bowel biopsies, and serological studies may be negative for Entamoeba histolytica, even in the presence of invasive amebic colitis. Invasive amebiasis may rarely be superimposed on IBD, which further complicates the issue. We report here a young patient with a 7-yr history of Crohn's colitis proven histologically who developed invasive amebic colitis during steroid and 6-mercaptopurine treatment for active disease. Stool specimens, mucosal biopsies, and serological studies were negative for E. histolytica, and the diagnosis was established on pathological examination of a surgically resected bowel. Anti-amebic therapy should be considered in endemic areas in cases of persistent IBD."
-What was the proportion of melanomas diagnosed in patients under 30 years old during the study period?,"Malignant melanoma occurring in those aged under 30 in the west of Scotland 1979-1986: a study of incidence, clinical features, pathological features and survival. The study population consisted of the 95 patients who presented with cutaneous malignant melanoma in the west of Scotland between 1979 and 1986 and who were aged under 30 at the time of diagnosis. Over this 7-year period, 1299 melanomas were diagnosed in all age groups in this geographical area, increasing in incidence by 82% from 135 in 1979 to 246 in 1986. The proportion of melanomas diagnosed before the patients' thirtieth birthday remained constant at 6%. None were diagnosed in the under-15 age-group, and none developed on giant congenital naevi. Forty-two of the 95 melanomas (44%) in the under-30 group developed on a small naevus present either from birth or early childhood. These melanomas were thicker than those apparently developing on normal skin, but once controlled for tumour thickness and sex the presence of a pre-existing naevus did not affect 5-year survival. The overall 5-year survival was 76% with poorer survival associated with thicker tumours and male sex. This study suggests that small early onset naevi may have a higher potential for post-pubertal malignant change than has been previously recognized."
-What were the haemodynamic changes observed during the apnoea test for diagnosing brain death?,"Haemodynamic changes during the apnoea test for diagnosis of brain death. Haemodynamic responses to the apnoea test for the diagnosis of brain death were investigated in nine patients with severe head injury or cerebrovascular disease. To prove apnoea, the ventilator was disconnected for ten minutes and oxygen was insufflated to avoid hypoxaemia. No respiratory movement was seen in any patient. Ten minutes after disconnecting the ventilator, PaCO2 was increased to 78 +/- 3 mmHg and pH was reduced to 7.17 +/- 0.02. Adequate oxygenation was maintained in all patients. Cardiac output increased from 4.8 +/- 0.7 to 5.7 +/- 0.8 L.min-1 (P less than 0.05), and mean pulmonary artery pressure increased from 11 +/- 1 to 17 +/- 2 mmHg (P less than 0.01). However, mean arterial pressure, heart rate, pulmonary artery wedge pressure and right atrial pressure did not change. Plasma catecholamines were measured in three patients. Plasma norepinephrine concentrations increased in all three patients but the changes in plasma epinephrine were minimal. These circulatory responses to acute hypercapnia were less than those reported in awake volunteers and in patients during general anaesthesia. However, since plasma norepinephrine concentration increased during the test, some sympathoadrenal response, probably of spinal origin, was present, and may have prevented the direct depressant circulatory effects of acute hypercapnia. In conclusion, the apnoea test did not produce haemodynamic disturbances when respiratory acidosis was limited to a pH 7.17 +/- 0.02 and PaCO2 60-80 mmHg."
-How do energy-absorbing steering wheels compare to standard steering wheels in terms of facial injury severity?,"Traumatic facial injuries with steering wheel loading. This study was conducted to evaluate the biomechanics of facial fractures caused by steering wheel loading. Twelve intact fresh human cadaver heads were impacted onto standard or energy-absorbing steering wheels with a custom-designed and validated vertical-drop apparatus. Either zygoma was impacted once at a velocity of 2.0-6.9 m/s. The specimens were oriented to permit a direct comparison between pretest and posttest radiography, and two-dimensional and three-dimensional CT images. Bone mineral content was determined, and biomechanical forces, accelerations, and deformations were recorded. More severe fractures were associated with higher forces on the zygoma. With increasing velocities, fractures initiated at the zygomatic region propagated to other unilateral regions such as the mandible and orbit or to the contralateral side. Less facial trauma was observed with energy-absorbing steering wheels compared with standard wheels at similar impact velocities. Bone mineral content did not correlate well with specimen age or with fracture severity. Clinically significant fractures were identifiable on 3-D CT images. The flexibility of 3-D CT in evaluating the spatial extent of facial abnormalities in different orientations may have significant impact in planning surgical procedures."
-What was the relationship between nocturnal hypoxaemia and serum erythropoietin concentrations in patients with obstructive sleep apnoea?,Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
-What are the key components of the computer-assisted neurosurgical navigational system described in the context?,"A frameless, armless navigational system for computer-assisted neurosurgery. Technical note. A computer-assisted neurosurgical navigational system has been developed which displays intraoperative manipulation on the preoperative computerized tomography (CT) scans or magnetic resonance (MR) images. The system consists of a three-dimensional digitizer, a personal computer, and an image-processing unit. Utilizing recently developed magnetic field modulation technology, the three-dimensional digitizer determines the spatial position and orientation angles of the resin probe, triangle-shaped pointer, or suction tube with a small attached magnetic field sensor. Four fiducial markers on the scalp were used to translate the spatial data of the probe onto the preoperative CT scans or MR images of the patient. With this frameless, armless navigational system, CT or MR-imaging stereotaxy can be applied to conventional open neurosurgery without limiting the operative field or interfering with the surgical procedures."
-How does diclofenac affect the healing of gastroduodenal mucosal lesions according to the study?,"Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions."
-What are the three main types of pharmacologic agents used in the treatment of congestive heart failure according to the context?,"Progressive congestive heart failure. Ways to approach office management. Treatment of congestive heart failure depends on the cause, precipitating factors, and symptoms of the disease in each patient. Dr Kahn outlines the use of the three main types of pharmacologic agents given for heart failure--diuretics, vasodilators, and digoxin. He describes a stepwise regimen, whereby agents are added as needed to improve symptoms and prolong life."
-What method was used to evaluate the main parameters of liver circulation in this study?,"Combined evaluation of total and functional liver plasma flows and intrahepatic shunting A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation."
-What is the primary treatment method described for superior vena cava thrombosis in this case report?,Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator. Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).
-What characterizes the subtype of global aphasia described in this study?,"The aphasic isolate. A clinical-CT scan study of a particularly severe subgroup of global aphasics. This paper outlines the clinical and CT scan features of a subtype of global aphasia, characterized by an extreme loss of communicative abilities, verbal as well as nonverbal. Three to four weeks after a left hemisphere stroke, 17 patients were completely unable to communicate with people addressing them. Though there were differences in their willingness to interact with the environment, they were characterized by complete loss of speech output and by inaccessibility to any kind of message, whether given verbally or through gestures. Patients who survived were reassessed 6 and 12 mos later and half of them were still found in a state of complete communicative isolation. The remainder had somewhat improved, but remained globally aphasic. The attempt to find a CT scan basis for this picture was disappointing. Only 35% of patients had a lesional pattern in agreement with the traditional view that ascribes global aphasia to the involvement of Broca's and Wernicke's areas. The location of lesion in the other cases spanned from anterior cortical damage, to posterior cortical damage, to deep nuclei damage and none of the lesions that have been proposed to account for subcortical global aphasia was consistently observed."
-What were the success and mortality rates for different clinical scenarios in PTCA for patients with unstable angina?,"Clinical factors affecting the immediate outcome of PTCA in patients with unstable angina and poor candidates for surgery. Percutaneous Transluminal Coronary Angioplasty (PTCA) has been successfully applied in unstable angina to carefully selected patients. In this study, PTCA was performed in 277 consecutive patients suffering from unstable angina and for whom bypass surgery was not a valid alternative because either of inoperable conditions or of emergency, or because surgery was not the best option. All patients were admitted first to the intensive care unit where an attempt was made to control unstable angina under conventional medical therapy using at least iv nitroderivative, heparin, and calcium blockers. After a standardized preparation PTCA was performed either as an emergency procedure in medically refractory unstable angina (107 cases) or as an elective procedure in controlled situations after a 7 to 10 days symptom-free period. Three hundred fifty-three coronary vessels were attempted. Results of this group are compared with those of a control group made of 670 consecutive stable patients recruited during the same period, and clinical characteristics are envisaged as potential predictive factors. Unstable angina is undoubtedly associated with a higher overall complication rate, but the immediate outcome is strongly affected by the clinical context. As an example, respective success and mortality rates are: 93% and 0% when a full revascularization is attempted; 91% and 0% in elective procedures in patients under 60; 87% and 1.2% in elective PTCA for multiple vessel disease; 80% and 6.5% in emergency PTCA; 80% and 11% in the overall triple vessel disease; 84% and 16% in patients with deeply altered ejection fraction; and 58% and 26% in triple vessel disease with 2 previously occluded coronary arteries."
-What are the hemodynamic effects of octreotide in patients with autonomic neuropathy?,"Hemodynamic effects of octreotide in patients with autonomic neuropathy. BACKGROUND. The somatostatin analogue, ectrootide, is being used to treat postprandial hypotension in patients with autonomic neuropathy. Although the therapeutic effect of the drug is presumably secondary to a splanchnic vasoconstrictor action, its effect on splanchnic hemodynamics has never been characterized in patients with autonomic neuropathy. Moreover, it is unknown whether octreotide acts on other vascular beds in this group of patients or whether it affects cardiac output. We, therefore, measured splanchnic, forearm, and systemic vascular resistance and cardiac output before and after administering octreotide (0.4 microgram/kg s.c.) to patients with idiopathic autonomic neuropathy and diabetic autonomic neuropathy. METHODS AND RESULTS. Splanchnic blood flow was determined from the clearance of indocyanine green in seven patients. We observed that octreotide decreased splanchnic blood flow (from 850 +/- 77 to 664 +/- 48 ml/min, p less than 0.005), increased mean blood pressure (from 97 +/- 6 to 115 +/- 3 mm Hg, p less than 0.005), and increased splanchnic vascular resistance (from 0.118 +/- 0.012 to 0.18 +/- 0.018 mm Hg/ml/min, p less than 0.005). Forearm blood flow was measured by plethysmography in 13 patients. Octreotide increased forearm vascular resistance in patients with idiopathic autonomic neuropathy (n = 8) from 19.1 +/- 1.0 to 27.2 +/- 3.8 mm Hg/ml/min/100 ml forearm volume (p less than 0.01) and from 25.2 +/- 3.9 to 41.0 +/- 6.8 mm Hg/ml/min/100 ml (p less than 0.01) in patients with diabetic autonomic neuropathy (n = 5). Cardiac output was measured by two-dimensional echocardiography. Octreotide administration increased cardiac output in five of six patients with idiopathic autonomic neuropathy (from 4.4 +/- 0.4 to 5.0 +/- 0.5 l/min, p less than 0.02) and five of five patients with diabetic autonomic neuropathy (from 3.8 +/- 0.4 to 5.1 +/- 0.4 l/min, p less than 0.02). Systemic vascular resistance increased in patients with idiopathic autonomic neuropathy from 21.2 +/- 2 to 24.9 +/- 2.6 (p less than 0.05) but did not change in patients with diabetic autonomic neuropathy. CONCLUSION. The pressor effect of octreotide in patients with autonomic neuropathy is associated with increased splanchnic and forearm vascular resistance and with increased cardiac output."
-What is the difference between disease and illness according to the given context?,"Medical aspects of delayed convalescence. Disease and illness are not synonymous. In most instances, disease is demonstrable by anatomic, physiologic, biochemical, microbiologic, or immunologic abnormalities. Disease is a pathologic process. Not all persons with a disease are sick or ill. Symptoms of illness associated with a disease may be manifest or persist after the disease has disappeared. The absence of demonstrable disease, however, does not necessarily mean that symptoms of illness are unreal. Recovery from disease and recovery from illness are not always equated. Many factors, including personal characteristics and social circumstances, can be responsible for recovery from disease and illness. Chronic fatigue syndrome or symptoms of illness can persist in some patients but not in others after many different diseases."
-What are the six characteristic features that help identify psychogenic disorders of stance and gait?,"How to identify psychogenic disorders of stance and gait. A video study in 37 patients. Thirty-seven patients with psychogenic disorders of stance and gait were clinically evaluated, recorded on video, and analysed with regard to clinical phenomenology. Characteristic, suggestive and unspecific features were identified. Six characteristic features proved most valuable for diagnosis of psychogenesis, as they occurred alone or in combination in 97% of patients: (1) momentary fluctuations of stance and gait, often in response to suggestion; (2) excessive slowness or hesitation of locomotion incompatible with neurological disease; (3) ""psychogenic"" Romberg test with a build-up of sway amplitudes after a silent latency or with improvement by distraction; (4) uneconomic postures with wastage of muscular energy; (5) the ""walking on ice"" gait pattern, which is characterized by small cautious steps with fixed ankle joints; (6) sudden buckling of the knees, usually without falls. Seventy-three percent of patients had additional suggestive features. Classification into characteristic subtypes was not found useful because predominant features varied from patient to patient and occurred in various combinations. Factitious impairment of stance and gait was studied in 13 healthy drama students. Simulated gait dysfunction appeared less conspicuous and more difficult to diagnose than the clinical psychogenic disorders."
-What are the key management recommendations for orbital lymphangioma based on the analysis of thirty cases?,"An analysis of thirty cases of orbital lymphangioma. Pathophysiologic considerations and management recommendations. Thirty cases of orbital lymphangioma were reviewed. Clinical, imaging, and microscopic findings were integrated to develop a pathophysiologic construct and management guidelines. The basic lesion might be considered an abortive vascular system which arborizes among normal structures. Intrinsic hemorrhage expands portions of the small-caliber network into large blood cysts, prompting clinical recognition. While major hemorrhage led to early surgery in 12 cases, long pretreatment intervals could be analyzed in 17 others. Twelve patients had second hemorrhages of varied magnitude, from 2 weeks to 15 years after initial recognition; five patients did not in an average of 6.8 years. Some blood cysts contracted spontaneously. Among 23 operated cases, 12 patients had major new bleeds from 4 days to 12 years after initial surgery; 11 patients did not in an average of 4.2 years. Poor final visual acuity was associated with multiple surgeries. The authors advocate conservatism in surgical case selection and in operative dissection."
-What was the success rate of laser-assisted balloon angioplasty in this multicenter study?,"Percutaneous coronary excimer laser-assisted angioplasty: initial multicenter experience in 141 patients. Initial multicenter clinical experience with percutaneous coronary excimer laser-assisted angioplasty is described for 158 lesions in 141 patients. Using a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% improvement in luminal diameter) was achieved in 138 (87%) of 158 lesions, with a reduction to less than 50% stenosis noted in 77 lesions (49%). Overall, laser-assisted balloon angioplasty success (less than 50% residual stenosis without major complication) was observed in 129 (91%) of 141 patients. Procedural complications (abrupt closure 1.3%, side branch occlusion 1.9%, intimal dissection 6.3%, embolization 1.3%, filling defect 1.3%, perforation 1.9% and spasm 1.3% and major complications (non-Q wave myocardial infarction 4.8%, emergency coronary bypass surgery 3.5% and death 0%) were infrequent and predominantly related to subsequent balloon angioplasty. In the early follow-up period (range 1 to 10 months, mean 7), 111 (79%) of the 141 patients remain asymptomatic, whereas symptoms have recurred in 27 (19%) and 3 patients (2.1%) have died. Thus, percutaneous coronary excimer laser angioplasty appears to be a feasible and safe procedure. Assessment of the impact of this technology on the acute complications of and restenosis rates after angioplasty awaits further follow-up analysis."
-How does the frequency of Helicobacter pylori infection change with age according to the study?,"Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. This study investigates whether patients who take nonsteroidal antiinflammatory drugs are more likely to have Helicobacter pylori gastritis than age-matched individuals who do not take nonsteroidal antiinflammatory drugs, and whether patients who take nonsteroidal antiinflammatory drugs who are also infected with H. pylori are more likely to have dyspepsia, mucosal damage, or ulcers than those who are not infected. Two studies were performed, one serological and the other endoscopic, both in arthritis patients receiving nonsteroidal antiinflammatory drugs chronically. The presence of H. pylori was identified with a sensitive enzyme-linked immunosorbent assay test. One hundred eighty-three patients participated in the serological study and 75 patients in the endoscopic study. The frequency of H. pylori infection increased with age, independent of nonsteroidal antiinflammatory drug use; the age-adjusted frequency of H. pylori infection in arthritis patients paralleled that of 351 asymptomatic individuals without arthritis. The frequency of H. pylori infection increased from 30.7% in age group 21-30 years to 73.4% in age group 61-75 years. Nonsteroidal antiinflammatory drug-induced mucosal injury, either hemorrhages or erosions, was more frequent in those without H. pylori infection than with infection (61% vs. 32% for hemorrhages and 57% vs. 34% for erosions for those without and with H. pylori infection; only the difference in the frequency of hemorrhages was significant, P less than 0.05). No difference was observed in the presence of dyspeptic symptoms between those with and without H. pylori infection. These data suggest that nonsteroidal antiinflammatory drug-induced damage to the gastroduodenal mucosa does not increase the susceptibility to H. pylori infection."
-How did changes in carbon dioxide tension (PCO2) affect respiratory resistance in healthy and asthmatic subjects?,"Effects of hypercapnia and hypocapnia on respiratory resistance in normal and asthmatic subjects. The effects of hypercapnia and hypocapnia on respiratory resistance were studied in 15 healthy subjects and 30 asthmatic subjects. Respiratory resistance (impedance) was measured with the pseudo-random noise forced oscillation technique while the subjects rebreathed from a wet spirometer in a closed respiratory circuit in which end tidal carbon dioxide tension (PCO2) could be controlled. Hypercapnia was induced by partially short circuiting the carbon dioxide absorber, and hypocapnia by voluntary hyperventilation. The circulating air was saturated with water vapour and kept at body temperature and ambient pressure. A rise of end tidal PCO2 of 1 kPa caused a significant fall in respiratory resistance in both normal and asthmatic subjects (15% and 9% respectively). A fall of PCO2 of 1 kPa did not cause any significant change in impedance in the control group. In the asthmatic patients resistance increased by 13%, reactance fell by 45%, and the frequency dependence of resistance rose 240%. These findings confirm that hypocapnia may contribute to airway obstruction in asthmatic patients, even when water and heat loss are prevented."
-What is a gliofibroma and why is it considered a rare type of tumor?,"Gliofibroma. Case report. The case history of an infant with a large gliofibroma is presented. Gliofibromas are rare mixed glialmesenchymal tumors that have been poorly characterized. The computerized tomography appearance and a detailed light and electron microscopic description are presented, along with immunoperoxidase studies of this tumor. This case is compared with gliofibromas described elsewhere in the literature."
-What ultrasound findings can help sonologists suspect midgut malrotation complicated by volvulus in infants?,"Midgut volvulus in infants: diagnosis with US. Work in progress. The authors present findings from ultrasound (US) studies that can alert sonologists to the possibility of midgut malrotation complicated by volvulus in neonates and infants. A fluid-filled, distended duodenum seen at US examination in infants is a nonspecific sign of duodenal obstruction, as well as one of the signs of midgut malrotation. In addition, dilated, thick-walled bowel loops, mainly to the right of the spine, and peritoneal fluid were found at abdominal US examinations of three infants with midgut malrotation complicated by volvulus. In one infant with uncomplicated midgut malrotation, only signs of duodenal obstruction were present. The findings at US of duodenal obstruction associated with thickened bowel loops to the right of the spine and peritoneal fluid should lead the sonologist to suspect midgut malrotation complicated by volvulus, a potentially fatal condition, and an upper gastrointestinal series should then be performed to confirm the diagnosis."
-What was the impact of higher haloperidol doses compared to neuroleptic threshold (NT) doses on patients with schizophrenia in this study?,"Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose. After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects."
-What are the three different types of colonic contractions that achieve the basic motor functions of the colon?,"Physiology and pathophysiology of colonic motor activity (2). The basic motor function of the colon is to mix and knead its contents, propel them slowly in the caudad direction, hold them in the distal colon until defecation, and provide a strong propulsive force during defecation. Infrequently, it also produces mass movements in the proximal colon. These motor functions are achieved in most species by three different types of contractions: the individual phasic contractions that include the short- and long-duration contractions, organized groups of contractions that include the migrating and nonmigrating motor complexes, and special propulsive contractions (giant migrating contractions). The spatial and temporal patterns of all of these contractions are controlled by myogenic, neural, and chemical control mechanisms. The individual phasic contractions are highly disorganized in time and space in the colon. For this reason, they are effective in mixing and kneading and slow distal propulsion. The underlying cause of the disorganization of short duration contractions is the irregularity in the frequency and waveshape of colonic electrical control activity and its phase unlocking throughout the colon. The individual contractions in many species occur in cyclic bursts called contractile states. At least in some species, these contractile states exhibit mostly caudad and sometimes orad migration. However, there are also nonmigrating or randomly migrating contractile states in the colon. These two patterns of contractile states are called colonic migrating motor complexes and colonic nonmigrating motor complexes, respectively. The giant migrating contractions provide the strong propulsive force for defecation and mass movements. The neural control of colonic contractions is organized at three levels--enteric, autonomic, and central. The enteric nervous system contains cholinergic and peptidergic neurons and plays a major role in the control of colonic contractions. The autonomic nerves, the vagi, pelvic, lumbar colonic, hypogastric, and splanchnic nerves, seem to continuously monitor the state of the colon and provide a modulatory input when necessary. These nerves play a major role in the reflexive control of colonic motor function. The voluntary input from the central nervous system coordinates the motor activity of the colon, rectum, anal canal and sphincters for orderly evacuation of feces during defecation. The role of acetylcholine, nonadrenaline, and the yet to be completely identified nonadrenergic, noncholinergic neurotransmitter, possibly VIP, in the control of contractions is fairly well established. Besides these, there are several other peptides and chemicals that are localized in the colonic wall; their physiological roles remain unknown. Colonic motor activity has been studied in several disease states. The findings have not always been consistent.(ABSTRACT TRUNCATED AT 400 WORDS)."
-How does food restriction affect the daily concentration pattern of plasma corticosterone in male Fischer 344 rats?,"Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. The Glucocorticoid Cascade Hypothesis of Aging and the hypothesis that food restriction retards the aging processes by preventing the development with age of hyperadrenocorticism were investigated. A longitudinal life span study of the daily concentration pattern of plasma corticosterone was conducted in male Fischer 344 rats fed ad libitum or restricted to 60% of the mean food intake of ad libitum fed rats. In another group of ad libitum fed and food-restricted rats, the influence of age on the response of plasma corticosterone levels to restraint stress was measured as was the time course of the return of plasma corticosterone to basal levels following the stress. The findings do not support the hypothesis that food restriction retards the aging processes by preventing the development of hyperadrenocorticism with advancing age. They also indicate that the Glucocorticoid Cascade Hypothesis does not describe a major aspect of the aging processes. Rather, the results suggest the possibility that a lifetime of daily periods of mild hyperadrenocorticism may, if anything, retard the aging processes."
-How do calcium antagonists and agonists affect halothane-induced contracture in muscle bundles from patients susceptible to malignant hyperthermia?,"Effects of calcium-free solution, calcium antagonists, and the calcium agonist BAY K 8644 on mechanical responses of skeletal muscle from patients susceptible to malignant hyperthermia. The purpose of this investigation was to determine if alteration in the function of the dihydropyridine receptor may in turn modify halothane-induced contractures in muscle bundles from patients susceptible to malignant hyperthermia (MH). The effects of Ca(2+)-free Krebs Ringer (KR) solution, 5 microM verapamil, 5 microM nifedipine, and 10 microM of the Ca2+ agonist BAY K 8644 on halothane-induced contracture were therefore investigated. The halothane-induced contracture was prevented in the absence of extracellular Ca2+ and significantly reduced in the presence of verapamil or nifedipine. BAY K 8644 significantly enhanced the 0.5-, 1.0-, and 1.5-vol % halothane-induced contracture in MH-susceptible muscle bundles. When BAY K 8644 was dissolved in Ca(2+)-free KR solution, no contracture was observed in MH-susceptible muscle bundles. These results on cut MH-susceptible human muscle bundles support the hypothesis that halothane-induced contracture in MH can be modified by the binding of Ca2+ agonists or antagonists to the dihydropyridine receptor. The role of Ca2+ entry phenomena remains unclear, but the results suggest that extracellular Ca2+ is required to reprime or to bind to some sites of the dihydropyridine receptors."
-How does the effect of TNF-alpha on IFN-gamma-induced MHC class II expression vary depending on the cell's maturation and differentiation stage?,"Regulation of MHC class II antigen expression. Opposing effects of tumor necrosis factor-alpha on IFN-gamma-induced HLA-DR and Ia expression depends on the maturation and differentiation stage of the cell. MHC class II induction by cytokines has been suggested to play a major role in the initiation and propagation of immune and autoimmune processes. TNF-alpha has been found both to enhance and also to inhibit IFN-gamma-induced MHC class II expression. In the present studies, the effect of TNF-alpha on IFN-gamma induced MHC class II expression was tested in various cell lines. On the basis of the data, we propose that, depending on the stage of differentiation and maturation of the cells, TNF-alpha might synergize or antagonize the affects of IFN-gamma on the regulation of MHC class II expression. Thus, in immature cells such as HL-60 or THP-1, TNF-alpha enhances IFN-gamma-induced class II expression. However, when differentiation was induced in these cells by TPA or IFN-gamma, the additive effect of TNF-alpha on the IFN-gamma induced DR expression was eliminated. Furthermore, TNF-alpha down-regulates the IFN-gamma-induced class II expression in differentiated cells such as human skin fibroblasts or activated macrophages. In bone marrow cells induced to differentiate in vitro, TNF-alpha decreased the IFN-gamma-induced MHC class II expression in a maturation-dependent fashion. These results provide a rational explanation for the conflicting reports regarding the effect of TNF-alpha on IFN-gamma-induced class II expression. But more importantly they may be relevant to the biologic function of TNF-alpha. Thus, we show that TNF-alpha-treated mice have reduced level of Ia expression on peritoneal macrophages and in vivo treatment with TNF-alpha antagonizes the ability of IFN-gamma to induce class II expression on these macrophages."
-What were the key findings of the study comparing enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure?,"A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure BACKGROUND. To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS. Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS. The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination."
-What was the main purpose of comparing endoscopic injection sclerotherapy (EIS) with conservative treatment in patients with unresectable hepatocellular carcinoma and bleeding esophageal varices?,"Endoscopic injection sclerotherapy versus conservative treatment for patients with unresectable hepatocellular carcinoma and bleeding esophageal varices. We performed endoscopic injection sclerotherapy (EIS) in the treatment of 37 patients with bleeding esophageal varices due to unresectable hepatocellular carcinoma (HCC). The results were compared with those in another 33 HCC patients treated only conservatively, without EIS, during the same period. A majority of both groups died within 3 weeks after treatment. Comparing the two groups, there was no significant difference in fatal bleeding (66% vs 75%), but significantly fewer of the EIS patients died of the index hemorrhage (43% vs. 83%; p less than 0.01). Also, in the absence of portal vein thrombosis, EIS significantly reduced the risk of fatal bleeding (31% vs. 73%; p less than 0.25). The mean days of survival were 32 +/- 15 (range, 2 to 320) in the EIS group and 10 +/- 14 (range, 2 to 270) in the compared group (p less than 0.001). We conclude that EIS provides temporary control of acute esophageal variceal bleeding in patients with unresectable HCC. The major factors contributing to EIS failure are the lethal propensity of the underlying disease and portal vein thrombosis."
-What is the relationship between proteinuria and tubulointerstitial nephritis in experimental nephrosis in rats?,"A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. The relationship between tubulointerstitial nephritis and proteinuria was characterized in experimental nephrosis in rats. In one group, proteinuria induced by aminonucleoside of puromycin (PAN) was reduced by using an 8% protein diet and adding the angiotensin I-converting enzyme (ACE) inhibitor enalapril to the drinking water. Two control groups were injected with saline and PAN, respectively, and fed a 27% protein diet. The first group had significantly reduced albuminuria and a definite attenuation of tubular cell injury. There was a strong positive correlation between the number of interstitial macrophages and albuminuria. The beneficial effect was reproduced by dietary-protein restriction alone, whereas ACE inhibition alone had an insignificant effect on the degree of proteinuria. Depletion of circulating T lymphocytes in one group of nephrotic rats eliminated interstitial lymphocytes but did not affect interstitial macrophage influx. Inhibition of the in situ proliferation of resident interstitial macrophages by unilateral kidney irradiation failed to change the intensity of the macrophage infiltration. Treatment of rats with sodium maleate produced proximal tubular cell toxicity but interstitial inflammation did not develop, suggesting that the latter is not a nonspecific response to tubular injury. These studies demonstrate a strong relationship between tubulointerstitial nephritis and the severity of proteinuria in experimental nephrosis."
-What are the key categories of etiologic treatments for dizziness mentioned in the context?,"The dizzy patient: etiologic treatment. The basis for the vestibular complaint in dizzy patients should be viewed as having an etiology rather than a description of its clinical presentation. Effective treatment of vestibular disorders is based on the stabilization of the vestibular abnormality, to allow for central vestibular compensation. While not all of the etiologies for dizziness have been described, there are effective etiologic treatments available. These fit into categories of neurotransmitters, blood sugar and blood fat control, hormones, minerals, and treatments for autoimmune dizziness."
-How does the contractile response of aorta to alpha 1-adrenergic stimulation differ between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in a calcium-free medium?,"Contractile response of aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium is reduced in spontaneous hypertension. Vascular responses of aortic rings to alpha 1-adrenergic stimulation by phenylephrine (Phe) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied in Ca(2+)-containing medium and Ca(2+)-free medium plus 50 mumol/L EGTA. Although there was no difference in the sustained force development between SHR and WKY vessels in response to 100 mmol/L KCl or 10 mumol/L Phe in Ca(2+)-containing medium, the transient contractile response to 10 mumol/L Phe in Ca(2+)-free medium was substantially smaller in SHR compared to that in WKY. Subsequent addition of 2.5 mmol/L Ca2+ restored the sustained contractile response to a similar level in both SHR and WKY vessels. The transient contractile response to Phe in Ca(2+)-free medium containing EGTA, presumably due to the release of intracellular Ca2+, decreased progressively with preincubation time in Ca(2+)-free medium, indicating intracellular Ca2+ depletion. Such a temporal change of aortic response was more pronounced in SHR than in WKY. The subsequent response to Ca2+ repletion in the presence of Phe, on the other hand, increased progressively with Ca(2+)-depletion period and was higher in SHR than in WKY. The rate of relaxation after washout of Phe was slower in SHR aorta compared to WKY aorta. These results, together with our earlier findings, collectively suggest that the previous known deficiency in Ca2+ pumping mechanisms of vascular muscle microsomes leading to a reduced functional size of intracellular Ca2+ pool may account for the smaller contractile response of SHR aorta to alpha 1-adrenergic stimulation in Ca(2+)-free medium and the slower rate of relaxation."
-What did the twin study reveal about the genetic factors in epilepsy and febrile seizures?,"The occurrence of epilepsy and febrile seizures in Virginian and Norwegian twins. Twin studies provide an efficient method for examining the importance of genetic and environmental factors in the etiology of disorders such as epilepsy. Population-based twin registries are especially valuable for studies of this type since effects of reporting and self-selection biases on the resulting data are minimized. Among 14,352 twin pairs contained in the Virginia and Norwegian twin panels for whom questionnaire information was available, there was a history of epilepsy in one or both members of 286 pairs; febrile seizures were reported in 257 pairs. Analyses of questionnaire data revealed no significant differences in concordance rates between Virginian and Norwegian twins for either epilepsy or febrile seizures. Probandwise concordance rates for epilepsy were 0.19 in monozygotic twins and 0.07 in dizygotic twins. Analogous rates for febrile seizures were 0.33 (monozygotic) and 0.11 (dizygotic). These results provide further evidence that genetic factors do have a role in the expression of epilepsy and febrile seizures."
-What unusual combination of neurological and vascular symptoms was observed in the patient with primary antiphospholipid antibody syndrome?,"Retinal migraine, chorea, and retinal artery thrombosis in a patient with primary antiphospholipid antibody syndrome. We report the case of a patient with the unusual combination of migraine, chorea, and retinal arterial thrombosis along with laboratory evidence of autoimmunity. In the absence of systemic lupus erythematosus, the clinical manifestations suggest the presence of the primary antiphospholipid antibody syndrome."
-What were the limitations of coronary flow reserve measurements in assessing the efficacy of coronary angioplasty within the first 24 hours?,"Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. To determine functional and anatomic changes in the first 24 hours after coronary angioplasty, we studied at random 15 patients (9 men, mean age 60 years) who underwent coronary angioplasty of 16 coronary arteries. Quantitative coronary angiography and coronary flow reserve measurements from digitized coronary angiograms were performed before, immediately after, and 24 hours after coronary angioplasty. Calculated were the minimal luminal diameter, obstruction area, and percentage diameter stenosis from two preferably orthogonal projections. Prior myocardial infarction in the myocardial region of interest was present in four patients. Seven patients had multivessel disease. Collateral vessels supplying the compromised flow region were observed in three patients. Six patients had refractory unstable angina pectoris. After coronary angioplasty, angiographically visible dissection was noted in six patients, whereas side branch occlusion was observed in one. Minimal luminal diameter before, immediately after, and 24 hours after was 0.93 +/- 0.18 mm, 1.53 +/- 28 mm, and 1.53 +/- 0.21 mm, respectively; obstruction area was 0.70 +/- 0.26 mm2, 1.92 +/- 0.69 mm2, and 1.87 +/- 0.51 mm2, respectively; diameter stenosis was 60.4 +/- 8.0%, 36.8 +/- 11.4%, and 37.6 +/- 5.3%, respectively. The coronary flow reserve (lower limit of normal with this technique 3.4) was essentially the same before and immediately after coronary angioplasty (1.26 +/- 0.59 vs 1.30 +/- 0.42, p = NS) with a slight improvement to 1.78 +/- 0.90 (p less than 0.05) 1 day later. Coronary artery dimensions correlated poorly with coronary blood flow reserve before and after angioplasty."
-What are the key clinical features of posterior cortical dementia as described in this case study?,"Posterior cortical dementia with alexia: neurobehavioural, MRI, and PET findings. A progressive disorder of relatively focal but asymmetric biposterior dysfunction is described in a 54 year old right handed male. Initial clinical features included letter-by-letter alexia, visual anomia, acalculia, mild agraphia, constructional apraxia, and visuospatial compromise. Serial testing demonstrated relentless deterioration with additional development of transcortical sensory aphasia, Gerstmann's tetrad, and severe visuoperceptual impairment. Amnesia was not an early clinical feature. Judgment, personality, insight, and awareness remained preserved throughout most of the clinical course. Extinction in the right visual field to bilateral stimulation was the sole neurological abnormality. Early CT was normal and late MRI showed asymmetrical bioccipitoparietal atrophy with greater involvement of the left hemisphere. Results from positron emission tomography (PET) showed bilaterally asymmetric (left greater than right) occipitotemporoparietal hypometabolism. The metabolic decrement was strikingly asymmetric with a 50% reduction in glucose consumption confined to the left occipital cortex. The picture of occipitotemporoparietal compromise verified by MRI, PET, and neurobehavioural testing would be unusual for such degenerative dementias as Alzheimer's (AD) and Pick's disease, although atypical AD with predominant occipital lobe involvement cannot be excluded. This case supports the concepts of posterior cortical dementia (PCD) as a clinically distinct entity and for the first time documents its corresponding metabolic deficit using PET."
-What was the overall 5-year actuarial disease-free survival rate after salvage surgery for patients with carcinoma of the buccal mucosa?,"Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05)."
-What is the significance of reactive astrogliosis in the subcortical white matter of amyotrophic lateral sclerosis (ALS) brains?,"Reactive astrogliosis is widespread in the subcortical white matter of amyotrophic lateral sclerosis brain. Widespread astrogliosis exists in the subcortical white matter in amyotrophic lateral sclerosis (ALS). As revealed by glial fibrillary acidic protein (GFAP) immunostaining, the gliosis has the morphological properties of an active process. It is present in the midfrontal, inferior parietal, temporal, cingulate, and occipital cortices, as well as in the motor cortex. Compared to matched regions from other neurological diseases, the gliosis in ALS does not appear to be the nonspecific result of a progressive, degenerative disease. In cell number and apparent cell size, the gliosis is comparable to that present in neurological diseases known to have white matter gliosis. Cytologically, the gliosis most closely resembles that present in cases of cerebral infarction. The basis for this similarity is unknown."
-What were the key findings of the serial echocardiographic study on HIV-infected individuals regarding cardiac abnormalities?,"Reversibility of cardiac abnormalities in human immunodeficiency virus (HIV)-infected individuals: a serial echocardiographic study. Seventy adults who tested positive for human immunodeficiency virus (HIV) were prospectively studied with serial echocardiography to better define the prevalence and progression of cardiac disease in such patients. Fifty outpatients (Group A), including 44 with acquired immunodeficiency syndrome (AIDS) and 6 with AIDS-related complex, and 20 additional patients (Group B) with asymptomatic HIV infection had baseline echocardiographic studies at a time when no patient had symptomatic heart disease. Follow-up studies were performed at 9 +/- 3 months in 52 patients (74%) and again at 15 +/- 3 months after baseline studies in 29 patients (41%). During the study, 22 patients (44%) in Group A and 1 patient (5%) in Group B died. Cardiac abnormalities were noted in 26 patients (52%) in Group A and 8 patients (40%) in Group B (p = NS) on initial or follow-up study. An abnormal left ventricular ejection fraction (less than 45%) or fractional shortening (less than 28%) was seen in seven patients in Group A; of these, three had normal left ventricular function on a later echocardiogram. One patient in Group B had persistent left ventricular dysfunction. All patients in Group A with left ventricular dysfunction on two serial studies died within 1 year after the initial echocardiogram. Ejection fraction did not change between baseline and two follow-up studies in either group (A: 52 +/- 9 vs. 56 +/- 9 vs. 55 +/- 5%, p = NS; B: 58 +/- 6 vs. 58 +/- 5 vs. 59 +/- 6%, p = NS). Right-sided cardiac enlargement resolved in 18 patients (44%), including 5 of 10 in Group A and 3 of 8 in Group B."
-How does a single gluten challenge affect intestinal permeability in patients with coeliac disease compared to healthy controls?,"Intestinal permeability after single dose gluten challenge in coeliac disease. The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood."
-What was the mortality rate associated with class IC antiarrhythmic drug overdose in this study?,"Clinical course and outcome in class IC antiarrhythmic overdose. 120 cases of class IC antiarrhythmic overdose, including propafenone, flecainide, ajmaline and prajmaline overdose, were evaluated with respect to clinical course, therapy and outcome. Whereas drug overdose in general has an overall mortality of less than 1%, intoxication with antiarrhythmic drugs of class IC was associated with a mean mortality of 22.5%. Nausea, which occurred within the first 30 minutes after ingestion, was the earliest symptom. Spontaneous vomiting probably led to self-detoxication in about half the patients. Cardiac symptoms including bradycardia and, less frequently, tachyrhythmia occurred after about 30 minutes to 2 hours. Therapeutic measures included administration of activated charcoal, gastric lavage and a saline laxative, catecholamines, and in some patients, hypertonic sodium bicarbonate, insertion of a transvenous pacemaker and hemoperfusion. Fatal outcome was mainly due to cardiac conduction disturbances progressing to electromechanical dissociation or asystolia. Resuscitation, which had to be performed in 29 patients, was successful in only two of them. No correlation was found between fatal outcome, the type of antiarrhythmic, and ingested dose. Since a specific treatment is not available and resuscitive procedures including sodium bicarbonate and insertion of a pacemaker are of limited therapeutic value, early diagnosis and primary detoxification are most important for prevention of fatal outcome."
-What were the key findings of the pilot study on sphincter-sparing management of rectal adenocarcinoma?,"A pilot study of sphincter-sparing management of adenocarcinoma of the rectum. After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy."
-How does transesophageal echocardiography compare to transthoracic echocardiography in detecting valvular vegetations in patients with suspected infectious endocarditis?,"Value of transesophageal echocardiography as an adjunct to transthoracic echocardiography in evaluation of native and prosthetic valve endocarditis. To determine if transesophageal echocardiography provides better visualization of valvular vegetations than transthoracic echocardiography, we used both methods to evaluate 24 consecutive patients (mean age, 54 years; 15 female patients and nine male patients) referred for symptoms suggestive of infectious endocarditis. Ten of the 24 patients had one or more valvular prostheses. Echocardiograms were classified as positive or negative based on visualization of valvular vegetations or abscesses. Of ten patients with a final diagnosis of infectious endocarditis on extended follow-up, transthoracic echocardiography was positive in five patients. Transesophageal echocardiography not only yielded abnormal findings in all ten of these patients, but also revealed additional information in four of the five patients with abnormal transthoracic echocardiographic examinations. Among the 14 patients who, on subsequent follow-up, were found not to have infectious endocarditis, transthoracic echocardiography was normal in 13 and falsely abnormal in one. Transesophageal echocardiography revealed no evidence of infectious endocarditis in any of these patients. The ten patients who were determined to have infectious endocarditis all had positive blood cultures and no alternative cause for their clinical presentation; in seven patients in this group who underwent operative or postmortem evaluation, infectious endocarditis was confirmed. All patients without infectious endocarditis were demonstrated to have other causes for their clinical presentation. We conclude that transesophageal echocardiography is a highly valuable test in the work-up of patients with suspected infectious endocarditis, especially those patients with inconclusive or normal transthoracic echocardiograms. In addition, transesophageal echocardiography may be of benefit to patients with previously documented infectious endocarditis and a complicated clinical course in whom additional cardiac lesions are suspected but not demonstrated by transthoracic echocardiography."
-How does native C5a (nC5a) differ from recombinant C5a (rC5a) in inducing histamine release from cutaneous mast cells in BALB/c mice?,"C5a, cutaneous mast cells, and inflammation: in vitro and in vivo studies in a murine model. To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin."
-How does elevated intravesical pressure affect blood perfusion in colocystoplasty according to the fluorometric study?,"Elevated intravesical pressure causes arterial hypoperfusion in canine colocystoplasty: a fluorometric assessment. Since 1988 there have been 15 reported cases of late, spontaneously ruptured intestinal cystoplasties at bowel sites remote from the anastomosis. Ischemic necrosis has been suggested as a possible etiology. We examined this hypothesis by quantifying the uptake of intravascular fluorescein in the augmented bowel of adult mongrel canines. There was a statistically significant decrease in fluorescein uptake at high intravesical pressures, which appeared to be most pronounced at the antimesenteric border. This laboratory study supports a recent clinical report of histological changes pathognomonic for chronic ischemia in the augmented bowel of patients with spontaneous rupture."
-What is the relationship between ventricular arrhythmias and the patency of the infarct-related coronary artery after thrombolytic therapy?,"Predictive value of ventricular arrhythmias for patency of the infarct-related coronary artery after thrombolytic therapy. In animal studies reperfusion of coronary arteries is commonly accompanied by ventricular arrhythmias. It is not certain, however, whether ventricular arrhythmias can be used as a reliable non-invasive marker of reperfusion in humans. Two-channel Holter recordings were obtained from the start of an intravenous infusion of streptokinase until coronary angiography (2.8 (2.7) hours (mean SD)) afterwards) in 57 patients with acute myocardial infarction of less than four hours who were generally not treated with antiarrhythmic drugs. Ventricular arrhythmias occurred in 21 (37%) of the 57 patients: accelerated idioventricular rhythm in 13 patients and non-sustained ventricular tachycardia in 15 patients. Seven patients had both accelerated idioventricular rhythm and non-sustained ventricular tachycardia. Coronary angiography showed a patent infarct-related vessel in 12 (92%) of the 13 patients with accelerated idioventricular rhythm (95% confidence interval 66 to 99%), in 22 (50%) of the 44 patients without accelerated idioventricular rhythm (95% CI 34 to 66%), in 11 (73%) of the 15 patients with non-sustained ventricular tachycardia (95% CI 45 to 92%), and in 23 (55%) (95% CI 39 to 71%) of the 42 patients who did not have non-sustained ventricular tachycardia. Seventeen (81%) of the 21 patients with accelerated idioventricular rhythm, or non-sustained ventricular tachycardia, or both, had a patent infarct-related vessel (95% CI 58 to 94%) as did 17 (47%) of the 36 patients with no ventricular arrhythmia (95% CI 29 to 65%). In patients with accelerated idioventricular rhythm after thrombolysis the infarct-related vessel is almost certain to be patent; but the infarct-related coronary artery can still be patent when no arrhythmia is seen."
-What percentage of atypical hyperplasia cases showed a direct mammographic-histologic correlation in the study?,"Atypical hyperplasia of the breast: mammographic appearance and histologic correlation. The mammograms and histologic slides of 58 cases of atypical hyperplasia (AH) of the breast were retrospectively reviewed to determine the geographic correlation (direct, near, or remote) between mammographic abnormalities (if present) and the histologic findings. A direct mammographic-histologic correlation was found in 24 of the 58 cases (41%), near correlation in 15 (26%), and remote correlation in 19 (33%). Clustered microcalcifications were the most common mammographic abnormality that was directly correlated with AH at histologic examination. Atypical ductal hyperplasia was much more frequently associated with a direct mammographic-histologic correlation than was atypical lobular hyperplasia (48% vs 9%). The authors conclude that, although no pathognomonic appearance of AH was discovered, mammographic abnormalities similar to those of small cancers could be directly correlated with histologic findings in 41% of cases. Since AH has been shown to be associated with a five- to tenfold increased risk of subsequent invasive carcinoma, frequent clinical and at least yearly mammographic follow-up is suggested once AH is discovered."
-What was the main hypothesis tested in this randomized study of cesarean delivery?,"A randomized study of closure of the peritoneum at cesarean delivery. This study was conducted to test the hypothesis that nonclosure of the visceral and parietal peritoneum during low transverse cervical cesarean delivery is not associated with increased intraoperative or immediate postoperative complications. One hundred thirteen patients scheduled for low transverse cervical cesarean were randomized to either closure of both the visceral and parietal peritoneum with absorbable suture (N = 59) or no peritoneal closure (N = 54). Patients were cared for in the usual postoperative manner without reference to treatment group. There were no demographic differences between the groups and no differences in method(s) of anesthesia, operative indication(s), or use of peripartum epidural narcotics. The incidence of fever, endometritis, or wound infection was similar between groups. There were no differences in the number of patients requiring parenteral narcotic analgesia or in the number of doses per patient. The number of oral analgesic doses was significantly greater with closure than without (P = .014). The frequency with which postoperative ileus was diagnosed in each group was similar, and there was no difference regarding the day on which patients were advanced to liquid or select diets. Bowel stimulants were administered more frequently to the closure than to non-closure patients (P = .03). The average operating time was shorter for the open group than for the closure group (P less than .005). We conclude that non-closure of the visceral and parietal peritoneum at low transverse cervical cesarean delivery appears to have no adverse effect on immediate postoperative recovery, may decrease postoperative narcotic requirements, allows less complicated return of bowel function, and provides a simplified and shorter surgical procedure."
-What was the primary purpose of performing transcervical resection of the endometrium (TCRE) in this study?,"Experience with the first 250 endometrial resections for menorrhagia [published erratum appears in Lancet 1991 Jan 1;337(8753):1362] 234 patients with menorrhagia were treated hysteroscopically by transcervical resection of the endometrium (TCRE) instead of hysterectomy. 250 procedures were performed under general anaesthesia (63%) or under sedation plus local anaesthesia (38%). The endometrium was excised either totally (91%) or partially (9%) in all but one case, and 56 (22%) of the patients underwent simultaneous resection of submucous fibroids. Surgical time (range 10-100 min) varied with the gynaecologist's experience. 479 ml was the average volume of uterine irrigant absorbed by the patient. Blood loss was usually slight. Operative complications were uncommon, but 4 (2%) women sustained a uterine perforation (without serious sequelae), 7 (3%) absorbed more than 2 litres of fluid, and 1 required tamponade to control postoperative bleeding. Hospital stay was short and full recovery usual by 1-2 weeks. Menstrual symptoms improved in over 90% of the patients throughout the follow-up of up to 2 1/2 years; 27-42% of the women became amenorrhoeic at some time after total TCRE. Results were best in women greater than 35 years of age, but was not influenced by the presence of fibroids or pretreatment dysmenorrhoea. 10 (4%) women later underwent hysterectomy. Hysteroscopy 3 and 12 months after surgery revealed a small, fibrotic uterine cavity in the majority."
-How does the increased collagen content in hypertrophic cardiomyopathy affect heart function?,"Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. To evaluate scar-type and matrix connective tissue and to assess their role in the diastolic dysfunction of hypertrophic cardiomyopathy, surgically resected subaortic myectomy specimens and several autopsy hearts from patients with hypertrophic cardiomyopathy were studied. Eighteen specimens were differentially stained by a newly developed method that precisely determines relative collagen content; these tissues were compared with postmortem hypertrophied and normal control subaortic specimens. Quantitation revealed a 72% higher level (36.5 vs. 22.1 micrograms collagen/mg protein) of stainable collagen in the hearts with hypertrophic cardiomyopathy than in hypertrophied control hearts. The endocardial plaque was quantitated morphometrically, and it constituted only 4.6 +/- 1.7% of the total increased collagen content in the cardiomyopathy specimens. For the matrix studies, the cardiomyopathy specimens were stained by a silver impregnation technique that identifies connective tissue elements not normally visible with routine histologic methods. There was a marked increase in content of all matrix components, both in areas of pathologic scarring and in ""normal"" zones. Whorls of matrix connective tissue were noted in regions of myocyte whorls, as well as independent of them. Thus, these studies revealed a striking increase of both scar-type and matrix connective tissue in hypertrophic cardiomyopathy. The extensive scarring and the pronounced interstitial and intercellular matrix connective tissue may contribute to the increased ventricular chamber stiffness and impaired relaxation in this disease."
-What was the relationship between nocturnal hypoxaemia and serum erythropoietin concentrations in patients with obstructive sleep apnoea?,Erythropoietin concentrations in obstructive sleep apnoea. Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.
-What suture technique and material were found to result in less stenosis when performing tracheal anastomosis in a growing animal model?,"Growth of tracheal anastomoses: advantage of absorbable interrupted sutures [published erratum appears in Ann Thorac Surg 1991 Jul;52(1):176] Growth of the trachea after complete transection and anastomosis was studied in four groups of 1-month-old New Zealand white rabbits. The trachea was transected at the fifth cartilaginous ring and then anastomosed with continuous 6-0 polypropylene (Prolene) (group 1), interrupted 6-0 polypropylene (group 2), continuous 6-0 polydioxanone (PDS) (group 3), or interrupted 6-0 PDS (group 4). The animals were followed up for 90 to 103 days (mean follow-up, 95 days). At the time the animals were killed, body weight had increased 125% (1.2 to 2.7 +/- 0.18 kg). Growth of the trachea was assessed at the time of death. Results from this study suggest that growth of a tracheal anastomosis is retarded in a growing animal model. The degree of resultant stenosis was significantly less when an absorbable suture material (PDS) and an interrupted suturing technique were used."
-What is the purpose of using impedance plethysmography in monitoring muscle perfusion after free tissue transfer?,"Impedance plethysmography: a new method for continuous muscle perfusion monitoring. Vigilant postoperative monitoring of the buried muscle flap is critical after free transfer because early diagnosis of vascular insufficiency is essential to allow prompt correction. We have identified a monitoring method utilizing needle electrodes and impedance plethysmography that gives a beat-to-beat representation of muscular perfusion. In 25 New Zealand White rabbits the gastrocnemius muscle was isolated on its vascular pedicle, and two intramuscular needle electrodes were placed. The instantaneous impedance changes of the muscle (corresponding to the pulsatile volume changes of perfusion) were measured and recorded. Using this representation of perfusion, an independent judge was able to correctly diagnose muscular ischemia 100 percent of the time (n = 25). Further, the judge was able to correctly distinguish the ischemia as arterial (n = 10) or venous (n = 10) in origin 100 percent of the time. Additionally, we monitored muscle perfusion transcutaneously in five free muscle flaps and demonstrated a reliable impedance signal that correlated with perfusion."
-What pathological features were observed in the small vessels of the nonelderly demented patients with sclerosing vasculopathy?,"Sclerosing vasculopathy of the central nervous system in nonelderly demented patients. Three nonelderly patients without hypertension whose clinical and radiologic features otherwise resembled Binswanger's subcortical arteriosclerotic encephalopathy underwent biopsy of the hyperintense periventricular lesions seen on magnetic resonance imaging. The pathologic findings of the periventricular lesions consisted of gliosis with mild rarefaction and edema of the white matter. All patients had a sclerosing vasculopathy of unknown cause, which involved numerous small vessels within the periventricular lesions. The vessels stained negatively for amyloid, amyloid precursors, desmin, vimentin, keratin, immunoglobulin, and complement. On electron microscopy, small arteries, arterioles, venules, and capillaries were characterized by swollen astrocytic foot processes surrounding the vessels; dense, perivascular collagen packing; crystalline arrays of filaments within basement membrane; giant lipid-laden lysosomes within perivascular cells; and narrowing of the vascular lumina. Similar changes were not seen in a control group of 19 patients. The pathologic features of the vessels in these cases are distinct from the vasculopathy associated with Binswanger's subcortical arteriosclerotic encephalopathy. We suggest that a spectrum of vasculopathies may be associated with dementia and periventricular hyperintense lesions on magnetic resonance imaging."
-What were the different management approaches used for treating pancreatic fluid collections in this study?,"Invasive treatment of pancreatic fluid collections with surgical and nonsurgical methods. Pancreatic fluid collections (PFC) can be drained surgically or nonsurgically with endoscopic or radiologic techniques. To define subgroups of patients with PFC who would benefit from the new modalities, we reviewed a period (1977 to 1990) during which both surgical and nonsurgical invasive techniques were available. Patients with phlegmon or necrosis at initial diagnosis were excluded. Sixty-five patients (35 male, 30 female) underwent 1 or more drainage procedures. A mean postprocedure follow-up of 10.2 months was available for 59 patients. Initial management was nonsurgical in 80% of patients. Procedures in patients with follow-up comprised invasive nonsurgical drainage (n = 25), invasive nonsurgical drainage plus surgery (n = 22), and surgery only (n = 12). Results for each group, respectively, were: morbidity, 20%, 20%, and 24%; mortality, 8%, 5%, and 0%; and successful drainage, 92%, 82%, and 83%. The choice of management appeared to be based on etiology and radiologic characteristics. Patients with nonalcohol- and nonbiliary-associated pancreatitis without a radiographically defined wall were more common in the invasive nonsurgical group and were successfully treated without surgery. Nonsurgical invasive techniques are efficacious in the treatment of PFC in this subgroup of patients."
-What was the primary objective of the seromuscular enterocystoplasty experiment in rats?,"Seromuscular enterocystoplasty in rats. Enterocystoplasty is commonly used in clinical practice. Many of its undesirable effects, that is infections, stones, mucus production, absorption of urinary components into the blood stream and risk of cancer, result from the intestinal mucosa lining the urinary tract. We report on the feasibility of creating an enterocytoplasty with a seromuscular colonic segment that acquires a transitional epithelial lining. Augmentation enterocystoplasty was performed in 51 male, 500 gm., Sprague-Dawley rats with a 1.82 cm.2 patch of left colon from which the mucosa had been stripped. The serosal surface was used as lining for the enterocystoplasty. The intestinal patch and the bladder capacity at known pressure were measured at operation and at sacrifice. The histology of the enterocystoplasty was studied in detail following sacrifice. Of the animals 40 survived without significant complications and were sacrificed at a mean postoperative time of 30 days (range 5 to 80 days). In the remaining 11 rats a bladder stone developed but it did not seem to affect the outcome of the experiment. The size of the patch could be measured in 22 rats: it was 1.82 cm.2 (standard deviation +/- 0.86) at operation and 2.30 cm.2 (standard deviation +/- 1.1) at sacrifice. In none of the rats did the patch decrease in size. The bladder capacity at a known pressure (mean 17 cm. water) could be measured in 26 animals: it was 2.35 ml. (standard deviation +/- 0.65) at operation and 5.18 ml. (standard deviation +/- 1.19) at sacrifice. Histological analysis was done in 40 rats. In all cases the serosal surface was lined with transitional epithelium, there was no fibrosis or inflammation and the structure of the muscular layer of the bowel remained intact. The earliest growth of uroepithelium in the serosal surface of the bowel was noted at 5 days. This model suggests that the seromuscular enterocystoplasty can be constructed successfully in the rat model. The seromuscular intestinal patch does not shrink. The bladder capacity increases and histology shows a uroepithelial lining of the augmentation."
-What are the key causes of obesity according to the given context?,"Obesity: types and treatments. Causes of obesity include a low resting metabolic rate, environmental factors, family behavior patterns, a poorly developed satiety response and reactive eating due to stress or anxiety. Morbid obesity is characterized by an increased number of adipocytes and a degree of irreversibility. Overeating increases the size of adipocytes; however, once adipocytes achieve their maximal size, proliferation is induced and massive, irreversible obesity may result. A syndrome of restrained eating produced by chronic dieting leads to hunger, frustration and rebound overeating. Treatment may be unsuccessful because of the failure to address specific causes of obesity in individual patients and the use of reducing regimens that are not designed to maintain weight loss. Recognition of the diverse clinical forms of obesity and their different etiologies permits treatment regimens to be more specific, increasing the likelihood of success. Even with this approach, treatment failure is common."
-What variations in transmembrane domain length were observed in the MHC class I genes of Peromyscus leucopus?,"Transmembrane domain length variation in the evolution of major histocompatibility complex class I genes. The fifth exons of major histocompatibility complex (MHC) class I genes encode a transmembrane domain (TM) that is largely responsible for class I antigen cell-surface expression usually through conventional hydrophobic amino acid-membrane interactions or, less often, through phosphatidylinositol linkage. In this report we show that Peromyscus leucopus, a Cricetidae rodent, has MHC class I genes (Pele-A genes) encoding three distinct sizes of TMs. Increases in TM lengths were due to tandem duplications of sequences similar to human hypervariable minisatellite repeats and the lambda chi site. We discerned remnants of a similar duplication event in comparable rodent and primate MHC class I genes. Furthermore, several duplications and deletions appear to have occurred independently in H-2, RT1, Pele-A, and ChLA genes in near-identical positions. Accumulated data suggests that sequences in the fifth exon of MHC class I genes may, therefore, constitute a mutational or recombinational hot spot that is mediated by minisatellite- and chi-like sequences imbedded within the coding region. The MHC class I genes may thus have recruited ""selfish"" DNA in their evolution to encode cell surface proteins. Expression of Pele-A genes was examined by the polymerase chain reaction (PCR) using oligonucleotide primers specific for exon 4 and 5 sequences. The PCR product sizes indicated that genes encoding each TM domain length are ubiquitously transcribed."
-How does FDG-PET imaging help in detecting and assessing the prognosis of malignant lymphoma in the head and neck region?,"The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis. Twenty-one patients with untreated malignant lymphoma in the head and neck region were evaluated with positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) and gallium-67 SPECT imaging. Tumor-to-normal soft-tissue contrast ratios (TCRs) obtained 60 min after injection of FDG were higher than 2.6, and all malignant lymphomas were clearly visualized. In patients with poor prognosis, higher TCRs and glucose utilization rates (GURs) were observed, whereas low TCR and GUR were shown in a patient with low-grade malignancy. In comparison with 67Ga scintigraphy, patients with high TCRs and GURs were likely to show increased accumulation of gallium-67, but accumulation of gallium-67 was not increased as much as FDG in poor prognostic patients. FDG-PET may be useful in the detection and management of malignant lymphoma."
-Where and when did the Campylobacter enteritis outbreak occur in New Zealand?,"Campylobacter enteritis--New Zealand, 1990. In August-September 1990, an outbreak of Campylobacter enteritis occurred at a camp near Christchurch, New Zealand. This report provides a preliminary summary of the investigation of this outbreak by the New Zealand Communicable Disease Centre and the Canterbury Area Health Board."
-How effective was transesophageal echocardiography in diagnosing conditions in patients initially suspected of having aortic dissection?,"Usefulness of transesophageal echocardiography in the diagnosis of conditions mimicking aortic dissection. Between September 1987 and April 1989, forty patients suspected to have aortic dissection were evaluated by transesophageal echocardiography. Aortic dissection was identified in 18 patients. This study evaluated the ability of transesophageal echocardiography in the assessment of the 22 patients in whom aortic dissection was not found. A range of pathologic conditions was diagnosed in these patients. Five patients had ischemic heart disease when they were initially seen. Among the remaining 17 only one patient had a normal aorta. Aortic disease was present in the other 16 patients with aortic dilatation in 10. Atheromas were detected in seven patients with concomitant aortic dilatation in five of them. An extrinsic aortic mass was present in two patients. Transesophageal echocardiography correctly identified an anastomotic leak at the site of left coronary artery implantation in a patient with a recent Bentall procedure, and a large mobile clot within the proximal descending aorta in a patient with blunt chest trauma. These findings obviated the need for other tests in 15 patients and led to surgery in four with no ancillary tests performed in three of them. Thus transesophageal echocardiography has an important role in assessing patients with suspected dissection. Aortic disease is common even in patients in whom aortic dissection is excluded, and some of the conditions can be just as life-threatening as dissection. Transesophageal echocardiography not only reliably identifies dissection but can also detect luminal and extraluminal diseases not adequately visualized by other modalities."
-How did the researchers measure local refractoriness during ventricular fibrillation in dogs?,"Dispersion of refractoriness in canine ventricular myocardium. Effects of sympathetic stimulation. In 18 dogs on total cardiopulmonary bypass, the average interval between local activations during artificially induced ventricular fibrillation (VF interval) was measured from extracellular electrograms, simultaneously recorded from up to 32 ventricular sites. VF intervals were used as an index of local refractoriness, based on the assumption that during ventricular fibrillation, cells are reexcited as soon as they have recovered their excitability. In support of this, microelectrode recordings in two hearts during ventricular fibrillation did not show a diastolic interval between successive action potentials. Refractory periods determined at a basic cycle length of 300 msec with the extrastimulus method correlated well with VF intervals measured at the same sites. Thus, this technique allows assessment of spatial dispersion of refractoriness during brief interventions such as sympathetic stimulation. The responses to left, right, and combined stellate ganglion stimulation varied substantially among individual hearts. This was observed both in dogs with an intact (n = 12) and decentralized (n = 6) autonomic nervous system. Individual ventricular sites could show effects of both left and right stellate ganglion stimulation (42% of tested sites) or show effects of left-sided stimulation only (31%) or right-sided stimulation only (14%). In 13% of sites, no effects of stellate stimulation were observed. Apart from these regional effects, the responses could be qualitatively different; that is, within the same heart, the VF interval prolonged at one site but shortened at another in response to the same intervention, although shortening was the general effect and prolongation the exception. Whenever sites responded to stellate ganglion stimulation with a shortening of VF interval, this shortening was approximately 10% for left, right, or combined stimulation, whether the autonomic nervous system was intact or decentralized. In six of 12 hearts in the intact group, there was a distinct regional effect of left stellate ganglion stimulation; in the other six hearts, the effects were distributed homogeneously over the ventricles. In three hearts, the effect of left stellate ganglion stimulation was strongest in the posterior wall, and in the other three hearts, in the anterior wall. The effects of right stellate ganglion stimulation were restricted to the anterior or lateral part of the left ventricle. Dispersion of VF intervals increased after left and combined stellate ganglion stimulation in the intact group and after right stellate ganglion stimulation in the decentralized group, but not significantly in every heart. This points to a marked individual variation with regard to the effects of sympathetic stimulation on electrophysiological properties of the heart."
-How does mitral valve replacement affect contractile function in a canine model of mitral regurgitation?,"Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload [published erratum appears in J Clin Invest 1991 Aug;88(2):723] It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload."
-What are the key hemodynamic characteristics of septic shock?,"Septic shock. Septic shock (SS) is the most common type of shock encountered by internists, and its prevalence appears to be increasing. SS complicates all types of infections. The hemodynamic characteristics of SS include a low systemic vascular resistance and an elevated, but relatively inadequate, cardiac output. A cardiomyopathy frequently occurs. The major endogenous mediator of SS is tumor necrosis factor, and interleukins-1 and -2 may also contribute. Important secondary phenomena include release of platelet activating factor, vasodilator prostaglandins, and upregulation of adhesion molecules on polymorphonuclear leukocytes and endothelial cells. Current therapy is often ineffectual, and potentially promising new therapeutic approaches are reviewed."
-What were the key findings of the study regarding cervical spine injuries in alert trauma patients?,"Clinical indications for cervical spine radiographs in alert trauma patients. Cervical spine fracture/dislocation is a potentially devastating injury that may be clinically difficult to diagnose. Therefore, a vast majority of trauma patients undergo cervical spine X rays when only a relatively small number of them will actually have a cervical spine injury. Because of the costly overuse of radiography, studies have been undertaken to define high yield criteria for evaluation of patients. This study examined the characteristics of acute cervical spine fracture/dislocation in alert trauma patients. Of 79 patients with this discharge diagnosis at St. Elizabeth Hospital Medical Center between 1982 and 1987, 47 met the criteria of Class I level of consciousness. All 47 patients complained of neck pain or demonstrated cervical tenderness to palpation. Other parameters (such as loss of consciousness, paresthesias, decreased sensation, weakness, cervical muscle spasm, decreased anal tone, and associated injuries) did not, individually or in combination with each other, consistently predict cervical spine injury. Although occult or painless cervical spine injuries have been reported in the literature, a careful review of these cases revealed that these injuries were not truly asymptomatic. Our study suggests that selected patients can be excluded from radiologic evaluation of the cervical spine. However, large prospective studies are needed to validate this finding."
-What precaution should be taken when using suxamethonium in a patient with a permanent pacemaker during anaesthesia?,"Pacemaker failure on induction of anaesthesia. A patient with a permanent pacemaker presented for repair of a strangulated hernia. During induction of anaesthesia, the pacemaker generator stopped discharging, thus causing cardiac arrest. The likely cause of the generator failure was inhibition by suxamethonium-induced muscle fasciculations. Following defibrillation, and increase in stimulation threshold necessitated urgent insertion of a transvenous pacing system. It is suggested that, when suxamethonium is to be used in a patient with a permanent pacemaker, consideration should be given to reprogramming the pacemaker to asynchronous mode before induction of anaesthesia. If a patient with a pacemaker requires defibrillation, an acute increase in stimulation threshold may result and cause loss of capture. Rapid insertion of a transvenous pacing system may be necessary."
-What potential complication can occur to the pancreas during extracorporeal shock wave lithotripsy (ESWL) for renal calculus fragmentation?,"Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed."
-What are the three different types of skew deviation described in the context?,"Different types of skew deviation. Although all manifest skew deviations appear the same for the clinician, skew deviation can result from different combinations of dysconjugate vertical ocular deviations. Evidence is presented for three different types of skew deviation when it occurs as a feature of an ocular tilt reaction. In type 1 (utricle) there is upward deviation of both eyes with different amplitudes, as described for otolith Tullio phenomenon in humans. In Type 2 (dorsolateral medulla oblongata) hypertropia of one eye occurs while the other eye remains in the primary position, the hypothetical mechanism of skew deviation in Wallenberg's syndrome. In Type 3 (midbrain tegmentum) there is simultaneous hypertropia of one eye and hypotropia of the other eye, as described for electrical stimulation of midbrain tegmentum in monkeys and observed in clinical cases with a paroxysmal ocular tilt reaction."
-What was the main objective of the study on P6 acupressure in children undergoing strabismus correction?,"Effect of P6 acupressure on postoperative vomiting in children undergoing outpatient strabismus correction. A prospective, double-blind study was conducted to compare the effect of pressure at the P6 (Neikuan) point with placebo as an antiemetic in children. Sixty-six patients, ages 3-12 yr, undergoing outpatient surgery for correction of strabismus, were allocated randomly to receive either bilateral P6 acupressure or placebo during the perioperative period. The study was designed to detect a 50% difference in the incidence of postoperative vomiting between the two groups, with a 90% power of achieving a statistically significant result at the 5% level (two-tailed). The incidence of postoperative vomiting for the placebo group was 58% before discharge from hospital, 73% at home and 82% in the first 24 h after surgery. The corresponding results for the acupressure group were 58% before discharge, 71% at home and 94% in the first 24 h. These differences were not significant; P6 acupressure did not reduce the incidence of postoperative vomiting in children undergoing strabismus surgery."
-What were the significant prognostic factors for recovery of awareness in patients with prolonged posttraumatic unawareness?,"Prognosis for recovery from prolonged posttraumatic unawareness: logistic analysis. This study reviews the course and outcome of 130 patients who remained in a state of prolonged unawareness 30 days after severe cranio-cerebral trauma. Prognostic indicators and outcome were fitted by a logistic model. The significant prognostic factors observable in the first week after trauma were found to be ventilatory status, motor reactivity and significant extraneural trauma. The significant prognostic factors after the first month of unawareness were early ventilatory status, early motor reactivity, late epilepsy and hydrocephalus. The estimated probability of recovery of awareness (that is, consciousness) ranged from 0.94 in patients with early decorticate posturing in the absence of both extraneural trauma and ventilatory disturbance to 0.06 in patients with flaccidity, extraneural trauma and ventilatory disturbance in the first week after injury."
-Which thrombolytic agent is most effective in restoring patency in coronary arteries according to clinical trials?,"Coronary artery thrombolysis: comparison of approved agents. Three agents approved for the lysis of thrombi in coronary arteries--alteplase, anistreplase and streptokinase--have undergone critical clinical experimental trials in Europe and the United States. Global comparison of their efficacy shows that alteplase is slightly more effective (71 percent) in restoring patency than anistreplase (60 percent) and streptokinase (58 percent). Streptokinase and anistreplase are allergenic, and repeat administration is not feasible in the short-term, a distinct advantage for alteplase. More accurate dosing of thrombolytic agents and skillful use of aspirin and heparin improve the efficacy of thrombolytic therapy but can also increase the risk of bleeding. A recanalization rate of 90 percent or more could be achieved if the thrombolytic agent is administered within the first hour after thrombosis. Administration this soon after the development of thrombosis may be possible if the agent is given outside the hospital by practicing physicians or, perhaps, paramedics."
-"What were the predictive values of digital rectal examination, transrectal ultrasound, and MRI for tumor confinement and extracapsular disease in prostate cancer?","Preoperative prediction of pathological tumor volume and stage in clinically localized prostate cancer: comparison of digital rectal examination, transrectal ultrasonography and magnetic resonance imaging. Accurate preoperative staging is important for proper selection of patients for radical retropubic prostatectomy. Preoperative staging by digital rectal examination, transrectal ultrasound, magnetic resonance imaging (MRI), Gleason grade and prostate specific antigen was compared to pathological stage for 25 patients who underwent radical retropubic prostatectomy. The predictive value for tumor confinement was 36% by rectal examination, 37% by ultrasound and 30% by MRI. The predictive value for extracapsular disease was 100% by rectal examination, 83% by ultrasound and 66% by MRI. Preoperative determinations of tumor volume by any modality did not correlate with pathological tumor volume. Digital rectal examination, ultrasound and MRI clinically understage the disease in most patients but they may be reliable to predict extracapsular disease."
-"What was the purpose of using sublaminar fixation in lumbosacral fusions, and what were the outcomes of the study?","Sublaminar fixation in lumbosacral fusions. Sublaminar fixation to stainless steel rectangles was employed in an effort to improve the fusion rate in lumbar and lumbosacral arthrodesis. Thirty-seven patients had spondylolisthesis, and 26 had other causes of pain secondary to lumbar mechanical instability. Of the 63 patients, 53 achieved fusion and 52 had relief of pain. No infections or neurologic complications were encountered. This fusion rate of 84% does not significantly differ from rates obtained with noninstrumented methods, and this construct is no longer used for lumbar fusions."
-What is the primary genetic mechanism behind Leber's hereditary optic neuropathy?,"Leber's hereditary optic neuropathy and Kearns-Sayre syndrome: mitochondrial DNA mutations. Mitochondrial DNA (mt DNA) supplies extranuclear (cytoplasmic) genes which program the manufacture of 13 of the 67 peptides of the mitochondrial respiratory enzymes. The remaining 54 are coded by nuclear DNA. All human children and adults, male and female, are entirely dependent on the cytoplasm of the ovum for their complement of mt DNA; the sperm contributes none. Accordingly, mutations in the mt DNA in a mother's ova will be passed on to all her children, although not all are clinically affected. Leber's hereditary optic neuropathy is in most cases due to a mutation that leads to the replacement of guanine by adenine at position 11778 in mt DNA. This causes histidine to be inserted instead of the normal arginine at the site of the 340th amino acid in the respiratory enzyme NADH subunit 4, hence its defective function. Other point mutations in the mt DNA coding for polypeptides of the respiratory chain complex or controlling sequences coded by mt DNA have been found in other families with Leber's hereditary optic neuropathy. Mitochondrial DNA is the site of other mutations as well. For ophthalmologists, the most important of these is the rare Kearns-Sayre syndrome (pigmentary retinopathy plus muscular dystrophies, especially of the extraocular muscles). Kearns-Sayre syndrome is due to deletions in the mt DNA, which vary in size and so affect a number of different respiratory enzymes, hence the variable manifestations. Cases are usually sporadic because the disease is often so severe that affected individuals do not reproduce if they survive, but in some cases inheritance from the mother has been reported."
-What was the main objective of the study on luteinizing hormone-releasing hormone agonist (LH-RH-a) treatment for uterine leiomyomata?,"Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women. OBJECTIVE: To evaluate the efficacy of luteinizing hormone-releasing hormone agonist (LH-RH-a) in the treatment of leiomyomata. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Twenty-five women, ages 36 to 54 years with symptomatic uterine leiomyomata, were divided into two groups according to the responsiveness to LH-RH-a: group A patients reached menopause after LH-RH-a, whereas resumption of menstruation occurred within 12 weeks after cessation of therapy in group B. INTERVENTIONS: Luteinizing hormone-releasing hormone agonist was administered intranasally three times a day with 150 micrograms insufflation of one spray in each nostril (total dose: 900 micrograms/d). MAIN OUTCOME MEASURES: Efficacies of treatment were assessed in terms of uterine volume, hemoglobin concentrations, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and bone density during and after treatment. RESULTS: In both groups, hemoglobin concentrations increased significantly after 16 weeks of treatment. A significant reduction in uterine volume was observed in both groups. After completing therapy, there was no further significant change in uterine volume in group A, whereas uterine volume in group B returned to pretreatment values. Serum LH and FSH concentrations were suppressed during treatment, but those gonadotropins in group A increased significantly up to the menopausal levels after treatment. Serum E2 concentrations in both groups showed consistent suppression by the end of the first treatment cycle. After cessation of therapy, serum E2 levels on group A remained in the castrate range, whereas E2 in group B returned to pretreatment levels, concomitant with the return of normal ovulation. CONCLUSIONS: Intranasal administration of LH-RH-a was successful in significantly decreasing uterine volume and increasing hemoglobin concentration in premenopausal women with leiomyomata."
-"What are the differences in the expression of Tn, sialosyl Tn, and T antigens across normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma?","Expression of Tn, sialosyl Tn, and T antigens in human pancreas. Carbohydrate antigens representing some of the initial steps in mucin O-linked glycosylation were examined in specimens of normal pancreas, chronic pancreatitis, and pancreatic adenocarcinoma. Tn antigen, recognized by Vicia villosa lectin, was expressed by all specimens of normal pancreas (acinar cells) and pancreatic cancers and all but one case of chronic pancreatitis. Sialosyl Tn antigen, recognized by monoclonal antibody TKH2, was expressed in a cancer-associated fashion, being completely absent in normal pancreas but expressed by 56% of chronic pancreatitis and 97% of pancreatic cancers. T antigen, recognized by monoclonal antibody AH9-16, was expressed in 68% of normal pancreas (acinar cells), 67% of chronic pancreatitis, and 48% of pancreatic cancer tissues. These results indicate that normal acinar cells of the pancreas are capable of expressing selected carbohydrate structures associated with the initial steps of mucin glycosylation. The marked expression of sialosyl Tn compared with T antigen in pancreatic cancers suggests that with malignant transformation there is selective usage of glycosyltransferase enzymes involved in mucin oligosaccharide synthesis."
-What was the main finding of the study regarding epithelial migration in patients with unilateral cholesteatoma?,"Patterns of epithelial migration in the unaffected ear in patients with a history of unilateral cholesteatoma. Epithelial migration in a centrifugal manner is an established phenomenon in the normal human tympanic membrane. This pattern of migration is symmetrical in both ears of any one individual. We present a prospective study on the pattern of tympanic ink dot migration on the normal drum, in patients with a history of cholesteatoma in one ear. It was demonstrated that patients who develop cholesteatoma have a normal migratory pattern and rate in the unaffected ear. The conclusion from this study is that defective migration is not the initiating factor in the development of acquired cholesteatoma."
-Can CT scanning help determine which patients with minimal head injury can be safely discharged from the emergency department?,"The use of CT scanning to triage patients requiring admission following minimal head injury. Recent data have suggested that patients with both a normal cranial CT scan and normal neurologic examination following minimal head injury (MHI) have no risk of neurologic deterioration. This study prospectively examined the safety of discharging patients from the emergency department (ED) after MHI whether or not there was a responsible observer at home. MHI was defined as a history of loss of consciousness (LOC), a Glasgow Coma Scale (GCS) score of 14 or 15, and no focal neurologic findings. In a 4-month period 111 patients with MHI were evaluated. Fifteen (14%) patients had a CT scan which revealed an intracerebral injury; 96 patients had a normal CT scan; five patients with normal CT scans were admitted because of persistent lethargy; and one patient was admitted after his CT that demonstrated an old infarct; the remaining 90 patients were discharged. There were 71 men and 19 women with a mean age of 29 years. The mechanism of injury was assault in 55, MVA in 30, and falls in five. The initial GCS in was 15 in 79 and 14 in 11. Fifty-eight per cent of patients were intoxicated. Fifty-seven (63%) patients were successfully contacted by telephone; none had developed any neurologic symptoms. Thirty-one patients who could not be followed up gave fictitious phone numbers. These data suggest that CT can reliably triage patients who can be discharged from the ED following MHI, even in the absence of a responsible observer. Hospital admission can be avoided in more than 80% of patients sustaining MHI, better utilizing scarce hospital resources."
-How does the extent of coronary collateral circulation relate to the presence of viable myocardium in patients with recent myocardial infarction?,"Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction. The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area."
-What were the four radiological examinations investigated for acoustic neuromata in this study?,"Patient dose and associated risk due to radiological investigation of the internal auditory meatus. The radiation doses and associated somatic risks due to four radiological examinations for acoustic neuromata (AN) have been investigated. These examinations were (1) plain film radiography of the internal auditory meatus (IAM), (2) computed tomography (CT) of the IAM, (3) CT of the posterior fossa and (4) CT of the IAM with air contrast. Organ dose measurements were performed using lithium fluoride thermoluminescent dosemeters loaded in a patient equivalent phantom. Dose equivalents to various organs are presented, together with the effective dose equivalent and collective effective dose equivalent for each examination. Hypothetical fatal somatic risks for each examination studied here have been estimated from the effective dose equivalents. The estimated number of hypothetical fatal cancers induced by radiological examinations for AN is between approximately 110 and 820 times lower than the number of detected AN, depending on the method of assessing the radiation dose to the remainder organs. It is concluded that in this particular study the radiological examinations are of net benefit to this group of patients."
-What is the key finding regarding the origin of fetal tissue in the reported cases of repetitive hydatidiform mole?,"Hydatidiform mole and fetus with normal karyotype: support of a separate entity. Repetitive hydatidiform mole was observed in four pregnancies. The pregnancies presented with heavy bleeding and vomiting, but the post-evacuation courses were uncomplicated, with rapid regression of serum hCG levels. Cytogenetic investigations, analyses of restriction fragment length polymorphisms, and flow cytometry in three pregnancies were consistent with diploid, biparental conception as the origin of fetal tissue and molar and nonmolar villi. In one pregnancy, the analyses of cytogenetic markers suggested the coexistence of two different cell lines of dizygotic, biparental origin, whereas DNA analysis was consistent with a single conception. With incomplete genetic information, a hydatidiform mole with coexistent normal fetus is generally considered to result from dizygous twinning comprising an androgenetic complete mole and a normal conception. In the present gestations, the results based on several techniques applied on numerous samples from different tissues render this possibility unlikely. Some of the contradictions between histologic and cytogenetic classifications of hydatidiform mole may be explained by diploid, biparental partial mole, which seems to constitute a separate subgroup within hydatidiform mole. Following chorionic villus sampling or amniocentesis, continued pregnancy may be considered, depending on prenatal diagnosis including genetic marker analysis."
-What potential side effect did two siblings experience after receiving phenothiazine-containing medications?,"Phenothiazine-associated apnea in two siblings. A two-month-old white girl presented to our facility with increasing lethargy and new onset apnea and bradycardia following a week of upper respiratory tract infection symptoms. The patient had been receiving a cough syrup containing promethazine hydrochloride during the previous five days, which was temporally correlated with the onset of lethargy and apneic episodes. Upon further investigation, it was discovered that the patient's older sibling also may have experienced phenothiazine-associated apnea after receiving a combination of meperidine hydrochloride, promethazine hydrochloride, and chlorpromazine as a premedication prior to an endoscopic examination. In addition to the presentation of these cases, the literature pertaining to phenothiazine-associated apnea is reviewed."
-What was the primary objective of using the miniaturized infrared end-tidal CO2 detector in this study?,"Confirmation of endotracheal tube placement: a miniaturized infrared qualitative CO2 detector. STUDY OBJECTIVES: A miniaturized, infrared, solid-state, end-tidal CO2 detector was used to confirm emergency endotracheal tube (ETT) placement. DESIGN: This prospective, clinical study used a miniature, infrared, solid-state end-tidal CO2 detector to confirm ETT placement in an acute setting. SETTING: The ICU, emergency department, and hospital floor. TYPE OF PARTICIPANTS: There were 88 consecutive adult patients requiring 100 emergency intubations. MEASUREMENTS AND MAIN RESULTS: The indication for airway intervention was considered urgent in 79% and under arrest conditions in 21%. The mean number of intubation attempts was 1.83 (range, one to five) with difficulty of intubation of 6.48 and confirmation of 7.75, on a linear scale from 0 (lowest) to 10 (highest). Determination of ETT position revealed intratracheal intubation in 96% and esophageal intubation in 4%. Placement was confirmed by direct visualization or radiography in all cases. Sensitivity and specificity for ETT localization was 100% (P less than .0001). CONCLUSION: This hand-held infrared capnometer reliably confirms ETT placement under emergency conditions."
-What is the primary aim of the modified lateral rhachotomy procedure for thoracic spinal lesions?,"Lateral rhachotomy for thoracic spinal lesions. Capener's ""Lateral Rhachotomy"" was modified by additional excision of the pedicle, articular facets, part of the lamina, and a posterior half of the vertebral bodies on one side through a transpleural approach to the thoracic spine, and a retroperitoneal approach to the lumbar spine. The aim was to excise a space-occupying lesion, which exists in front of the thoracic or lumbar spinal cord, safely. This modification enable the authors to expose more than 50% of the spinal canal, and decompress it from its anterior, lateral, and posterior compressing mass. The utmost important point of this procedure is the excision of the lesion under the direct visualization of the dura. In ossification of the posterior longitudinal ligament (OPLL), the dura is usually indented by the thick bony mass, and the lesion extends over a few segment with adhesion. Using ""Modified Lateral Rhachotomy,"" it was possible to explore three or four vertebral levels in continuity through the same skin incision. In the present report, the authors described their ""Modified Lateral Rhachotomy"" procedure, and reviewed the case material."
-How do Factor XIII subunits change in patients with ulcerative colitis during active and quiescent stages of the disease?,"Factor XIII subunits in relation to some other hemostatic parameters in ulcerative colitis. The hemostatic parameters, particularly with respect to F.XIII subunits, were examined in 48 untreated UC patients (22 at active and 26 at quiescent stage). UC active patients showed a significant decrease of F.XIII subunit ""a,"" compared with healthy subjects, as well as in UC patients in remission. In contrast, the level of F.XIII subunit ""b"" in each group was similar. Compared with normal subjects, UC active patients revealed a significant decrease in AT III concentration, prolonged ELT, and elevated fibrinogen level. In addition, the elevated titer of SDPS test for SFMC appeared in approximately 40% of those patients. However, no strict relationship was found between the presence of positive SDPS and diminution of AT III, as well as of F.XIIII subunit ""a"" in active UC state. In patients in remission, AT III level and ELT were similar to those as in the control group, but fibrinogen concentration was elevated. Such constellation of hemostatic parameters may indicate a tendency to blood hypercoagulability in UC active patients, whereas, in general, these changes are not associated with the stage of remission. The present data may also suggest that F.XIII behavior pattern should be taken into account in the clinical management of UC."
-What were the key differences in characteristics between palpable and mammographically detected breast lesions in this study?,"The prevalence of carcinoma in palpable vs impalpable, mammographically detected lesions. Concern over excessive numbers of false-positive mammograms, leading to unnecessary investigations and surgical interventions, has been cited as a barrier to mammographic screening for breast cancer. We compared the biopsy results from palpable vs impalpable, mammographically detected lesions from one experienced breast surgeon's practice from July 1980 through July 1989. Overall, there were 372 biopsies in 346 women. Of 143 biopsies for palpable abnormalities, 48 (34%) yielded a primary malignant lesion. The length of the palpable cancers averaged 3.7 cm (median, 2.8 cm). Sixteen (33%) of the 48 biopsies were in patients who had positive axillary lymph nodes, and five (10%) were in patients who had distant metastases at the time of biopsy. Of 229 biopsies for impalpable, mammographically detected lesions, 72 (31%) yielded a primary breast carcinoma. Excluding 34 carcinomas that had only calcifications, the length of the mammographically detected tumors averaged 2.0 cm (median, 1.5 cm). Eleven (15%) of the 72 biopsies were in patients who had positive axillary nodes, and none were in patients who had distant metastases at the time of biopsy. The positive predictive values (number of cancers detected divided by the number of biopsies recommended) were not significantly different when comparing biopsies indicated for palpable, clinically detected (34%) vs impalpable, mammographically detected (31%) abnormalities (p = .669). However, the mammographically detected cancers were smaller, more often noninvasive (32% vs 4%), less often associated with axillary metastases (15% vs 33%), and without distant metastases (0% vs 10%)."
-What is the significance of the modified endoscopic classification of burns in the management of corrosive ingestion?,"The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. We prospectively evaluated the role of fiberoptic esophagogastroduodenoscopy in the management of 81 patients with corrosive ingestion. A total of 381 endoscopic examinations were performed: 88 within 96 hours following corrosive ingestion, 108 between the third and ninth week, and 185 during the period of follow-up after bougie dilation of esophageal strictures. The customary endoscopic classification of burns (grades 0 to 3) was modified by subdividing grade 2 burns into 2a and 2b, and grade 3 burns into 3a and 3b for prognostic and therapeutic implications. There was no significant correlation between oropharyngeal and upper gastrointestinal tract injury. Early major complications and deaths were confined to patients with grade 3 burns. All patients with grade 0, 1, and 2a burns recovered without sequelae. The majority of patients (71.4%) with grade 2b injury and all survivors with grade 3 injury developed esophageal or gastric cicatrization, or both, which needed endoscopic or surgical treatment. There were no complications related to endoscopy. We conclude that early endoscopy is not only a safe, reliable, and accurate diagnostic tool in such patients, but also is of crucial importance in management and prognosis."
-How does corneal hypesthesia affect the duration of proparacaine anesthetic eyedrops?,"The effect of corneal hypesthesia on the duration of proparacaine anesthetic eyedrops. The duration of action of proparacaine is known in the normal cornea but not in the hypesthetic cornea. To determine this, we examined both eyes in seven patients with documented unilateral corneal hypesthesia associated with inactive herpetic disease. Cochet-Bonnet measurements were made in both eyes before and at two- to five-minute intervals after the instillation of one drop of 0.5% proparacaine until baseline corneal sensitivity levels were again achieved. Mean recovery time was 34.86 minutes in eyes with normal corneal sensitivity, compared to 45.43 minutes in hypesthetic corneas. In all patients, the recovery time was remarkably longer in the hypesthetic eye than it was in the normal fellow eye. These data demonstrate the need to wait up to one hour after the instillation of proparacaine in eyes suspected of having corneal hypesthesia if corneal sensitivity is to be determined accurately. Additionally, the duration of action of topically instilled anesthetic may be a useful method of discovering subtle differences in corneal sensitivity."
-What are the three hypotheses proposed to explain neurobehavioral impairments following cranial radiation therapy and intrathecal chemotherapy?,"Absence of synergistic effects of CNS treatments on neuropsychologic test performance among children. Three hypotheses are proposed to account for neurobehavioral impairments following treatment with cranial radiation therapy (CRT) and intrathecal (IT) chemotherapy: CNS treatments exert a synergistic effect (A x B), an additive effect (A + B), or a single-agent effect (A or B). Eighty-five long-term survivors of non-CNS cancers aged 6 to 16 years were classified into groups on the basis of CNS treatments: CRT-IT (n = 25), CRT-No IT (n = 11), No CRT-IT (n = 24), and No CRT-No IT (n = 25). Study I findings did not provide support for synergistic mechanisms; nonorthogonal analysis of variance showed interaction effects (CRT x IT) restricted to tactile-perceptual speed. However, main effects were significant for a single agent (CRT) across a wide range of measures. General intelligence, academic achievement, verbal knowledge and reasoning, and perceptual-motor abilities were found to be significantly lower among CRT-treated groups. Study II findings provided additional support for the role of CRT; Pearson correlations within the CRT-No IT group indicated significant negative associations between CRT dose estimates for cortical regions and perceptual-motor abilities."
-What percentage of lupus nephritis patients in the study were found to have renal vascular lesions (RVL)?,"Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the ""Gruppo Italiano per lo Studio della Nefrite Lupica"" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL."
-What is the significance of 99mTc-sestamibi in assessing myocardial area at risk during myocardial infarction?,"Perfusion imaging with 99mTc-sestamibi for the assessment of myocardial area at risk and the efficacy of acute treatment in myocardial infarction. There is a clear need to develop better measurement tools for assessment of the effect of acute therapy in myocardial infarction. Such tools must permit accurate measurement of the amount of myocardium that is initially at risk. 99mTc-sestamibi is a new radiopharmaceutical with unique properties that are well suited to the measurement of myocardium at risk without any delay in acute therapy. Tomographic imaging with this agent has been shown to provide accurate quantitative estimates of the myocardium at risk, which varies widely, even for patients with a similar coronary occlusion. For example, there is more than a threefold range in myocardium at risk for patients with a nonproximal occlusion of the left anterior descending coronary artery. The determination of the myocardium at risk before intervention and the change in this region after intervention constitute a promising measurement tool for the assessment of the effect of acute therapy. Initial studies with tomographic imaging have shown a significant improvement in a group of patients treated with thrombolysis, although the magnitude of improvement is highly variable in individual patients. Qualitatively similar results have been reported with planar imaging. Although it has a number of technical limitations, sequential imaging with 99mTc-sestamibi seems to have a clear advantage over those end points that have previously been used to assess acute therapy. This new measurement tool should facilitate future clinical trials of different treatments in acute myocardial infarction."
-What is the relationship between chronic pleural inflammatory disease and the development of soft tissue sarcoma in the pleural cavity?,"Soft tissue sarcoma of the pleural cavity. Seventeen cases of soft tissue sarcoma (STS) developing in the pleural cavity were collected from Japanese hospitals, and their clinical and pathologic findings summarized. Eight of the 17 patients had a 15-year to 50-year (mean, 28.8) history of chronic pleural inflammatory disease (pleuritis, pyothorax, and pulmonary tuberculosis) before the onset of the pleural sarcoma. Histologically, malignant fibrous histiocytoma was the most common tumor type (11 cases), followed by angiosarcoma (four). The age at diagnosis of the sarcoma ranged from 15 to 74 years (mean, 58); the male-to-female ratio was 3.3:1. In the eight cases of sarcoma associated with chronic pleural inflammatory disease, male preponderance was more marked (7:1). The commonest presenting symptom was chest pain. A mass could be detected by chest roentgenograms in 13 patients and computed tomographic scans in 15 patients. No patient had distant metastases at first admission. Thirteen patients were treated by surgery, chemotherapy, and/or radiation therapy. Thirteen of the 17 patients died 1 to 87 months (mean, 14.2) after therapy for STS. The actuarial 1-year survival rate was 38.5%. These findings suggest that long-standing pleural inflammation might be an etiologic factor for development of pleural STS."
-What changes in mucosal hemodynamics were observed in the canine model of gastric ulceration after ethanol injection?,"Endoscopic assessment of mucosal hemodynamic changes in a canine model of gastric ulcer. In studying the side effects of sclerosants injected into the gastric submucosa in dogs (N = 7), we noted that 3 ml of absolute ethanol induced a large gastric ulceration. We describe the time course of change in the ulcer size, and suggest that such ulceration can be used for the endoscopic assessment of factors important in ulcer genesis and healing. Endoscopic reflectance spectrophotometric measurement of indices of mucosal hemoglobin concentration (IHB) and oxygen saturation (ISO2) were performed in a separate group of dogs (N = 4) with ethanol-induced gastric ulceration. We found a significant difference (p less than 0.05) in IHB and ISO2 immediately before (97 +/- 8 and 37 +/- 3, respectively) and after (138 +/- 7 and 21 +/- 5, respectively) the ethanol injection. At 24 hours after the ethanol injection, the IHB at the lesion margin (141 +/- 14) was significantly higher (p less than 0.05) than that at the adjacent mucosa (101 +/- 4), whereas the ISO2 measurements were not significantly different in these two locations, 34 +/- 2 and 31 +/- 2, respectively. We conclude that (1) injection of 3 mol of absolute ethanol into the submucosa of the canine stomach provides an animal model of gastric ulceration in which the ulcer can be examined repeatedly with the aid of the endoscope; (2) in this ulcer model, ischemia with congestion (increases IHB, decreases ISO2) precedes the development of gross mucosal ulcerations; and (3) the margin of the established ulceration in this model exhibits hyperemia (increases IHB, normal ISO2) which mimics that of a healing gastric ulcer."
-What are the two main clinical presentations of orbital lesions with granulomatous inflammation observed in the study?,"Orbital lesions with granulomatous inflammation. Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis)."
-What was the primary purpose of the clinical trial involving felbamate for complex partial seizures?,"Felbamate: a clinical trial for complex partial seizures. We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experience were observed during the trial. FBM reduced CBZ level (p less than 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM."
-How do cytokines like interleukin-1 and tumor necrosis factor influence leukocyte-endothelial adhesion and contribute to inflammatory responses?,"Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. This paper reviews the evidence that cytokines induce a variety of functional and structural alterations in endothelium and that cytokine-endothelial interactions play important roles in the evolution of inflammatory and immune responses. The effect of cytokines, particularly interleukin-1 and tumor necrosis factor, on leukocyte-endothelial adhesion has led to the discovery of several endothelial adhesion molecules, and the molecular and biological characteristics of these are described. Finally, the review discusses the possible contribution of cytokine-induced activation to vascular injury in such pathological processes as septic shock, the Shwartzman reaction, delayed hypersensitivity, and immune-mediated vasculitis."
-What is central pontine myelinolysis and what causes it in burn patients?,Pontine myelinolysis after correction of hyponatremia during burn resuscitation. Central pontine myelinolysis is a neurologic disease produced by the rapid correction of hyponatremia. This report describes the occurrence of central pontine myelinolysis in a patient with burns. The natural history of this paralyzing condition and suggestions for its prevention are discussed. Severely burned and hyponatremic patients are at risk for this disorder because a large amount of sodium ion is typically required for the treatment of burn shock. Awareness of this phenomenon and avoidance of rapid correction of hyponatremia are essential to its prevention.
-What are the main endoscopic techniques used for palliation of tracheobronchial malignancies?,Endoscopic palliation of tracheobronchial malignancies. The prognosis for tracheobronchial tumours remains poor. Most patients can be offered only palliation. When the main symptom is breathlessness or refractory haemoptysis from a large airway tumour endoscopic treatment may be very effective. Over the last decade most attention has focused on the neodymium YAG laser. This often produces dramatic effects but has some important limitations. In the last few years better techniques for stenting and intrabronchial radiotherapy (brachytherapy) have also been developed. This article discusses the range of techniques now available and aims to help clinicians decide which patients may benefit from referral to centres providing these techniques.
-In how many primary brain lymphomas was Epstein-Barr virus (EBV) DNA detected?,"Detection of Epstein-Barr virus sequences in primary brain lymphoma without immunodeficiency. We searched for Epstein-Barr virus (EBV) sequences by enzymatic DNA amplification in nine primary brain lymphomas from patients without immunodeficiency. We used seven nonlymphoma brain tumors as negative controls, and the Raji cell line as a positive control. We detected EBV DNA, using ethidium bromide-stained-agarose minigel electrophoresis and dot blot hybridization, in the positive control and in only one brain lymphoma tumor; we did not detect EBV DNA in the other tumors. The EBV-positive patient had a second B-cell monoclonal population in the peripheral blood without detectable EBV DNA, suggesting a direct role for EBV in the development of the brain lymphoma."
-What factors are associated with increased delay in seeking treatment for acute myocardial infarction?,"Treatment-seeking behavior among those with signs and symptoms of acute myocardial infarction. Significant delays in seeking definitive treatment for the signs and symptoms of acute myocardial infarction increase morbidity and mortality. In most studies, delay times average more than 4 hours. The following variables are associated with increased delay: a medical history of angina, diabetes mellitus, or hypertension; older age; black race; seeking advice from a family member or a physician; symptom onset on a weekday; and attempts at self-treatment. Variables associated with reduced delay times are the following: pain recognized as cardiac in origin, hemodynamic instability, severe chest pain, younger age, and consultation with a coworker. Surprisingly, patients who have already experienced a myocardial infarction are just as likely to delay as patients who have not had this experience. These findings provide direction for developing and testing patient and family interventions, establishing community education programs, and reducing patient delay in response to the signs and symptoms of acute myocardial infarction."
-What are the characteristic features of nevoid basal cell carcinoma syndrome that pediatricians should be aware of?,"Cardiac tumors and the nevoid basal cell carcinoma syndrome. Nevoid basal cell carcinoma syndrome is a multisystem disease with a wide range of initial symptoms that can be seen at any age. The most characteristic features are vertebral or rib anomalies, intracranial falx calcification, multiple basal cell carcinomas, odontogenic keratocysts of the jaw, and palmar and/or plantar pits. Pediatricians need to be aware that if any one of these major anomalies is seen, this diagnosis should be considered. There now appears to be an established association between cardiac tumors and nevoid basal cell carcinoma syndrome. Primary cardiac tumors have been associated with cerebral tuberous sclerosis and neurofibromatosis, and evaluation of cardiac status is recommended when these genetically determined syndromes are diagnosed. This communication should serve to alert pediatricians to the need for complete cardiac evaluation and genetic counseling when a diagnosis of nevoid basal cell carcinoma is made."
-How rare is Hodgkin's disease involvement in the gastrointestinal tract according to the study?,"The surgical pathology of gastrointestinal Hodgkin's disease. The files of the National Cancer Institute were searched for all surgical specimens from the gastrointestinal (GI) tract with the diagnosis of Hodgkin's disease (HD) that were accessioned during the years 1953-1990; six patients with a histologically reconfirmed diagnosis were identified. Of these patients, four presented with GI HD and two had recurrent HD. Primary HD appeared in the stomach (three patients) and the duodenum (one patient); recurrent HD after diagnosis in a conventional nodal site appeared in the stomach (one patient) and the colon (one patient). One of the cases of primary gastric disease was a composite lymphoma consisting of HD and diffuse large cell lymphoma. In view of the rarity of GI tract involvement by HD, a diagnosis of primary GI HD should be viewed with skepticism; support for such a diagnosis may be provided by both classic histopathologic features of HD and immunostaining, but no single feature can be regarded as pathognomonic."
-What is the potential complication described in this medical case involving a saphenous vein graft and a native coronary artery?,Dislodgement of a vein graft thrombus by angiographic injection of native coronary artery. A case of retrograde dislodgement of thrombus in a saphenous vein graft during injection of the native right coronary artery is presented. Attention to this previously undescribed complication may allow for timely treatment with emergency surgery or thrombolysis.
-What is the recommended intervention for significantly increased plantar tissue pressure after a calcaneal fracture?,"Compartment syndrome of the foot after intraarticular calcaneal fracture. Seventeen patients with a total of 21 intraarticular calcaneal fractures were examined at up to 30 days after trauma for the development of tissue pressure in the central plantar muscle compartment. Twelve patients had a significant increase in tissue pressure with values greater than 30 mmHg because of primary fracture hematoma or interstitial fluid accumulation. This increase in pressure persisted for three to five days after trauma, so that ischemic damage to the short plantar foot muscles had to be suspected. Plantar muscle scarring and claw-toe formation were observed in seven patients with a total of 11 fractures during a mean observation period of 18 months. The plantar aponeurosis, which forms the constricting fascial envelope of the plantar muscles, is the anatomic structure responsible for the compartment syndrome that may develop after calcaneal fracture. Therefore, to avoid functional deficit, plantar compartmental pressures should be regularly measured after calcaneal fracture. Significantly increased plantar tissue pressure greater than 30 mmHg should be relieved by longitudinal incision of the plantar aponeurosis, preferably by a plantar incision as soon as the diagnosis is made."
-What percentage of patients with IgG antibody to hepatitis C virus also had IgM antibody to hepatitis C virus?,"IgM antibody to hepatitis C virus in acute and chronic hepatitis C. To assess possible role of testing for IgM-specific antibody in the diagnosis and monitoring of patients with hepatitis C, we tested sera from 14 patients with acute and 97 patients with chronic non-A, non-B hepatitis for IgG and IgM antibody to hepatitis C virus. IgG antibody to hepatitis C virus was detected in 93% of acute cases and 91% of chronic cases. Of the 101 patients with IgG antibody to hepatitis C virus, 57% had IgM antibody to hepatitis C virus. None of the 20 healthy subjects or 40 patients with acute or chronic hepatitis A or hepatitis B had IgM antibody to hepatitis C virus. At the onset of clinical symptoms in acute hepatitis C, IgG antibody to hepatitis C virus was detected in 8 (57%) and IgM antibody to hepatitis C virus in 9 of 14 patients (64%). Eventually, both IgG and IgM antibody to hepatitis C virus became detectable in 13 of 14 patients with acute hepatitis C. Seven patients with antibody to hepatitis C virus resolved the acute infection within 6 mo and all seven cleared IgM antibody to hepatitis C virus, whereas two cleared IgG antibody to hepatitis C virus. Six patients had a chronic outcome of the acute infection and IgM antibody to hepatitis C virus persisted in detectable amounts for more than 6 mo in all (mean = 15.5 mo). Among 88 patients with chronic non-A, non-B hepatitis with IgG antibody to hepatitis C virus, IgM antibody to hepatitis C virus was detected in 45 (51%)."
-What are the key challenges emergency physicians face when treating patients with headaches?,"Emergency treatment of headache. Headache is a frequent presenting complaint in the emergency department. Once a diagnosis is established, and significant organic disease can be ruled out, relief of pain must be addressed. Referral for follow-up care and narcotic habituation is a recurrent problem for the emergency physician. This article discusses the differential diagnosis of headache, evaluation of the emergency room patient, and treatment of the patient with headache."
-How effective was desipramine in treating pain for patients with diabetic neuropathy in this clinical trial?,"Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect."
-"What is the treatment approach for cystoid macular edema in Coats' disease, and what potential side effects should patients be aware of?","Cystoid macular edema secondary to juxtafoveolar telangiectasis in Coats' disease. A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema."
-What were the key findings of the study on hypertonic saline resuscitation in burn patients?,"Hypertonic saline resuscitation: efficacy in a community-based burn unit. Many have discussed hypertonic saline for resuscitation in burned patients only to discourage its use or to emphasize it only as a research tool and not as standard resuscitation. We reviewed the records of 47 adults with burns over 20% or more of the total body surface area (TBSA) in whom hypertonic saline was used as standard resuscitation fluid in a large community burn unit. The solution consisted of sodium, 300 mEq/L, acetate, 200 mEq/L, and chloride, 100 mEq/L, with an osmolality of 600 mOsm/L. The mean TBSA burned was 37% and the mean patient age was 44.8 years. Eighteen patients (mean age 39.7 years, mean TBSA burned 27%) received hypertonic saline alone. They required an average of 75% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value over the first 48 hours was 44.2% and the mean serum sodium level was 141.6 mEq/L. Twenty-nine patients (mean age 51.8 years, mean TBSA burned 47.8%) received hypertonic saline plus colloid (albumin or fresh frozen plasma). Colloid was used in older patients with more serious burns. This group required 57% of the Parkland calculated volume to achieve a urinary output of 1 mL/kg/hr. The mean hematocrit value was 45.1% and mean sodium level was 143.8 mEq/L. The mean weight gain for both groups was 7.3% of the admission weight. None of the patients had changes in pH or renal function. All patients survived the resuscitation phase of their injury; the overall death rate was 49%. We conclude that hypertonic saline is a safe, effective means of resuscitation even in a community-based unit. It allows less fluid to be delivered for adequate resuscitation. The usual hyponatremia, hemoconcentration, and significant weight gain associated with administration of isotonic solutions was avoided. Colloid may further improve the resuscitation capabilities of hypertonic saline."
-What were the key findings of the TIMI II-B Study regarding the timing of beta-blocker therapy in patients with acute myocardial infarction?,"Immediate versus deferred beta-blockade following thrombolytic therapy in patients with acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) II-B Study In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality."
-What was the effect of thoracic epidural analgesia on catecholamine levels during coronary artery bypass grafting in a patient with bilateral phaeochromocytoma?,"Thoracic epidural analgesia in a patient with bilateral phaeochromocytoma undergoing coronary artery bypass grafting. A patient suffering from phaeochromocytoma and coronary artery stenoses needed coronary artery bypass grafting before adrenalectomy. High thoracic epidural analgesia (T1-T2) with bupivacaine and sufentanil in combination with general anaesthesia was used. Plasma adrenaline and noradrenaline concentrations decreased during the period before bypass grafting compared to the baseline value and no important haemodynamic changes were seen during this period. Thoracic epidural analgesia failed to suppress the release of catecholamine during the bypass period. After the operation, the plasma catecholamine concentrations returned to the baseline value. Excellent analgesia (visual analogue scale = 1-2) was achieved with a postoperative epidural, but the plasma catecholamine concentration increased considerably."
-What was the prevalence of antibodies to hepatitis C virus among patients with chronic hepatitis B virus infection in this study?,"The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus-associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection."
-How does amiodarone affect the mitochondrial beta-oxidation of fatty acids in mice?,"Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice. Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from [U-14C]palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of [14C]CO2 from [U-14C]palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of [U-14C]palmitic acid. One hour after 100 mg.kg-1, the exhalation of [14C]CO2 from [1-14C]palmitic acid, [1-14C]octanoic acid or [1-14C]butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of [14C]CO2 from [1-14C]palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice."
-How does DNA ploidy status and proliferative fraction correlate with the clinical behavior of atrial myxomas?,"DNA analysis of atrial myxomas. The atrial myxoma is a primary tumor of the heart which may have an uncertain clinical course. In this study, we performed flow cytometric DNA analysis of 15 paraffin-embedded atrial myxomas and correlated DNA ploidy status and proliferative fraction with clinical findings. Twelve of 15 cases (80 percent) were diploid and the remaining three cases (20 percent) were aneuploid. Two patients with aneuploid histograms were free of tumor at the time follow-up; the third patient experienced local tumor recurrence and metastases. Five patients with diploid myxomas demonstrated an elevated (greater than or equal to 17 percent) proliferative cell cycle fraction; four of these patients experienced embolic phenomenon or tumor recurrence. This pilot study suggests that an atrial myxoma with either aneuploid DNA content or elevated proliferative fraction may be associated with aggressive biologic behavior."
-What psychological effects were observed in women undergoing different stages of breast screening?,"Assessment of the psychological impact of a breast screening programme. In order to assess the psychological effect of mammographic screening, questionnaires (which included psychometric tests) were sent to 750 women at invitation and, 6 weeks after screening, to 420 women normal after the first mammograph, to 240 women normal after special assessment, and to 68 women normal after open biopsy. Increasing degree of the investigation was associated both with increasing frequency of breast self examination (10% were practising breast self-examination at least once a week before screening compared with 24% for women after special assessment and 35% of women who had had an open biopsy (p less than 0.001)), and with greater confidence that any malignancy in the breast would have been found. Psychometric scores showed no increase of general levels of anxiety or depression in the screened groups. For anxiety, percentages abnormal were 5, 4, 2 and 6 for the four groups, respectively, and for depression the percentages abnormal were 5, 4, 4 and 6, respectively; 10% of screened women were more anxious about having breast cancer as a result of the screening. At least 10% of women proceeding to open biopsy of benign lesions require professional counselling and support. Psychological ill effects were not detected by the psychometric test among women who did not proceed to this final investigation. Behavioural changes did suggest a raised awareness or fear of potential cancer among the screened population."
-What percentage of infants with neonatal seizures experienced an unfavorable neurologic outcome in this study?,"Neurologic outcome after electroencephalographically proven neonatal seizures. Infants in whom neonatal seizures were confirmed by randomly recorded ictal electroencephalographic (EEG) tracings were retrospectively examined to determine their global neurologic outcome and the specific frequency of epilepsy, development delay, and cerebral palsy. Perinatal and postnatal clinical and EEG variables were also examined for their relevance to the neurologic outcome. Forty infants with EEG documented seizures of diverse etiologies were studied. The 27 survivors were followed up at a mean of 31 months. The outcome was unfavorable in 70%. The rate of epilepsy was 56%, of developmental delay 67%, and of cerebral palsy 63%. The etiology of seizures was an important factor influencing the outcome. Other clinical factors that showed a significant relationship with global or specific aspects of the neurologic outcome included the age at the onset of seizures, birth weight, and neurologic examination results. The EEG parameters that significantly predicted the neurologic outcome were interictal EEG background, increased seizure frequency, and decreased seizure duration."
-What are the primary acute triggers for sudden cardiac death?,"Sudden cardiac death: management of high-risk patients Sudden cardiac death remains a leading cause of death in the United States, accounting for more than 350,000 deaths each year, and the survival rate of victims remains low. Most survivors face a significant risk for recurrence. The typical substrate is chronic--abnormal myocardium with fibrosis (often from previous myocardial infarction) and left ventricular dysfunction. Acute triggers for sudden cardiac death are primarily electrical, ischemic, metabolic, neurohormonal, and pharmacologic. In most electrocardiographically documented cases of sudden cardiac death, the trigger-substrate interaction appears to result in ventricular tachycardia and fibrillation. After initial resuscitation, survivors need a thorough cardiovascular evaluation, including definition of coronary anatomy, left ventricular function, and wall-motion abnormalities, as well as an electrophysiologic evaluation. An attempt must be made to determine what each survivor's correctable triggers are. Management should address all reversible triggers, such as acute ischemia and electrolyte abnormalities, and should include modifying or correcting the arrhythmogenic substrate. Empiric antiarrhythmic therapy offers no advantage in such modification. Pharmacologic therapy with antiarrhythmic drugs should be guided by an objective therapeutic endpoint, which is best accomplished through the use of programmed ventricular stimulation and serial electrophysiologic studies. Other therapeutic options include surgical suppression of ventricular tachycardia and implantation of a cardioverter defibrillator."
-What is the relationship between serum aminoterminal propeptide of type III procollagen levels and liver fibrosis in psoriasis patients?,"Serum aminoterminal propeptide of type III procollagen in psoriasis and psoriatic arthritis: relation to liver fibrosis and arthritis. Levels of serum aminoterminal propeptide of type III procollagen were measured in 170 patients with psoriasis (49% with coexistent psoriatic arthritis) who had liver biopsies performed during or before treatment with methotrexate or, in some cases, with retinoids. Psoriasis patients with fibrosis or cirrhosis in their liver biopsy specimens had a significantly higher mean serum aminoterminal propeptide of type III procollagen than did patients without fibrosis and without arthritis. Only 4% of patients without cirrhosis or fibrosis and no arthritis had an elevated serum aminoterminal propeptide of type III procollagen. In contrast, 38% of patients with psoriatic arthritis had an increased aminoterminal propeptide of type III procollagen in the absence of detectable liver fibrosis. It is concluded that the number of liver biopsies performed on methotrexate-treated psoriasis patients with or without arthritis may be reduced to a minimum as long as serum aminoterminal propeptide of type III procollagen is normal. Increased serum aminoterminal propeptide of type III procollagen in the absence of arthritis is a strong indicator of liver fibrogenesis and suggests the need for liver biopsy to monitor possible methotrexate-induced toxicity. In patients with psoriatic arthritis an increased aminoterminal propeptide of type III procollagen may be related to the joint disease. Patients with psoriatic arthritis and increased levels of aminoterminal propeptide of type III procollagen should therefore follow the established guidelines for the use of methotrexate in psoriasis."
-How did melatonin affect sleep onset and wake times in subjects with delayed sleep phase syndrome?,"Delayed sleep phase syndrome response to melatonin. The actions of melatonin on the sleep-wake cycle were investigated by means of a randomised, double-blind, placebo-controlled trial in 8 subjects with a delayed sleep phase syndrome attending a sleep disorders clinic. In randomised order the subjects received placebo or melatonin 5 mg daily for 4 weeks with a 1 week washout period between the treatments. Drug or placebo was given at 2200 h, 5 h before the mean time of sleep onset determined by pretrial sleep logs. In all 8 subjects sleep onset time (mean advance 82 [range 19-124] min; p less than 0.01) and wake time (117 [10-187] min; p less than 0.01) were significantly earlier during melatonin treatment than during placebo. Mean total sleep time was slightly less on melatonin (8 h 12 min) than on placebo (8 h 46 min). Alertness acrophase calculated from the subjects' ratings of alertness made every 2 h while awake was unaltered. Melatonin may act as a phase-setter for sleep-wake cycles in subjects with a delayed sleep phase syndrome."
-What were the two leading causes of overseas fatalities among US citizen travelers according to the study?,"Overseas fatalities of United States citizen travelers: an analysis of deaths related to international travel. STUDY OBJECTIVE: Studies of travel-related mortality and morbidity have been limited to nonfatal events. Causes of travel-related mortality may differ significantly from morbidity and thus have different prevention strategies. DESIGN: We examined the overseas fatalities of US citizen travelers for the years 1975 and 1984. The death certificates were abstracted; all deaths under age 60 and a 20% sample of deaths 60 and older were examined. SETTING AND TYPE OF PARTICIPANTS: All overseas travel fatalities of US citizens were examined excluding those occurring in Canada. INTERVENTIONS: None. RESULTS: Cardiovascular events (including myocardial infarctions and cerebrovascular accidents) and injuries accounted for 49% and 25% of the overseas deaths of US citizen travelers, respectively. Infectious diseases other than pneumonia accounted for only 1% of the deaths. Eighty percent of injury deaths occurred outside of hospitals. Injury death rates for male travelers were greater than US age-specific death rates. CONCLUSIONS: Greater emphasis on the prevention of fatal events, especially those resulting from injury, must be given by physicians and other individuals and organizations who advise travelers. Further studies are needed to explore the issues of preventable injury deaths, emergency medical services, and overseas travel."
-How did isradipine affect blood pressure control in patients with mild essential hypertension during a 24-hour period?,"Twenty-four-hour blood pressure control with isradipine in mild essential hypertension. The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine."
-What potential risks did the study find when using EMLA cream on wounds?,"Damage to tissue defenses by EMLA cream. EMLA is a new topical agent that safely anesthetizes intact skin. The purpose of this study was to determine if this cream could be safely used for anesthetizing wounds. This investigation evaluated the potential toxicity of EMLA cream in wounds by measuring its effect on host defenses and on the biology of wound repair. In contaminated wounds, EMLA cream elicited an exaggerated inflammatory response that damaged host defenses, inviting the development of infection. As a result of these investigations, we do not recommend the use of EMLA cream in wounds."
-What is a carotid cavernous fistula and how can it develop after minimal facial trauma?,"Carotid cavernous fistula after minimal facial trauma. Report of a case. The carotid cavernous fistula has historically been associated with extensive facial trauma as a result of direct or indirect forces. Most fistulas of traumatic origin develop as a result of a fracture through the base of the skull, which produces a force causing laceration of the internal carotid artery in the region where it approximates the cavernous sinus. We report a case in which apparently minimal head trauma resulted in the development of a carotid cavernous fistula. The rather innocuous presentation of this complication requires particular attention by the caregiver in assessing the patient sustaining maxillofacial trauma."
-What were the mortality rates for ischaemic heart disease and cerebrovascular disease among different ethnic groups in England and Wales during the 1970s and 1980s?,"Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade."
-What were the three protocols used to determine the effect of exercise supplementation on dipyridamole thallium image quality?,"Effect of exercise supplementation on dipyridamole thallium-201 image quality To determine the effect of different types of exercise supplementation on dipyridamole thallium image quality, 78 patients were prospectively randomized to one of three protocols: dipyridamole infusion alone, dipyridamole supplemented with isometric handgrip, and dipyridamole with low-level treadmill exercise. Heart-to-lung, heart-to-liver, and heart-to-adjacent infradiaphragmatic activity ratios were generated from anterior images acquired immediately following the test. Additionally, heart-to-total infradiaphragmatic activity was graded semiquantitatively. Results showed a significantly higher ratio of heart to subdiaphragmatic activity in the treadmill group as compared with dipyridamole alone (p less than 0.001) and dipyridamole supplemented with isometric handgrip exercise (p less than 0.001). No significant difference was observed between patients receiving the dipyridamole infusion, and dipyridamole supplemented with isometric handgrip exercise. We conclude that low-level treadmill exercise supplementation of dipyridamole infusion is an effective means of improving image quality. Supplementation with isometric handgrip does not improve image quality over dipyridamole alone."
-What is the connection between the patient's Creutzfeldt-Jakob disease and the cadaveric dural graft?,Creutzfeldt-Jakob disease in a patient with a cadaveric dural graft. We report a 26-year-old woman with Creutzfeldt-Jakob disease (CJD) who had received cadaveric dural material 33 months before the onset of neurologic symptoms. This is the fourth case in which a dural graft was the putative source of the CJD agent. All four cases had the grafting before changes in the sterilization procedure adopted in 1987 to inactivate the CJD agent.
-What was the main purpose of the retrospective study involving 498 women with 666 breast lesions?,"Mammographic follow-up of nonpalpable low-suspicion breast abnormalities: one versus two views. A retrospective study involving 498 women with a total of 666 breast lesions was undertaken to determine the relative efficacy of one- and two-view mammography in the follow-up evaluation of ""low-suspicion"" abnormal mammographic findings. These abnormalities consisted of well-defined masses (47.1%), well-defined punctate microcalcifications (20.9%), and parenchymal asymmetry (32.0%). Confidence in the adequacy of the single-view follow-up was high in 91% of cases. The addition of the second mammographic view changed the one-view interpretation in approximately 1% of all cases. Two cancers were detected during the initial follow-up period. Both cancers were detected with single-view and standard two-view follow-up examinations, with high confidence. In this controlled retrospective study, the single-view follow-up examination was adequate for follow-up of most low-suspicion mammographic abnormalities. Monitoring by physicians, however, would be necessary to prevent an unacceptable number of patient recalls, which could make the one-view follow-up study impractical to use in some practices."
-"What is the ""two week syndrome"" observed in patients receiving injection treatment for chronic pain?","The ""two week syndrome"" associated with injection treatment for chronic pain--fact or fiction? Many patients attending the pain clinic for regular injections of local anaesthetic state that the pain returned ""two weeks"" ago. This study demonstrates that 85% of these patients have a ""return of pain"" interval which coincides with the proximity of their next clinic appointment."
-What imaging techniques were used to diagnose choledochal cyst and biliary atresia in the neonates?,"Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management."
-How did the cardiac myocytes change in size and shape in rats with aortocaval fistulas at 1 week and 1 month after surgery?,"Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 1. Developing and established hypertrophy. The effects of a large arteriovenous fistula on left and right ventricular hemodynamics and cardiac myocyte size were examined in adult rats at 1 week and 1 month after surgery. Cardiac output, left ventricular function, and right ventricular function were evaluated before obtaining isolated myocytes for cell size measurements. Average heart weight increased 35% at 1 week and 86% at 1 month in rats with fistulas. In general, myocyte hypertrophy was due to a proportional increase in length and width (length/width ratio remained constant). This change was more evident in the large hearts from rats with 1-month fistulas. At both the 1-week and 1-month intervals, the hypertrophic response of right ventricular myocytes was slightly greater than that observed in the left ventricle or interventricular septum. Left ventricular systolic pressure and dP/dtmax were significantly reduced at 1 week but returned to normal after 1 month of overloading. Left ventricular end-diastolic pressure was increased approximately fivefold and twofold at 1 week and 1 month, respectively. Right ventricular systolic pressure and dP/dtmax were increased at both intervals examined. We conclude that severe volume overloading from a large aortocaval fistula in the rat is characterized by 1) depressed left ventricular function at 1 week followed by a large compensatory hypertrophy and near normal function at 1 month, 2) right ventricular pressure overload, and 3) changes in myocyte shape that resemble normal physiological growth."
-What is EXOSURF and how was it used in the clinical trials for treating hyaline membrane disease in neonates?,"Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease. EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial."
-What was the survival rate of patients who received defibrillation during the Heartstart Scotland initiative?,"""Heartstart Scotland""--initial experience of a national scheme for out of hospital defibrillation. OBJECTIVE--To determine the outcome of out of hospital defibrillation in Scotland during the year after the introduction of automated external defibrillators in October 1988. DESIGN--Retrospective analysis of ambulance service reports and hospital records. SETTING--Scottish Ambulance Service and acute receiving hospitals throughout Scotland. MAIN OUTCOME MEASURES--Delay from cardiac arrest to first defibrillator shock; vital state on arrival at hospital accident and emergency department; survival to hospital discharge. RESULTS--During the study period 268 defibrillators were purchased by public subscription and 96% of the 2000 ambulance crew underwent an eight hour training programme in cardiopulmonary resuscitation and defibrillation. A total of 1111 cardiac arrests were recorded, and defibrillation was indicated and undertaken in 602 (54%) patients, mean age 63 (range 14-92) years. A spontaneous pulse was present on arrival at hospital in 180 (30%) of the defibrillated patients, and 75 (12.5%) were subsequently discharged alive. As expected, the likelihood of survival was inversely related to the delay from the onset of cardiac arrest to the time of the first shock and was greater in the case of witnessed arrest. If ventricular fibrillation occurred after the arrival of the ambulance, survival to discharge was 33%. CONCLUSIONS--An effective scheme for out of hospital defibrillation can be introduced rapidly, and with limited training implications and costs, by the use of automated external defibrillators in ambulances."
-"What is the relationship between interleukin-2, interferon-alpha, and colonic ischemia in cancer patients?","Colonic ischemia complicating immunotherapy with interleukin-2 and interferon-alpha. Colonic ischemia (CI) is a rare complication of high-dose interleukin-2 (IL-2) immunotherapy. This complication occurred in three of 141 patients (2.1%) with metastatic cancer treated with high-dose IL-2 therapy; CI only developed in patients receiving interferon-alpha (IFN) with IL-2 (three of 21, 14%) compared with none of 120 in those patients receiving IL-2 alone (P equals 0.0009). Severe diarrhea (greater than or equal to 7 bowel movements/day) also was significantly more common in patients receiving IFN with IL-2 (six of 21, 29%) than in those receiving IL-2 alone (three of 120, 2.5%, P equals 0.001) and preceded the clinical diagnosis of CI in all three patients. Three of nine patients with severe diarrhea had CI. Hematochezia occurred in four patients, all of whom received IFN with IL-2; three had CI, and the other patient had nonspecific colitis. Differences in vasopressor use did not explain the increased risk of CI in patients receiving IFN; those receiving IFN with IL-2 required phenylephrine less often than patients receiving IL-2 alone (P equals 0.01). The administration of lymphokine-activated killer (LAK) cells had no significant effect on the incidence of CI, severe diarrhea, peritonitis, or vasopressor use; two of three patients with CI, however, had their ischemic episode within 24 hours after the last of three LAK cell infusions. In conclusion, CI is an unusual complication of high-dose IL-2 and IFN immunotherapy. In patients receiving such combination therapy, severe diarrhea is a risk factor for the subsequent occurrence of CI."
-What was the median patient survival time for patients with pancreatic cancer in this study?,"Carcinoma of the pancreas: a personal experience with 100 cases. One hundred patients with pancreatic cancer were evaluated between March 1981 and December 1989. This study showed that 61 were not candidates for definitive surgery because of nonoperability (28 patients) or nonresectability (33 patients). An additional 25 patients had cancers that were unresectable because of metastases (13 patients) or local spread of disease (12 patients) discovered at laparotomy. Fourteen patients had resectable cancers. Ten were treated by total pancreatectomy, three by distal pancreatectomy and one by pancreatoduodenectomy (Whipple). There were two operative mortalities. The median patient survival time was 20.5 months. Two patients survived 5 years. Five patients are alive at 3, 14, 18, and 47 months. Palliative surgical procedures performed in 18 patients included 10 biliary bypasses, 9 gastrojejunostomies, and 6 T-tube placements. This was associated with an operative mortality rate of 11%. The median survival time was 5 months. Other palliative measures included endoscopic placement of biliary and pancreatic stents (47 patients, 2.7% mortality rate), endoluminal radiation therapy, interstitial radiation therapy and external beam radiation therapy. The median survival time of patients so treated was 4.5 months."
-What treatment approach was used to successfully manage Candida endocarditis in the three critically ill infants described in the study?,"Successful medical treatment of presumed Candida endocarditis in critically ill infants. Few infants have been reported who survived fungal endocarditis; all have required both surgical and intensive antifungal therapy. We describe three infants, two weighing less than 1000 gm, who survived Candida endocarditis without surgery. Two had Candida parapsilosis, an agent not previously reported as a cause of neonatal endocarditis. All three infants were treated with amphotericin B and 5-flucytosine. Despite administration of 44, 38, and 48 mg/kg amphotericin B, respectively, no nephrotoxicity was noted; 5-flucytosine therapy was stopped in one infant because of thrombocytopenia. One infant died of an unrelated cause 6 months later; there was no evidence of Candida or endocarditis at autopsy. The other two infants are thriving 2 and 3 years after the completion of antifungal therapy; no remaining evidence of endocarditis is present on echocardiography. We conclude that antifungal therapy without surgery is an option for Candida endocarditis in critically ill infants."
-What clinical factors were independently associated with a positive response to esophageal balloon distension?,"Clinical correlates of abnormal sensitivity to intraesophageal balloon distension. Sixty-five patients with esophageal complaints were studied to determine clinical associations with abnormal sensitivity to intraesophageal balloon distension (esophageal sensory dysfunction). Associations were examined in four categories: motility, esophageal symptoms, recent psychological symptoms, and general clinical features. A positive response to balloon distension (pain with less than or equal to 8 ml volume) was found in 29 (45%) of the subjects. This response was associated with specific findings in each category except recent psychological symptoms. A multiple logistic regression analysis indicated that an increased frequency of multipeaked waves on motility testing, presence of dysphagia, and shorter height of the subject each had an independent association with positive response to balloon distension (P less than or equal to 0.05 for each). Further comparison of subjects with sensory dysfunction, motor dysfunction, or both (sensorimotor dysfunction) indicated that subjects with the combined disorder appeared more symptomatic than those with either finding alone. These observations indicate that: (1) esophageal motor and sensory dysfunction are partially associated, but both contribute to the symptomatic state; (2) dysphagia may be representative of sensory dysfunction in some cases; and (3) subject height should be taken into consideration when interpreting balloon distension results."
-How do smoking and oral contraceptive pills potentially contribute to the exacerbation of Crohn's disease?,"Smoking, the oral contraceptive pill, and Crohn's disease. Both cigarette smoking and the oral contraceptive pill have been implicated as aggravating factors in Crohn's disease. Based upon the recent demonstration of multifocal gastrointestinal infarction in Crohn's disease, a possible pathogenic mechanism for this condition, we propose how smoking and the oral contraceptive pill may potentiate a tendency for focal thrombosis and hence exacerbate the activity of Crohn's disease."
-What was the treatment approach and outcome for HIV-associated Kaposi's sarcoma patients using recombinant interferon alpha-2a?,"Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon alpha-2a. Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy."
-How can dual-energy CT help differentiate focal fatty infiltration of the liver from low-density masses?,"Value of dual-energy CT in differentiating focal fatty infiltration of the liver from low-density masses. Focal (irregular, partial) fatty infiltration of the liver may simulate neoplastic or other hypodense masses on CT. On the basis of previous observations of the phenomenon that differences in X-ray attenuation diminish with increasing energy of X-rays used, we performed a preliminary study to determine if dual-energy CT could be used to discriminate between fatty infiltration and hypodense liver masses. Dual-energy CT at 140 and 80 kVp was performed in 14 patients undergoing liver biopsy and in seven control subjects with presumedly normal liver. Attenuation measurements were taken, and the changes in attenuation between 140 and 80 kVp were calculated. The mean changes in attenuation were 3.5 H for normal liver (n = 7), 2.5 H for hypodense liver masses (n = 6), 13 H for fatty liver (n = 5), 0.3 H for fatty liver combined with hemochromatosis or hemosiderosis (n = 3), and 2 H for the spleen (n = 18). The change in attenuation increased as the fat content in the liver increased. Analysis of variance showed a statistically significant difference (p less than .001) between fatty liver and the other groups. A difference greater than 10 H was unique to fatty infiltration. These results suggest that dual-energy CT may help to differentiate focal fatty infiltration of the liver from low-density neoplastic or other lesions, but only if the iron content of the liver is not increased."
-What specific autoantibodies have been implicated in the pathogenesis of dilated cardiomyopathy (DCM)?,"Abnormal expression of histocompatibility and mitochondrial antigens by cardiac tissue from patients with myocarditis and dilated cardiomyopathy. Autoantibodies against the adenine nucleotide translocator (ANT), the branched chain alpha-ketoacid dehydrogenase (BCKD) complex proteins, and myosin have been implicated in the pathogenesis of human dilated cardiomyopathy (DCM). Cardiac tissue from patients with DCM and, for control purposes, cardiac tissue from patients with other forms of cardiomyopathy and from patients with no history of cardiac disease were stained with heterologous and ANT-, BCKD-, and myosin-specific affinity-purified sera from DCM patients. Data demonstrate that although anti-myosin stains tissues from both patients and normal controls, the ANT- and BCKD-specific heterologous and affinity-purified sera from DCM patients stain only cardiac tissues from DCM patients. Intense staining in patchy areas of cardiac tissue suggests that abnormal increased expression of these putative autoantigens occurs in discrete areas of cardiac myocytes. The reactivity of the antisera was organ specific and only seen in tissues from DCM patients. The organ and disease specificity of these findings suggests that such expression may play an important role in the pathogenesis of human DCM."
-What was the purpose of the randomized study involving nifedipine and nitroglycerin in patients undergoing coronary artery bypass grafting?,"Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS]."
-How does isradipine potentially protect the brain from damage in stroke models?,"Prevention of stroke and brain damage with calcium antagonists in animals. In a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery [MCAO]), various 1,4-dihydropyridine calcium antagonists have been shown to attenuate brain damage and the resultant functional impairment when administered after MCAO. Dose-response curves reveal that isradipine is one of the most potent and efficacious representatives of this class of compounds, reducing the infarct size by more than 60%. These results suggest that isradipine, when administered shortly after stroke onset, may have beneficial effects in patients suffering from brain ischemia. When isradipine is used to normalize the high blood pressure in spontaneously hypertensive rats, it will, in addition, also protect the brain from damage engendered by a subsequent stroke. This is not the case if blood pressure is controlled with a calcium antagonist which does not cross the blood-brain barrier, suggesting that the brain protection seen with isradipine is not due to blood pressure normalization. Isradipine, when used as an antihypertensive, appears to have an additional beneficial effect within the brain itself. As high blood pressure is a major risk factor for stroke, such an additional benefit with isradipine would be particularly valuable in antihypertensive therapy."
-What was the relationship between inflammatory cells and metaplasia in asbestos workers?,"The relationship between large airway inflammation and airway metaplasia. To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers."
-What is the main finding of the study regarding the management of gallbladder in elderly patients after endoscopic sphincterotomy for bile duct stones?,"Risks of leaving the gallbladder in situ after endoscopic sphincterotomy for bile duct stones. There is controversy concerning the subsequent clinical course of patients whose gallbladder is left in situ following successful endoscopic removal of stones from their common bile ducts. A total of 191 patients (median age 76 years) were reviewed between 12 and 100 months (mean 38 months) after endoscopic sphincterotomy. Ten patients (5.2 per cent) had symptoms requiring cholecystectomy which was uneventful, nine in the first year. Cholangitis at presentation or failure to fill the gallbladder by endoscopic retrograde cholangiography were not helpful in identifying these patients. Forty-nine (25.6 per cent) patients died during the review period from non-biliary pathology (usually cardiovascular). Elective cholecystectomy is not required in elderly patients with symptomatic bile duct stones if the common bile duct can be cleared of stones after endoscopic sphincterotomy."
-What factors were found to be significantly associated with progression-free interval in the multi-variate analysis of cervical carcinoma patients treated with radiation therapy?,"Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Between 1977 and 1985, the Gynecologic Oncology Group (GOG) conducted three clinical trials in locally advanced carcinoma of the cervix, clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics (FIGO). All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para-aortic (PA) lymph nodes. Patients received standardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications. To date, no statistically significant differences in progression-free interval (PFI) or survival time have been identified between the randomization treatment arms on any of these studies. Basic similarities among these studies led us to pool these data to identify patient characteristics and tumor characteristics associated with an increased risk of treatment failure. Multi-variate analysis showed patient age, performance status (PS), PA lymph node status, tumor size, and pelvic node status to be significantly associated with PFI. When modeling for survival, all these factors and clinical stage and bilateral extension were significant."
-What diagnostic techniques were used to identify and confirm the intrahepatic arterioportal fistula in this patient?,"Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed."
-What is the significance of the changing appearance of the cephalocele during transvaginal sonographic follow-up between 13-19 weeks of gestation?,"Transvaginal sonographic follow-up on the formation of fetal cephalocele at 13-19 weeks' gestation. An occipital meningocele was detected by transvaginal sonography in a fetus of 13 weeks' gestation. This changed at 14 weeks to a cephalocele, which disappeared at 15-16 weeks and was detected again at 19 weeks. It is possible that sliding backward and forward of the herniated brain tissue caused this sequence of events."
-How do anesthesiologists help prevent respiratory complications during and after surgery?,"Respiratory problems in emergence from anesthesia. In conclusion, anesthesia and mechanical ventilation have major effects on respiratory function, both intraoperatively and postoperatively. Recognition that mechanical ventilation represents a major departure from spontaneous ventilation should enable anesthesiologists to compensate for the increases in dead space ventilation and the propensity for alveolar collapse that accompany low volume mechanical ventilation. The use of postoperative regional analgesic techniques to alleviate respiratory compromise constitutes both current clinical practice and an area of active, ongoing investigation. Gone are the days when the anesthesiologist's responsibility stopped at the recovery room door. Today, anesthesiologists with expertise in postoperative pain management, cardiovascular physiology, and intensive ventilatory care are able to provide patients an improved likelihood of avoiding postoperative respiratory complications."
-How can red blood cell deformability index (DI) be used as an early indicator of infection in trauma patients?,"Red cell deformability is an early indicator of infection. Red blood cells (RBC) have been shown to become less deformable during infection. The RBC deformability index (DI) was measured within 24 hours of admission in 37 patients who had suffered trauma and every 48 to 72 hours thereafter while they were in the surgical intensive care unit to assess whether DI could be used as an early indicator of infection after injury. Infection was defined as a temperature of 101 degrees F or more and a white blood cell count of more than 12,000/cm3 associated with a positive culture. Eighteen patients developed an infection, and 19 patients did not. On day 1, both groups showed a significant decrease in DI, compared to controls (0.33 +/- 0.18 and 0.34 +/- 0.25 for patients with infection and patients with no infection vs 1.52 +/- 0.12 for control volunteers; p less than 0.05). In the group with no infection, the DI improved in 16 of 19 patients after injury; the DI in patients with infection continued to decrease in 17 of 18 patients. The decrease in DI occurred 4 +/- 2 days (range, 2 to 8 days) before the diagnosis of infection. No significant differences were apparent in the absolute white blood cell count between the group with infection and the group with no infection at any time after injury. Differences in maximal temperature were noted on day 3 and beyond; however, 30% of patients with no infection had a temperature of more than 101 degrees F for 7 days. These data show that trauma results in a significant decrease in RBC deformability and that serial changes in DI appeared to predict which patients would develop an infection and which patients would recover uneventfully. RBC deformability may be helpful in early detection of infection in patients who have suffered trauma."
-What was the main finding of the study regarding the sensitivity of the gastric mucosa in patients with nonulcer dyspepsia?,"Sensitivity of the gastric mucosa to acid and duodenal contents in patients with nonulcer dyspepsia. Nonulcer dyspepsia is a common clinical syndrome whose etiology is unknown. The sensitivity of the gastric mucosa to acid and duodenal contents in 18 patients with nonulcer dyspepsia was studied. The patients had a normal upper gastrointestinal endoscopy and biopsy specimens were obtained for determination of Helicobacter pylori status. Fifteen of the 18 patients were infected with H. pylori. All patients underwent intubation with double-lumen tube and collection of cholecystokinin-stimulated pancretico-biliary secretions. Subsequently, normal saline, 0.1N hydrochloric acid, and autologous duodenal secretions were infused into the stomach in a randomized blinded fashion. A positive response was defined as the production of epigastric pain by acid and/or bile but not by saline. By this definition, only 6 patients (33%) had a positive response and none had reproduction of their usual symptoms. In patients with a negative response, only 4 remained asymptomatic during all infusions. The remaining 8 had symptoms during infusion of saline, 7 of whom also had symptoms during infusion of acid and/or duodenal secretions. Two of these patients had reproduction of their usual symptoms. In conclusion, the gastric mucosa in patients with nonulcer dyspepsia is not abnormally sensitive to acid or duodenal contents."
-What was the mean maximum temperature during an infection in the nursing home residents studied?,"Fever response in elderly nursing home residents: are the older truly colder? OBJECTIVE: To test the hypothesis that many nursing home residents with an apparently blunted fever response (maximum temperature less than 101 degrees F) may actually have a significant change in temperature (delta T greater than or equal to 2.4 degrees F) which is not recognized because of a low baseline temperature. DESIGN: Retrospective chart review for cases of infection that met specific criteria and for chart-recorded baseline and infection temperatures. Chart-recorded baseline temperatures were prospectively compared with re-measurement of morning temperatures. SETTING: Nursing Home Care Unit of the VAMC West Los Angeles. PATIENTS: Random review of 40 residents' charts resulted in the detection of 69 infections among 26 residents over a 20-month period. Fifty randomly selected residents prospectively underwent comparison of chart-determined and actual re-measurement of baseline temperatures. RESULTS: In 50 randomly selected residents, the mean oral baseline temperature of 97.4 +/- 0.2 (degrees F +/- SEM) closely approximated the mean nurse-recorded measures in the charts (97.6 +/- 0.1). Chart review detected 69 infections among 26 residents, with 53 episodes having a temperature recorded during the infection. The mean maximum temperature (Tmax) during an infection was 101.3 +/- 0.3 (degrees F +/- SEM) but 47% (25/53) of the episodes had a ""blunted"" fever response (Tmax less than 101 degrees F). Of the 25 ""blunted"" fevers (Tmax less than 101 degrees F), about one-fourth demonstrated an adequate change in temperature from baseline (delta T greater than or equal to 2.4 degrees F) but failed to reach 101 degrees F because of a low baseline. Most infections (89%) had a Tmax greater than 99 degrees F. CONCLUSION: Establishing a nursing home patient's basal temperature and monitoring for changes in temperature (delta T greater than 2.4 degrees F) and/or lowering the threshold for recognition of fevers (to 99 degrees or 100 degrees F) in nursing home residents with a change in function should assist in early recognition of infections."
-What percentage of primary neurogenous tumors arise from peripheral nerves in the head and neck region?,"Primary tumors of the facial (extracranial) nerve. Nearly 25% of all primary neurogenous tumors arise from peripheral nerves in the head and neck. The extracranial parts of the facial nerve, however, rank low as potential sites. Their tumors nonetheless pose diagnostic and management problems. In the intraparotid location the neurogenous tumors most often present as mass lesions, accompanied, in one third of patients, by various degrees of facial weakness. With the exception of a peculiar predilection of childhood plexiform neurofibromas to afflict the facial nerve, the majority of the tumors are neurilemomas. Recurrences are unusual after surgical removal of either neurilemomas or neurofibromas. The rare facial nerve sarcoma is a high-grade malignancy."
-What diagnostic challenges are associated with mucinous pancreatic tumors according to the ERCP findings?,"Mucinous pancreatic tumors: ERCP findings Mucin-producing tumors of the pancreas are rare and difficult to diagnose neoplasms. To further characterize the nature of these lesions, four such cases are described here in which the diagnosis was suspected at endoscopic retrograde cholangiopancreatography by the presence of ampullary or intraductal mucus. In one patient, pancreatoscopy directly visualized the tumor. Ultrasound and computed tomography failed to suggest the presence of a neoplasm in the majority of these cases, but endoscopic ultrasound was performed in one and correctly identified the multi-cystic tumor. A high incidence of acute pancreatitis was seen in these cases and was felt to be secondary to intermittent ductal obstruction by mucus. The characteristic appearance of intra-ductal mucus provides an important clue to the presence of this type of pancreatic neoplasia."
-What was the main purpose of the study on hepatitis C virus antibodies in blood donors?,"Antibody to hepatitis C virus and liver disease in volunteer blood donors. OBJECTIVE: To evaluate the specificity of antibodies to hepatitis C virus (anti-HCV) and their relation to liver disease in blood donors. DESIGN: Case series of consecutive blood donors found positive for anti-HCV by enzyme-linked immunosorbent assay (ELISA). Patients were evaluated for antibody specificity using a recombinant immunoblotting assay (RIBA) and were evaluated for biochemical evidence of liver disease. Patients showing increased alanine aminotransferase (ALT) levels had a liver biopsy. SETTING: University hospital. PARTICIPANTS: Fifty consecutive blood donors found to be anti-HCV positive on both an initial and repeat ELISA. Inclusion criteria were as follows: an absence of hepatitis B surface antigens and non-organ-specific autoantibodies; a daily alcohol intake of less than 50 g; no history of recent hepatotoxic drug use; and normal serum levels of alpha 1 antitrypsin, ceruloplasmin, and copper. MAIN RESULTS: Anti-HCV positivity was confirmed by RIBA in only 13 of 50 donors (26%) who had positive ELISA results. These 13 donors had an elevated ALT level and histologic evidence of chronic hepatitis, which was active in 8 patients (62%) and had already produced cirrhosis in 2 patients (15%). In contrast, the 17 donors with an intermediate RIBA pattern had only mild and often nonspecific histologic liver abnormalities. The 20 patients with a negative RIBA result had normal ALT levels. CONCLUSION: In blood donors, the anti-HCV RIBA is not only more specific than the anti-HCV ELISA, but is also useful in identifying patients who have an underlying chronic liver disease."
-How does gadopentetate dimeglumine-enhanced magnetic resonance imaging improve the detection and staging of uterine carcinomas?,"Carcinoma of the uterus: use of gadopentetate dimeglumine in MR imaging. This prospective study assessed the role of gadopentetate dimeglumine-enhanced magnetic resonance imaging in the detection and staging of carcinomas of the endometrium and cervix. Surgical-pathologic findings were used as the standard of reference. In the evaluation of endometrial carcinoma, contrast-enhanced imaging improved tumor detection and differentiation between viable tumor and retained debris. Use of contrast material significantly improved the staging accuracy. The ability to assess the depth of myometrial invasion was also improved. In the evaluation of cervical carcinoma, assessment of tumor location and size did not improve following contrast enhancement. Use of gadopentetate dimeglumine resulted in overestimation of stromal, parametrial, vaginal, and/or bladder wall invasion in eight patients. However, evaluation of intratumoral architecture and large lesions was easier with contrast-enhanced imaging. When only stage II and higher disease was analyzed, use of contrast material improved the evaluation of disease extent. The authors conclude that gadolinium enhancement adds to the accuracy of evaluation of endometrial carcinoma but is useful in only advanced cases of cervical carcinoma."
-What rare combination of tumors is described in this case report?,Osteogenic sarcoma arising adjacent to a long-standing ameloblastoma. A case report. Ameloblastoma is an uncommon odontogenic tumor usually occurring in the mandible. Rarely do other primary tumors occur with or arise from ameloblastoma. We describe a patient with simultaneous osteogenic sarcoma of the maxilla and recurrent ameloblastoma.
-What is the relationship between radiation therapy and the development of monomelic amyotrophy in the described cases?,"Postradiation lower motor neuron syndrome presenting as monomelic amyotrophy. Monomelic amyotrophy developed 16 months, nine and 12 years after irradiation of the lumbosacral spinal cord for seminoma in one patient and for Hodgkin's disease in two others. In two patients, involvement was clinically limited to one leg, with a subacute course followed by plateau in the first case and with progressive worsening in the second one. In the third patient, the course was progressive with involvement of the other lower limb occurring five years later. From clinical and electrophysiological data, it seems probable that the disease process was a result of a selective injury to the lower motor neuron in the lower spinal cord."
-How can transesophageal echocardiography help in diagnosing and managing cardiac tamponade with a patent foramen ovale?,"Right-to-left shunt across a patent foramen ovale caused by cardiac tamponade: diagnosis by transesophageal echocardiography. Cardiac tamponade can manifest as profound hypoxemia from intracardiac shunting across a patent foramen ovale. As a consequence, pulmonary embolus can be erroneously diagnosed. As demonstrated in the case described herein, transesophageal echocardiography can be useful in determining the correct diagnosis, especially if transthoracic echocardiography is technically limited. In our patient, the findings on transesophageal echocardiography also helped determine the appropriate treatment. The relative inaccessibility of the pericardial effusion to needle drainage prompted open surgical drainage."
-What was the primary finding regarding EMG activity in patients with chronic tension-type headache compared to healthy volunteers?,"EMG activity in pericranial muscles during postural variation and mental activity in healthy volunteers and patients with chronic tension type headache. EMG activity was recorded over frontalis, temporalis and trapezius muscles in a supine position, a standing position and during a mental task in 32 female patients suffering from chronic tension-type headache and in 20 healthy volunteers. Measurements in patients were made before and after biofeedback therapy. All EMG levels were on average significantly higher in patients than in controls. 62.5% of patients had at least one abnormal EMG level, but only 34% were beyond the normal range, if 1 muscle and 1 recording condition was considered. EMG levels were not correlated with headache severity, anxiety or response to biofeedback treatment. It is therefore suggested that pericranial EMG activity is not pathogenetic in chronic tension type headache, but merely one of several pathophysiologic changes, that are produced by a central dysfunction."
-What is the relationship between HLA B27 and the incidence of hypopyon in anterior uveitis?,"Anterior uveitis and hypopyon. We undertook a study to determine the incidence of hypopyon, as well as the most common anterior uveitis entities with which hypopyon is associated. A total of 216 patients with anterior uveitis were studied. The uveitis was acute in 155. Of the 155 patients, 11 (7.1%) had hypopyon. Nine of the 11 patients with hypopyon were positive for HLA B27. Of these nine, two had Reiter's syndrome and one had ankylosing spondylitis; the other six had no confirmed systemic disease. Of the two patients with hypopyon who were HLA B27-negative, one had mixed connective-tissue vascular disease, and one had idiopathic anterior uveitis. Of the 155 patients with acute anterior uveitis, 62 were HLA B27-positive. Thus, the incidence of hypopyon uveitis among HLA B27-positive patients was 14.5% (nine of 62 patients), whereas the incidence among HLA B27-negative patients was only 2.2% (two of 93 patients). These results suggest that HLA B27-related anterior uveitis is the most common cause of hypopyon uveitis, and that most patients with anterior uveitis associated with hypopyon will test positive for HLA B27. Although these results reflect a referral population, they should be of benefit in the treatment of patients with anterior uveitis."
-What is the relationship between eosinophilic fasciitis and cutaneous T-cell lymphoma in this case study?,"Concurrent eosinophilic fasciitis and cutaneous T-cell lymphoma. Eosinophilic fasciitis as a paraneoplastic syndrome of T-cell malignant neoplasms? Eosinophilic fasciitis has been reported to precede hematologic malignant neoplasms such as myelomonocytic leukemia, lymphocytic leukemia, and Hodgkin's lymphoma. In this case study, eosinophilic fasciitis occurred concurrently with cutaneous T-cell lymphoma (mycosis fungoides). The clinical diagnosis of eosinophilic fasciitis was based on painful sclerodermatous lesions on the extremities and trunk without acrosclerosis. There was histologic confirmation with edema and lymphocytic inflammation in the superficial muscular fascia and dermis. Deposition of immune reactants was found in the fascia and dermis. In addition, peripheral eosinophilia and circulating immune complexes were detected. The diagnosis of cutaneous T-cell lymphoma (mycosis fungoides) was based on extensive erythematous cutaneous plaques, dermal and epidermal lymphocytic atypia, loss of pan-T-cell immunologic markers, and a cutaneous lesional T-cell receptor beta-chain rearrangement by Southern blot analysis. Eosinophilic fasciitis may occur as a paraneoplastic syndrome associated with hematologic malignant neoplasms, including mycosis fungoides. Cytokines or lymphokines released by activated immunocytes, either malignant leukocytes or normal leukocytes reacting to malignant cells, may be responsible for the eosinophilia and sclerosis seen in these associated hematologic malignant neoplasms."
-What was the rate of adhesion formation after ovarian electrocauterization in the selective and unselective groups of patients with polycystic ovarian syndrome?,"Adhesion formation after ovarian electrocauterization on patients with polycystic ovarian syndrome. The rate of adhesion formation after ovarian electrocauterization has been described in two selective and unselective groups of patients with PCOS. The rate of this complication in the selective group was 0 from 16 ovaries and in the unselective group (5/25). However, the rate of major adnexal adhesion in the unselective group was 1 from 25 ovaries."
-How did the diagnosis of Asperger's syndrome impact the understanding of the children's emotional needs and their relationships with their parents?,"Asperger's syndrome: who is being abused? Six case histories of children referred and admitted to a psychiatric inpatient unit at a tertiary referral centre because of concerns about poor functioning and possible emotional abuse are presented. On initial assessment the children appeared to be well functioning and the impression was confirmed that their emotional needs were not being met by their parents. After detailed inpatient appraisal the diagnosis of Asperger's syndrome was made in all six cases, exemplified mainly by a formal concrete way of thinking and an inability to identify and understand human emotions and relationships. The impact of the diagnosis on the parents and their consequent relationships with their child and their willingness to work with professionals is discussed."
-How does the proportion of large molecular form of HBeAg relate to the severity of liver damage in chronic hepatitis B?,"Large molecular form of serum HBeAg in chronic hepatitis B virus infection: relation to liver cell damage. We have separated circulating HBeAg into small and large molecular forms by agarose gel electrophoresis and analyzed the relationship between the two forms and other clinical features of chronic hepatitis B, especially in regard to liver cell damage. The large HBeAg accounted for 7.3% +/- 3.4% of serum HBeAg in 9 subjects with normal liver histological findings or nonspecific reactive hepatitis, 38.0% +/- 27.8% in 32 patients with chronic persistent hepatitis and 65.6% +/- 23.3% in 21 patients with chronic active hepatitis (p less than 0.01). A positive correlation was seen between the height of aminotransferase elevations and the percentage of large HBeAg. Three patients who progressed from histologically normal liver or nonspecific reactive hepatitis to chronic active hepatitis had dramatic increases in the percentage of large HBeAg. The finding that the presence of large HBeAg in serum correlated with the severity of hepatitis suggests that HBeAg may play an important role in determining the degree of liver injury in chronic hepatitis B."
-"What neurological condition did the 39-year-old AIDS patient develop, and what was the underlying cause of his myelopathy?","Ischaemic myelopathy secondary to disseminated intravascular coagulation in AIDS. A 39-year-old patient with AIDS presented with a rapidly progressive myelopathy with a partial Brown-Sequard syndrome. He died, 9 weeks after onset of the first neurological signs, from diffuse encephalopathy. Neuropathological examination revealed multiple, usually small, frequently haemorrhagic, infarcts or various ages and numerous fibrin thrombi in medium and small penetrating vessels and capillaries of the brain and spinal cord, characteristic of disseminated intravascular coagulation. There were no inflammatory changes. Immunohistochemical studies for human immunodeficiency virus, cytomegalovirus, varicella zoster virus, herpes simplex virus type 1 and type 2 were negative. Ischaemic spinal cord lesions due to disseminated intravascular coagulation may represent an unusual cause of focal, non-inflammatory, non-tumoral, myelopathic syndrome in AIDS."
-How do mink cell focus-forming (MCF) viruses affect the interleukin-2 (IL-2) dependence of a rat T-cell lymphoma line?,"Infection by mink cell focus-forming viruses confers interleukin 2 (IL-2) independence to an IL-2-dependent rat T-cell lymphoma line. The development of T-cell lymphomas in rodents infected with type C retroviruses has been linked to the generation of a class of envelope (env) recombinant viruses called mink cell focus-forming viruses (MCF viruses) in the preleukemic thymus. To determine whether infection by MCF viruses altered the growth phenotype of retrovirus-induced T-cell lymphomas, a Moloney murine leukemia virus-induced interleukin-2 (IL-2)-dependent rat T-cell lymphoma line (4437A) was infected with MCF-247, modified MCF-V33 (mMCF-V33), or NZB-xenotropic (NZB-X) virus. The effects of virus infection on the IL-2 dependence of these cells was examined by cultivating them in the absence of IL-2. After IL-2 withdrawal, the uninfected and NZB-X-infected cells went through a crisis period characterized by massive death. All the independently maintained cultures of MCF- and mMCF-V33-infected cells, on the other hand, became IL-2 independent without a crisis. All the polytropic virus-infected IL-2-independent cultures contained a population of cells that was polyclonal with regard to polytropic provirus integration. Over this polyclonal background each culture produced multiple clones of cells that were selected rapidly after IL-2 withdrawal. Furthermore, the resulting MCF- or mMCF-V33-infected IL-2-independent cells retained the expression of IL-2 receptor. These data show that MCF and mMCF-V33 viruses may alter the growth phenotype of a T-cell lymphoma line and suggest that their effect on cell growth may be due to the direct interaction of the MCF envelope glycoprotein with cellular components, perhaps the IL-2 receptor."
-What are the key characteristics of pulmonary angiitis and granulomatosis syndromes in terms of clinical presentation and radiologic features?,"Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions."
-What is Acanthoma fissuratum and what is its primary cause according to the given context?,Acanthoma fissuratum. Acanthoma fissuratum secondary to the use of spectacles is a rare clinical finding associated with an ill-fitting frame. An interesting case is presented to highlight such a problem. Surgical excision of such lesions is recommended with advice to the patient regarding the suitable fitting of spectacles.
-What percentage of patients in the study had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex?,"Electrophysiologic and anatomic characteristics of ventricular tachycardia induced at the right ventricular outflow tract but not at the apex. The site of ventricular stimulation is an important variable in the initiation of ventricular tachycardia (VT) by programmed ventricular stimulation. Among 169 patients studied consecutively, 17 (10%) had ventricular tachycardia induced by programmed electrical stimulation from the right ventricular outflow tract but not from the apex. Fourteen of these 17 patients had had prior myocardial infarction (12 had inferior, and two had both inferior and anterior myocardial infarction), two had a dilated cardiomyopathy, and one had a localized cardiomyopathy. Fourteen patients had echocardiograms suitable for analysis. Of these, 12 had posterior/inferior ventricular wall motion abnormalities located at the base of the heart. The ventricular effective refractory periods from the right ventricular outflow tract and right ventricular apex were 237 +/- 4 and 244 +/- 5 msec, respectively (p less than 0.05, mean +/- SEM). Induced VT had a cycle length of 229 +/- 4 msec and had the morphology of right bundle branch block in 12 patients, of left bundle branch block in three patients, and had both morphologies in two patients. In 14 patients the axis was superior. VT was initiated with two extrastimuli in 15 patients and with burst right ventricular pacing in two patients. Similar pacing techniques with identical pacing intervals did not induce VT at the right ventricular apex in 14 of these 17 patients. Further, among the 15 patients whose VT was induced at the right ventricular outflow tract with two extrastimuli, neither burst pacing (n = 13) nor two extrastimuli introduced at faster paced rates (n = 12) induced VT at the right ventricular apex."
-How does sphincterotomy prevent gallstone formation in prairie dogs fed a high-cholesterol diet?,"Effect of bile diversion and sphincterotomy on gallbladder muscle contractility and gallstone formation. Feeding prairie dogs a diet rich in cholesterol induces gallstone formation that is preceded by a sustained decrease in gallbladder smooth muscle contractility. Sphincterotomy is known to prevent gallstone formation in cholesterol-fed prairie dogs. Experiments were designed to determine whether the effect of sphincterotomy is a consequence of hepatic bile diversion, and whether bile diversion prevents the altered contractility. Following sham operation, surgical biliary enteric bypass, or sphincterotomy, prairie dogs were fed a high-cholesterol or a regular diet. Gallbladder muscle contractility and the presence of crystals and stones were determined. In sham-operated animals, the cholesterol diet induced a decrease in gallbladder muscle contractility and caused the formation of cholesterol gallstones. In animals with bile diversion and sphincterotomy, the effects of cholesterol feeding were reduced or prevented. Thus, these procedures may prevent stone formation by preventing a reduction in gallbladder contractility. Contractility was depressed in animals with bile diversion fed a regular diet, compared with animals with a sham operation fed a regular diet. The mechanism for this depression may differ from that induced by the cholesterol diet. Diversion, and perhaps sphincterotomy, impairs gallbladder filling. Thus, gallbladder muscle is not stretched and does not contract against a load. This could result in a ""disuse atrophy."" If the results from our study apply to humans, sphincterotomy may reduce stone formation by preventing the effects of lithogenic bile on gallbladder muscle contractility and by enhancing the ability of the muscle to empty the lithogenic bile."
-What was the prevalence of hepatitis C antibodies among patients with alcoholic liver disease in this study?,"Antibody to hepatitis C is common among patients with alcoholic liver disease with and without risk factors. Thirty-seven patients with clinically suspected alcoholic liver disease were retrospectively studied for the prevalence of antibody to hepatitis C virus (HCV) by enzyme-linked immunosorbent assay (ELISA) and immunoblot assay. Twenty-four had biopsy-proven cirrhosis. Nineteen had identifiable risk factors for non-A, non-B viral hepatitis, and 18 did not. Five of 19 high-risk (26%) and 6 of 18 low-risk (33%) patients had positive antibody, compared with two of 179 healthy blood donors (p less than 0.01 for either group of alcoholics compared with blood donors). Nine of 11 ELISA-positive patients were also either positive or indeterminable by immunoblot testing. Histologic scores for parameters commonly associated with chronic viral hepatitis were numerically worse among anti-HCV-positive patients, but none reached statistical significance. Clinically, seven of 11 (64%) of anti-HCV-positive patients versus 14 of 26 (54%) anti-HCV-negative patients were Child's class C. Among the 21 Child's class C patients, seven (33%) were anti-HCV-positive versus four of 16 (25%) of Child's class A/B patients. A weak correlation between IgG and ELISA optical density was observed (r = 0.52). We conclude that antibody to hepatitis C by ELISA and immunoblot is common among alcoholics with liver disease even in the absence of known or suspected risk factors for viral hepatitis. Although hepatitis C-positive patients tended to have more severe histologic disease, neither histologic parameters nor clinical findings were adequate to predict antibody seropositivity."
-How did site-directed mutagenesis of the region around Cys-241 in human C2 affect its hemolytic activity?,"Site-directed mutagenesis of the region around Cys-241 of complement component C2. Evidence for a C4b binding site. We probed the functional significance of the region around Cys-241 in human C2 by testing the hemolytic activity of a series of mutant rC2. Mutant C2 cDNA were constructed by oligonucleotide-directed site-specific mutagenesis and expressed transiently in COS cells. Wild-type rC2 had threefold higher specific hemolytic activity than native serum C2. Substitution of Gly, Ala, or Ser for Cys-241 resulted in a slightly, but significantly, increased activity. In addition, I2 had no effect on the activity of these mutant C2. Substitution of Lys for Gln-243 increased the hemolytic activity by more than two-fold. Increased activity in all cases was due to slower decay rates of the C3 convertase. Finally, substitution of Leu or Ala for Asp-240 or Ser-244, respectively, resulted in more than 100-fold decrease of hemolytic activity. The results suggest that residues 240 to 244 of human C2 represent an important structural determinant of the C4b binding site of C2a. They also confirm that Cys-241 is the residue responsible for the increased activity of C2 reacted with I2."
-What is the main hypothesis tested in this study about Wolfram syndrome and psychiatric disorders?,"Psychiatric disorders in 36 families with Wolfram syndrome. OBJECTIVE: The purpose of this study was to test the hypothesis that heterozygous carriers of the gene for the Wolfram syndrome, who constitute about 1% of the population, are predisposed to significant psychiatric illness. The Wolfram syndrome is an autosomal recessive neurodegenerative syndrome in which 25% of the individuals who are homozygous for the condition have severe psychiatric symptoms that lead to suicide attempts or psychiatric hospitalizations. METHOD: The authors collected questionnaires, death certificates, and hospital records for blood relatives and their spouses in 36 families of individuals with the Wolfram syndrome and compared the proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness to the proportion of spouses with the same manifestations. RESULTS: The proportion of blood relatives who had had psychiatric hospitalizations, had committed suicide, or had self-reported mental illness significantly exceeded the proportion of spouses with the same manifestations. CONCLUSIONS: Since heterozygous carriers of the gene for the Wolfram syndrome are 50-fold more common among the blood relatives than among the spouses, the larger proportion among blood relatives is evidence that heterozygous carriers of the gene for the Wolfram syndrome are predisposed to significant psychiatric illness."
-How does sonography compare to chest radiography and CT in monitoring the therapeutic response of mediastinal lymphomas?,"Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT. The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas."
-"How does pyruvate kinase activity differ between normal fibrous tissue, benign proliferations, and malignant tumors?","Pyruvate kinase activity and isozyme composition in normal fibrous tissue and fibroblastic proliferations. Pyruvate kinase (PK) was studied in 57 fibroblastic and fibrohistiocytic proliferations and normal fibrous tissue (n = 10). The specific activity was significantly increased in malignant tumors (1.67 +/- 0.25) compared with normal tissue (0.26 +/- 0.04; P less than 0.001) and benign proliferations (0.52 +/- 0.05; P less than 0.005). Although an overlap exists between aggressive fibromatosis and the benign group, high values of PK activity are indicative of Grade 2 and 3 malignancy. Significant shifts in isozyme pattern, favoring the expression of K-type subunits were found in tumors with a metastasizing potential and aggressive fibromatosis. These changes in the isozyme pattern of PK in aggressive fibromatosis may act as another argument to place them in the category of malignant fibroblastic tumors."
-What method did the researchers use to detect mixed hematopoietic chimerism after allogeneic bone marrow transplantation?,"Evaluation of mixed chimerism by in vitro amplification of dinucleotide repeat sequences using the polymerase chain reaction. The influence of mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation remains unknown. Increasingly sensitive detection methods have shown that MC occurs frequently. We report a highly sensitive novel method to assess MC based on the polymerase chain reaction (PCR). Simple dinucleotide repeat sequences called microsatellites have been found to vary in their repeat number between individuals. We use this variation to type donor-recipient pairs following allogeneic BMT. A panel of seven microsatellites was used to distinguish between donor and recipient cells of 32 transplants. Informative microsatellites were subsequently used to assess MC after BMT in this group of patients. Seventeen of the 32 transplants involved a donor of opposite sex; hence, cytogenetics and Y chromosome-specific PCR were also used as an index of chimerism in these patients. MC was detected in bone marrow aspirates and peripheral blood in 18 of 32 patients (56%) by PCR. In several cases, only stored slide material was available for analysis but PCR of microsatellites or Y chromosomal material could be used successfully to assess the origin of cells in this archival material. Cytogenetic analysis was possible in 17 patients and MC was detected in three patients. Twelve patients received T-cell-depleted marrow and showed a high incidence of MC as revealed by PCR (greater than 80%). Twenty patients received unmanipulated marrow, and while the incidence of MC was lower (44%), this was a high percentage when compared with other studies. Once MC was detected, the percentages of recipient cells tended to increase. However, in patients exhibiting MC who subsequently relapsed, this increase was relatively sudden. The overall level of recipient cells in the group of MC patients who subsequently relapsed was higher than in those who exhibited stable MC. Thus, while the occurrence of MC was not indicative of a poor prognosis per se, sudden increases in the proportions of recipient cells may be a prelude to graft rejection or relapse."
-What was the impact of omentectomy on postoperative sepsis in patients undergoing proctocolectomy and ileoanal anastomosis?,"Let sleeping dogs lie: role of the omentum in the ileal pouch-anal anastomosis procedure. A surgical aphorism has long held that the omentum is the ""watchdog of the abdomen."" However, detractors believe that leaving the omentum behind after colectomy precipitates later small bowel obstruction. A retrospective comparison was made between a group of 406 patients (Group I) having omentectomy with proctocolectomy and ileoanal anastomosis and a group of 239 patients (Group II) having a similar procedure without omentectomy. Follow-up in this series of 645 patients was 4.3 +/- 2.1 years (mean +/- SEM). No difference was present in the rate of partial small bowel obstruction or complete small bowel obstruction between Group I patients (32 percent partial, 12 percent complete) and Group II patients (29 percent partial, 12 percent complete; P greater than 0.1). However, a better outcome with regard to postoperative sepsis and sepsis requiring operation was apparent in Group II patients retaining the omentum (4 percent and 3 percent, respectively) than in Group I patients (10 percent and 8 percent, respectively), in whom the omentum was removed (P less than 0.01). As this experience would support, we urge surgeons to ""let sleeping dogs lie"" and, when possible, retain the omentum when performing colectomy or proctocolectomy."
-What was the effectiveness of fluconazole in treating hepatosplenic candidiasis in patients who did not respond to previous antifungal treatments?,"Hepatosplenic candidiasis: successful treatment with fluconazole. PURPOSE: To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment. PATIENTS AND METHODS: Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole. RESULTS: All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis. CONCLUSION: Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy."
-How did colchicine affect renal function and fibrosis in a rabbit model of anti-glomerular basement membrane disease?,"Moderate protection of renal function and reduction of fibrosis by colchicine in a model of anti-GBM disease in the rabbit. A rabbit model of renal glomerulosclerosis induced by anti-glomerular basement membrane antibody was used to determine whether colchicine would protect renal function and reduce fibrosis. Initial studies established the time course of renal function changes and fibrosis. Colchicine at a dose of 0.02 to 0.04 mg/kg per day injected ip was begun at day 4 when injury had been initiated, and the experiment was ended at day 21 when fibrotic changes were established. Colchicine significantly reduced the rise in serum creatinine (serum creatinine = 2.7 +/- 0.3 mg% in vehicle-treated animals versus 1.8 +/- 0.1 mg% in colchicine-treated animals) and interstitial fibrosis (fibrosis score = 2.6 +/- 0.2 in vehicle-treated versus 1.5 +/- 0.2 in colchicine-treated animals). Colchicine treatment did not significantly affect weight, anti-guinea pig immunoglobulin level, % fibrocellular crescents formed, hydroxyproline per gram (dry weight) in tissue, or urine protein: creatine ratio. Regression analysis was performed to examine the interrelationships between variables for all animals and the effect of colchicine on pairs of variables. No clear-cut site of colchicine action could be identified. These data show that colchicine, in doses that could be used in humans, protected renal function by about 25% and reduced interstitial fibrosis in a model of severe crescentic nephritis."
-What age groups were most affected by diarrheal deaths in the United States between 1979 and 1987?,"Diarrheal deaths in the United States, 1979 through 1987. A special problem for the elderly. OBJECTIVE.--Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal death among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States. DESIGN/SETTING/PARTICIPANTS.--We reviewed national mortality data complied by the National Center for Health Statistics, Hyattsville, Md, which consists of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a ""diarrheal death"" and included in the analysis. RESULTS.--We found that 28,538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children (younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin. CONCLUSION.--For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population."
-What are the acute and chronic hemodynamic effects of xamoterol in patients with mild to moderate congestive heart failure?,"Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure. Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment."
-What is the significance of using interphase cytogenetics with in situ hybridization in studying trisomy 12 in chronic lymphocytic leukemia?,"Trisomy 12 in chronic lymphocytic leukemia: an interphase cytogenetic study. Interphase cytogenetics by means of in situ hybridization with the chromosome 12-specific biotinylated alpha satellite DNA probe pSP 12-1 was used for the study of trisomy 12, the most common chromosomal abnormality in chronic lymphocytic leukemia. In situ hybridization was performed on methanol/acetic acid fixed cells of conventional cytogenetic preparations from eight patients and on morphologically and immunologically classified cells of cytospin preparations from seven patients. The results show that trisomy 12 is more common than assumed on the basis of karyotype analysis of metaphase chromosomes: 2 of 13 patients with a normal karyotype in G-banding analysis were shown to have trisomy 12 by interphase cytogenetics. Immunophenotyping of the cells of one patient showed that the trisomy was restricted to cells with Ig light chain clonality. For the evaluation of the prognostic, therapeutic, and biologic significance of trisomy 12, in situ hybridization should be used in parallel with karyotype analysis because it allows the study of all cell populations of both interphase and mitotic cells, whether neoplastic or normal."
-What was the primary aim of the 10-year prospective screening study on multiple endocrine neoplasia type 1 (MEN 1)?,"Multiple endocrine neoplasia type 1: a 10-year prospective screening study in four kindreds. A total of 80 individuals in 4 kindreds with multiple endocrine neoplasia type 1 (MEN 1) have been subjected to repeated biochemical screening during a 10-yr period with the principal aim being to analyze characteristics of the developing pancreatic lesion. Age at presentation of the MEN 1 trait averaged 18 yr in 7 previously unaffected individuals, and this effect of the screening procedure represented a lowering by almost 2 decades. Pancreatic endocrine involvement was recognized at a mean age of 25 yr and constituted the presenting lesion in a majority of the patients. A standardized meal test and basal values of serum pancreatic polypeptide, insulin, proinsulin, and gastrin were the most efficient markers for the pancreatic lesion and preceded signs of pancreatic tumors upon radiological examinations by a mean of 3.5 yr. A 75% penetrance of the islet cell disease and 90% for primary hyperparathyroidism within the affected individuals equalled the prevalences reported in autopsy studies. Two of the kindreds showed signs of intrafamilial homogeneity with respect to the profile of peptide excess (P less than 0.05) and considerable discrepancy in the malignant potential of the pancreatic lesions. The results of early detection and surgical intervention of the pancreatic tumors in MEN 1 suggested an impact on morbidity, while any effect on the mortality of these individuals remains to be clarified."
-What is the relationship between neurosurgical intervention and the risk of cerebral hemorrhage in patients with cerebral amyloid angiopathy?,"Surgical risk of hemorrhage in cerebral amyloid angiopathy. Cerebral amyloid angiopathy is increasingly recognized as a cause of lobar cerebral hemorrhage in normotensive elderly individuals. Isolated reports have suggested that neurosurgical intervention entails a high risk of precipitated hemorrhage. We identified 16 pathologically confirmed cases of cerebral amyloid angiopathy. Fourteen of these patients presented with lobar cerebral hemorrhage. Fifteen neurosurgical procedures in eight patients included eight clot evacuations, three abscess drainage procedures, two ventriculoperitoneal shunts, one biopsy, and one lobectomy. Recurrent postoperative cerebral hemorrhage was seen in four patients at 2 days, 9 days, 6 weeks, and 10 months, but surgery was thought to have precipitated the cerebral hemorrhage in only one patient. Recurrent cerebral hemorrhage also was seen in two of the eight nonoperated cases. Recurrent cerebral hemorrhage is characteristic of cerebral amyloid angiopathy, but we conclude that neurosurgical intervention, particularly evacuation of hematomas, is not associated with major risk of precipitated hemorrhage."
-What is the primary purpose of transvenous endomyocardial biopsy in cardiac transplant recipients?,"Ventricular fibrillation complicating endomyocardial biopsy of a cardiac allograft. Transvenous endomyocardial biopsy remains the most useful diagnostic aid in assessing rejection in the transplanted heart. Although invasive, the complications associated with endomyocardial biopsy are few, and the procedure is generally regarded as safe. We report a case of apparent ventricular fibrillation complicating transvenous endomyocardial biopsy. Histologic section revealed evidence of moderate acute rejection. This case represents the first report of a life threatening ventricular dysrhythmia following routine endomyocardial biopsy in a cardiac transplant recipient."
-What percentage of patients had an excellent result after catheter-less suprapubic cystolithotomy in children?,"Catheter-less suprapubic cystolithotomy in children. Bladder stones in children are common in developing countries and the procedure of choice for their removal is suprapubic cystolithotomy. It is standard practice to drain the bladder for a few days post-operatively to prevent urinary leakage. We have observed that, if the bladder is closed meticulously in 2 layers, bladder drainage by means of a catheter is not required. We have analysed 86 children treated by suprapubic cystolithotomy without a catheter. Size of the stones and intra-operative findings were noted and it was found that 85% of the patients had an excellent result; 10% had a satisfactory result and 4.7% were unsatisfactory. The advantages of the procedure and selection of the patients are discussed."
-What evidence suggests a potential link between HTLV-I and mycosis fungoides in the study?,"Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Mycosis fungoides, a rare form of cutaneous T cell leukemia/lymphoma, is suspected of having a viral etiology on the basis of certain similarities to adult T cell leukemia, which is associated with human T cell leukemia/lymphoma virus type I (HTLV-I) infection. Cell lines were established from peripheral blood mononuclear cells (PBMC) of an HTLV-I-seronegative patient with mycosis fungoides. DNA hybridization analysis revealed the presence of HTLV-I-related sequences with unusual restriction endonuclease sites. Sequence analysis of subcloned fragments demonstrated the presence of a monoclonally integrated provirus with a 5.5-kilobase deletion involving large regions of gag and env and all of pol. Additional evidence for the presence of deleted proviruses was found by polymerase chain reaction (PCR) amplification of DNA from cutaneous lesions of five other HTLV-I-seronegative patients. The findings suggest that HTLV-I infection may be involved in the etiology of at least certain cases of mycosis fungoides."
-How does the pre-treatment PSA level correlate with treatment outcomes in prostate cancer patients receiving primary radiation therapy?,"Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy. The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures. Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence."
-What were the effects of DuP 753 and captopril on left ventricular end-diastolic pressure and volume in rats with heart failure?,"Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure. The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to AII parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 +/- 1.5 to 14.2 +/- 3.0 (P less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 +/- 1.1 to 59.4 +/- 3.0 and 64.9 +/- 3.9 mL/kg, respectively. Thus, direct blockade of AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction."
-What are the major risk factors for coronary heart disease in the elderly?,"Preventive maintenance of the aging heart. Coronary heart disease (CHD) is the major cause of mortality in the elderly. Important risk factors include hypercholesterolemia, systolic and diastolic hypertension, cigarette smoking, hyperglycemia, and obesity. Elderly patients with existing CHD should be treated aggressively to control these risk factors, along with other medical therapies to treat myocardial ischemia. For elderly patients without recognized CHD, however, a more conservative approach is recommended and includes behavioral interventions when appropriate and pharmacologic therapy for higher risk patients with persistent, uncontrolled risk factors."
-"How many American women are expected to be affected by ovarian cancer this year, and what is the estimated mortality rate?","Screening in ovarian cancer. Ovarian cancer will affect 20,000 American women this year and some 13,500 will die of the disease. Most patients will have stage III or IV disease at the time of diagnosis. Because ovarian cancer may be initially without symptoms, attempts have been made to develop screening tests that would lead to an early diagnosis. Two tests, serum CA 125 and pelvic ultrasonography, have been suggested by some to be accurate enough to be included in yearly screening for ovarian cancer. Although further testing of these techniques is encouraged, data to date do not justify yearly screening with CA 125 or pelvic ultrasonography in all women."
-What factors were associated with less favorable crude survival in patients undergoing hepatic resection for colorectal secondaries?,"Indicators of prognosis after hepatic resection for colorectal secondaries. From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding ""high risk"" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control."
-What was the effectiveness of palliative radiation therapy in treating epidural compression caused by metastatic malignant melanoma?,"The effect of palliative radiation therapy on epidural compression due to metastatic malignant melanoma. The efficacy of palliative radiation therapy in the treatment of spinal cord and cauda equina compression due to metastatic malignant melanoma was evaluated in 38 sites in 35 patients treated between 1970 and 1990. All patients had radiographic documentation of epidural compression. The median dose of radiation therapy was 2850 cGy (range, 500 to 4000 cGy), with daily fractions ranging from 200 to 800 cGy. Twenty-eight sites in 26 patients were evaluable 1 month after completion of radiation therapy, and symptoms responded completely in 11 of 28 (39%) sites. Fourteen sites (46%) showed a partial response of symptoms. Response lasting until death was documented in 21 of 26 patients (81%). Patients receiving a total dose of 3000 cGy or greater were more likely to achieve a complete response than those receiving less than 3000 cGy (62% versus 20%) by univariate (P = 0.025) and multivariate (P = 0.048) analyses. A treatment program of radiation therapy and corticosteroids is effective in palliating the symptoms of epidural compression due to metastatic malignant melanoma. It is recommended to deliver an accelerated course of radiation therapy to a dose of 3000 cGy or greater without exceeding spinal cord tolerance (e.g., 3000 cGy in ten fractions at 300 cGy per fraction)."
-"What behavioral modification technique was used to help a patient with adipsia, diabetes insipidus, and memory impairment achieve independent drinking and be discharged from the hospital?","Management of adipsia by a behavioural modification technique. Adipsia combined with diabetes insipidus after hypothalamic damage may produce major difficulties in clinical management. If there is an associated memory impairment it may be impossible to teach self-regulation of fluid balance, necessitating long-term hospital supervision. The successful use of a behaviour modification technique to achieve independent drinking and allow discharge from hospital into the community is described in a patient with adipsia, diabetes insipidus and memory impairment resulting from the removal of a craniopharyngioma."
-What was the primary objective of the study involving thermal ablation of the gallbladder in dogs?,"Thermal ablation of the gallbladder. Gallbladder ablation by means of injection of hot contrast medium was attempted in 13 dogs. Room temperature contrast medium was injected into the gallbladders of two additional dogs (controls). After midline laparotomy was performed to expose the gallbladder, temperature probes were placed in the liver adjacent to the gallbladder, and on the surface and in the lumen of the gallbladder. A 7-F catheter with multiple side holes was placed into the gallbladder. The cystic duct was clamped during the procedure. After injection of boiling contrast medium, the mean temperature in the gallbladder lumen was 80 degrees C; in the adjacent liver, 43.5 degrees C; and on the gallbladder surface, 45.8 degrees C. After the procedure, the cystic duct was unclamped, temperature probes and catheter were removed, and the laparotomy was closed in standard fashion. In the hot contrast medium group, one dog each was sacrificed at 2, 4, 8, and 12 weeks, and at 6 months. Six animals were sacrificed at 1 year. The gallbladder was completely ablated in 11 of 13 animals in the hot contrast medium group. One dog was sacrificed at 8 days because of bile leakage, and another was sacrificed at 17 days because of gallbladder rupture. The two control animals were sacrificed at 12 and 13 weeks, and their gallbladders were normal at that time."
-What were the key predictors of breast cancer screening among women aged 40 and older in the Rhode Island study?,"A study guided by the Health Belief Model of the predictors of breast cancer screening of women ages 40 and older. In late 1987, a total of 852 Rhode Island women ages 40 and older were interviewed by telephone (78 percent response rate) to measure their use of breast cancer screening and to investigate potential predictors of use. Predictors included the women's socioeconomic status, use of medical care, a provider's reported recommendations for screening, and the women's health beliefs about breast cancer and mammography. The Health Belief Model guided the construction of the interview questions and data analysis. Logistic regression was used to identify leading independent predictors of breast cancer screening according to contemporary recommendations: reporting that a medical provider had ever recommended a screening mammogram (odds ratio [OR] = 18.77), having received gynecological care in the previous year (OR = 4.92), having a regular source of gynecological care (OR = 2.63), having ever had a diagnostic mammogram (OR = 2.32), and perceiving mammography as safe enough to have annually (OR = 1.93). The findings suggest that programs intended to increase the use of breast cancer screening should include ""inreach"" and ""outreach"" elements; inreach to patients with established patient-provider relationships, by assuring that physicians recommend screening to all eligible patients, and outreach to all eligible women, by helping them overcome barriers to effective primary care, and by promoting mammography, emphasizing its effectiveness and safety. The findings also suggest that socioeconomically disadvantaged women, who are less likely to be screened than other women, should become special targets of inreach and outreach interventions."
-What was the effectiveness of percutaneous drainage for traumatic pancreatic pseudocysts in children according to this study?,"Percutaneous drainage of traumatic pancreatic pseudocysts in children. To determine the effectiveness of percutaneous drainage of traumatic pancreatic pseudocysts, we reviewed the courses of 13 children. Six pseudocysts resolved on complete bowel rest and total parenteral nutrition. Seven required further therapy. Two pseudocysts were treated operatively; five were drained percutaneously with fluoroscopic guidance. These five ranged from 5 to 15 cm in diameter and were present for 10 to 42 days (mean, 26 days). In all cases, the cyst fluid was clear, had an amylase level of greater than 40,000 IU/L, and grew no organisms. The pigtail catheters left in place in four of the five children were removed when drainage stopped. Patients were followed by ultrasound while still in the hospital and 1 month after discharge. There were no complications nor any pseudocyst recurrence. Percutaneous drainage of traumatic pancreatic pseudocysts in children is an effective alternative to the standard operative therapy of pseudocystenteric anastomosis."
-What was the efficacy of continuous intravenous diltiazem infusion in controlling heart rate during atrial fibrillation and atrial flutter?,"A placebo-controlled trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. The safety and efficacy of a 10- to 15-mg/h continuous infusion of intravenous diltiazem were evaluated in 47 patients with atrial fibrillation or flutter who first responded to 20 mg or 20 mg followed by one or more 25-mg bolus doses of open label intravenous diltiazem. Of the 47 patients, 44 responded to the bolus injection and were randomized under double-blind conditions to receive either a continuous infusion of intravenous diltiazem (10 to 15 mg/h) (23 patients) or placebo (21 patients) for up to 24 h. Seventeen (74%) of the 23 patients receiving diltiazem infusion and none of the 21 with placebo infusion maintained a therapeutic response for 24 h (p less than 0.001). Over 24 h, patients receiving diltiazem infusion lost response significantly more slowly than did those receiving placebo infusion (p less than 0.001). Nonresponders to the double-blind infusion were given an additional bolus injection of open label intravenous diltiazem and administered an open label 24-h intravenous diltiazem infusion. The overall proportion of patients maintaining a response to a 24-h infusion of intravenous diltiazem under double-blind or open label conditions combined was 83% (34 of 41). Efficacy of the 24-h infusion of intravenous diltiazem was similar in elderly versus young patients, those who did versus those who did not receive digoxin and those weighing less than 84 versus greater than or equal to 84 kg. However, intravenous diltiazem appeared to be more effective in atrial fibrillation than in atrial flutter. No significant untoward effects were noted."
-What are histamine H2-receptor antagonists and how do they work to reduce gastric acid secretion?,"Histamine H2-receptor antagonists. In summary, histamine initiates acid secretion by stimulating the H2 subtype histamine receptor on parietal cells. Cimetidine, rantidine, famotidine, and nizantidine are histamine H2-receptor antagonists that block this action of histamine, reducing gastric acid output and concentration under both basal and stimulated conditions. These agents are used for treatment and prevention of peptic and stress ulcers as well as for hypersecretory states. Because of their effectiveness and low incidence of side effects, H2-antagonists have largely replaced more traditional antiulcer regimens."
-"What percentage of patients with parenchymal brain hemorrhage experience seizures, and in what stages do these seizures typically occur?","Seizures caused by nontraumatic parenchymal brain hemorrhages. Seizures occurred in 15% of patients with parenchymal brain hemorrhage (early in 12% and delayed in 3%). Seizures were most frequent with lobar hemorrhages and uncommon with deep subcortical hemorrhages. Lobar hemorrhages in the frontal, parietal, or temporal region were more commonly associated with seizures, whereas occipital hemorrhages were not. Seizures were most common if the hemorrhage was due to an aneurysm, angioma, or neoplasm and less common if hypertensive or spontaneous. If the patient had recurrent seizures or developed delayed seizures, CT showed that the hemorrhage evolved to a hypodense appearance; if the seizure did not recur, CT showed that the hemorrhage evolved to an isodense appearance."
-What diagnostic technique was found to be more sensitive in identifying patent ductus arteriosus in an infant with atrioventricular septal defect?,Patent ductus arteriosus in an infant with atrioventricular septal defect and pulmonary hypertension: diagnosis by transesophageal color flow echocardiography. An infant with complete atrioventricular septal defect (atrioventricular canal) was examined by standard transthoracic two-dimensional pulsed Doppler and color Doppler echocardiography. No evidence of ductus arteriosus was present. Preoperative transesophageal echocardiography identified a patent ductus: the left-to-right shunt seen by color Doppler echocardiography was enhanced by pharmacologic maneuvers aimed at decreasing pulmonary vascular resistance and increasing systemic vascular resistance. Transesophageal echocardiography was found to be more sensitive than transthoracic echocardiography even in a small infant.
-How did the study use ADL dependencies to determine long-term care eligibility for individuals with dementia in the Oregon Medicaid program?,"Using ADLs to establish eligibility for long-term care among the cognitively impaired. Using a database from the Oregon Medicaid program, we examined the differences in the potential insurance coverage of demented persons by using different formulations of ADL (activities of daily living) dependencies in which the definition of dependency did or did not include the need for supervision. For those with clear dementia, 81-88% of the persons with significant behavioral problems were correctly identified when a cut score of three or more ADLs was used; this percentage was even higher for two or more ADLs. This approach was not as effective in correctly discriminating those who had no behavioral problems."
-What neurological and musculoskeletal complications were observed in a 75-year-old woman with untreated primary hypothyroidism?,"Neuropathy, myopathy and destructive arthropathy in primary hypothyroidism. A 75-year-old woman with untreated primary hypothyroidism was found with peripheral neuropathy (including carpal tunnel syndrome), severe myopathy (high levels of creatine phosphokinase) and destructive arthropathy, affecting fingers, toes and the left knee. Radiographs of her knee showed destructive lesions of the tibial plateau similar to a pathologic compression fracture, while the joints of the fingers and toes showed all signs of severe erosive osteoarthritis (OA), radiographically documented over a period of 7 years. It is suggested that hypothyroidism is causally related to the development of erosive OA."
-What evidence suggests an autoimmune mechanism in the patient's neuromyotonia?,"Autoimmune aetiology for acquired neuromyotonia (Isaacs' syndrome). Neuromyotonia is a rare disorder of unknown cause in which hyperexcitability of peripheral motor nerves leads to incapacitating muscle twitching, cramps, and weakness. We investigated an antibody-mediated mechanism for neuromyotonia in a 24-year-old man with a 7-year history of severe disease unresponsive to pharmacological treatment. Two periods of plasma exchange each produced almost complete disappearance of symptoms for 2-3 weeks, and a highly significant decrease in recorded neuromyotonic discharges. Injection of the patient's plasma or purified IgG into mice significantly enhanced in-vitro resistance to d-tubocurarine at the neuromuscular junction of phrenic nerve-diaphragm preparations. This finding suggests that an increase in neurotransmitter release might result from an antibody-mediated reduction in the number of functional potassium channels that normally regulate nerve excitability. The demonstration of pathogenic IgG autoantibodies in acquired neuromyotonia suggests that immunosuppressive treatment may be helpful in severe cases."
-What was the most common symptom among patients with lower esophageal mucosal rings in this study?,"Use of a marshmallow bolus for evaluating lower esophageal mucosal rings. Sixty-three patients (35 women, 28 men; mean age 55 yr) with lower esophageal mucosal ring shown radiographically were examined with a semi-solid bolus consisting of a portion of a standard marshmallow. The most common symptom was dysphagia, present in 46 (73%) patients. Impaction of the marshmallow bolus by the ring occurred in 40 (63%) of the 63 patients, and produced symptoms in 27 (68%) of these 40 patients. Nine (14%) rings were detected radiographically only with a solid bolus; eight of these patients had dysphagia and seven rings were 20 mm or less in caliber. Impaction related to ring caliber, and was found in all 17 (100%) rings that were 13 mm or less in diameter, in 17/24 (71%) 14- to 19-mm rings, and in 6/22 (27%) rings 20 mm or more in caliber. Endoscopy in 23 patients detected 16 (70%) rings, and also depended on ring caliber: less than or equal to 13 mm, 6/6 (100%); 14-19 mm, 5/9 (56%); greater than or equal to 20 mm, 5/8 (63%). Marshmallow impaction occurred in 17 (74%) of 23 patients who had endoscopy; three of the 23 patients had normal endoscopy. In conclusion, radiographic examination supplemented by the use of a marshmallow bolus best detects lower esophageal mucosal ring."
-What rare ictal phenomenon was investigated in two patients with epilepsy?,"Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions."
-What are the most common CT findings in patients with malignant pleural mesothelioma?,"Malignant pleural mesothelioma: CT manifestations in 50 cases. Malignant pleural mesothelioma, a rare and usually fatal neoplasm that is associated with asbestos exposure, is being encountered with increasing frequency. Pretreatment CT findings from 50 patients with malignant pleural mesothelioma are illustrated. Pleural thickening was found in 46 (92%) of the 50 patients, thickening of the pleural surfaces of the interlobar fissures in 43 (86%), pleural calcifications in 10 (20%), and pleural effusions in 37 (74%). The volume of the involved hemithorax varied appreciably. Contractions of the involved hemithorax was noted in 21 (42%) of 50 patients and contralateral mediastinal shift in seven (14%). Disease beyond the parietal pleura was found in the chest wall (nine patients), mediastinum, lymph nodes, and diaphragm."
-What was the clinical presentation and treatment of the 22-year-old patient with a prostatic mass?,"Pseudosarcomatous fibromyxoid tumor of the prostate. A case report with immunohistochemical, electron microscopic, and DNA flow cytometric analysis. A 22-year-old man presented with symptoms of urinary obstruction and was found to have a 5-cm mass protruding from the left side of the prostate into the prostatic urethra. The lesion was partially removed by transurethral resection (TURP). The patient's symptoms recurred, so he required another TURP four months later; at latest follow-up (four years later), there waas no evidence of disease. Light microscopy revealed a myxoid lesion characterized by an atypical fibroblastic proliferation associated with a prominent inflammatory component and granulation tissue-type vasculature. The lesion nearly replaced the prostatic parenchyma and invaded the bladder wall. Immunohistochemistry and electron microscopy showed a predominance of fibroblasts with occasional myofibroblasts. DNA flow cytometric analysis showed that the tumor cells had a diploid DNA content. Given these findings and the indolent clinical course, the authors think that this lesion represents a benign, reactive process consistent with a pseudosarcomatous fibromyxoid tumor, a recently described rare lesion of the genitourinary tract."
-What molecular weight of macrophage colony-stimulating factor (hM-CSF) was detected in serum and urine samples using immunoblot analysis?,"Characterization of macrophage colony-stimulating factor in body fluids by immunoblot analysis. We characterized the molecular species of human macrophage colony-stimulating factor (hM-CSF) found in serum and urine, using immunoblot analysis after partial purification on an antibody-bound affinity column. Although antibodies were prepared using the recombinant product of the large form of hM-CSF with a molecular weight (MW) of 85 Kd as the antigen, this immunoblot system was also capable of detecting the small form of hM-CSF with a MW of 40 to 60 Kd. A single band with a MW of 43 Kd, which reacted with anti-recombinant hM-CSF IgG but not with control IgG, was found when serum and urine from normal adults underwent electrophoresis on reduced sodium dodecyl sulfate-polyacrylamide gel and subsequent immunoblotting. This band represented a subunit of the large form of hM-CSF, because the large form of hM-CSF is a homodimer of a subunit with a MW of 43 Kd and the small form of hM-CSF is a homodimer of a subunit with a MW of 20 to 30 Kd. Analysis of serum and urine from leukemic patients and pregnant women, who had higher serum levels of hM-CSF than normal adults, showed only a single band with a MW of 43 Kd as a hM-CSF-specific molecule. These results suggest that the large form of hM-CSF is the major species in human body fluids."
-What is the significance of a positive direct antiglobulin test (DAT) in multiple myeloma patients?,"Positive direct antiglobulin tests in myeloma patients. Occurrence, characterization, and significance. Review of direct antiglobulin testing (DAT) in 88 patients with multiple myeloma (MM) and five with Waldenstrom's macroglobulinemia revealed 26 cases with a positive DAT. Twenty-two of these had immunoglobulin G-M protein, three had light chain MM, and one had immunoglobulin A-MM protein. None of the immunoglobulin GD-MM (n = 2), nonsecretory MM (n = 5), or Waldenstrom's macroglobulinemia patients (n = 5) were positive. None of the patients had hemolysis attributable to the adsorption of the M protein. The serum concentration of M protein was higher in DAT-positive patients (57.6 +/- 3.8 g/L, mean +/- SEM) than in the negative ones (35.7 +/- 6.4 g/L; probability value of the difference was less than 0.01). The erythrocyte eluates from DAT-positive patients contained a single immunoglobulin, of the same class as the M protein, and did not react with a panel of ABO-compatible erythrocytes. Addition of melphalan during incubation did not affect the results. The M protein of DAT-positive patients was of immunoglobulin G-3 subclass in 7 of 10 patients. A positive direct antiglobulin test frequently is seen in patients with multiple myeloma, the reaction is due to passive adsorption of the M protein onto the erythrocytes, is most frequently observed with immunoglobulin G3-MM, and usually does not produce hemolysis."
-What is the diagnostic value of mouse rosettes (M-rosette) and surface immunoglobulin (SIg) in differentiating B-chronic lymphocytic leukemia (B-CLL) from reactive lymphocytosis (RLC)?,"The importance of surface immunoglobulin, mouse rosettes, and CD5 in the immunophenotyping of chronic lymphocytic leukemia and reactive lymphocytosis. Peripheral blood from 167 B-chronic lymphocytic leukemia (B-CLL) and 119 reactive lymphocytosis (RLC) patients were analyzed to evaluate the immunophenotypic diagnostic value of mouse rosettes (M-rosette), and weak expression of monoclonal surface immunoglobulin (SIg). In B-CLL, 145 cases were M-rosette+ (86.83%), 135 surface immunoglobulin (SIg)+ (80.84%), and 117 M-rosette+ SIg+ (70.06%). Of 32 SIg- cases, 28 were M-rosette+; and of 22 M-rosette-cases, 18 were SIg+. By combining results of the two assays and accepting positivity of either one or both as sufficient for diagnosis, B-CLL was diagnosed in 163 cases (97.60%). CD5 was performed in 49 cases of the 167 with paired data for SIg and M-rosettes. By combining the results of the three assays and accepting positivity of any two or all three as sufficient for diagnosis, all 49 cases (100%) were diagnosed. Correlation analysis showed no significant association between M-rosette, SIg, and CD5 expression. The results demonstrate the independent expression of the three markers, and their complementary role in immunophenotyping B-CLL. In RLC, all 119 cases were T-lineage and SIg-, and 115 were M-rosette-, indicating the role of the two markers in differentiating B-CLL from RLC. Three of the four M-rosette+ T-RLC were subsequently diagnosed as B-CLL, suggesting the necessity of follow-up of such cases."
-How do different structural forms of hen egg lysozyme (HEL) affect its presentation by MHC class II molecules?,"Class II-restricted presentation of an endogenously derived immunodominant T-cell determinant of hen egg lysozyme. An in vitro model was used to investigate the potential for different structural forms of endogenous antigen to be processed and presented by major histocompatibility complex class II molecules. For this purpose the class II-restricted presentation of an immunodominant epitope of hen egg lysozyme [HEL-(46-61)] was studied in class II-positive B-lymphoma cells (M12.C3) transfected with genes encoding HEL molecules either (i) secreted in high (hi) or low (lo) amounts as soluble antigen [sHEL(hi/lo)], (ii) localized within the endoplasmic reticulum (ER)/salvage compartment (ER-HEL), or (iii) anchored on the cell surface as an integral membrane protein (mHEL). The corresponding sHEL, ER-HEL, and mHEL gene products were expressed as predicted except that HEL determinants accumulated in the culture supernatant as well as on the cell membrane of mHEL-transfected cells. Class II-positive cells endogenously expressing all three forms of HEL antigen constitutively presented the immunodominant HEL-(46-61) determinant with differential efficiency (mHEL, sHEL greater than ERHEL) to a class II-restricted T hybridoma. A second T hybridoma recognized endogenous HEL-(46-61) determinants constitutively presented on sHEL(hi) and mHEL transfectants but not on sHEL(lo) or ERHEL transfectants. The formation of HEL-(46-61)/I-Ak complexes in the ERHEL and sHEL(lo) transfectants was therefore limiting. Mixing experiments with different antigen-presenting cells indicated that the HEL-(46-61) determinant was derived from endogenous antigen rather than by reuptake of shed or secreted HEL determinants. We conclude that MHC class II molecules can present some antigenic determinants derived from endogenous proteins that are sequestered in the ER/salvage compartment as well as distally transported in the form of secretory or membrane antigens."
-What minimally invasive technique was used to successfully treat chylothorax after pneumonectomy when conservative therapy failed?,"Thoracoscopic diagnosis and treatment of chylothorax after pneumonectomy. Chylothorax after pneumonectomy was treated successfully by selective application of fibrin glue through a thoracoscope. Conservative therapy for 18 days failed to close the fistula. The site of leakage was identified during thoracoscopy, and fibrin glue was applied under direct vision. Leakage decreased immediately and eventually stopped completely. This technique is less invasive than standard surgical treatment and should be considered in all patients with postoperative chylothorax."
-What was the main strategy used for managing distal ileal Crohn's disease in this study?,"Strategy for management of distal ileal Crohn's disease. We have determined the outcome of a defined policy for the management of distal ileal Crohn's disease using a prospective computer-based analysis of 139 patients diagnosed between 1970 and 1988 with a mean follow-up of 10 years. The policy in outline consists of conservative treatment for acute obstructive episodes, resection or strictureplasty for recurrent obstructive episodes, surgical treatment for abscess and fistula formation and specific medical treatment (corticosteroids, immunosuppressive therapy or metronidazole) for symptomatic non-obstructive disease. Twenty-nine patients had a benign course without resection. The remainder were treated surgically at some time but only 28 of these patients had specific treatment before operation. Thirty-three needed more than one resection and five needed more than three surgical procedures. Immediate, early or delayed surgical treatment did not affect the reoperation rates or the long-term outcome. Eleven patients died, ten of causes unrelated to Crohn's disease. Of the 128 living patients, 114 are fit and well, and only two are currently taking specific medication. Fourteen are unwell of whom six either need or have refused further surgery which could restore them to good health. This management policy has achieved excellent long-term results in nearly all patients, and our findings suggest that the timing of surgery and its nature are more important in determining outcome than specific medical therapy."
-What modifications were made to the original T-shaped musculomucosal buccal flap method to improve cleft palate surgery outcomes?,"The modified buccal musculomucosal flap method for cleft palate surgery. We have reported previously on a palatoplasty method, called the T-shaped musculomucosal buccal flap method, for the primary repair of a cleft palate. This method has been used on more than 90 patients, and satisfactory outcomes have resulted in terms of maxillar development, the prevention of fistulation, and verbal functions. However, 14.3 percent of these patients exhibited a velopharyngeal incompetence that showed no potential improvement through training. In the majority of these patients, the entire raw surface of the oral cavity side could not be covered with a buccal musculomucosal flap, and as a result, postoperative contraction of the soft palate occurred. Thus a new surgical method has proven effective in which both buccal musculomucosal flaps are used as an oral lining, the nasal mucosa having been extended by Z-plasty. We have performed 25 operations using this new method and have observed no postoperative contractions of the soft palate, notwithstanding two cases (8.0 percent) of postoperative fistulation."
-What were the complete fragmentation rates and 3-month stone-free rates for the three different lithotripsy devices studied?,"Comparative studies of extracorporeal shock wave lithotripsy by Dornier HM3, EDAP LT 01 and Sonolith 2000 devices. During a 2-year period extracorporeal shock wave lithotripsy (ESWL) was done at our institution in 70 patients with the Dornier HM3, 113 with the EDAP LT 01 and 104 with the Sonolith 2000 lithotriptors. The size and location of stones were comparable in all 3 series, and all treatments were done by the same team of urologists. Complete fragmentation occurred in 79% of the patients treated by the Dornier, 82% treated by the EDAP and 79% treated by the Sonolith devices, with 3-month stone-free rates of 66, 67 and 58%, respectively. Auxiliary procedures were needed in 12% of the patients in the Dornier, 13% in the EDAP and 9% in the Sonolith groups. Repeat treatment was necessary in 4% of the Dornier group, 42% of the EDAP group and 26% of the Sonolith group. Therefore, all 3 lithotriptors are effective in stone disintegration and produce satisfactory results when selection criteria for ESWL are observed. The most significant difference among the 3 lithotriptors is the number of repeat treatments, which reflects the power and energy output of the lithotriptors. In conclusion, the Dornier HM3 device has the advantage of low repeat treatment rate and easier stone localization. The EDAP LT 01 unit has the advantage of lower treatment costs and anesthesia-free treatment with no irradiation. The Sonolith 2000 device has features of the other 2 lithotriptors with a superior ultrasound image."
-What were the key findings from linking the Illinois AIDS and Cancer Registries regarding neoplasia in people with AIDS?,"A systematic consideration of the neoplastic spectrum of AIDS: registry linkage in Illinois. To examine unexplored aspects of the association between AIDS and neoplasia, the Illinois AIDS and Cancer Registries were linked. The method integrated use of a personal computer to find exact matches on names and dates of birth with manual review to assure satisfaction of a match definition. Of the factors examined, white race and homosexuality predicted Kaposi's sarcoma (KS) among people with AIDS (PWAs), and white race predicted non-Hodgkin's lymphoma (NHL). Earlier reports of a declining proportion of PWAs with KS were confirmed. Lymphoma (mixed lymphocytic/histiocytic type), while not currently diagnostic of AIDS, occurred more frequently among PWAs than in the Illinois population. For the first time, rates of cancers other than KS and NHL were demonstrated to be significantly increased among PWAs compared with general populations. In the light of these findings, reconsideration of current neoplastic definitions may be useful."
-What treatment was used for children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and what were its outcomes?,"Chronic inflammatory demyelinating polyradiculoneuropathy of childhood: treatment with high-dose intravenous immunoglobulin. We treated four children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with high-dose intravenous immunoglobulin (IVIG). All patients received 400 mg/kg of IVIG a day for 5 days during relapses, and one patient received additional periodic infusions of 400 mg/kg. All patients showed excellent recovery of motor strength following each relapse that was treated with IVIG. Compared with plasmapheresis (which was used to treat relapses earlier), recovery of function with IVIG treatments was similar, and in two patients it was superior, to plasmapheresis. There were no side effects with IVIG treatments as compared with plasmapheresis with which two children had infection of central lines with Staphylococcus epidermidis, one had profuse bleeding from accidental extrusion of a central line, and one had multiple episodes of major venous thromboses. High-dose IVIG was a safe and effective adjunctive therapy for childhood CIDP in these four patients."
-What were the two-year clinical success rates for the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups?,"Experience with laser-assisted balloon angioplasty and a rotary angioplasty instrument: lessons learned. Favorable early results with mechanical angioplasty devices and laser-assisted balloon angioplasty have resulted in aggressive marketing and a rapid increase in the use of these devices for the treatment of femoropopliteal occlusive disease. Recent reports, however, have questioned the durability of these less invasive procedures. Since 1986 we have been involved in the clinical investigation of the Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty. One hundred two balloon angioplasty procedures assisted by the Nd:YAG laser (n = 56) and the Kensey dynamic angioplasty instrument (n = 46) were performed for the treatment of femoropopliteal occlusive lesions. Both Kensey dynamic angioplasty instrument and laser-assisted balloon angioplasty groups were similar with regard to age, operative indication, preoperative ankle-brachial index, lesion length, and distal runoff. Mean follow-up was 19 months in the Kensey dynamic angioplasty instrument group and 15 months in the laser-assisted balloon angioplasty group. Technically successful recanalization was achieved in 67% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 82% of laser-assisted balloon angioplasty procedures. Early hemodynamic and clinical improvement was obtained in 59% of Kensey dynamic angioplasty instrument-assisted balloon angioplasty procedures and 57% of laser-assisted balloon angioplasty procedures. Two-year clinical success by life-table analysis was 37% in the Kensey dynamic angioplasty instrument group and 19% in the laser-assisted balloon angioplasty group. The level of subsequent surgical revascularization was not altered in any patient by Kensey dynamic angioplasty instrument-assisted balloon angioplasty or laser-assisted balloon angioplasty."
-What was the impact of long-term passive anti-HBV immunoprophylaxis on HBV reinfection and survival in liver transplant patients?,"Passive immunoprophylaxis after liver transplantation in HBsAg-positive patients. 110 HBsAg-positive patients underwent orthotopic liver transplantation and received long-term anti-hepatitis B virus (HBV) passive immunoprophylaxis with anti-HBs immunoglobulin. During a mean follow-up period of 20 months, all patients became HBsAg negative after transplantation but circulating HBsAg reappeared in 25 (22.7%). Overall 1-year survival was 83.6% and overall 2 year actuarial recurrence of HBsAg was 29% (59% after posthepatitis B cirrhosis, 13% after posthepatitis B-delta cirrhosis, and 0% after fulminant hepatitis B). Patients with HBV cirrhosis who were HBV-DNA positive had a much greater risk of HBsAg recurrence than patients who were HBV-DNA negative (96% vs 29% at 2 years). Reappearance of HBsAg was associated with evidence of HBV replication and abnormal histological findings in the graft. Long-term passive anti-HBV immunoprophylaxis significantly reduced HBV reinfection and improved survival in patients without evidence of active HBV replication before orthotopic liver transplantation."
-How does the diaphragmatic activity differ between slow-wave sleep and rapid-eye-movement (REM) sleep in cats?,"Differential activation within costal diaphragm during rapid-eye-movement sleep in cats. Simultaneous recordings of the diaphragmatic electromyogram (EMG) were made from two separate regions of the costal diaphragm in six normal cats. The diaphragmatic activities were always synchronous and the amplitudes and rates of rise were similar during slow-wave sleep. In contrast, during natural rapid-eye-movement (REM) sleep, different activity was often present in the two leads. These differences were in the time of onset and offset, as well as in the amplitude and spike patterns, and occurred in approximately 5-20% of the diaphragmatic bursts averaged over the entire REM sleep period. With respect to eye movement density, the rate of differential activation was higher during periods of high density (26%) than in the absence of eye movements (1%) in the four animals for which these data were available. Differential activation of portions of the costal diaphragm is apparently a normal event of REM sleep. This could result from descending state-specific phasic neuronal activity that bypasses the medullary respiratory generator. Differential activation of portions of the diaphragm could contribute to disordered ventilation during REM sleep."
-What symptoms are commonly associated with posttraumatic headache as part of the postconcussion syndrome?,"Posttraumatic headache and the postconcussion syndrome. Although headache is the most common sequelae of head injury, the posttraumatic headache is associated frequently with dizziness, irritability, lack of concentration, and intolerance to alcohol ingestion as a part of a symptom complex known as the postconcussion syndrome. This article clarifies the definitions of acute traumatic headache, posttraumatic headache, and the postconcussion syndrome and improves diagnostic ability, making the assessment and treatment of patients with these three conditions more accurate and effective."
-What are the two bacterial factors identified as important in enteropathogenic Escherichia coli (EPEC) infection?,"Characterization of interactions of enteropathogenic Escherichia coli O127:H6 with mammalian cells in vitro. Previous studies have identified two bacterial factors involved in enteropathogenic Escherichia coli (EPEC) infection. A plasmid-mediated EPEC adherence factor (EAF) is responsible for initial and localized adherence. A chromosomally encoded E. coli attachment and effacement factor (eae) is involved in effacement of the eukaryotic cell surface and characteristic ""pedestal"" formation. By using isogenic strains deficient in either EAF, eae, or both, the process of EPEC adherence and entry in vitro was examined. While EAF proved necessary and sufficient for efficient bacterial association with HEp-2 cells, both EAF and eae were required for efficient effacement of and entry into these cells and other cultured cell lines. Invasion mediated by eae was markedly inhibited by cytochalasin D and colchicine. Afimbrial adhesion or type I pili from uropathogenic strains of E. coli substituted for EAF in EAF-Eae+ strains to provide initial adherence to HEp-2 cells and to facilitate actin condensation."
-What are the key initiatives proposed to address the shortage of trained eye care professionals in sub-Saharan Africa?,"Who will operate on Africa's 3 million curably blind people? About half the 6 million blind people in sub-Saharan Africa have surgically curable cataract. The available manpower and resources can only provide services for less than 10% of the new blind cataract patients each year, and little is being done for the estimated 3 million ""cataract backlog"". A serious limiting factor to the development of prevention of blindness programmes is lack of trained manpower. Despite an increase in the number of ophthalmologists trained in cataract surgery (which varies greatly from country to country), this number is not keeping pace with increased demand for eye-care services, especially in large rural populations. Initiatives that will help to overcome this dilemma are specific post-graduate courses in community ophthalmology in Africa, plans to develop a one-year diploma in ophthalmology course for English-speaking West African countries, and a proposal to upgrade a similar course in Zimbabwe. Additionally there is a need for the training of more ophthalmic assistants, cataract surgeons, and nurses in the diagnosis and management of common ophthalmic disorders. Experienced expatriate ophthalmologists also have an important role in the teaching of doctors and ophthalmic assistants how to select patients and carry out successful inexpensive cataract surgery with appropriate technology and limited facilities."
-What unique characteristics were observed in this case report of a pituitary adenoma?,"Ectopic pituitary adenoma in the suprasellar cistern: case report. The case of a 56-year-old man with an ectopic pituitary adenoma is reported. Neurological examinations, neurodiagnostic imaging, surgical observation, endocrinological evaluation, histological examination, and immunohistological study demonstrated evidence of ectopic prolactinoma in the suprasellar cistern and the presence of a normal pituitary in the sella turcica. The patient underwent total removal of the suprasellar mass by a pterional approach, leading to a surgical and endocrinological cure."
-What is neoplastic angioendotheliomatosis (NAE) and how did it manifest in the two described cases?,"Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months."
-What was the main finding of the study comparing low and high doses of ethanolamine oleate in treating esophageal varices?,"Treatment of esophageal varices: low versus high dose of 5% ethanolamine oleate. Twenty-four patients, undergoing sclerotherapy for esophageal varices, were injected with 10-20 ml of ethanolamine oleate 5% in the first treatment session (group A). Fourteen patients were injected with 40 ml of the same sclerosant in the first session (group B). Retrospective analysis was carried out to evaluate the efficacy and safety of the two doses. Variceal eradication was achieved in group B in significantly fewer sclerotherapy sessions. Rebleeding occurred in 16% of patients in group A, compared with no rebleeding in group B. There was no significant difference in the incidence of various complications. We conclude that the use of 40 ml of 5% ethanolamine oleate in the first session is more effective and as safe as the use of 20 ml of the same sclerosant."
-How do the responses of pial arterioles to bradykinin differ between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive (WKY) rats?,"Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP."
-What rare condition was reported in this medical case involving the gasserian ganglion?,Primary malignant melanoma of the gasserian ganglion associated with neurofibromatosis. A case of primary intracranial malignant melanoma of the left gasserian ganglion associated with temporal lobe gliosis in a patient suffering from von Recklinghausen's disease is reported. The association of primary malignant melanoma of the trigeminal nerve and neurofibromatosis is discussed.
-What was the average number of lymph nodes found in stations 1-11 and 1-16 in the cadaveric study?,"Lymph node counts in the upper abdomen: anatomical basis for lymphadenectomy in gastric cancer. The number of regional lymph nodes was determined in sites relevant to lymphadenectomy in gastric cancer in 30 cadavers. Tissue was cleared by dissolving fatty tissue, thus making lymph nodes with a diameter of at least 1 mm visible. All lymph node stations indicated by the Japanese Research Society for Gastric Cancer were studied. In stations 1-11 (corresponding with R2 resection) an average of 27 nodes (range 17-44 nodes) was found, whereas stations 1-16 (corresponding with R3 resection) showed an average of 43 nodes (range 25-64 nodes). These values are higher than those usually obtained from lymphadenectomy for gastric cancer. Striking individual differences in the total number of lymph nodes and the number of single stations was observed. The number of lymph nodes in these investigations are the normal anatomical values and serve as quality control of lymph node dissection in gastric carcinoma."
-How does gamma-interferon influence astrocyte proliferation and reactive gliosis?,"Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Reactive gliosis is a characteristic response of astrocytes to inflammation and trauma of the central nervous system. To investigate whether soluble factors (cytokines) from inflammatory mononuclear cells that accumulate at lesion sites can provide the cellular signals to initiate gliosis and to identify such cytokines, we have tested and found that supernatants derived from subsets of activated human T lymphocytes (CD8+ or CD4+) are potent mitogens for cultured human adult astrocytes. This effect is blocked by a neutralizing antibody to gamma-interferon (IFN). Recombinant IFN alone can induce proliferation of human adult astrocytes in vitro and increase the extent of trauma-initiated gliosis in the adult mouse brain. The astrocyte proliferation-inducing activity of supernatants of glial cultures treated with IFN can be completely blocked with IFN-neutralizing antibody, suggesting that the proliferative effect does not require intermediary cytokines or cells. These results implicate IFN as an important mediator of the gliosis observed in pathologic conditions of the adult central nervous system associated with infiltrating lymphocytes."
-What was the incidence of clinically significant pneumatosis intestinalis in patients who underwent abdominal operations or bariatric procedures with needle catheter jejunostomy?,"Clinically significant pneumatosis intestinalis with postoperative enteral feedings by needle catheter jejunostomy: an unusual complication. We evaluated the incidence of clinically significant pneumatosis intestinalis and intestinal necrosis with the use of needle catheter jejunostomy in 217 consecutive patients who had undergone complicated abdominal operations or selected bariatric procedures. The needle catheter jejunostomy was used to deliver immediate postoperative nutrition, maintenance, and replacement fluids, and selected medications. In this group, no serious complications requiring surgical intervention were related to the use of needle catheter jejunostomies. Clinically significant pneumatosis intestinalis was encountered in two of 217 patients (1%). With the needle catheter jejunostomy in place, both patients improved rapidly when enteral feedings were discontinued and parenteral antibiotics were administered. None of the 217 patients developed ischemic intestinal necrosis. We conclude that 1) clinically significant pneumatosis is a rare complication of enteric feeding via needle catheter jejunostomy when the intrajejunal feeding is begun with a diluted, hypoosmolar solution with stepwise increases in osmolality, and 2) patients who do develop clinically significant pneumatosis (n = 2) seem to respond rapidly to a temporary stoppage of enteral feedings and administration of parenteral antibiotics."
-What are the typical symptoms and clinical presentation of medially invasive petrous bone cholesteatoma?,"Facial nerve and medially invasive petrous bone cholesteatomas. Eight patients with extensive petrous bone cholesteatomas that invaded the labyrinth and fallopian canal are presented. The eight cases are added to a tabulation of prior literature reports to elucidate concepts of routes of extension of medially invasive temporal bone cholesteatoma. Medially invasive petrous bone cholesteatoma develops insidiously, often without symptoms other than facial palsy and/or unilateral deafness. Typically, a history of chronic ear disease can be obtained. While hearing is unlikely to be preserved in this group of patients, facial nerve function can usually be preserved, and a facial nerve graft was not necessary in our series. Acute facial nerve palsy or facial nerve paresis progressing to palsy in patients with a history of chronic ear disease should be studied radiographically for petrous bone cholesteatoma, even if there is no physical evidence of cholesteatoma."
-What were the four different 6-month chemotherapy regimens used in this study for treating pulmonary tuberculosis?,"Controlled trial of 2, 4, and 6 months of pyrazinamide in 6-month, three-times-weekly regimens for smear-positive pulmonary tuberculosis, including an assessment of a combined preparation of isoniazid, rifampin, and pyrazinamide. Results at 30 months. Hong Kong Chest Service/British Medical Research Council In a study in Hong Kong 1,386 Chinese patients with sputum smear-positive pulmonary tuberculosis were allocated at random to four 6-month regimens of chemotherapy, all given three times weekly from the start and all containing isoniazid (H) and rifampin (R) throughout. Three contained streptomycin (S) for the first 4 months and pyrazinamide (Z) for 2 months (Z2), 4 months (Z4), or 6 months (Z6); the fourth contained pyrazinamide for 6 months but no streptomycin (Z6noS). Every dose of all four regimens was given under the direct supervision of clinic staff on a predominantly outpatient basis. During the later part of the intake patients were allocated at random to be given their HRZ either as a combined formulation (Rifater), each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide, or as the three drugs separately. Among 892 assessable patients with drug-susceptible strains of tubercle bacilli pretreatment, bacteriologic failure during chemotherapy occurred in 4, all Z6noS (2% of 224; p less than 0.005 for the comparison with the S-containing regimens). During 30 months of follow-up after the end of chemotherapy, bacteriologic relapse occurred in 2 (3%) of 71 Z2, 2 (3%) of 72 Z4, 4 (6%) of 66 Z6, and 6 (9%) of 64 Z6noS patients allocated to Rifater, and in 4 (3%) of 149 Z2, 8 (6%) of 133 Z4, 2 (1%) of 142 Z6, and 6 (4%) of 135 Z6noS patients allocated to separate drugs. In the relapse rates there were no significant differences between the Rifater and separate drug regimens, the different durations of pyrazinamide, or the regimens with and without streptomycin."
-Does 24-hour esophageal pH monitoring predict the response of reflux esophagitis to standard medical therapy?,"Failure of initial 24-hour esophageal pH monitoring to predict refractoriness and intractability in reflux esophagitis. Prolonged esophageal pH monitoring is considered to be the most sensitive and specific test for the diagnosis of gastroesophageal reflux disease (GERD). However, the role of pH monitoring in predicting the clinical and endoscopic response of reflux esophagitis is not well defined. In this study, 106 patients with moderate to severe symptoms of GERD and esophagitis (grades 0-IV) by endoscopy were initially studied by ambulatory esophageal pH monitoring, and their clinical response to standard H2 antagonist therapy was monitored at 8 wk. Refractory patients were defined as those who failed to heal and/or had intractable reflux symptoms after 8 wk of H2 antagonist therapy, and who required continuous therapy with higher doses of H2 antagonists, addition of prokinetic agents, or omeprazole. There was a positive correlation (r = 0.89) between endoscopic severity of esophagitis upon entry into the study and refractoriness to standard medical therapy. However, there were no differences in the various pH parameters analyzed between the 58 patients who responded and the 48 patients who were refractory to medical therapy, regardless of the endoscopic grading of their esophagitis. We conclude that 24-h ambulatory esophageal pH monitoring does not predict refractoriness of reflux esophagitis to standard therapy. The decision for more aggressive methods of treatment probably requires assessment of symptomatic and endoscopic response after 8 week standard H2 antagonist therapy."
-What were the key findings of the morphometric study on gastric endocrine cells after 6 months of omeprazole treatment in duodenal ulcer patients?,"Ultrastructural morphometry of gastric endocrine cells before and after omeprazole. A study in the oxyntic mucosa of duodenal ulcer patients. Long-term toxicological experiments with inhibitors of acid secretion were found to induce hyperplasia and eventually carcinoid tumors of the enterochromaffin-like cells of the oxyntic mucosa. To evaluate the effects of 6 months' treatment with omeprazole in humans, the oxyntic endocrine cells were morphometrically investigated at the ultrastructural level in five patients with active duodenal ulcer. No omeprazole-induced changes were found in the volume density of the total endocrine cell population and specific cell types (including the enterochromaffin-like cell) as well as in the other cytological parameters investigated (number of cell profiles per unit area, mean cross-sectional area of cell profiles, nuclear-cytoplasmic ratio, and density of cytoplasmic secretory granules). Both pretreatment and post-treatment values in our patients with duodenal ulcer significantly differed from those of a previous investigation of healthy volunteers with regard to the volume density of enterochromaffin-like cells and non-granulated cells, which increased, and of D cells, which markedly decreased. The latter result may provide a cellular basis for impairment in the paracrine release of fundic somatostatin in peptic ulcer disease. Finally, morphometric data on endocrine cell volume density provided by electron microscopy were found to correlate with those obtained in the same patients using light microscopy techniques (Grimelius silver impregnation and chromogranin A immunostaining). It is concluded that 6 months' treatment with pharmacological doses of omeprazole is devoid of appreciable trophic effect on endocrine cells of human oxyntic mucosa."
-What were the key differences in outcomes between patients with thrombolysis-mediated patency and those with patency achieved by angioplasty in acute myocardial infarction?,"Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty. Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy."
-How do deletions in different domains of the dystrophin gene affect the clinical presentation of Becker muscular dystrophy?,"Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Becker muscular dystrophy (BMD) often results from in-frame mutations of the dystrophin gene that allow production of an altered but partially functional protein. To address potential structure-function relationships for the various domains of dystrophin, we examined both the dystrophin gene and protein in 68 patients with abnormal dystrophin. Eighty-six percent of BMD patients with dystrophin of altered size have deletions or duplications, and the observed sizes of dystrophin fit well with predictions based on DNA data. Deletions within the amino-terminal domain I tended to result in low levels of dystrophin and a more severe phenotype. The phenotypes of patients with deletions or duplications in the central rod domain were more variable. This region can be divided into three portions based on differences in clinical presentations of patients. Deletions around exons 4553 were most common and generally caused typical BMD; however, phenotypic variability among patients with similar mutations suggests that epigenetic and/or environmental factors play an important role in determining the clinical progression. In contrast, deletions or duplications in the proximal portion of this domain tended to cause severe cramps and myalgia. Finally, loss of the middle of this region probably causes a very mild phenotype, as only one such patient was found and his only symptom was elevated serum creatine phosphokinase levels."
-What are the typical symptoms associated with anterior urethral polyps in male patients?,"Anterior urethral polyp associated with hematuria in six-year-old child. Anterior urethral polyps are rare, occur only in male patients, and have been associated with obstruction, terminal hematuria, and enuresis. We believe this is the fifth reported case of anterior urethral polyp associated with terminal hematuria. The radiographic findings, treatment, and pathology are reviewed."
-What is the purpose of the study on percutaneous stimulation of the cauda equina?,"Percutaneous stimulation of the cauda equina. A new diagnostic method in spinal stenosis. A study to determine the feasibility of measurement of conduction velocities through the lumbosacral nerve roots by direct percutaneous stimulation of the cauda equina is reported. The technique was applied to a series of normal volunteers and its reliability and reproducibility confirmed. An electrophysiologic defect was demonstrated in most patients with surgically proven lateral recess stenosis. Electrophysiologic recovery was shown in patients examined after surgery. Although the technique can be refined, these early results are encouraging."
-What are the key noninvasive strategies to reduce stroke risk in elderly patients?,"Reducing the risk of stroke: identifying patients to refer for carotid endarterectomy. The most common causes of stroke are two diseases of aging: hypertension and atherosclerosis. Therefore, although stroke may occur at any age, the incidence is highest among the elderly population. Noninvasive efforts to reduce the risk of stroke in the elderly include control of hypertension and diabetes, smoking cessation, low-cholesterol dietary habits, and moderate exercise. Routine low-dose aspirin also provides some protective effect. High-risk patients (with asymptomatic high-grade stenosis, TIAs, or prior stroke) should be considered candidates for carotid endarterectomy in the absence of contraindications to surgery."
-"What was the effect of different doses of interferon alfa-2b on alanine aminotransferase levels in patients with chronic non-A, non-B hepatitis?","Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Ninety patients with histologically documented chronic non-A, non-B hepatitis were randomly allocated to receive SC injections of placebo or of 1 or 3 MU of recombinant interferon alfa-2b three times weekly for 24 weeks. Complete normalization of alanine aminotransferase levels occurred posttreatment in 43.3% of patients receiving 3 MU, in 20% of those receiving 1 MU, and in 6.7% of untreated patients (P less than 0.0005 vs. those treated with 3 MU). Alanine aminotransferase normalization was sustained for 6 months after therapy in 13.3% of the patients treated with 3 MU and in 3.3% of those given 1 MU or placebo. The decline of alanine aminotransferase levels following interferon therapy showed independent, positive correlations with female sex (P less than 0.03) and younger age (P less than 0.05). The Knodell's fibrosis score was strongly positively correlated with age (P less than 0.0001). It is concluded that 3 MU of interferon is a more effective dose than 1 MU for controlling disease activity in non-A, non-B chronic hepatitis patients. Women and younger and noncirrhotic patients are more likely to respond."
-What is the primary medical intervention discussed for managing retroperitoneal hemorrhage from renal angiomyolipoma in a patient with polycystic kidney disease?,"Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited."
-"What medical condition caused paraplegia in the pregnant thalassemic woman, and how was she successfully treated?","Paraplegia in a pregnant thalassemic woman due to extramedullary hematopoiesis: successful management with transfusions. The investigation and treatment of a pregnant thalassemic woman who developed severe paraplegia is presented. Magnetic resonance imaging showed a paravertebral mass infiltrating the epidural space, resulting from extramedullary hematopoiesis (marrow heterotopia). The patient was treated successfully with repeated blood transfusions and made a complete recovery. The literature (36 cases) is reviewed and the magnetic resonance imaging features of spinal extramedullary hematopoiesis are presented. The efficacy of transfusions in the management of spinal cord compression due to marrow heterotopia in thalassemic patients is discussed."
-What percentage of hemodialysis patients in the study developed hypertension after receiving recombinant human erythropoietin (rHuEpo) therapy?,"Hypertension following erythropoietin therapy in anemic hemodialysis patients. Recombinant human erythropoietin (rHuEpo) corrects the anemia of end-stage renal disease. However, hypertension has been observed as an adverse effect of increasing red cell mass. In our study, 44 of 63 patients (70%) treated with rHuEpo had an increase in mean arterial pressure greater than 10 mm Hg or required new or additional hypertensive medications. Retrospective analysis disclosed that increasing blood pressure was associated with pretreatment hematocrit level less than or equal to 0.20 (P = .05) and dependency on red cell transfusions (P less than .01). Factors not associated with hypertension included the rate of rise of the hematocrit, the net rise in hematocrit, age, sex, the number of years on dialysis, the presence or absence of kidneys, smoking, or the presence of pretreatment hypertension. Noninvasive hemodynamic studies in eight normotensive patients before and after improvement of the anemia demonstrated a normalization of the decreased peripheral vascular resistance and a reduction toward normal in the elevated cardiac output. In three of these patients, clinical hypertension subsequently evolved. Follow-up hemodynamic studies in nine other patients receiving new or additional antihypertensive medications were difficult to interpret. Although the hypertension can be controlled with routine medication, hypertensive encephalopathy may occur if the blood pressure increases rapidly when the hematocrit increases with rHuEpo therapy."
-What were the survival rates for children with malignant intracranial ependymomas based on different radiation treatment approaches?,"Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas? Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory."
-How can the measurement of free light chains in urine potentially help in monitoring multiple sclerosis disease activity?,"Increased free light chains in the urine from patients with multiple sclerosis. We quantitated free kappa (kappa) and lambda light (L) chains in coded urine specimens from subjects with clinically definite multiple sclerosis (MS) (N = 56), other neurologic diseases (OND) (N = 30), and age-matched normal controls (N = 28). Urine from MS patients showed statistically significant increases in free L chains compared with the other groups, although there was overlap between MS patients and OND patients. The ratio of kappa/creatinine was significantly greater in the relapsing-remitting MS group than in patients with clinically stable MS, OND, and normal controls. Elevated free L chains were usually independent of urinary albumin and beta 2-microglobulin levels. Serial studies showed that urinary free kappa/creatinine ratios were elevated during periods of clinical worsening in seven of eight MS patients and subsequently decreased during clinical recovery. The measurement of free L chains in urine obtained at intervals from MS patients may be useful as a marker to monitor disease activity."
-How do monoclonal antibodies help identify interaction sites of Plasminogen Activator Inhibitor 1 (PAI-1) with tissue-type plasminogen activator (t-PA) and fibrin?,"The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: localization of interaction sites and physiologic relevance. Plasminogen activator inhibitor 1 (PAI-1), an essential regulatory protein of the fibrinolytic system, harbors interaction sites for plasminogen activators (tissue-type [t-PA] and urokinase-type [u-PA]) and for fibrin. In this study, anti-PAI-1 monoclonal antibodies (MoAbs) were used to identify interaction sites of PAI-1 with these components. The binding sites of 18 different MoAbs were established and are located on five distinct ""linear"" areas of PAI-1. MoAbs, binding to two distinct areas of PAI-1, are able to prevent the inhibition of t-PA by PAI-1. In addition, two interaction sites for fibrin were identified on PAI-1. The area located between amino acids 110 and 145 of PAI-1 contains a binding site for both components and its significance is discussed in the context of the t-PA inhibition by fibrin-bound PAI-1. Subsequently, the MoAbs were used to assess the role of platelet-PAI-1 in clot-lysis. An in vitro clot-lysis system was used to demonstrate that clot-lysis resistance is dependent on the presence of activated platelets and that PAI-1 is a major determinant for lysis-resistance. We propose that, upon activation of platelets, PAI-1 is fixed within the clot by binding to fibrin and retains its full capacity to inhibit t-PA and u-PA."
-What is unique about the reported case of pulmonary zygomycosis in this medical report?,Granulomatous pulmonary zygomycosis in a patient without underlying illness. Computed tomographic appearances and treatment by pneumonectomy. Pulmonary zygomycosis rarely occurs in the absence of underlying disease. We report a patient with granulomatous pulmonary zygomycosis without underlying disease who presented with a pulmonary mass. We present the computed tomographic findings that we believe have not been described previously. We also report the successful treatment by pneumonectomy.
-What was the main finding regarding dysplasia and carcinoma in ulcerative colitis patients who underwent ileorectal anastomosis (IRA) in this follow-up study?,"Mucosal dysplasia and DNA content in ulcerative colitis patients with ileorectal anastomosis. Follow-up study in a defined patient group. In a follow-up study of an epidemiologically defined patient group comprising 1,274 patients with ulcerative colitis diagnosed in Stockholm County during 1955-1979, 55 patients had undergone colectomy with ileorectal anastomosis (IRA). Nine of these were found to have Crohn's disease after histopathologic review of the colectomy specimens. Of the 46 patients with ulcerative colitis remaining for evaluation, two died postoperatively. Twenty-five patients were subsequently reoperated with rectal excision owing to intractable inflammatory activity (n = 22, one postoperative death) or owing to dysplasia (n = 3). Of 19 patients with their IRA still intact at time of follow-up, 15 patients (median disease duration 23 years) had a flexible sigmoidoscopy with multiple biopsies performed. The average length of the remaining rectum and sigmoid colon was 26 cm. No patient had findings of dysplasia, carcinoma, or DNA aneuploidy. None of the four remaining patients had developed dysplasia or carcinoma at the time of the latest regular rigid sigmoidoscopy. The risk of malignant transformation in this selected group of patients with ulcerative colitis operated upon with colectomy and IRA derived from an epidemiologically defined population seems to be low."
-What did the study suggest about the relationship between erythrokeratoderma variabilis (EKV) and progressive symmetrical erythrokeratoderma (PSEK)?,"Is erythrokeratoderma one disorder? A clinical and ultrastructural study of two siblings. Two sisters with erythrokeratoderma are described. In the younger sister the clinical appearance corresponded to erythrokeratoderma variabilis (EKV), whereas in the older sister it corresponded to progressive symmetrical erythrokeratoderma (PSEK). Ultrastructural findings in both cases were identical. We suggest that EKV and PSEK are different manifestations of a single condition."
-How do oral contraceptive pills affect insulin-like growth factor binding protein-1 (IGFBP-1) concentration in women with polycystic ovarian disease (PCOD)?,"Oral contraceptives increase insulin-like growth factor binding protein-1 concentration in women with polycystic ovarian disease. Insulin-like growth factor-I (IGF-I) stimulates ovarian androgen production. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits IGF actions in vitro. OBJECTIVE: To investigate the effect of oral contraceptive (OC) pills, given for 3 months, on serum gonadotropin, androgen, IGF-I, and IGFBP-1 concentrations, and glucose tolerance in seven women with polycystic ovarian disease (PCOD) and in five healthy control subjects. PATIENTS: Seven women with PCOD and five healthy control subjects. INTERVENTIONS: An oral glucose tolerance test (OGTT) was performed before and after treatment with OC. RESULTS: After treatment with OC, serum luteinizing hormone, androstenedione, and free testosterone levels decreased, and sex hormone-binding globulin concentration increased in the women with PCOD as well as in the control subjects. The cumulative response of serum insulin to OGTT was larger in the women with PCOD than in the control subjects both before and after treatment. Serum IGF-I concentration, which was unchanged during OGTT, decreased from basal level of 326 +/- 70 micrograms/L to 199 +/- 28 micrograms/L after treatment with OC in the women with PCOD, whereas no change was found in the control subjects (from 235 +/- 11 micrograms/L to 226 +/- 11 micrograms/L). Treatment with OC caused an increase of the mean basal IGFBP-1 concentration from 24 +/- 7 micrograms/L to 73 +/- 14 micrograms/L in the women with PCOD. This increase was constant during the OGTT. In the control subjects, treatment with OC did not result in any significant change in IGFBP-1 concentrations (from 44 +/- 11 micrograms/L to 61 +/- 9 micrograms/L). CONCLUSION: The combination of decreased total IGF-I concentration and increased IGFBP-1 concentration induced by OC may decrease ovarian androgen production in PCOD."
-What is the significance of CD23 expression on lymphocytes in chronic inflammatory conditions?,"Immunohistochemical demonstration of CD23 expression on lymphocytes in rheumatoid synovitis. The leucocyte antigen CD23 is expressed by B lymphocytes following activation by a number of stimuli and functions as an IgE receptor, and in its soluble form, as a putative B cell growth factor. The expression of CD23 on the surface of lymphocytes in paraffin wax sections of synovial biopsy specimens was studied using a novel mouse monoclonal antibody, BU38. Specimens were investigated from nine cases of rheumatoid arthritis, six cases of osteoarthritis, and eight cases of chronic inflammation in articular and non-articular tissues. CD23 was expressed on a high proportion of lymphocytes in all forms of chronic inflammation and was not specific for rheumatoid arthritis. It may be a characteristic feature of any chronic inflammatory response. As CD23 was found on the surface of lymphocytes in many cases of these arthritides, sCD23 in serum or synovial fluid may yet prove a useful marker for the severity of the inflammatory infiltrate."
-What unique medical condition did the patient develop in her surgically reconstructed neovagina?,"Ulcerative colitis in the autotransplanted neovagina. A 33-year-old woman had undergone a radical surgical excision for carcinoma of the vagina at age 11. Vaginal reconstruction using a pedicled transplant of the sigmoid colon was successfully accomplished at age 19. Fourteen years later she developed vaginal bleeding, and a biopsy of the neovagina revealed changes consistent with ulcerative colitis. Within 2 weeks the patient developed bleeding per ano, and a rectal biopsy also revealed changes consistent with ulcerative colitis. Symptoms responded to sulfasalazine. This is believed to be the first case report of ulcerative colitis developing in colonic tissue used for a neovagina. The etiology, natural history, and surveillance of ulcerative colitis in relation to this unique case are reviewed. This case argues against the hypothesis that chronic ulcerative colitis is causally related to direct exposure to alimentary antigens."
-How did the administration of atrial natriuretic factor (ANF) affect the vasoconstrictor response during lower body negative pressure in patients with hypertension?,"An atrial natriuretic factor analogue at low doses attenuates forearm reflex vasoconstriction to cardiopulmonary receptor deactivation in patients with hypertension. Contrasting data exist about a possible modulation of the autonomic function by atrial natriuretic factor (ANF) in human beings, particularly at low, biologically, significant concentrations. We have evaluated that possibility by increasing plasma ANF levels through the infusion of a synthetic analogue (WY-47,663, anaritide) in five male patients with mild to moderate uncomplicated hypertension. Nonhypotensive lower body negative pressure (-10 mm Hg x 5 min) was used to selectively deactivate cardiopulmonary receptors and to stimulate sympathetic efferent tone reflexogenically. ANF was given at either a low rate (0.005 micrograms/kg/min x 60 min, which was previously shown to increase plasma ANF in a range compatible with physiologic stimuli) or at a high rate (0.05 micrograms/kg/min x 60 min, each). Administration of ANF was preceded and followed by vehicle infusion (Haemacell x 30 min). Forearm blood flow (venous plethysmography), intraarterial blood pressure, and heart rate were monitored continuously, and venous immunoreactive ANF, plasma renin activity, aldosterone level, and venous hematocrit were measured at the end of both control and infusion periods. Arterial norepinephrine values, an indirect index of sympathetic discharge, were measured at rest and during lower body negative pressure conditions. Graded systemic ANF infusion increased immunoreactive ANF and venous hematocrit, decreased aldosterone level and plasma renin activity, whereas resting norepinephrine levels, blood pressure, and heart rate did not change. Lower body negative pressure decreased forearm blood flow during vehicle infusion, but it lost its vasoconstrictor effect during infusion of ANF. To identify the site of that inhibitory action, ANF was also infused into the brachial artery at rates that raised local but not systemic levels of immunoreactive ANF."
-What immunological evidence suggests the co-existence of Lambert-Eaton myasthenic syndrome and myasthenia gravis in the two patients described?,"Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. Two patients are described in whom a clinical and electromyographic diagnosis of the Lambert-Eaton myasthenic syndrome (LEMS) was made. Serum antibodies to voltage-gated calcium channels (VGCCs), the antigenic target in LEMS and to acetylcholine receptors (AChRs), the antigen in myasthenia gravis, were detected at raised titres in both cases, using radioimmunoassays based on 125I-omega-Conotoxin labelled VGCCs and 125I-alpha-Bungarotoxin labelled AChRs. These data provide immunological evidence for the coexistence of the two disorders in these patients."
-What was the sensitivity and specificity of fine-needle aspiration biopsy in this pediatric head and neck masses study?,"Fine-needle aspiration biopsy: application to pediatric head and neck masses. Fine-needle aspiration biopsy cytology is widely used to screen masses in adults. The authors present a series of 89 fine-needle aspiration biopsies performed between January 1973 and December 1988 on 86 pediatric patients with clinically significant head and neck masses. All fine-needle aspiration diagnoses were confirmed by subsequent surgical biopsy, autopsy, or clinical follow-up for a minimum of 18 months. Of 21 tumors identified, 19 were malignant. Of the 89 aspirations performed, 67 required no subsequent surgical biopsy. In 11 of these cases, metastatic or recurrent tumor was diagnosed and appropriate therapy instituted. Fifteen of the 89 aspirates revealed previously undiagnosed tumors requiring surgical intervention. One false-negative and two false-positive results were obtained. No radical treatment resulted from the false-positive diagnoses, and no patient delay in treatment occurred because of the false-negative result. The sensitivity was 94.4%, and the specificity was 97.1%. The usefulness and cost-effectiveness of fine-needle aspiration is stressed."
-What medical procedure did the two patients with previous malignancy undergo to treat their congestive cardiomyopathy?,Orthotopic cardiac transplantation in two patients with previous malignancy. This report presents 2 patients with previous malignancy in whom congestive cardiomyopathy developed secondary to doxorubicin toxicity. Both patients underwent orthotopic cardiac transplantation 3 and 5 years ago and are now in functional class I with no evidence of malignant recurrence.
-What is priapism and how can it be related to vasculitis?,"Priapism as a manifestation of isolated genital vasculitis. Vasculitis may affect virtually any organ system in the body. We describe a patient who presented with priapism due to isolated genital vasculitis. This responded promptly to oral corticosteroids. In patients presenting with priapism, a possible underlying vasculitis should be considered in the differential diagnosis; the treatment for this may be nonsurgical."
-What symptoms were significantly more common in patients with infectious mononucleosis during the acute phase of illness?,"Acute and chronic symptoms of mononucleosis. BACKGROUND. The clinical symptoms and durations of illness of patients with infectious mononucleosis (IM) are variable and are poorly documented in the scientific literature. METHODS. Patients who presented for care at the Student Health Service of a Canadian university between September 1985 and May 1988 and had been diagnosed as having IM were surveyed. Health experience during the acute and convalescent phases of IM was compared with that of a group of patients matched for age, sex, date of diagnosis, and year of study, who had suffered acute upper respiratory tract infections (URI), other than Epstein-Barr virus (EBV)-induced, during the same period. RESULTS. Students were sicker for longer after IM than after non-EBV-induced URI. During the acute phase of illness, the symptoms of fatigue (P = less than .000001), night sweats (P = .000001), and painful neck swelling (P = .00003) were seen significantly more often in the IM group. The severity and duration of these symptoms were also significantly worse in IM patients. Getting tired easily (P = .002), diurnal somnolence (P = .002), and depression (P = .002) were significantly more common postacute symptoms. Eleven percent of IM patients reported persistence of symptoms longer than 100 days, and in 6% of patients the symptoms had persisted after 1 year. Convalescent cases showed a trend toward reduced alcohol intake and, perhaps, reduced alcohol tolerance. CONCLUSIONS. IM involves excessive morbidity in a student community compared with URI that was other than EBV-induced, during both the acute and the postacute phases of infection."
-How do plasma atrial natriuretic peptide (ANP) levels change during dynamic exercise in patients with effort angina pectoris?,"Dynamic exercise-induced elevation in plasma levels of atrial natriuretic peptide in patients with effort angina pectoris. We investigated the relationship between plasma atrial natriuretic polypeptide (ANP) levels and hemodynamic indices during dynamic exercise testing in 15 patients with effort angina pectoris. Patients exercised on an angina-limited, supine, multistage bicycle ergometer, and plasma ANP levels and hemodynamic indices were measured at rest, at peak exercise, and 6 minutes after exercise. Plasma ANP levels increased significantly at peak exercise. Pulmonary artery wedge pressure (PAWP) and coronary sinus blood flow (CSBF) were significantly correlated with plasma ANP levels before and at peak exercise (PAWP: r = 0.69, p less than 0.001; CSBF; r = 0.45, p less than 0.05). In six of eight patients whose PAWP exceeded 20 mm Hg at peak exercise, plasma ANP levels were increased at 6 minutes after exercise, whereas PAWP had decreased relative to the values obtained at peak exercise. Plasma ANP concentrations at 6 minutes after exercise were not correlated with PAWP at the same time. However, PAWP at peak exercise was correlated with the plasma ANP levels at 6 minutes after exercise (r = 0.80, p less than 0.001). These results suggest that in patients with effort angina pectoris left ventricular dysfunction resulting from exercise-induced myocardial ischemia may increase preload excessively and may contribute to the excess secretion of ANP after dynamic exercise."
-How does acute appendicitis present differently in patients with AIDS/HIV infection compared to immunocompetent patients?,"Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality."
-How has the use of antihypertensive agents changed in different age groups in the United States?,"Changes in hypertension treatment and in congestive heart failure mortality in the United States. The use of antihypertensive agents has increased in recent years and has been more marked among individuals in older age groups (65-74 years) than in middle-aged groups (45-54 years). Because hypertension is a strong risk factor for the development of congestive heart failure, more common use of antihypertensive agents would be expected to reduce the incidence of congestive heart failure. Examination of the national death statistics reveals decreases in congestive heart failure mortality at younger ages with mortality increases at older ages. The reasons for these divergent trends in congestive heart failure mortality in different ages and the apparent inconsistency with respect to the changes in the use of antihypertensive drugs are explored. We speculate that antihypertensive treatment does not completely prevent congestive heart failure but merely postpones its development by several decades."
-What was the most common cause of death among patients with tuberous sclerosis complex (TSC) in the Mayo Clinic study?,"Causes of death in patients with tuberous sclerosis. Of the 355 patients with tuberous sclerosis complex (TSC) examined at the Mayo Clinic, 49 had died (9 of causes other than TSC). We attempted to determine what pattern of organ involvement occurred most often in the 40 patients who died of TSC. One baby died of cardiac failure due to cardiac rhabdomyomas, and one child died of rupture of an aneurysm of the thoracic aorta. Eleven patients died of renal disease, which was the commonest cause of death. Ten patients died as a result of brain tumors, and four patients (who were 40 years of age or older) died of lymphangiomyomatosis of the lung. Thirteen patients with severe mental handicaps died of either status epilepticus or bronchopneumonia; in all but one of these patients, the only source of information was the death certificate. Survival curves show a decreased survival for patients with TSC in comparison with that for the general population. Patients with TSC need lifelong follow-up for early detection of potentially life-threatening complications."
-What imaging technique is recommended for diagnosing sigmoid sinus thrombosis?,"Sigmoid sinus thrombosis diagnosis by contrasted MRI scanning. Septic thrombosis of the transverse-sigmoid sinuses and the jugular bulb is a highly lethal condition. The presenting signs and symptoms of this disease entity are subtle and not in proportion to the magnitude of the problem. Later in the disease course, sudden fulminant findings appear. A high index of suspicion, combined with scanning techniques of either enhanced MRI or CT, allows prompt diagnosis and treatment. MRI enhanced with gadolinium-DTPA (Gd) is a valuable adjunct that confirms the diagnosis and delineates the extent of suspected pathology."
-What is the prevalence of transverse aortic arch hypoplasia in infants undergoing coarctation repair?,"Coarctation and hypoplasia of the aortic arch: will the arch grow? Hypoplasia of the transverse aortic arch of various degrees of severity is commonly seen in infants who have coarctation of the aorta. It is more often present when the coarctation is associated with intracardiac lesions that diminish or limit forward flow in the ascending aorta and promote right to left flow through an arterial duct. The increased frequency of surgical treatment of infants with complex coarctation, which is in part related to the ability to stabilize their condition with prostaglandin E1, has posed the question of the potential for growth and development of the originally hypoplastic aortic arch after conventional repair of aortic coarctation. Review of our experience with transverse aortic arch hypoplasia, found in 33 (32%) of 102 infants undergoing coarctation repair by subclavian flap aortoplasty or classic resection and end-to-end anastomosis, revealed excellent growth of the transverse arch after repair in all patients available for linear follow-up. The currently proposed extended arch repair should be reserved for the small group of infants with transverse aortic arch to ascending aorta diameter ratios (arch indices) of less than 0.25."
-"How does the left atrial pump function differ between normal subjects, patients with essential hypertension, and patients with healed myocardial infarction?","Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure-dimension relation. To analyze left atrial (LA) pump function in normal subjects, in patients with essential hypertension and in patients with a healed myocardial infarction, LA dimension (aortic-root echogram) and pressure (catheter-tip manometer) were simultaneously recorded in 25 patients (8 normal subjects, 7 with hypertension and 10 with myocardial infarction). The pressure-dimension relation of the left atrium was composed of 2 loops: the A loop (expressing the pump function of the left atrium) and the V loop. LA dimension at the beginning of active LA shortening was significantly greater in hypertensive subjects (33 +/- 3 mm) and in those with myocardial infarction (32 +/- 4 mm) than in normal subjects (28 +/- 3 mm) (p less than 0.01, p less than 0.05, respectively). The area of the A loop significantly increased in subjects with hypertension (48 +/- 3 mm Hg.mm, p less than 0.01) and in subjects with myocardial infarction (29 +/- 10 mm Hg.mm, p less than 0.05), compared with normal subjects (20 +/- 8 mm Hg.mm). The mean fractional shortening velocity of the left atrium significantly increased in subjects with hypertension, compared with normal subjects and those with myocardial infarction (p less than 0.05 for both). LA peak wall tension during the LA active contraction period significantly increased with hypertension and with myocardial infarction, compared with normal subjects (p less than 0.01, p less than 0.05, respectively). The area of the A loop was directly proportional to the LA dimension at the beginning of active LA shortening (r = 0.53), p less than 0.01)."
-What are the potential benefits and complications of using small-diameter flexible fiberscopes for visual diagnosis of spinal canal diseases?,"Observation of spinal canal and cisternae with the newly developed small-diameter, flexible fiberscopes. Small-diameter (0.5-, 0.9-, and 1.4-mm) flexible fiberscopes were developed for visual diagnosis of spinal canal diseases. The fiberscopes were introduced via a Tuohy needle into the subarachnoid and epidural spaces of ten patients with various pain syndromes. Clear visualization of the subarachnoid space was achieved using the fiberscopes. The epidural space could be visualized only during withdrawal of the fiberscope. In five cases, the fiberscope could be advanced up to the level of the cisternae without causing the patient any discomfort. A slight headache and transient fever were noted after the examination in five and two cases, respectively, but no other complications occurred. Interestingly, preexisting pain diminished (two cases) or disappeared (one case) after the myeloscopy in three of five cases in which the myeloscopy revealed aseptic adhesive arachnoiditis. Further studies should be carried out to evaluate the usefulness of this technique."
-"What is the ""cuff sign"" in the context of sonographic evaluation of pancreatic cancer and superior mesenteric artery involvement?","Thickening at the root of the superior mesenteric artery on sonography: evidence of vascular involvement in patients with cancer of the pancreas. Thickening of the root of the superior mesenteric artery (SMA) was studied by using preoperative sonography in 23 patients with pancreatic cancer and in 10 healthy control subjects. Of the 23 with cancer, 11 had neoplastic involvement of the SMA and 12 did not. Prominent thickening of the area around the SMA with (six patients) or without (five patients) decreased echogenicity compared with the adjacent retropancreatic connective tissue was observed in patients with involvement of the SMA, a finding called the ""cuff sign."" Mean thickness of the periarterial area in the cancer patients with and without involvement of the SMA and in control subjects were 8.5 mm, 4.0 mm, and 2.9 mm, respectively. With an upper limit of normal of 7.0 mm for the thickness of the SMA, the sensitivity, specificity, and overall accuracy of this sign in the evaluation of involvement of the SMA were 91%, 100%, and 96%, respectively. Decreased echogenicity of the periarterial area was not observed in patients without involvement of the SMA or in control subjects. Our results show that sonographic evidence of periarterial thickening of the root of the SMA (cuff sign), especially with decreased echogenicity, is a reliable finding of tumor infiltration of the SMA in patients with pancreatic carcinoma."
-What is the incidence of masseter muscle spasm (MMS) in children during anesthesia with succinylcholine?,"Masseter muscle spasm in children: implications of continuing the triggering anesthetic. This retrospective study was undertaken to examine the management and outcome of children who developed isolated masseter muscle spasm (MMS) after the administration of intravenous succinylcholine during anesthetic induction. The inhalation anesthetics used for induction were continued in all of these cases. The medical records of 68 patients (male/female ratio, 1.7:1), identified from approximately 42,000 anesthetics given during the period 1980-1989, were reviewed. Fifty-seven children (2.3-12 yr old) were diagnosed as having isolated MMS, i.e., MMS without spasm of other muscles; 11 experienced generalized rigidity in combination with MMS. Anesthetic and postoperative management of these two groups differed. The overall incidence of MMS was 0.3% of inhalation anesthetics during which succinylcholine was given. Intraoperative arrhythmias occurred in 33% of the patients who developed isolated MMS and more frequently in older children. Most children experienced some degree of hypercarbia and/or metabolic acidosis, but the significance of these abnormalities in the spontaneously ventilating, fasting child is unknown. Serum creatine kinase levels when measured 18-24 h postoperatively were elevated in all but one child (n = 45). There was no long-term morbidity and no mortality. We conclude that failure of the masseter muscles to relax after succinylcholine is not uncommon in children. Based on our experience, and accepting that MMS may be part of the clinical spectrum of malignant hyperthermia, we believe that anesthesia can be continued safely in cases of isolated MMS when careful monitoring accompanies diagnostic evaluation. This differs from the current practice of discontinuing the anesthetic or switching to a nontriggering anesthetic technique."
-How does unilateral brain damage in the left hemisphere affect decision-making accuracy compared to right hemisphere damage?,"Hemisphere asymmetry in decision making abilities. An experimental study in unilateral brain damage. Thirty control subjects and 60 unilateral brain-damaged patients, 30 with left hemisphere (LH) damage and 30 with right hemisphere (RH) disease, underwent a disjunctive 4-choice reaction time study. Speed of reaction (as defined by the reciprocal of reaction time (RT), movement time (MT) and total response time (TRT] and accuracy of response (as represented by the sum of errors in selecting the correct response key) were investigated comparatively as a function of side of lesion and of performance on Raven's Coloured Progressive Matrices (PM47). In contrast to movement speed (1/MT), reaction speed (1/RT) as well as total response speed (1/TRT) showed a lesion effect independent of side of damage. Conversely, accuracy was differentially impaired, LH damage being associated with a significantly higher number of errors. Speed and accuracy had different relationships with the performance on the PM47 in the two hemisphere groups. Speed was affected in parallel with changes in PM47 performance both in the LH and in RH groups, whereas accuracy was altered only in LH patients. It was concluded that speed of motor reaction is affected by unilateral brain lesions irrespective of their side, whereas decision making processes, as expressed by accuracy of response, seem to be specifically impaired by LH damage."
-"What were the key findings of the study comparing cisplatin and etoposide (PE) with cyclophosphamide, methotrexate, and fluorouracil (CMF) as first-line chemotherapy for metastatic breast carcinoma?","Cisplatin and etoposide as first-line chemotherapy for metastatic breast carcinoma: a prospective randomized trial of the Italian Oncology Group for Clinical Research. In this prospective randomized study, first-line treatment with the combination of cisplatin (P) and etoposide (E) was compared with the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in 140 patients. Complete remissions were obtained in 11% of 65 assessable patients on CMF and in 12% of 65 assessable patients on PE. Complete plus partial remission rates were 48% on CMF and 63% on PE (P = .08). Time to progression (median, 32 v 31 weeks), duration of response (48 v 39 weeks), and survival (75 v 76 weeks) were not different. Hematologic toxicity was significantly higher with PE, and gastrointestinal side effects were frequent with this treatment. This study demonstrated that the PE combination is effective as front-line chemotherapy. As far as response rate is concerned, a trend of superiority over CMF was observed, which was of borderline significance. Due to the lack of survival advantage and to toxicity, this combination is not recommended for routine clinical use. However, its high level of activity should be taken into account for further research."
-What is idiopathic colonic perforation in a neonate and how is it typically diagnosed?,"Idiopathic colonic perforation in the neonate. We describe a premature infant in whom spontaneous perforation of the colon was initially detected on routine abdominal films. There was no clinical evidence of necrotizing enterocolitis, peritonitis, or bowel obstruction. Surgical and pathologic findings confirmed the diagnosis of idiopathic bowel perforation. Since spontaneous gastrointestinal perforation in the neonate is often difficult to diagnose clinically, radiographic evaluation may allow earlier diagnosis and prompt surgical treatment of this life-threatening condition."
-What were the key determinants of outcome in the cervical cerclage study?,"Prognostic factors and complication rates for cervical cerclage: a review of 482 cases. Charts from 482 singleton pregnancies undergoing cerclage placement in patients over a 6-year period were reviewed. Cervical dilatation at time of surgery, number of previous spontaneous losses, and gestational age at placement were key determinants of outcome. The most frequent complication, premature rupture of the membranes, ultimately occurred in 38% of patients. The 6.6% infection rate was increased in patients undergoing emergent versus elective surgery (12.7% vs 4.7%, p less than 0.005) and in patients at increased dilatation at time of surgery (5.7% for less than or equal to 2 cm vs 41.7% for greater than 2 cm, p less than 0.005). McDonald and Shirodkar procedures had similar obstetric outcomes in patients undergoing their first cerclage. The subgroup of patients with prior cerclage surgery showed improved birth weight when the Shirodkar procedure was performed instead of the McDonald cerclage (mean birth weight 3020 vs 2470 gm, p less than 0.005). An increased rate of primary cesarean section was found in the Shirodkar group (31% vs 17%, p less than 0.005). Complication rates and pregnancy outcome appear to reflect cervical dilatation more than gestational age at time of surgery."
-What diagnostic tests were found to be most useful in identifying extraspinal causes of lumbosacral radiculopathy in this study?,"Extraspinal causes of lumbosacral radiculopathy. Twelve of 12,125 patients who had been referred during a seven-year period to a specialist in spinal disorders were found to have an extraspinal cause of radiculopathy or neuropathy of the lower extremity. The records of these twelve patients were reviewed retrospectively. The average age of the twelve patients was sixty-five years (range, forty-two to seventy-seven years). The cause of the symptoms was an occult malignant tumor in nine patients and a hematoma, an aneurysm of the obturator artery, or a neurilemoma of the sciatic nerve in the others. The average time from the onset of symptoms to the final diagnosis was eight months (range, one month to two years). The most useful test for determination of the correct diagnosis was computed tomography or magnetic resonance imaging of the abdomen and pelvis. Computed tomography or magnetic resonance imaging of the spine and bone-scanning of the whole body were of little help in localizing the disease. In four of the twelve patients, an operation was performed on the basis of an incorrect diagnosis. In dealing with elderly patients who have radiculopathy, one should be suspicious that the cause is outside the spine."
-What percentage of patients in the study were confirmed to have hepatitis A and hepatitis B through IgM antibody testing?,"Hepatotoxicity of rifampin and isoniazid. Is it all drug-induced hepatitis? Serologic markers for hepatitis viruses were studied in 40 children who developed acute hepatitis during antituberculosis therapy with rifampin and isoniazid, with the aim of assessing the contributory role of these viruses toward producing hepatic injury. Hepatitis A and B were confirmed in 7.5 and 35% patients, respectively, by IgM antibodies. Epidemiologic evidence suggested the possibility of non-A, non-B hepatitis in at least a few of the remaining 23 children. Hepatitis B was seen more often in children with severe tubercular disease (72%) and was largely (92.8%) parenterally transmitted. The study highlights that the endemicity of viral hepatitis in developing countries, among other factors, could also be responsible for the reported higher incidence of hepatotoxicity from developing countries and also for the increased risk of hepatotoxicity seen in severe tubercular disease."
-What are the key differences observed between women with single and multiple admissions for hyperemesis gravidarum in this study?,"Hyperemesis gravidarum. A comparison of single and multiple admissions. Recurrent hyperemesis gravidarum is a frustrating and poorly studied complication of early pregnancy. Between 1979 and 1987, 140 women with emesis severe enough to require parenteral fluid and electrolyte replacement were admitted to the Medical University of South Carolina Hospital, Charleston, on 220 occasions. Thirty-nine of the 140 women were admitted on multiple occasions. A comparison of clinical characteristics of women with single and multiple admissions revealed no significant differences except that women admitted repeatedly for hyperemesis gravidarum were more likely to be nulliparous (P less than .05). Ptyalism (59% vs. 9%) and persistent vomiting for greater than 24 hours after admission (69% vs. 23%) were significantly more common among women who were admitted repeatedly (P less than .05). Despite published reports that hyperemesis gravidarum has no impact on ultimate perinatal outcome, this study indicated that women admitted repeatedly have a more severe nutritional disturbance, associated with significantly reduced maternal weight gain and neonatal birth weight. These risks argue for more aggressive antenatal treatment and increased fetal surveillance in pregnancies complicated by recurrent hyperemesis gravidarum."
-What was the main finding of the study regarding the use of vancomycin in empirical antibiotic therapy for febrile granulocytopenic cancer patients?,"Vancomycin added to empirical combination antibiotic therapy for fever in granulocytopenic cancer patients. European Organization for Research and Treatment of Cancer (EORTC) International Antimicrobial Therapy Cooperative Group and the National Cancer Institute of Canada-Clinical Trials Group [published erratum appears in J Infect Dis 1991 Oct;164(4):832] A total of 747 febrile granulocytopenic patients with cancer were randomized to receive ceftazidime plus amikacin (CA) with or without vancomycin (V) as initial empirical therapy. Single gram-positive bacteremias responded in 29 (43%) of 68 patients treated with CA and in 48 (72%) of 67 treated with CAV (P = .001). For single gram-negative bacteremias and clinically documented and possible infections the response rates of CA and CAV were 80% and 63% (P = .17), 55% and 75% (P = .009), and 74% and 81% (P = .16), respectively. However, for patients with gram-positive bacteremia and for all other patients, there were no differences by treatment regimens in the proportion of febrile patients on each trial day (P = .85, P = .82, respectively) or in the duration of fever (P = .22, P = .93, respectively). Moreover, no patient with gram-positive bacteremia died during the first 3 days of true empirical therapy. Antibiotic-associated nephrotoxicity was more frequent in patients treated with vancomycin (6% vs. 2%, P = .02). These results do not support the empirical addition of vancomycin to initial antibiotic therapy in cancer patients with fever and granulocytopenia."
-What are the key enzymes involved in the bioconversion of primaquine's side chain?,"The conversion of primaquine into primaquine-aldehyde, primaquine-alcohol, and carboxyprimaquine, a major plasma metabolite. Although efficacy and toxicity of primaquine (PQ) depend on bioconversion, the process is poorly understood, even for carboxyprimaquine (CPQ), the major plasma metabolite. Earlier work to clarify drug metabolism showed that PQ could be converted quantitatively into CPQ, in vitro, with human erythroleukemic K562 cells or nonleukemic bone marrow supplemented with calf serum. We have now found--using systems with serum only, as well as with K562, bone marrow, and adult or embryonic liver cells--that the bioconversion of the side chain of PQ involves a branched pathway with at least three separate enzymes and two derivatives other than CPQ. An oxidase activity in serum converted PQ first into a novel side chain aldehyde (Y). Aldehyde dehydrogenase transformed PQ-aldehyde into CPQ in cell-free systems and in K562, bone marrow, and adult liver cells. Embryonic hepatocytes or bone marrow treated with 1,3-bis(2-chloroethyl)-1-nitrosourea did not produce CPQ; instead, they made a metabolite (Xc) that we could synthetize via PQ-aldehyde and identify as PQ-alcohol. PQ-alcohol replaced CPQ as the final product whenever alcohol-dehydrogenase prevailed over aldehyde dehydrogenase. These enzymes operated in intact cells and controlled the biotransformation of PQ absolutely. Unless both dehydrogenase were absent, inhibited, or deprived of coenzyme, potentially cytotoxic PQ-aldehyde intermediate did not accumulate. Some of the unique tissues schizonticidal and gametocidal effects of PQ may depend on the distribution pattern and relative activities of PQ oxidase, aldehyde dehydrogenase, and alcohol dehydrogenase in human subjects and in parasites."
-What is an inflammatory pseudotumor of the liver and how was it treated in this case report?,"Inflammatory pseudotumor of the liver causing biliary obstruction. Treatment by biliary stenting with 5-year follow-up. Inflammatory pseudotumors of the liver are rare lesions that are becoming increasingly recognized, possibly because of frequent use of abdominal computed tomography (CT) and ultrasonography. Most previously reported cases have been treated by hepatic resection. For this reason, we describe a patient with obstructive jaundice secondary to an inflammatory hepatic pseudotumor in the porta hepatis. Bilateral internal biliary stents were inserted, and the patient remains well 5 years later. The clinicopathologic features of inflammatory pseudotumors of the liver are described, as are the implications of accurate diagnosis. There have been no previous reports of biliary stenting in management of inflammatory hepatic pseudotumors."
-What percentage of patients with syncope were found to have orthostatic hypotension in this study?,"Syncope and orthostatic hypotension. PURPOSE: The purpose of this study was to determine the postural blood pressure response over time, the prevalence of orthostatic hypotension in patients with syncope, and the relationship of orthostatic hypotension to recurrence of symptoms. PATIENTS AND METHODS: We prospectively evaluated 223 patients with syncope in a standardized manner. Orthostatic responses were measured in a standardized fashion at 0, 1, 2, 3, 5, and 10 minutes or until symptoms occurred. Follow-up was obtained at 3-month intervals. Causes of syncope were assigned by predetermined criteria. RESULTS: Orthostatic hypotension (20 mm Hg or greater systolic blood pressure decline) was found in 69 patients (31%). The median time to reach minimal standing systolic blood pressure was 1 minute for all subjects. In patients with orthostatic hypotension (20 mm Hg or greater), mean time to reach minimum blood pressure was 2.4 minutes. The vast majority of patients with significant orthostatic hypotension had this finding within 2 minutes of standing. Orthostatic hypotension was common in patients for whom other probable causes of syncope were assigned. The recurrence of syncope was not related to the degree of orthostatic hypotension; however, the recurrence of dizziness and syncope as end-points was lower in patients with 20 mm Hg or greater systolic blood pressure reductions as compared with patients with lesser degrees of orthostatic blood pressure declines. CONCLUSION: Orthostatic hypotension is common in patients with syncope and is detected in the vast majority of patients by 2 minutes. Although symptom recurrence on follow-up was lower in patients with more severe orthostatic hypotension, the clinical significance of this finding needs to be further defined by future studies."
-What did the meta-analysis reveal about the effectiveness of prophylactic antibiotics in head and neck surgery?,"A meta-analysis of prophylactic antibiotics in head and neck surgery. Although it is generally agreed that prophylactic antibiotics are necessary for the prevention of postoperative wound infection, the choice of antibiotic regimen is controversial. In an attempt to determine the most effective antibiotic regimen, a meta-analysis of published clinical trials of prophylactic antibiotics for head and neck surgery was undertaken. The meta-analysis revealed a relative difference in infection rates of 43.7 percent in favor of the use of antibiotics versus placebo, of 8.3 percent in favor of multiple antibiotics versus a single antibiotic, of 13.7 percent in favor of multiple antibiotics versus cefazolin, and of 4.1 percent in favor of multiple-day prophylaxis versus single-day prophylaxis. This meta-analysis suggests that a 1-day course of clindamycin may be the most effective prophylactic antibiotic regimen for head and neck surgery."
-What are the key immunohistochemical and electron microscopic findings of the ossifying fibromyxoid tumor of soft parts?,"Ossifying fibromyxoid tumor of soft parts. Additional observations of a distinctive soft tissue tumor. The author studied four subcutaneous soft tissue tumors, similar to those recently described by Enzinger and associates (Am J Surg Pathol 1989;13:817) by the name ""ossifying fibromyxoid tumor,"" by immunohistochemistry and electron microscopy to further understand the cellular nature of this lesion. The four tumors were composed of uniform round cells often surrounded by a lacunar space. The tumors often contained a peripheral zone of metaplastic bone. The cellularity was high, but the mitotic rate was low, suggesting a benign or borderline nature of the lesion. Longer follow-up was available for three cases, showing recurrence-free survival times of 11, 8, and 3 years. Immunohistochemistry studies revealed that all tumors were strongly positive for S-100 protein and focally positive for Leu-7, whereas melanoma-specific marker HMB45 was negative. Vimentin was the main type of intermediate filament protein, and one case also contained scattered glial fibrillary acidic protein-positive cells. Epithelial markers (keratins, epithelial membrane antigen), desmin, and muscle actins were negative. Electron microscopic examination showed partial, sometimes reduplicated, basal lamina surrounding many cells. Complex cell processes were also present. No myofilaments were found. The immunohistochemical and electron microscopic results may suggest that this tumor has Schwann's cell differentiation."
-What changes in colonic mucosal blood flow were observed after exposure to 10% acetic acid in the rat study?,"Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. The hypothesis that a significant reduction in colonic mucosal perfusion, and hence ischemic injury, precedes the development of mucosal ulceration and inflammation is tested in this report. The microcirculatory changes in the rat colonic mucosa within 1 hr of topical exposure to 10% acetic acid were assessed. Colonic mucosal blood flow signals measured by laser Doppler flowmetry were significantly reduced to 61 +/- 8, 52 +/- 10, and 37 +/- 13% (mean +/- SEM) of baseline values at 1 min, 4 min, and 10 min after the colonic mucosa was exposed to 10% acetic acid, respectively, but not in controls exposed to saline. After the start of application of 10% acetic acid (for 4 min), in vivo microscopy studies demonstrated that colonic mucosal ischemia (stasis of the red blood cells in the mucosal capillaries) occurred at 9 +/- 5 min (mean +/- SEM). Evidence of endothelial cell death (failure to exclude a fluorescent dye, propidium iodide, by endothelial cells) developed at 25 +/- 10 min (mean +/- SEM). These findings indicate that within minutes after contact of the colonic mucosa with 10% acetic acid, colonic mucosal ischemia develops, followed shortly by death of endothelial cells. The data do not establish a cause-and-effect relationship between the reductions in mucosal blood flow and loss of endothelial cell viability in response to acetic acid. Nevertheless, because these events occur at such an early time point, they may play a pathogenetic role in the development of the subsequent inflammatory and ulcerative changes in this animal model of colitis. Further studies to define the potential causal relationships between these parameters are warranted."
-What alternative agents were used in epidural infusions for patients with intractable non-cancer pain?,"Sufentanil citrate and morphine/bupivacaine as alternative agents in chronic epidural infusions for intractable non-cancer pain. Intraspinal narcotic (usually intrathecal morphine) infusions with implanted pumps are increasingly used in patients with intractable chronic pain not caused by cancer. In some patients, pain control is difficult with infusions of morphine. Seven patients with diagnoses of arachnoiditis, epidural scarring, and/or vertebral body compression fracture were treated with alternative solutions in an epidural route. For maximal flexibility, Medtronic implanted programmable infusion pumps with catheters to T6-T10 were used, and pain was monitored by verbal pain scales. In three patients, epidural infusions of morphine in 0.5% bupivacaine (MS-MARC) resulted in little or no pain relief without significant side effects (e.g., headache, nausea, or vomiting). In these same patients, epidural infusions of sufentanil citrate resulted in pain scale reductions of 92%, 82%, and 40%, respectively, with no side effects. Four other patients found more effective pain relief when switched from initial sufentanil citrate infusions to MS-MARC. Pain scale reductions (with no side effects) were 92%, 76%, 59%, and 47% in these patients. Pain relief and minimal side effects with sufentanil citrate is theorized to result from its higher lipophilicity promoting local transdural diffusion to spinal cord and limiting upward diffusion to the brain stem. Sufentanil citrate is also advantageous for programmable pumps because it is 100 times more potent than morphine and therefore allows longer pump refill times and higher infusion doses. Although this study was done on a limited number of patients, sufentanil citrate and MS-MARC in epidural infusions using programmable infusion pumps for non-cancer patients provide significant alternative drug combinations and routes."
-How does the HIV-1 protease affect the processing of the NF-kappa B precursor (p105) during infection?,"Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. Transcription of the human immunodeficiency virus type-1 (HIV-1) genome is regulated in part by cellular factors and is stimulated by activation of latently infected T cells. T-cell activation also correlates with the induction of the factor NF-kappa B which binds to two adjacent sites in the HIV-1 long terminal repeat. This factor consists of two DNA-binding subunits of relative molecular mass 50,000 (50K) associated with two 65K subunits. It is located in the nucleus in mature B cells, but is present in other cell types as an inactive cytoplasmic complex. External stimuli, including those that activate T cells, result in nuclear translocation of active NF-kappa B. The cloning of the complementary DNA for the 50K subunit helped to identify an exclusively cytoplasmic 105K precursor (p105) (V.B., P.K. and A.I., manuscript submitted). The expression of active NF-kappa B might therefore also be regulated by the extent of processing of p105. Because HIV-1 requires active NF-kappa B for efficient transcription, we tested the effect of HIV-1 infection on the processing of the human 105K precursor. We show here that the HIV-1 protease can process p105 and increases levels of active nuclear NF-kappa B complex."
-How does Trichinella spiralis infection affect small intestinal motor activity and transit time?,"Trichinella spiralis infection alters small bowel motor activity in the fed state. The effect of Trichinella spiralis infection on small intestinal transit and motor activity in the fed state during the intestinal phase of infection was studied. Contractions were recorded by strain gauge transducers, and mean transit time was measured by marker dilution technique. The mean amplitude and area of individual phasic contractions decreased, but no change occurred in their mean duration during trichinosis. The total amplitude and area of phasic contractions also decreased; this was caused by a decrease in the frequency of contractions as well as a decrease in the mean parameters. The reduction in the total duration was entirely caused by the decrease in frequency. The reduction in the total parameters of all contractions was the result of a reduction in the same parameters for both propagating and nonpropagating contractions. However, the decrease in the parameters of propagating contractions was much greater. Also, there was a decrease in the distance of propagation of phasic contractions. The transit time as a result of phasic contractions increased during T. spiralis infection. Additionally, T. spiralis infection induced giant migrating contractions in the fed state that were never observed during control. Chyme was propelled very rapidly and effectively by giant migrating contractions. The findings of the present study suggest that during diarrhea induced by T. spiralis infection, the phasic contractions may act to decrease transit and, hence, allow more contact time for absorption of water and nutrients. However, this response may be counter-balanced by giant migrating contractions that rapidly propel chyme into the colon and compound the diarrhea associated with T. spiralis infection."
-What is the significance of the STRO-1 monoclonal antibody in identifying stromal cell precursors in human bone marrow?,"Identification of stromal cell precursors in human bone marrow by a novel monoclonal antibody, STRO-1. Murine IgM monoclonal antibody STRO-1 identifies a cell surface antigen expressed by stromal elements in human bone marrow (BM). STRO-1 binds to approximately 10% of BM mononuclear cells, greater than 95% of which are nucleated erythroid precursors, but does not react with committed progenitor cells (colony-forming unit granulocyte-macrophage [CFU-GM], erythroid bursts [BFU-E], and mixed colonies [CFU-Mix]). Fibroblast colony-forming cells (CFU-F) are present exclusively in the STRO-1+ population. Dual-color cell sorting using STRO-1 in combination with antibody to glycophorin A yields a population approximately 100-fold enriched in CFU-F in the STRO-1+/glycophorin A+ population. When plated under long-term BM culture (LTBMC) conditions, STRO-1+ cells generate adherent cell layers containing multiple stromal cell types, including adipocytes, smooth muscle cells, and fibroblastic elements. STRO-1+ cells isolated from LTBMC at later times retain the capacity to generate adherent layers with a cellular composition identical to that of the parent cultures. The STRO-1-selected adherent layers are able to support the generation of clonogenic cells and mature hematopoietic cells from a population of CD34+ cells highly enriched in so-called long-term culture-initiating cells. We conclude that antibody STRO-1 binds to BM stromal elements with the capacity to transfer the hematopoietic microenvironment in vitro."
-What was the success rate of the percutaneous posterolateral lumbar discectomy procedure in this study?,"Percutaneous posterolateral lumbar discectomy and decompression with a 6.9-millimeter cannula. Analysis of operative failures and complications. The operative failures and complications of percutaneous posterolateral lumbar discectomy were analyzed in 100 patients who had a herniated nucleus pulposus and were prospectively studied and treated with use of a 6.9-millimeter outer-diameter (4.9-millimeter inner-diameter) sheath and manual insertion of the instruments. Twelve operations were considered to have failed, regardless of the length of postoperative follow-up or the incidence of reinjury; eleven patients had a repeat operation at the index level, and one patient was a chronic drug-abuser. In eight of the eleven patients, subsequent laminectomy was successful. Two patients had a psoas hematoma and one had a transitory sensory and distal motor deficit; all of these complications resolved without sequelae. There were no major complications, including superficial or deep infection, and no patient had neurovascular compromise."
-What factors contribute to the varying prevalence of obesity across different population groups?,"Obesity in minority populations: policy implications of research. Obesity is a major health problem for many Americans, with an overall prevalence for adults of approximately 25% and a range for specific subgroups of 24-75%. This range is striking and reflects many factors shown to influence the development and maintenance of obesity, including physical activity, diet, ethnicity, income, education, and genetic susceptibility. Many minority populations have higher prevalences of obesity and, thus, experience its adverse health consequences disproportionately. Research in diverse populations indicates that the relative importance of risk factors for cardiovascular disease varies in many populations. Data characterizing the profile of risk factors, including obesity and physical activity, for various special populations are limited and some, such as obesity, are based on standards developed in the general population. For public health policy and interventions to succeed, they must address the needs of special populations and of the overall population. This paper discusses some of the relevant broader social and research issues."
-What method was used to evaluate body composition in alcohol-induced migraine patients?,"Bioelectrical impedance assay (BIA) of total body composition in alcohol-induced migraine patients. Preliminary report. ""Whole body composition"" was investigated in 30 people subject to alcohol-induced migraine. The control group was 30 people matched for age, sex, height and weight, who were not subject to migraine and who consumed moderate amounts of alcohol. The following were evaluated: anthropometric data, alcohol intake in grams per day, total body water, fat-free mass, fat mass, and body mass index (kg/m2). Two methods of measurement were used: skin fold thickness evaluation, and bioelectric impedance assay (BIA). BIA is a non-invasive method based on the principle that lean tissues conduct a low frequency alternating current of electricity better than do fatty tissues. Body mass index was increased in the alcohol-induced migraine patients (p less than 0.04), as was fat mass, (p less than 0.03) as evaluated by skin fold measurements. Bioelectric impedance assay demonstrated a slight total body water increase in alcohol-induced migraine patients (p less than 0.07). Possibly, if this total body water increase was reflected at the neuronal level, the bioelectric properties of the migrainous brain may be altered, thus creating a hypothetical link with the phenomenon of spreading depression."
-What percentage of families with alcohol-related problems were identified by physicians in the study?,"Detection of alcoholism in hospitalized children and their families The study sought to measure provider recognition of family alcohol-related problems among hospitalized children and to identify characteristics distinguishing ""positive"" families. The study sample (N = 147) was drawn from admissions to the general pediatric medical service of a metropolitan teaching hospital. Positivity was assessed through parent and patient interviews that included standard alcohol abuse screening instruments. Provider recognition was assessed through record review and physician interview. Of the 22 families screened positive, only one was so identified by the child's attending or resident physician. Positive and ""negative"" families were similar in most respects, although parents in positive families were more likely to report stress and sleeping problems and adolescents were more likely to report being troubled by a parent's drinking. The similarity of positive and negative families and the low pediatrician recognition rate suggest that alcohol problems are likely to go unnoticed without a conscious screening effort."
-What is Generalized Resistance to Thyroid Hormone (GRTH) and how was it detected in this case study?,"Neonatal detection of generalized resistance to thyroid hormone [published erratum appears in JAMA 1991 Feb 20;265(7):869] Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. We detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L (normal, 84 to 232 nmol/L). Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels (liothyronine sodium, 21 micrograms/kg per day, and levothyroxine sodium, 44 micrograms/kg per day) were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH."
-What were the clinical results and Harris hip ratings for different types of hip prostheses in this study?,"Total hip replacement with cemented, uncemented, and hybrid prostheses. A comparison of clinical and radiographic results at two to four years. One hundred and thirty-one patients who had 144 cemented or uncemented hip prostheses were followed prospectively for two to four years. A cemented or a hybrid prosthesis (consisting of a cemented femoral component and an uncemented acetabular component) was used in men older than seventy years, in women older than sixty years, and in younger patients in whom adequate initial fixation could not be obtained without cement. Uncemented, porous-surfaced implants were used in all other patients. The over-all clinical results were similar for the three groups. For the fifty-two hips that had a cemented prosthesis, the mean total Harris hip rating was 91 points and the score for pain, 42 points; for the twenty-seven hips that had a hybrid prosthesis, 90 and 43 points; and for the sixty-five hips that had an implant allowing ingrowth of bone in both the acetabulum and the femur, 95 and 43 points. Two prosthetic stems that were designed to allow ingrowth of bone had aseptic loosening; one was revised. Pain in the thigh, usually slight and not disabling, occurred at one year in 24 per cent of the patients in whom a femoral component allowing ingrowth had been used; the prevalence of pain then declined. The incidences of migration of the components and of radiolucent lines were greater in the acetabula that had a cemented component than in those that had a cup allowing ingrowth of bone."
-What was the effect of oral nitroglycerin on portal blood velocity in cirrhotic patients according to this study?,"The effect of oral nitroglycerin on portal blood velocity as measured by ultrasonic Doppler. A double blind, placebo controlled study. We studied the effect of oral nitroglycerin on portal blood velocity (PBV) in 20 cirrhotic patients by a double blind, placebo controlled method using noninvasive Doppler sonography. After we obtained baseline Doppler in the fasting state, 0.6 mg nitroglycerin or placebo was given orally and the mean of 3 s averaged mean PBVs was repeated at 5 min intervals for 60 min. Ten patients each received nitroglycerin or placebo. Portal vein flows were antegrade in all. Of the 10 patients receiving nitroglycerin, seven (P = 0.002) showed a greater than 10% fall in the mean PBVs for at least 15 min. Of these seven ""responders,"" five patients had a 10% decrease in mean systemic blood pressure for at least 15 min. None of the ""nonresponders"" had systemic hypotension. Our study suggests that the PBV-reducing effect of nitroglycerin in cirrhotics may be explained in part by systemic hypotension."
-What factors were considered in determining the safety of vaginal delivery for the second twin?,"Twin delivery: influence of the presentation and method of delivery on the second twin. To ascertain the perinatal mortality and morbidity in the second twin as related to its presentation and method of delivery, we reviewed the data on 578 sets of twins delivered from 1980 to 1987 and included 397 sets in whom both twins were greater than or equal to 1000 gm, without lethal anomalies, and in whom the first twin presented as a vertex. The perinatal outcome comparing twin A (all vertex) with twin B (vertex or nonvertex) with cesarean section or vaginal delivery was analyzed. No statistically significant difference in perinatal mortality or morbidity was found in comparing the nonvertex second twin delivered vaginally or by cesarean section. The one perinatal death and significant perinatal morbidity occurred in infants weighing less than 1500 gm or at less than 32 weeks' gestational age. It is concluded that vaginal delivery, irrespective of the position of the second twin, is valid in selected cases as long as fetal weight is greater than 1500 gm and the gestational age is greater than or equal to 32 weeks."
-What was the objective response rate of menogaril in patients with cisplatin-refractory advanced ovarian carcinoma?,"A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic. Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment."
-What were the key findings of the study comparing calcium channel receptors in normal and myelodysplastic bladders?,"The binding and functional properties of voltage dependent calcium channel receptors in pediatric normal and myelodysplastic bladders. The present study was designed to compare the binding and functional properties of calcium channel receptors in normal and myelodysplastic bladders. Normal bladders were obtained from children with vesicoureteral reflux undergoing ureteral reimplantation. Myelodysplastic bladder specimens were obtained from patients undergoing bladder augmentation. The functional studies included agonist (calcium chloride) dose response experiments and the determination of apparent antagonist dissociation constants for various calcium channel antagonists. The receptor binding studies were performed using the ligand (+)-3H-PN200-110 (specific activity 86.6 Ci./mmol.). The mean maximal response of myelodysplastic bladders to calcium ions was 31% less than normal bladders (p greater than 0.05). The mean EC50 for calcium mediated isometric tension and the mean -log antagonist dissociation constant values of nifedipine, diltiazem and verapamil were similar in normal and myelodysplastic bladders. The radioligand receptor binding studies demonstrated that the equilibrium dissociation constant of (+)-3H-PN200-110 in myelodysplastic bladders was 4-fold greater than in normal bladders. The density of dihydropyridine binding sites in myelodysplastic and normal bladders was similar. Our study demonstrated that the pathophysiology of the poorly compliant hyperreflexic bladder is not related to up regulation of dihydropyridine calcium channel receptors or alterations in the response of detrusor muscle to calcium ions. The relative abundance of calcium channel receptors in the normal and myelodysplastic bladders, and the regulation of detrusor contraction by calcium ions suggest that calcium channel receptors have a meaningful role in detrusor function."
-What did the study reveal about the relationship between IgA2 allotypes and IgA nephropathy in Black patients?,"IgA nephropathy in blacks: studies of IgA2 allotypes and clinical course. The prevalence of IgA nephropathy (IgAN) varies among racial groups, being most common among Caucasians and Orientals and rare in Blacks. Other investigators have hypothesized that the risk for IgAN may be influenced by the IgA2 allotype. It has been suggested that the rare Black patients with IgAN may be homozygous for the A2m(1) allele which predominates in Whites, but is less common in Blacks. In a multicenter study, 27 Black IgAN patients were enrolled to investigate this hypothesis and analyze the clinical course of disease in Blacks. The IgA2 allotypes of 18 Black patients and 14 controls were determined using restriction fragment length polymorphism analysis. Three patients were homozygous for the A2m(1) allele, four were homozygous for A2m(2) and 11 were heterozygous. The respective allelic frequencies of A2m(1) and A2m(2) were 0.47 and 0.53 and did not differ significantly from Black controls. Most clinical manifestations of disease did not significantly differ with respect to distribution of the two alleles, although the gender ratio differed between the homozygous A2m(1) and heterozygous patients. The presence of the A2m(1) allele did not increase the risk for IgAN, and the presence of the A2m(2) allele or homozygosity for this allele did not protect Blacks from the development of IgAN."
-What diagnostic tests were performed on patients with angina pectoris-like pain and normal coronary angiograms?,"Coronary artery vasoregulation and left ventricular function in patients with angina pectoris-like pain and normal coronary angiograms. Twenty patients with angina pectoris-like pain, normal coronary angiography and abnormal exercise 201Tl scans were investigated by means of haemodynamic, coronary sinus blood flow and lactate determinations before and after cold provocation, pacing and dipyridamole infusion. Radionuclide angiography, a new exercise 201Tl scan and noninvasive hyperventilation and ergonovine tests were performed. Intracoronary infusions of acetylcholine were given in increasing doses and a second coronary angiogram in combination with a 201Tl scintigram was performed. Despite a previously pathological 201Tl scintigram, with reversible perfusion defects, only ten of the patients had reversible perfusion defects at the second investigation. Hyperventilation and ergonovine tests did not result in ECG signs indicative of coronary spasm. Intracoronary infusion of acetylcholine resulted in a diffuse coronary constriction in 3 of 14 patients, and in one patient a perfusion defect was observed on thallium scintigram. In conclusion, although most of the common methods for inducing coronary vasospasm were used, no consistent pattern of reaction was found to explain the chest pains experienced in this group of patients."
-What are the key pathological characteristics of Erdheim-Chester disease?,"Erdheim-Chester disease. Case report with autopsy findings. Erdheim-Chester disease is a rare pathologic entity characterized by symmetrical radiodensities in the metaphyseal and the diaphyseal portions of the long bones. Fibrosis, osteoblastic cortical bone deposition, and fibroxanthomatous granulomas with lipid-laden macrophages and multinucleated giant cells, which have a particular tropism for connective and adipose tissues, are the pathologic hallmarks. To our knowledge, 27 cases have been reported in the literature since the entity was first described in 1930. Protean clinical features range from a focal and asymptomatic process to a multisystemic infiltrative disease. We describe the clinical course of a new case and review the extensive pathologic findings at autopsy, including those demonstrated by light and electron microscopy and cytochemical and immunocytochemical studies."
-What were the minor complication rates for different trocar insertion methods in this laparoscopic study?,"Comparison of direct insertion of disposable and standard reusable laparoscopic trocars and previous pneumoperitoneum with Veress needle. A randomized prospective study was conducted to evaluate the ease of use and safety of direct insertion of laparoscopic trocars. Comparison of previous pneumoperitoneum by Veress needle insertion with direct insertion of the reusable conventional laparoscopic trocar and direct insertion of the disposable shielded trocar revealed minor complication rates of 22, 6 and 0%, respectively. No major complications occurred in this series of 200 patients."
-What percentage of acoustic tumors showed no detectable growth or apparent regression in this conservative treatment study?,"Conservative treatment of patients with acoustic tumors. Seventy of 178 patients with acoustic tumors initially were treated conservatively and have been followed up for an average of 26 +/- 2 months. The tumor size was determined by the mean maximum anteroposterior and mediolateral diameters, using computed tomographic or magnetic resonance imaging scans obtained sequentially throughout the follow-up period. The average tumor growth was 1.6 +/- 0.4 mm the 1st year, and 1.9 +/- 1.0 mm the 2nd year (range, -2 to 17 mm/y): 4 tumors showed apparent regression, 28 (40%) had no detectable growth, and 37 (53%) exhibited growth (average, 3.8 +/- 1.2 mm/y). Within individual patients, the tumor growth rate determined during the 1st year of follow-up was predictive of tumor growth rate determined during the following year. Rapid tumor growth or clinical deterioration in 9 of the 70 patients (13%) who initially were treated conservatively necessitated subsequent surgery an average of 14 +/- 5 months after the patient was initially seen. This group had a larger initial tumor size (27.0 +/- 3.4 mm vs. 21.3 +/- 0.9 mm, P less than 0.05), and a faster 1-year growth rate (7.9 +/- 2.3 mm/y vs. 1.3 +/- 0.3 mm/y, P less than 0.05) than the 61 patients who did not require surgery. Two patients, however, experienced neurological deterioration that required surgery, even though there was no tumor growth. The high incidence of acoustic tumors with no detectable growth or apparent spontaneous regression must be taken into account when evaluating the indications for surgery and the efficacy of radiotherapy."
-What is the rare medical condition described in this case report involving a plasmacytoma and superior vena cava syndrome?,"Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described."
-How does hypoxic ventilation affect the pulmonary arterial pressure-flow relationship in a canine preparation?,"Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation. We investigated the effects of hypoxic ventilation on the pulmonary arterial pressure- (P) flow (Q) relationship in an intact canine preparation. Mean pulmonary P-Q coordinates were obtained during hypoxic ventilation and during ventilation with 100% O2 at normal and at increased left atrial pressure. Specifically, we tested the hypothesis that, over a wide range, changes in left atrial pressure would alter the effects of hypoxic ventilation on pulmonary P-Q characteristics. Seven dogs were studied. When left atrial pressure was normal (5 mmHg), the mean value of the extrapolated intercept (PI) of the linear P-Q relationship was 10.9 mmHg and the slope (incremental vascular resistance, IR) of the P-Q relationship was 2.2 mmHg.l-1.min. Hypoxic ventilation increased PI to 18 mmHg (P less than 0.01) but did not affect IR. Subsequently, during ventilation with 100% O2, when left atrial pressure was increased to 14 mmHg by inflation of left atrial balloon, PI increased to 18 mmHg. IR was 1.6 mmHg.l-1.min. Again, hypoxic ventilation caused an isolated change in PI. Hypoxia increased PI from 18 to 28 mmHg (P less than 0.01). As in the condition of normal left atrial pressure, hypoxic ventilation did not affect IR. We conclude that, in an anesthetized intact canine preparation, hypoxic ventilation causes an isolated increase in the extrapolated pressure intercept of the pulmonary P-Q relationship. Furthermore the effects of hypoxic ventilation on pulmonary P-Q characteristics are not affected by the resting left atrial pressure."
-What is the significance of detecting antineutrophil cytoplasmic antibodies (ANCA) in classifying patients with necrotizing arteritis?,"Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. PURPOSE: Assessment of the value of determination of antineutrophil cytoplasmic antibodies (ANCA) and its specificities for classification of patients with biopsy-proven necrotizing arteritis. PATIENTS AND METHODS: The serum samples of 28 consecutive patients with biopsy-proven vasculitis involving medium- and/or small-sized arteries were tested for ANCA by an indirect immunofluorescence technique, by neutrophil extract enzyme-linked immunosorbent assay (ELISA), and by catching ELISA. RESULTS: Eight patients had Churg-Strauss syndrome; six had myeloperoxidase (MPO) antibodies, and in the other two patients, ANCA were not detected. Six patients had polyarteritis nodosa (PAN) limited to the skin and the musculoskeletal system; ANCA were not detected in these patients. Two patients had systemic PAN and both had MPO antibodies. The remaining 12 patients had overlapping clinical features of the different forms of vasculitis. Five patients had polyarteritis in combination with chronic nasal inflammation and glomerulonephritis compatible with Wegener's granulomatosis (WG) but without granulomas in the respiratory tract. All five patients had 29-kd serine protease antibodies. Two patients had polyarteritis in combination with nasal polyposis and asthma compatible with Churg-Strauss syndrome, but eosinophilia was not detected. Both patients had MPO antibodies. Three patients with unclassified granulomatous arteritis had either elastase antibodies or ANCA of unknown specificity. One patient with unclassified systemic vasculitis had 29-kd serine protease antibodies, and one patient with necrotizing arteritis of the bowel in combination with Schonlein-Henoch purpura was negative for ANCA. CONCLUSION: Determination of ANCA and its specificities is a useful adjunct to the classification of patients with biopsy-proven necrotizing arteritis. Within the spectrum of idiopathic vasculitides, 29-kd serine protease antibodies are associated with WG, MPO antibodies are associated with Churg-Strauss syndrome and systemic PAN, and PAN limited to the skin and the musculoskeletal system is not associated with ANCA."
-What are the current challenges in lung transplantation despite its improved success rates?,"Current status of lung transplantation. Techniques and indications for single and bilateral lung transplantation have evolved significantly in the past several years. Lung transplantation has entered a new era in which transplantation can be achieved with the same degree of success as that achieved with other major organ transplants. Many problems, common to organ transplantation remain to be solved including availability of suitable donor organs, improved immunosuppressive regimens, and the ability to properly diagnose and effectively treat organ rejection."
-What percentage of patients experienced complications in this five-year vascular audit?,"Five-year vascular audit from a district hospital. Vascular patients under the care of one surgeon over a 5-year period have been reviewed, from computer-based discharge records, with regard to in-hospital measures of outcome to determine whether or not surgery was being performed to an acceptable standard. Out of 466 procedures, 30 per cent of patients had at least one complication, 14 per cent had further surgery and 9 per cent died. Outcome was examined within the following treatment groups: aorto/iliac aneurysm, aortofemoral bypass, femoroproximal popliteal bypass, femorodistal popliteal bypass, femorocrural bypass, embolectomy and percutaneous transluminal angioplasty. Patients having below-knee bypass surgery were found to have an unacceptably high rate of complications, reoperations and amputations. An overall rate of reoperation for postoperative bleeding of 5 per cent was also considered to be high. With these exceptions, it was concluded that the surgery was being performed to an acceptable standard, but that comparative audit of this type remained difficult while there was a deficiency of national statistics against which the work of individual surgeons could be judged."
-What were the most common causes of persistent vegetative state (PVS) among the patients in this study?,"Clinical characteristics of patients in the persistent vegetative state Little is known concerning the specific clinical characteristics of patients in persistent vegetative states (PVS). Fifty-one patients from four nursing homes, approximately 3% of the total patients, were identified as being in a PVS. The mean age of the patients was 64.8 +/- 3.2 years (range, 19 to 96 years) and the mean duration of the PVS was 3.3 +/- 5.0 years (range, 1 to 16.8 years), with 13 patients' PVS being longer than 5 years. Cerebrovascular accidents and dementia were the most common causes of the PVS, accounting for 32 of the cases (63%). In the younger patients cerebral trauma secondary to motor vehicle accidents was the most common cause. All 51 patients were fed via tube feeding and 35 patients had urinary catheters (75%). All patients were receiving daily medications, with greater than 50% taking daily vitamins. Over 30% were taking digitalis and/or diuretics and over 32% were taking H2 blockers. Transfer of patients to an acute care hospital was not uncommon, with 31 patients (61%) requiring 63 acute care hospitalizations during their stay in the nursing home. As expected, infections were the most common reason for acute care hospitalization, although 15 of the patients were hospitalized for surgical procedures. Another common problem encountered by the patients was pressure sores, with 78% of patients requiring specific therapy for at least one pressure sore. Surprisingly, only 27 (53%) of 51 patients had a specific resuscitation status designation in the medical chart, and neither presence of a chart designation nor specific resuscitation order was related to the patient's age or the cause or duration of PVS. From these data it would appear that clinical characteristics of patients in PVS are variable. Some patients are young, others are old. The cause varies from cerebrovascular accidents to cerebral trauma. Survival may be prolonged; complications are not uncommon, with some patients requiring acute care hospitalization."
-What was the distribution of ischemic episodes in patients with stable angina pectoris during a 24-hour period?,"Attenuation of circadian variation by combined antianginal therapy with suppression of morning and evening increases in transient myocardial ischemia. The circadian variation of total ischemic activity was examined during 3289 hours of ambulatory ECG monitoring in 101 patients with stable angina pectoris and proved coronary artery disease, who were not receiving any prophylactic antianginal therapy. The 101 patients displayed 411 episodes of ischemia, 312 (76%) of which were silent; a circadian rhythm was noted for the occurrence of total and silent ischemia. Thirty-eight percent of the ischemic episodes occurred between 6 AM and 12 noon, and total and silent ischemia were significantly more frequent during this period compared with the other three 6-hour periods (p less than 0.01); a lesser peak was noted in the evening. The effects of metoprolol and combined therapy with metoprolol and nifedipine on the circadian variation of ischemic activity were studied in two subgroups of patients in a random, double-blind study design (31 patients receiving metoprolol and 42 receiving combined therapy). During therapy with metoprolol the morning increase in ischemic activity was attenuated, and the highest frequency of ischemia was then noted in the evening (6 AM to 12 noon compared with 6 PM to 12 midnight; p less than 0.05). Combined therapy abolished the morning peak as did metoprolol monotherapy, but even the evening increase in ischemic activity was attenuated (p less than 0.05). The diurnal distribution of the mean heart rate at the onset of ischemia, when patients were off therapy, showed a morning increase similar to the increase in ischemic activity but no second peak in the evening."
-What is lymphedema-distichiasis syndrome and why is it important for ophthalmologists to be aware of it?,Hereditary lymphedema and distichiasis. Two patients with lymphedema-distichiasis syndrome illustrate that both Milroy's disease and late-onset hereditary lymphedema are sometimes associated with distichiasis. It is important for ophthalmologists to be aware of the lymphedema-distichiasis syndrome because of its ophthalmic manifestations and the associated systemic abnormalities that can be potentially life threatening.
-What is the primary goal of rapidly controlling severe hypertension?,"Management of hypertensive emergencies: changing therapeutic options. Rapid lowering of severe hypertension is essential to prevent irreversible damage to vital organs. The patient's clinical status should be evaluated, noting particularly cardiac, neurologic, and renal functions. Choice of treatment should be based on speed and efficacy of action and on hemodynamic, vascular, and renal consequences. It is also important to preserve circulatory homeostasis and vital organ function. Sodium nitroprusside, labetalol, diazoxide, and hydralazine have been used parenterally for rapid control of severe hypertension, but they do not always produce optimal, balanced hemodynamic effects. Calcium antagonists have been advocated because of their beneficial circulatory effects. Nicardipine, a new dihydropyridine calcium antagonist, produces significant antihypertensive effects, and when given intravenously, results in a rapid fall in blood pressure. Studies have confirmed that nicardipine is effective and safe in the management of severe hypertension and hypertensive crises. Because the aim of rapidly controlling severe hypertension is to prevent target organ dysfunction, nicardipine therapy offers a useful additional option in the clinical management of severe hypertension and hypertensive crises."
-How did the picture book help children cope with venous blood sampling in the study?,"Preparing children for venous blood sampling. A convenience sample of 100 children, aged 6-12 years, attending Kuwait government hospital laboratories for venous blood sampling was studied. A picture book was used to prepare half of the children for the procedure. Preparation was carried out just prior to sampling and took less than 5 min. The story provided a simple description of venous blood sampling, and why it is carried out; it stressed that the pain is noticeable but not unbearable, and that children will experience less pain if they relax their arm and cooperate with the technician. Prepared children reported significantly less pain, and radial pulse rates confirmed that they were less distressed by the procedure. Observers' and parents' evaluations also indicated that prepared children coped better. Various explanations for the benefits observed are discussed, together with requirements for managing the pain, fear and stress experienced by children during medical treatment."
-How does outlet obstruction constipation affect urinary flow parameters in women?,Relationship between outlet obstruction constipation and obstructed urinary flow. Ten women with symptoms and radiological features of outlet obstruction constipation underwent urodynamic bladder studies. The results were compared with ten age- and sex-matched controls. The mean (s.e.m.) peak flow rate for patients was 19.4 (6.4) ml/s compared with 32.1 (7.2) ml/s for controls (P less than 0.05). The mean (s.e.m.) voiding time for patients was 62.9 (23.7) s against a corresponding value of 15.6 (6) for controls (P less than 0.05). The mean (s.e.m.) bladder volume in patients was 482 (80) ml compared with a control value of 254 (112) ml (P less than 0.03). The mean (s.e.m.) detrusor pressure during the voiding phase was 53.3 (12) cmH2O. These results demonstrate that patients with outlet obstruction constipation have a generalized pelvic floor disorder resulting in obstructed urinary flow.
-What are the key characteristics of peritoneal cystic mesothelioma based on the three reported cases?,"Cystic mesothelioma of the peritoneum. A report of three cases. Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis."
-"What were the three surgical techniques used for treating chronic ear disease in this study, and how did their post-operative outcomes compare?","Surgery for chronic ear disease in a non-university hospital: open cavity, obliteration and intact canal wall techniques. The long-term results of surgery for chronic suppurative middle ear disease at a non-university ENT-clinic (Vasa Central Hospital, Finland) are reported. The material consisted of 273 ears, 65 of which had been operated on by open cavity techniques, 178 by the original Palva obliteration method, and 30 by the intact canal wall method. Post-operative cholesteatoma occurred equally frequently with the two canal wall down methods (7.7 and 7.3%, respectively) but was more frequent after intact canal wall surgery (23.3%). Hearing was better and the infection rate lower with obliteration than with open cavity techniques. Post-operative infection was the least frequent and the hearing result best in the intact canal wall ears, but compared to the other two groups the extent of disease found at surgery was considerably less in this group. The obliteration operation proved to be a safe method in the hands of a practising otologist outside university clinics."
-What unique technique was used to establish the DuPro-1 human prostate adenocarcinoma cell line?,"Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). A new human prostate adenocarcinoma cell line (DuPro-1) has been established from the athymic nude mouse supported xenograft DU5683. This was accomplished by embedding dispersed xenograft cells in 0.1 by 5.0 cm. spaghetti-like strands of Basement Membrane MATRIGEL [BMM (Collaborative Research, Inc.)], a unique technique facilitating the transition to tissue culture. Now passed over 30 times, the cells display anchorage and serum concentration independent growth with a doubling time of 22 to 24 hours. Cells exhibit pronounced morphological differences when grown on BMM coated culture dishes, assuming a pseudoglandular configuration, in contrast to typical homogeneous monolayer growth on plastic culture dishes. Light and electron microscopy show cohesive sheets of anaplastic epithelial cells, consistent with prostate carcinoma. Karyotypic analysis revealed all human chromosomes, near tetraploidy, 10 to 12 markers, and 3 to 4 X chromosomes, without a Y chromosome. Cells injected s.c. or embedded in BMM and implanted in the subrenal capsule space are equally tumorigenic in male and female athymic mice, suggesting that DuPro-1 cells are hormonally insensitive. Embedding cells in BMM may be useful in developing other tissue culture cell lines from neoplasms difficult to initiate in vitro. DuPro-1 should provide a valuable means to study the biology, immunology, and chemosensitivity of human prostate cancer."
-How does induced hypertension affect neuronal injury and edema formation after temporary middle cerebral artery occlusion in rats?,"Induced hypertension during restoration of flow after temporary middle cerebral artery occlusion in the rat: effect on neuronal injury and edema. The effect of hypertension instituted during restoration of flow after focal ischemia was studied. After the middle cerebral artery (MCA) of 12 rats was occluded for 2 hours, the ligatures were released and flow was restored for a period of 2 hours. In the control group, mean arterial pressure (MAP) was not manipulated. In the hypertensive group, the MAP was elevated by 25-30 mm Hg immediately after reestablishment of MCA patency. The area of neuronal injury, determined by 2,3,5-triphenyltetrazolium staining, was significantly smaller in the hypertensive group. Specific gravity, determined by microgravimetry, did not differ between groups. The data demonstrate that modest hypertension, when induced during reperfusion after 2 hours of MCA occlusion, reduces neuronal injury and does not exacerbate edema formation."
-What percentage of breast reconstructions performed at the University of Texas M.D. Anderson Cancer Center experienced some degree of flap necrosis?,"The early management of flap necrosis in breast reconstruction. Flap necrosis is a potential complication of any type of breast reconstruction. Of 302 breast reconstructions performed by the author at the University of Texas M.D. Anderson Cancer Center, some degree of flap necrosis occurred in 59 (19.5 percent). Small areas of flap necrosis can be managed with simple observation, but secondary healing may not be complete for months. Early and aggressive excision of the ischemic tissue with immediate primary closure often can achieve rapid primary healing. In addition, early revision and reshaping of the breast may, in selected patients, permit achievement of a significantly better final result. This is true not only for TRAM and latissimus dorsi flaps, but also for the mastectomy flap necrosis sometimes encountered in immediate reconstruction with simple implants or tissue expanders."
-How did monthly pulses of vincristine and prednisone impact the relapse-free survival of children with low-risk acute lymphoblastic leukemia in the CCG-161 study?,"Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group. On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX."
-How did the researchers find that IGFBP-3 gene expression is increased in renal adenocarcinoma tissues?,"Expression of the insulin like growth factor-binding protein 3 (IGFBP-3) gene is increased in human renal carcinomas. After we had established that the IGFBP-3 gene is expressed in normal human kidney we examined renal adenocarcinoma tissue for alterations of the expression of this gene. For this purpose we prepared poly(A)+ RNA from normal kidney tissue and adjacent renal adenocarcinoma of 18 adult patients and compared the levels of IGFBP-3 mRNA by Northern analysis in both samples. The mean content by densitometry was markedly increased in the carcinoma tissues; in 17 of 18 patients the carcinoma contained significantly more IGFBP-3 mRNA than the normal kidney sample. The highest mRNA levels were found in patients with N2 and N3 lymph node extensions. Comparative Southern analysis of paired samples of four of these patients did not reveal amplification of the gene as the cause of these increased mRNA levels. In one patient, however, we identified a restriction fragment length polymorphism (RFLP) present in normal and malignant cellular DNA. This suggests a participation of the IGFBP-3 gene in the development of human renal cell cancer."
-What differences in mortality and kernicterus were observed between the jaundiced RHA/N-j and ACI/N-j rat strains?,"A difference in mortality between two strains of jaundiced rats. Homozygous Gunn rats lack bilirubin glucuronyltransferase, become jaundiced, and often develop kernicterus, thus providing a model for neonatal hyperbilirubinemia. Two new, inbred rat strains that carry the Gunn mutation are described. These were developed by breeding the mutant Gunn gene (j) into the RHA/N and ACI/N strains, producing the new lines, which were designated RHA/N-j and ACI/N-j. Liver assay confirmed the absence of transferase activity in jaundiced rats from both of the new strains, but marked differences in mortality between the strains were observed. The mortality of jaundiced RHA/N-j rats through 8 weeks was the same as that of their nonjaundiced littermates (20%). In contrast, mortality of jaundiced ACI/N-j rats was distinctly greater than that of their nonjaundiced littermates (81% vs 34%, P less than .001). Signs of kernicterus such as ataxia were much more frequent in jaundiced ACI/N-j rats than in jaundiced RHA/N-j rats (73% vs 11%, P less than .001). Both strains had comparable albumin concentrations through 8 weeks of age. Serum bilirubin concentrations were also comparable, except for a small but significant difference at 20 days of age (ACI/N-j = 294 mumols/L, RHA/N-j = 248 mumols/L, P less than .01). Similarly, the bilirubin-to-albumin ratios were comparable except for a significantly higher ratio at 20 days of age in the ACI/N-j rats (ACI/N-j = 0.70, RHA/N-j = 0.51, P less than .01). Thus, the RHA/N-j strain is unusual in that the jaundiced animals remain healthy. Conversely, the ACI/N-j animals demonstrate a high incidence of kernicterus with mortality."
-What is asymptomatic bacterascites and how does it differ from spontaneous bacterial peritonitis?,"Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required."
-What was the primary objective of the study on fetal sheep?,"Fetal hypertension induced by norepinephrine infusion and umbilical artery flow velocity waveforms in fetal sheep. This study was designed to examine the effects of fetal hypertension on the umbilical artery pulsatility index. Fetal arterial blood pressure and umbilical venous pressure were measured in eight sheep, 3 to 5 days after surgery. Umbilical blood flow was measured with an electromagnetic flowmeter around the common umbilical vein. Umbilical artery flow velocity waveforms were obtained either by an indwelling 5 MHz pulsed Doppler device (n = 4) or transcutaneously by a 4 MHz continuous-wave Doppler device (n = 4). Fetal blood pressure was raised by intravenous infusion of norepinephrine 10 micrograms/min during 5 minutes. Norepinephrine infusion resulted in elevated arterial and umbilical venous pressures, accompanied by a bradycardia during the first 3 minutes. Umbilical blood flow, calculated placental vascular resistance, and umbilical artery pulsatility index did not change. After atropine administration, the norepinephrine-induced elevated arterial and umbilical venous pressures were accompanied by tachycardia, increased umbilical blood flow, and no change in placental vascular resistance and umbilical artery pulsatility index. It is concluded that fetal arterial hypertension provoked by norepinephrine infusion has no effect on placental vascular resistance, umbilical blood flow, and umbilical artery pulsatility index."
-What makes this case of prolactin-producing pituitary carcinoma unique in medical literature?,"Prolactin-producing pituitary carcinoma with pulmonary metastases. Pituitary adenomas rarely are metastatic. Extracranial visceral metastases of prolactinomas were not previously reported. The authors report a case of a 34-year-old man with a prolactin-producing pituitary carcinoma and histologically proven lung metastases. Pathologic examination of the pulmonary spread included electron microscopy and immunohistochemistry; these confirmed prolactin production by the tumor. The patient's presentation at initial diagnosis, disease recurrence, clinical course, management, and response to therapy (with its theoretic basis) are detailed. Despite the use of dopamine analogues (to tolerance and in combination), there was documented intracranial and extracranial disease progression. Possible future therapeutic maneuvers are discussed."
-What potential complication occurred during the ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma?,Renal pelvic explosion during conservative management of upper tract urothelial cancer. Ureteroscopic fulguration of a renal pelvic papillary transitional cell carcinoma is a relatively new and limited procedure. We present a case of intrarenal explosion during ureteroscopic fulguration.
-What are the five response subtypes observed in the cutaneous test examining the flushing response to ethanol and acetaldehyde among Chinese of Han ethnicity?,"Cutaneous vasomotor sensitivity to ethanol and acetaldehyde: subtypes of alcohol-flushing response among Chinese. A cutaneous test has been applied in examination of the flushing response to ethanol and acetaldehyde in 402 Chinese of Han ethnicity. Using this noninvasive method, five response subtypes have been observed: (A) fast flushing to both ethanol and acetaldehyde; (B) fast flushing only to ethanol but not to acetaldehyde; (C) slow flushing to ethanol only; (D) no response either to ethanol or to acetaldehyde; (E) vasoconstriction to ethanol, or to both ethanol and acetaldehyde. A total of 94% in subtype (A) are reported to be flushers, while only 25% was reported in subtype (D). Other physiological responses, such as tachycardia, dizziness, headache, drowsiness, and nausea are less frequent after alcohol ingestion. The recent history of consumption of alcohol of the subjects in different subtypes was also obtained. Although alcohol-induced flushing is thought to be a deterrent factor to heavy consumption of alcohol, the frequency of drinking of alcoholic beverages was not found to be different between flushers and nonflushers."
-What were the key findings regarding parental occupational exposures and childhood leukaemia risk in this study?,"Parental occupations of children with leukaemia in west Cumbria, north Humberside, and Gateshead OBJECTIVE--To determine whether parental occupations and chemical and other specific exposures are risk factors for childhood leukaemia. DESIGN--Case-control study. Information on parents was obtained by home interview. SETTING--Three areas in north England: Copeland and South Lakeland (west Cumbria); Kingston upon Hull, Beverley, East Yorkshire, and Holderness (north Humberside), and Gateshead. SUBJECTS--109 children aged 0-14 born and diagnosed as having leukaemia or non-Hodgkin's lymphoma in study areas during 1974-88. Two controls matched for sex and date and district of birth were obtained for each child. MAIN OUTCOME MEASURES--Occupations of parents and specific exposure of parents before the children's conception, during gestation, and after birth. Other adults living with the children were included in the postnatal analysis. RESULTS--Few risk factors were identified for mothers, although preconceptional association with the food industry was significantly increased in case mothers (odds ratio 2.56; 95% confidence interval 1.32 to 5.00). Significant associations were found between childhood leukaemia and reported preconceptional exposure of fathers to wood dust (2.73, 1.44 to 5.16), radiation (3.23, 1.36 to 7.72), and benzene (5.81, 1.67 to 26.44); ionising radiation alone gave an odds ratio of 2.35 (0.92 to 6.22). Raised odds ratios were found for paternal exposure during gestation, but no independent postnatal effect was evident. CONCLUSION--These results should be interpreted cautiously because of the small numbers, overlap with another study, and multiple exposure of some parents. It is important to distinguish periods of parental exposures; identified risk factors were almost exclusively restricted to the time before the child's birth."
-What is L-tryptophan-induced eosinophilia-myalgia syndrome and what symptoms did the patients in this study experience?,"L-tryptophan-induced eosinophilia-myalgia syndrome. This report describes three Belgian cases of the eosinophilia-myalgia syndrome associated with the use of L-tryptophan-containing products. Three women, aged 51, 53 and 73 years, were taking L-tryptophan for 2 months to 2 years, at 500, 1500, and 2250 mg d-1, respectively. All developed disabling myalgias, fatigue, and a variable skin rash, in association with marked eosinophilia. In one patient, symptoms and eosinophilia reappeared after rechallenge with L-tryptophan. Discontinuation of the drug resulted in gradual disappearance of the symptoms, signs and laboratory abnormalities in two patients. One patient was treated with corticosteroids because of persisting myalgias. Because of the non-specific clinical manifestations, clinicians from all subspecialties of internal medicine might be confronted with such patients and should be aware of this new entity."
-What are the common symptoms shared by mitral valve prolapse and panic disorder?,"Mitral valve prolapse, panic disorder, and chest pain. Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS)."
-How do nitrone free-radical spin traps affect c-fos induction and ATP recovery in a rat model of hepatic ischemia and reperfusion?,"Induction of the protooncogene c-fos and recovery of cytosolic adenosine triphosphate in reperfused liver after transient warm ischemia: effect of nitrone free-radical spin-trap agents. Ischemia and reperfusion stimulate several adenosine triphosphate (ATP)-dependent processes involving release of substances including free radicals. This cellular response is mediated through receptors responsive to transcriptional products of gene expression; c-fos acts as a transcriptional factor involved in the regulation of genes associated with cellular proliferation and differentiation. We hypothesized that nitrone free-radical spin traps promote restoration of cytosolic ATP during reperfusion and prevent c-fos induction. Four control rats had no ischemia. Global hepatic ischemia was induced in 19 rats in four groups: saline solution, phenyl-N-tert-butyl nitrone (PBN), alpha 1-pyridyl-N-oxide N-tert-butyl nitrone (POBN), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). ATP and intracellular pH were measured at intervals before, during, and after ischemia. At 90 minutes of reperfusion, liver c-fos mRNA was measured. A fourfold elevation of c-fos occurred in the saline-treated group (p less than 0.001). PBN and POBN groups did not differ from the saline group. DMPO resulted in significantly less induction of c-fos than did NS. ATP depletion and recovery in all treatment groups was similar to that of the saline group. We conclude that (1) nitrone spin traps do not prevent c-fos induction or alter the pattern of ATP recovery after hepatic ischemia and reperfusion and (2) c-fos induction is not necessary for restoration of ATP, but the rate of ATP restoration is inversely related to c-fos induction."
-Where is the translocation breakpoint located in the patient with Menkes syndrome?,"Localization of the translocation breakpoint in a female with Menkes syndrome to Xq13.2-q13.3 proximal to PGK-1. Menkes syndrome is a rare X-linked recessive disorder characterized by an inability to metabolize copper. A female patient with both this disease and an X; autosome translocation with karyotype 46,X,t(X;2)(q13;q32.2) has previously been described. The translocation breakpoint in Xq13 coincides with a previous assignment of the Menkes gene at Xq13 by linkage data in humans and by analogy to the mottled mutations which are models for Menkes disease in the mouse. Therefore, this translocation probably interrupts the gene for Menkes syndrome in band Xq13. We describe here experiments to precisely map the translocation breakpoint within this chromosomal band. We have established a lymphoblastoid cell line from this patient and have used it to isolate the der(2) translocation chromosome (2pter----2q32::Xq13----Xqter) in human/hamster somatic cell hybrids. Southern blot analyses using a number of probes specific for chromosomes X and 2 have been studied to define precisely the location of the translocation breakpoint. Our results show that the breakpoint in this patient--and, therefore, likely the Menkes gene--maps to a small subregion of band Xq13.2-q13.3 proximal to the PGK1 locus and distal to all other Xq13 loci tested."
-What are the key findings from the report of five cases of solitary extradural cavernous hemangiomas in the spinal canal?,"Solitary extradural cavernous hemangiomas in the spinal canal. Report of five cases. Five cases of solitary extrathecal cavernous hemangioma in the spinal canal are reported. In one case, two coexistent massive cerebral venous medullary malformations were found. The symptomatology and prognosis of extrathecal spinal cavernous hemangiomas are discussed, as is the significance of various diagnostic measures. The patient material further permitted a rough calculation of the incidence of symptomatic extrathecal cavernous hemangiomas in the spinal canal."
-What is the accuracy of transesophageal echocardiography in evaluating the patency of ventriculoatrial shunts?,"Transesophageal echocardiography: a simple method for monitoring the patency of ventriculoatrial shunts. Technical note. A new method for evaluating the patency of a ventriculoatrial shunt is described, and early experience with it is reported. Transesophageal echocardiography can demonstrate a cerebrospinal fluid leak in the right atrium through the atrial tip of a shunting device. This capability was an incidental discovery, and since then the accuracy of the technique in evaluating the patency of a ventriculoatrial shunt has been prospectively studied in 20 observations of 16 patients. The method proved to be accurate in 90% to 100% of cases. It is concluded that transesophageal echocardiography offers a rapid and accurate assessment of ventriculoatrial shunt function, is well tolerated, and is easy to perform."
-What is heterotopic ossification and how can it potentially impact peripheral nerves?,"Heterotopic ossification and peripheral nerve entrapment: early diagnosis and excision. Heterotopic ossification can occur in neurologic disorders, burns, musculoskeletal trauma, and metabolic disorders. In addition to producing the complications of contracture, skin breakdown, and pain, it can cause peripheral nerve entrapment. Nerve entrapment due to heterotopic ossification may be misdiagnosed, and it is difficult to evaluate and treat without recurrence. Computed tomography is especially useful in localization before surgical release of the entrapped nerve. Resection of heterotopic ossification can be successful using disodium etidronate to decrease the risk of recurrence, and resection can improve range of motion and nerve function. Two case studies of nerve entrapment due to heterotopic ossification are presented with the results of computed tomography localization, successful resection, and long-term follow-up. Clinicians should be aware of this complication and the potential for rapid nerve injury. If heterotopic ossification is causing clinically significant peripheral nerve entrapment, early surgical treatment may be indicated, and may be successful."
-How does a multidisciplinary approach help in managing chronic orthopedic infections?,"The effect of chronic orthopedic infection on quality of life. The patient with chronic orthopedic infection presents a unique challenge to the orthopedic surgeon. The orthopedic surgeon must not only possess an expertise in constantly evolving diagnostic and treatment techniques but also be able to identify numerous related problems and direct the patient in receiving the most appropriate treatment. This demands a commitment of time by the treating surgeon to the individual patient to properly assess the need for support, the extent of psychologic distress, the intensity of pain, and the requirement for medication management. The effective utilization of a multidisciplinary team of health care providers (e.g., specialists in infectious disease, physical medicine and rehabilitation, psychiatry, nursing, pharmacology) can provide an optimal treatment program for this multifaceted problem and maximize the potential for a favorable outcome."
-How do cells generate ATP during hypoxic conditions when aerobic metabolism is compromised?,"Cellular energy metabolism during hypoxia. Tissue hypoxia is frequently seen in critically ill patients and it perhaps predisposes these patients to development of multiple system organ failure. In cellular terms, hypoxia is characterized by decreases in the intracellular concentration of oxygen, leading to a decline in aerobically produced adenosine triphosphate (ATP). The deficit arising from unequal levels of cellular ATP requirements and aerobic ATP production is partially satisfied by anaerobic sources of ATP, including glycolysis, the creatine kinase reaction, and the adenylate kinase reaction. These reactions can set in motion cellular mechanisms that ultimately may lead to cellular dysfunction and death. A clear understanding of the relative importance of these reactions is impossible to acquire from global measures of oxygen delivery and oxygen consumption; therefore, the clinical monitoring of tissue oxygenation also should include the measurement of metabolically relevant, organ-specific variables."
-What was the perioperative mortality rate in the acoustic neuroma surgery series from Manchester Royal Infirmary between 1978 and 1990?,"Acoustic neuroma (schwannoma) surgery 1978-1990. A series of 151 patients with 154 acoustic schwannomas have been operated upon in Manchester Royal Infirmary by a joint Otological and Neurosurgical team, employing either the translabyrinthine or the suboccipital approach. The perioperative mortality rate was 3 per cent. Anatomical preservation of the facial nerve was achieved in 89 per cent of tumour removals and a good to normal functional result in 79 per cent of cases. Attempts at hearing preservation have been unsuccessful, largely because of the small number of patients in the series in whom useful hearing was present preoperatively. Complications included major brain stem ischaemia (1.2 per cent), CSF fistula (5 per cent) and facial dysaesthesia (7 per cent). The incidence of mortality and morbidity is directly related to tumour size and to the experience of the surgeons. A number of patients experienced an unusual type of post-operative dreamlike state which appeared to be a form of hypnagogic hallucination, and the possible neurophysiological mechanism responsible for this phenomenon is discussed. The continuing failure to attain the ideal of early diagnosis is lamented, and the importance of a flexible bidisciplinary surgical approach emphasized."
-What are the main syndromes of mitochondrial encephalopathies observed in children during the 1984-1988 study?,"Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders."
-What medical condition did the 2-year-old boy have that led to difficulty swallowing and spasticity due to compression of the medulla and cervical spine?,Cervicomedullary junction decompression in a case of Marshall-Smith syndrome. Case report. The case is reported of a 2-year-old boy born with Marshall-Smith syndrome who had difficulty in swallowing and who exhibited spasticity and quadriparesis due to compression of the medulla and cervical spine. This is the first child with this rare condition reported to have brain-stem compression from bone abnormalities at the craniovertebral junction and who has required surgery.
-"What morphometrical parameters were found to be most useful in distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis?","Histological and morphometrical indicators for a biopsy diagnosis of well-differentiated hepatocellular carcinoma. Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well-differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid-sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well-differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well-differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular tissue."
-What is pure akinesia and how does it relate to progressive supranuclear palsy (PSP)?,"Pure akinesia: an atypical manifestation of progressive supranuclear palsy. Two patients with ""pure akinesia"" who showed the characteristic changes of progressive supranuclear palsy (PSP) at necropsy are described. They had akinesia but no rigidity or tremor, and ophthalmoplegia was not observed during the course of illness. The symptoms of ""pure akinesia"" was not improved by levodopa therapy but was considerably improved by L-threo-3,4-dihydroxy-phenylserine. At necropsy, pathological findings were not different from those reported for PSP. It is suggested that ""pure akinesia"" is an atypical manifestation of PSP, and that norepinephrinergic neurons may be involved in some types of PSP."
-What unusual characteristic was observed in the Listeria monocytogenes isolate from the patient's cerebrospinal fluid culture?,"Catalase-negative listeria monocytogenes causing meningitis in an adult. Clinical and laboratory features. A 63-year-old previously healthy woman presented with acute meningitis. Cultures of the cerebrospinal fluid yielded a serotype 1/2a isolate of Listeria monocytogenes that was biochemically typical in all respects, other than the reproducible lack of catalase production. During therapy, the patient developed oculomotor dysfunction that was attributed to an abscess in the internal capsule. This case report documents the existence of catalase-negative L. monocytogenes indicating that catalase production should not be a strict criterion for identification of Listeria. Furthermore, this clinical experience extends in vitro and experimental animal studies indicating that catalase production is not a necessary virulence factor for invasion by Listeria."
-What percentage of patients achieved complete thrombolysis based on the duration of their limb ischaemia symptoms?,"Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected."
-What were the key selection criteria for surgical resection in cirrhotic patients with liver cancer in this study?,"Limited hepatic resection for selected cirrhotic patients with hepatocellular or cholangiocellular carcinoma: a prospective study. From 1 January 1983 to 1 January 1989 123 cirrhotic patients with hepatocellular cancer (n = 122) or cholangiocarcinoma (n = 1) were screened using liver function tests, alpha-fetoprotein determination, ultrasonography with biopsy (and in selected cases computed tomography or nuclear magnetic resonance), laparoscopy and angiography, Child-Pugh classification and urea-nitrogen synthesis rate. Twenty-three patients were selected for surgical resection because the tumour was smaller than 5 cm, not centrally located and at least 1 cm away from main structures; there was no evidence of multicentricity or metastatic disease; and the Child-Pugh classification was A or B and the urea-nitrogen synthesis rate at least 6 g/day. Upper gastrointestinal endoscopy was used routinely to identify oesophageal varices which were present in 17 cases; ten patients with a history of variceal haemorrhage (43 per cent) had preoperative endoscopic sclerotherapy. In cases with recurrent haemorrhage, surgery was used to prevent intraoperative and postoperative bleeding. Tumour resection was carried out using controlled hypotension and hepatoduodenal ligament clamping. Twelve bisegmentectomies, ten segmentectomies and one atypical resection were performed. The operative mortality rate was 13 per cent with liver failure and sepsis as the causes of death. The 'recurrence rate' was 26 per cent and the late mortality rate for the whole group up to 1 January 1990 was 30 per cent; 13 patients were still alive. The 12-month survival rate was 77 per cent and after 5 years it was 49 per cent. Thus, surgical resection of small liver tumours is the treatment of choice in this selected group of patients."
-What are the key clinical features associated with T-cell ALL cases having the t(11;14) translocation?,"Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations."
-What imaging technique was found to accurately demonstrate the spread of disease in a case of spinal leptomeningeal metastasis from cerebral glioblastoma?,"Spinal leptomeningeal metastasis from cerebral glioblastoma. Appearance on magnetic resonance imaging. A case of circumferential leptomeningeal metastasis to the spinal cord from an intracranial glioblastoma multiforme (spinal meningeal gliomatosis) is presented. The clinical, radiographic, and pathological features are described. Spinal magnetic resonance imaging with gadolinium-diethylenetriaminepentaacetic acid accurately demonstrated the spread of disease when compared with autopsy findings. The value of spinal magnetic resonance imaging in patients with symptoms attributable to cerebrospinal fluid metastases is discussed."
-What surgical approaches were used to treat localized and diffuse supravalvar aortic stenosis (SVAS) in this study?,"Supravalvar aortic stenosis: a 29-year review of surgical experience Between February 1960 and August 1989, 73 consecutive patients underwent surgical correction for supravalvar aortic stenosis (SVAS) at the Texas Heart Institute. There were 43 male (59%) and 30 female patients (41%) ranging in age from 5 days to 27 years (mean age, 12 years). Preoperatively, 8 patients were in New York Heart Association functional class I, 43 in class II, 18 in class III, and 4 in class IV. Of the 73 patients, 62 had localized SVAS and 11 (15%), diffuse SVAS. For all procedures, patients were placed on cardiopulmonary bypass. Those with localized SVAS were successfully treated with patch aortoplasty, whereas those with diffuse SVAS required either an apicoaortic conduit or extensive end-arterectomy with extended patch aortoplasty. There were eight early deaths (less than or equal to 30 days postoperatively) (11%) and four late deaths (greater than 30 days postoperatively) (6%) in a follow-up period ranging from 2 months to 28 years. Sixteen patients (25%) underwent one or more additional operations in the follow-up period. Postoperatively, there were 44 patients in New York Heart Association functional class I and 17 in class II. Preoperative functional class III and class IV (p less than 0.0005), diffuse SVAS (p = 0.05), and the presence of associated congenital defects (p less than 0.01) were important determinants of death."
-How did the visual evoked potentials change in patients after transurethral resection of the prostate using glycine as an irrigating fluid?,"Visual evoked potentials and visual acuity after transurethral resection of the prostate. Changes in visual evoked potentials, visual acuity, blood ammonia levels and serum electrolytes (Na+ and K+) after transurethral resection of the prostate using glycine as an irrigating fluid performed under subarachnoid block were studied in 12 patients, in the pre-operative and immediate postoperative periods. Visual evoked potentials (p100 latency), recorded by shift of a checkerboard pattern, increased significantly from a pre-operative value of mean (SEM) 101.18 (1.63) msec in the right eye, and 102.5 (1.47) msec in the left eye to 108.91 (1.8) msec (p less than 0.01) and 108.08 (2.53) msec (p less than 0.01) respectively in the postoperative phase. There were no changes in visual acuity as assessed by a Snellen's chart, blood ammonia levels and serum electrolyte concentrations. The amount of glycine used intra-operatively for irrigation ranged from 3 to 31 litres."
-How do delusions and hallucinations impact the progression and neuropsychological characteristics of Alzheimer's disease patients?,"Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates. We longitudinally evaluated the neuropsychological functions, rate of progression, and waking EEG findings in 17 patients with probable Alzheimer's disease (AD) with delusions and hallucinations, and compared them with those of matched AD patients without delusions and hallucinations. AD patients with delusions and hallucinations had a more rapid rate of decline, as measured by the Mini-Mental State Examination, a specific defect in receptive language, and a greater frequency of aggression and hostility. Visual EEG analysis showed that these patients had a significantly greater proportion of moderately abnormal EEGs, and spectral analysis confirmed the increased amount of delta and theta activity. These data demonstrate that AD patients with delusions and hallucinations have a greater degree of cerebral dysfunction and a relatively focal neuropsychological defect, which may indicate a localized pathologic abnormality."
-What is the specific anesthesia-related complication observed in the 4-year-old boy with Williams syndrome?,Williams syndrome: masseter spasm during anaesthesia. A 4-year-old boy with Williams syndrome developed masseter spasm after halothane and suxamethonium. He did not develop malignant hyperthermia; the surgery was accomplished with a nontriggering anaesthetic and no further problems.
-What was the concern regarding the use of transillumination for breast cancer screening in Wisconsin in 1990?,"Inappropriate use of transillumination for breast cancer screening--Wisconsin, 1990. The overall effectiveness of early breast cancer detection efforts requires the appropriate use and maintenance of dedicated radiographic mammography systems. However, the effectiveness of early detection efforts can be compromised if proven technology is improperly used and/or maintained or if ineffective technology is successfully marketed as an equivalent or superior alternative to mammography. This report summarizes state and federal responses to the inappropriate use of a nonradiographic imaging technique in a breast cancer screening service advertised and used in Wisconsin in 1990."
-What was the purpose of the study on thallium stress testing in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation?,"Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. PURPOSE: This study assessed the usefulness of thallium stress testing as a predictor of perioperative cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Demographic factors influencing the exercise performance in these patients were also examined. PATIENTS AND METHODS: The medical records of 189 consecutive patients with diabetic nephropathy who were evaluated for cadaveric renal transplantation were reviewed. Thallium stress testing was the initial examination of cardiovascular status in 141 patients. An adequate examination was one in which at least 70% of maximum heart rate was achieved. A thallium stress test was normal if there were no ST segment depressions on the electrocardiogram and no perfusion abnormalities on the thallium scan. Forty-four patients underwent cardiac catheterization as the initial evaluation (Group C) and four patients underwent transplantation without a formal cardiovascular evaluation (Group D). RESULTS: Sixty-four of the 141 patients undergoing thallium stress testing had an adequate and normal examination (Group A). The incidence of perioperative cardiac events in this group was 2%. Seventy-seven patients (Group B) had an abnormal (n = 41) or an inadequate (n = 36) thallium stress test and most (n = 61) then underwent coronary angiography. The use of beta-blockers was the only predictor of an abnormal or inadequate thallium stress test (10 of 64 versus 27 of 77, chi 2 = 6.66, p less than or equal to 0.025). Forty-three percent (26 of 61 in Group B) of patients with inadequate or abnormal thallium stress tests had significant coronary artery disease on cardiac catheterization. The perioperative risk of cardiac events was not different in Group A versus Groups B, C, and D combined. Survival of Group A and B patients was not different but was significantly longer than that of Group C patients (p less than 0.001). Thallium stress testing was less expensive than cardiac catheterization ($1,000 versus $4,000 to $5,000). CONCLUSIONS: Thallium stress testing allowed 45% of patients to avoid cardiac catheterization before renal transplantation. Discontinuing beta-blockers before thallium stress tests may improve exercise performance. The risk of perioperative cardiac events after transplantation was low and not different among patient groups. The relatively low predictive value of thallium stress testing for significant coronary artery disease and perioperative cardiac events in diabetic patients with end-stage renal disease suggests the need for the development of a more cost-effective, noninvasive screening test for this patient population."
-What is the sensitivity and specificity of color Doppler imaging in detecting portal vein thrombosis according to this study?,"Diagnosis of portal vein thrombosis: value of color Doppler imaging. This study was undertaken to determine the accuracy of color Doppler imaging in the diagnosis of portal vein thrombosis. Two hundred fifteen patients were studied with color Doppler imaging to determine patency of the main portal vein. Sonographic findings were confirmed in 75 patients, aged 19 to 66 years. Correlation with angiography was obtained in 13 patients, and surgical correlation was obtained in the remaining 62. Nine patients had portal vein thrombosis on the basis of these gold standards. Sonograms were classified as showing either patency or thrombosis, depending on the ability to show color flow within the main portal vein. Agreement between sonography and angiography or surgery was found in 69 patients (61 patent, eight thrombosed). One patient with a patent portal vein at sonography was found to have a thrombosed vessel at surgery, whereas five patients without portal venous flow at sonography had patent vessels at angiography (one patient) or surgery (four patients). Overall sensitivity and specificity for detection of portal vein thrombosis were 89% and 92%, with an accuracy of 92%, a false-negative rate of 0.11, a negative predictive value of 0.98, and a positive predictive value of 0.62. We postulate that the majority of errors in our study occurred in vessels that, although patent, had only sluggish flow, which could not be resolved because of technical limitations. We conclude that color Doppler imaging is a valuable screening procedure for the assessment of portal vein patency. If the sonogram shows a patent portal vein, no further studies are required. However, a lack of demonstrable flow does not always indicate thrombosis, and other imaging studies should be performed for confirmation."
-How has aggressive chemotherapy impacted the cure rate and treatment of osteosarcoma?,"Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable."
-What was the incidence rate of posterior wall left ventricular rupture during mitral valve replacement surgeries between 1970 and 1989?,"Rupture of the posterior wall of the left ventricle after mitral valve replacement. During a 20 year period from 1970 to 1989, 1100 patients underwent mitral valve replacement. Rupture of the posterior wall of the left ventricle occurred in seven patients (0.6%); four in the operating room and three in the postoperative room. It was possible to institute CP bypass in six patients and in all of them bleeding was controlled successfully, with repair by an external approach. Only one patient survived. We believe that institution of CP bypass and reinfusion of cardioplegic solution is a major determinant of the outcome."
-What technique was used to detect and differentiate heat-labile enterotoxins from enterotoxigenic Escherichia coli strains of human origin?,"Heterogeneity of immunotypes of heat-labile enterotoxins of enterotoxigenic Escherichia coli of human origin. A new technique, checkerboard immunoblotting (CBIB), has been applied to detect and to differentiate heat-labile enterotoxins, (LTs), from enterotoxigenic strains of Escherichia coli of human origin using polyclonal and monoclonal antibodies. Optimal conditions of production and release of LTs were defined using CBIB. LT release was enhanced when E. coli cells were treated with 8 M urea. LT production was highest when E. coli strains were incubated with shaking (200 rpm) at 37 degrees C for 12 h in CAYE-2 medium. Two hundred and five strains of E. coli, isolated from patients with diarrhea in Japan, Thailand, the United States, Mexico, and Brazil, were examined for LT. Of 133 LT-positive strains, 4 (3%) produced an LT that reacted like H-LT-1 (originally isolated from E. coli strain H-74-114) while 126 strains (94.7%) produced LT that reacted like H-LT-2 (originally isolated from strain H-10407) or H-LT-3 (from strain H-240-3). Three strains of human origin (2.3%) produced an LT that reacted like P-LT (produced by E. coli strains of porcine origin). This study shows that CBIB, a simple, efficient, and practical assay, might be useful for epidemiologic surveys and for evaluation of serologic responses to LTs and antitoxic vaccines."
-How does von Willebrand factor (vWF) influence platelet activation and occlusive arterial thrombosis in normal and von Willebrand disease pigs?,"Role of von Willebrand factor in arterial thrombosis. Studies in normal and von Willebrand disease pigs. With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis. Two methods of arterial injury have been used to determine the thrombotic response of flowing blood in vivo. The first involves balloon catheter injury. After superficial denudation of endothelium from coronary intima, platelets adhere to the subendothelium in a monolayer. Similar numbers of adherent platelets are found in both phenotypes, but platelets in vWD pigs have impaired pseudopod formation and are less well spread morphological indexes of limited platelet activation. Deeper injury, which involves the media, produces nonocclusive platelet-fibrin microthrombi. The second injury method involves pinching the artery at a site of superimposed stenosis, a procedure that almost always exposes media. This procedure induces platelet-fibrin microthrombi in normal and vWD pigs, but only normal pigs develop occlusive thrombosis. Both methods of arterial injury have also been performed in normal and vWD pigs with diet-induced hypercholesterolemia and atherosclerosis. Atherosclerosis promotes platelet spread in vWD pigs but does not abolish the protection from stenosis and injury-induced occlusive thrombosis. In addition, neutralization of vWF activity in normal pigs by a monoclonal antibody prevents the induction of occlusive thrombosis by the stenosis and pinch-injury procedure. This monoclonal antibody also causes performed platelet aggregates to break up. These experimental models of inducing arterial thrombosis have been used in normal and vWD pigs to demonstrate interactions between normal and atherosclerotic vessel wall constituents, circulating platelets and vWF that are fundamental in the process of arterial thrombosis."
-How do serum zinc levels differ between patients with active inflammatory bowel disease and healthy controls?,"Serum zinc, copper, and selenium levels in inflammatory bowel disease: effect of total enteral nutrition on trace element status. Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed."
-How did tranexamic acid help in treating hemothorax in patients with malignant mesothelioma?,Tranexamic acid treatment of hemothorax in two patients with malignant mesothelioma. Patients with malignant mesothelioma may present with hemothorax. We used a combination of oral and intrapleural tranexamic acid to treat two patients with this severe complication. Initiation of treatment with this potent anti-fibrinolytic drug resulted in rapid reduction of bleeding and of transfusion requirements.
-What was the most commonly involved nerve in peripheral nerve lesions among hemophilia patients at the Nuffield Orthopaedic Centre?,"Peripheral nerve lesions in hemophilia. Between 1962 and 1986, eighty-one of the 1351 admissions of patients who had hemophilia to the Nuffield Orthopaedic Centre were for peripheral nerve lesions. Eighty-eight such lesions were identified in fifty-four patients, and thirty-nine of these patients (sixty-one lesions) had adequate follow-up (mean, 8.4 years; range, four months to eighteen years). The femoral nerve was most commonly involved, but involvement of other peripheral nerves also occurred. In thirty (49 per cent) of the sixty-one lesions, the nerve had full motor and sensory recovery; in twenty-one (34 per cent), a residual sensory deficit; and in ten (16 per cent), both a persistent motor and sensory deficit. Patients who had antibodies to factor VIII were significantly less likely to recover full motor or sensory function than were those who did not have such antibodies, and the time to full motor recovery in these patients was significantly longer."
-How did mammography impact the treatment approach for patients with small breast cancers in this study?,"Mammography in the management of patients with small breast cancers. Findings on mammography resulted in a change of treatment policy in 17 of 200 patients with small breast cancers (T1/T2 less than 4 cm, N0/N1, M0). Twelve patients were considered unsuitable for conservation therapy because of mammographic evidence of either extensive in situ carcinoma or more than one focus of invasive carcinoma. These patients were treated by mastectomy and histology confirmed widespread in situ carcinoma or multifocal/multicentric invasive carcinoma. Seven patients were found to have unsuspected contralateral lesions on mammography, of which five were subsequently shown to be malignant. Routine preoperative mammography is essential in the management of patients with small breast cancers."
-"How does metformin treatment affect insulin resistance and metabolic risk factors in non-obese, non-diabetic men with hypertension?","Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors. Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease."
-What are the key neuropathologic features of generalized cortical dysplasia observed in the three children studied?,"Generalized cortical dysplasia. Clinical and pathologic aspects. Three children with profound mental retardation and intractable seizures died at ages 10 months, 3 years, and 7 years, respectively. Complete examination of their brains showed generalized cortical dysplasia, without any major malformation of the external gyral pattern. The neuropathologic features of cortical dysplasia include abnormally thickened cortex with indistinct demarcation of the gray-white matter junction. In many areas, the cortex contained increased numbers of large neurons with disordered cortical lamination. Heterotopic neurons were scattered throughout the white matter with decreased myelination of the underlying white matter. To our knowledge, these cases represent the first fully detailed neuropathologic study of diffuse cortical dysplasia--a newly recognized entity of abnormal neuronal migration."
-How does alcohol affect ferritin expression in the HepG2 human hepatoblastoma cell line?,"Alcohol induction of ferritin expression in a human hepatoblastoma cell line (HEP G2). Hyperferritinemia, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression."
-What was the relationship between preoperative dipyridamole perfusion scintigraphy findings and intraoperative transesophageal echocardiography in identifying myocardial ischemic risk?,"Comparison of the findings on preoperative dipyridamole perfusion scintigraphy and intraoperative transesophageal echocardiography: implications regarding the identification of myocardium at ischemic risk. The evidence of myocardium at potential ischemic risk on preoperative dipyridamole perfusion scintigraphy was compared with that of manifest ischemia on intraoperative transesophageal echocardiography in 26 patients at high risk of a coronary event undergoing noncardiac surgery. The clinical outcome was also assessed. Induced intraoperative wall motion abnormalities were more common in patients and myocardial segments with, than in those without, a preoperative reversible perfusion defect (both p less than 0.05). Conversely, a preoperative reversible perfusion defect was more common in patients and segments with, than in those without, a new intraoperative wall motion abnormality (both p less than 0.05). Six patients, five with a reversible scintigraphic defect but only three with a new wall motion abnormality, had a hard perioperative ischemic event. Events occurred more often among patients with, than in those without, a reversible perioperative scintigraphic defect (5 [33%] of 15 vs. 1 [9%] of 11) but this difference did not reach significance (p = 0.14), probably owing to the sample size. Intraoperative wall motion abnormalities were all reversible and did not differentiate between risk groups; these findings were possibly influenced by treatment. These preliminary data support the known relation between reversible scintigraphic defects and perioperative events and identify another manifestation of ischemic risk in the relation between reversible scintigraphic defects and induced intraoperative wall motion abnormalities. The value of intraoperative echocardiography in identifying ischemia and guiding therapy in patients with a reversible scintigraphic abnormality should be further assessed."
-What diagnostic method is recommended for identifying Clostridium septicum abscesses in immunosuppressed patients?,"Recognition, management, and prevention of Clostridium septicum abscess in immunosuppressed patients. Spontaneous gas gangrene due to Clostridium septicum is a rapidly progressing disease that usually ends in fatal toxemia. We report three cases of asymptomatic C septicum abscesses to document the clinical course of this entity and to establish guidelines for its prevention and treatment. In contrast to previously reported data, C septicum infections can produce abscesses in solid organs, the retroperitoneum, and the extremities. These lesions often occur in patients with cancer, producing liver abscesses without gas formation that may be misinterpreted as metastatic carcinoma. Symptoms may be minimal or nonspecific before fulminant toxemia. Asymptomatic bacteremia should prompt a search for unsuspected cancer and an abscess. Computed tomography is the diagnostic modality of choice. The treatment consists of surgical debridement of necrotic tissue in concert with an appropriate course of antibiotics. We have found recurrences after adequate debridement and short-term antibiotic therapy, suggesting that prolonged and even lifelong prophylactic oral penicillin G potassium may be necessary to prevent further recurrences."
-How does endotoxin (LPS) infusion affect hypoxic pulmonary vasoconstriction in unanesthetized sheep?,"Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep. Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS."
-How did damage to the fornix affect memory function in the two patients after colloid cyst removal?,"Anterograde amnesia with fornix damage following removal of IIIrd ventricle colloid cyst. Two patients developed anterograde amnesia following the apparently uncomplicated transcallosal-transventricular removal of a colloid cyst. Damage to the fornical columns was demonstrated on CT and MRI scans, whilst other memory related structures were entirely normal. Longitudinal neuropsychological evaluation, over 12-24 months, has revealed a very similar pattern of deficit in the two cases: verbal memory has remained persistently impaired whilst nonverbal anterograde memory has improved to some degree. Formal tests of remote public (famous faces and events) and personal autobiographical memory have supported the clinical impression that neither patient has a temporally extensive retrograde amnesia. These findings address the role of the fornix, and the dissociation of memory processes in humans."
-How do nasal and pharyngeal resistances change during progressive normocapnic hypoxia in normal men?,"Changes in upper airway resistance during progressive normocapnic hypoxia in normal men. The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia."
-What were the predictive factors for thrombotic complications in venous coronary bypass graft angioplasty?,"Long-term angiographic follow-up after angioplasty of venous coronary bypass grafts. From April 1981 to June 1987, 57 patients underwent venous coronary bypass graft percutaneous angioplasty and had a minimal follow-up of 18 months. The procedure was elective for 28 patients, urgent for 19, and was considered as an emergency for 10. A total of 64 grafts were dilated that had been bypassed 58 +/- 48 months previously (range 2 to 184 months); lesions were located on the aortic anastomosis in 12 grafts, on the body in 38, and on the coronary anastomosis in 14. Technical success was 95.3% (61 of 64) per lesion; clinical success was 84.4% (54 of 64) per lesion and 82.5% (47 of 57) per patient. Thrombotic complications with images of a lacunar defect occurred in 11 grafts (17.2%). Predictive factors for these complications were: age of grafts 38.5% for greater than 60 month grafts versus 2.6% for less than 60 month grafts (p less than 0.01); site of lesion, body lesion 28.9% versus anastomosis none (p less than 0.01); type of lesion, concentric and short 6% versus other 29% (p less than 0.05); and recent fibrinolysis in 66% versus 10.6% (p less than 0.05). Long-term follow-up is available in the 47 successful patients and the three limited non-Q wave myocardial infarction patients. Two patients died at 13 and 17 months. Long-term angiographic follow-up is available in 45 of 48 patients or 94%. At the end of the study, 35 of 57 (61.4%) venous bypass grafts in 32 patients (64%) were patent after one or more percutaneous transluminal angioplasties."
-What differences were observed in the expression of primary response genes between renal compensatory hypertrophy (uninephrectomy) and renal hyperplasia (folic acid injection)?,"Differences in ""primary response"" gene expression in renal compensatory hypertrophy and hyperplasia. The induction of a family of primary response genes (ie, genes whose transcription is not dependent on new protein synthesis) occurs within minutes after stimulation of quiescent 3T3 cells by phorbol esters and growth factors. A similar pattern of gene expression is seen in PC-12 pheochromocytoma cells induced to differentiate by nerve growth factor (NGF), suggesting that a common set of activating signals occur in different forms of cell growth. To determine whether the same ""activation"" process occurs in renal hypertrophy, we measured mRNA levels in mice subjected to uninephrectomy (UNX) or sham operation. Regenerative renal hyperplasia was induced by intraperitoneal folic acid (FA) injection with vehicle as control. Northern blots showed induction of these genes by FA with elevated mRNA levels persisting for up to 24 to 48 hours. UNX and sham operation demonstrated a slight and transient elevation of mRNA levels, with a prompt return to basal levels by 60 minutes."
-How did the long-term psychological stress of patients with congenital heart disease compare to normative data in this 25-year follow-up study?,"Long-term psychologic implications of congenital heart disease: a 25-year follow-up. Patients with various types of congenital heart disease were contacted 25 years after their original examination at the Mayo Clinic. In addition to providing their current health status, level of education achieved, and current occupation, they were asked to complete a detailed standardized questionnaire to assess their degree of psychologic stress. Of the original 463 patients, 168 completed and returned the psychologic questionnaires. These patients had evidence of psychologic stress in excess of that expected on the basis of normative data. Furthermore, the degree of stress was unrelated to the clinical severity of the original cardiac defect. In addition, the psychologic stress occurred despite ""success"" as defined by educational achievement and occupational level. One can speculate that as children these patients were exposed to environmental stresses that may well have been colored by parental attitudes and perceptions."
-What is the most serious complication of thrombolytic therapy that can limit its usefulness?,"Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy. Bleeding is the most serious complication of thrombolytic therapy and limits its usefulness. We have reported a case of epidural hematoma, a rare occurrence after combined therapy with tissue plasminogen activator (TPA) and heparin. We emphasize that in patients treated with thrombolytic agents, any trauma may increase the risk of bleeding. The sudden onset of back pain and neurologic deficits should alert the clinician to the possibility of spinal hematoma with cord compression."
-What is the primary cause of death in children with maple syrup urine disease (MSUD) as described in this context?,"Cerebral edema causing death in children with maple syrup urine disease. Four children with the classic form of maple syrup urine disease (MSUD) died of cerebral edema during an intercurrent infection that caused severe dehydration and acidosis. The diagnosis of MSUD had been established during the neonatal period in all four patients, on day 1 of life in three of them. All were in satisfactory control before the intercurrent illness. Two patients underwent peritoneal dialysis. Signs of brain-stem compression occurred after treatment, when biochemical abnormalities were improving. Computed tomography of the head, which was done in two patients, revealed cerebral edema; one of these patients also had subarachnoid hemorrhage. Autopsy in one case revealed cerebral edema with herniation. Our experience documents that cerebral edema may occur in the older child with MSUD as well as in the neonate. The pathogenesis of cerebral edema in MSUD remains unclear. Early treatment of dehydration and acidosis may prevent the catastrophic consequences that we have observed."
-How do personality traits and life events relate to the frequency of headaches in adults?,"The association of frequent headaches with personality and life events. The associations between personality traits, life events and frequent headaches were studied in a sample of 5766 adult subjects between 20 and 65 years of age from the general population. Subjects with at least weekly headaches had more life events and higher inadequacy, social inadequacy, rigidity and injuredness than subjects with less frequent headaches. These relationships were not observed in subjects of 50 years of age and older, with the exception of the association with inadequacy. From the traits measured, inadequacy had the highest odds ratios for frequent headaches and showed a modest interaction with the presence of a life event. These findings are in agreement with Sarason's interactional model."
-What inflammatory changes were observed at the neuromuscular junction in patients with myasthenia gravis?,"Inflammation at the neuromuscular junction in myasthenia gravis. To better define the pathogenic mechanisms in the antibody-mediated autoimmune disease myasthenia gravis (MG), we analyzed the morphology and electrophysiology of the neuromuscular junction in anconeus muscle biopsy specimens from eight patients with MG and seven control subjects. There were inflammatory cells at the neuromuscular junction in seven of the eight biopsies from MG patients. The endplate index (length of the postsynaptic membrane divided by the length of the apposed presynaptic membrane) was abnormally reduced in all the MG patients, and fiber type grouping, suggestive of reinnervation, was present in six of the eight MG patients. Intracellular recording revealed diminished amplitude of miniature endplate potentials and miniature endplate currents in the MG patients compared with the controls. The time constant of decay of miniature endplate currents did not differ from that of controls, suggesting no change in mean channel open time of the acetylcholine receptor. The endplate receptor sensitivity to iontophoretically applied acetylcholine was also decreased in MG patients compared with controls. The quantal content of neurally evoked endplate potentials was reduced in six of the eight MG patients, demonstrating abnormal presynaptic function as well. The presence of inflammatory cells at the neuromuscular junctions of limb muscles in MG reconciles an apparent disparity between the animal model of MG, experimental autoimmune myasthenia gravis, and the human disease. This study also demonstrates a frequent presynaptic component to the abnormal neuromuscular transmission in MG."
-What is the significance of lowering cholesterol levels in patients with coronary heart disease (CHD)?,"On lowering lipids in the post-infarction patient. In patients with coronary heart disease (CHD) elevated serum cholesterol levels, like other classical risk factors, remain predictive of further coronary events. The excess risk attributable to raised cholesterol levels is considerable, and greater than that in subjects without CHD. A recent meta-analysis of all eight qualifying trials of secondary prevention of CHD by cholesterol lowering is reviewed. There were significant reductions in recurrent non-fatal and fatal CHD, with a downward trend in total mortality. Mechanisms underlying the relationship between cholesterol lowering and secondary prevention are reviewed. The implication of this analysis of trials for clinical practice is that hypercholesterolaemia should be sought and effectively treated in patients with CHD, unless contraindications are present."
-What was the clinical outcome for children with glutathione peroxidase deficiency after discontinuing anticonvulsant medication and receiving selenium substitution?,"Glutathione peroxidase deficiency and childhood seizures. 4 children with intractable seizures, repeated infections, and intolerance to anticonvulsants had evidence of glutathione peroxidase deficiency. 2 had low intracellular enzyme activity but normal blood selenium and high plasma glutathione peroxidase concentrations. The other 2 had low intracellular glutathione peroxidase activity with low circulating glutathione peroxidase and selenium concentrations. The clinical state of the children improved after discontinuation of anticonvulsant medication and selenium substitution."
-How does polysialic acid help distinguish small cell lung carcinoma from carcinoids?,"Polysialic acid of the neural cell adhesion molecule distinguishes small cell lung carcinoma from carcinoids. The neural cell adhesion molecule (NCAM) exists in various types of neuroendocrine cells and their tumors. A typical feature of NCAM is polysialic acid, of which the chain length is developmentally regulated. The authors have performed a comparative immunohistochemical study on small cell lung carcinomas and bronchial as well as gastrointestinal carcinoids with the monoclonal antibody (MAb) 735 reactive with the long-chain form of polysialic acid. The small cell lung carcinomas, irrespective of their histological type, were positive for polysialic acid. Metastatic tumor cell complexes also exhibited immunostaining. The tumor cell-surface-associated immunostaining for polysialic acid was sensitive to endoneuraminidase. The mature and atypical bronchial and gastrointestinal carcinoids were not immunoreactive for polysialic acid. Cytoplasmic staining in groups of cells of carcinoids (2 of 28 cases) was due to nonspecific antibody binding, which could be prevented by increased ion strength. These data indicate that neuroendocrine tumors of the lung can be distinguished by their content of highly sialylated NCAM."
-What are the potential consequences of malignant eye tumors in geriatric patients?,"Malignant tumors of the eye in geriatric patients. The ocular tissues can be the site of a number of malignant tumors in adults and geriatric patients. In addition to posing a threat to the patient's life, these tumors can cause severe visual loss or blindness. Therefore, the primary care clinician should be capable of prompt diagnosis of the various malignant ocular tumors and be prepared to refer the patient for appropriate management. This article provides a photographic guide to the most common primary and secondary malignancies that can affect the eyelid, conjunctiva, intraocular structures, and orbit in the geriatric patient."
-What factors were found to have the strongest univariate relations to the restenosis rate in this study?,"Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators. The Multi-Hospital Eastern Atlantic Restenosis Trial group obtained follow-up angiography in 510 patients with 598 successfully dilated coronary lesions who were enrolled in a controlled trial of the effects of a single dose of 1 g of methylprednisolone on restenosis after coronary angioplasty. The overall restenosis rate was 39.6%. The strongest univariate relations to the restenosis rate were found for lesion location (saphenous vein graft, 68%; left anterior descending artery, 45%; left circumflex artery and right coronary artery, 32%; p = 0.002); lesion length (less than or equal to 4.6 mm, 33%; greater than 4.6 mm, 45%; p = 0.001); percent stenosis before angioplasty (less than or equal to 73%, 25%; greater than 73%, 43%; p = 0.005), percent stenosis after angioplasty (less than or equal to 21%, 33%; greater than 21%, 46%; p = 0.017) and arterial diameter (less than 2.9 mm, 44%; greater than or equal to 2.9 mm, 34%; p = 0.036). Two multivariate models to predict restenosis probability were developed with use of stepwise logistic regression. The preprocedural model, which included only variables whose values were known before angioplasty, entered lesion length, vein graft location, left anterior descending artery location, percent stenosis before angioplasty, eccentric lesion and arterial diameter. The postprocedural model, which also included variables whose values were known after angioplasty was performed, was similar to the preangioplasty model except that it also entered postangioplasty percent stenosis and ""optimal"" balloon sizing but did not enter eccentric lesion. These data indicate that the probability of restenosis after angioplasty is determined predominantly by the characteristics of the lesion being dilated. They are consistent with the known intimal proliferative mechanism of restenosis, offer a means of identifying lesions at unusually high or low risk of restenosis, and of predicting the likelihood that a particular lesion will restenose after angioplasty and provide a rationale for stratification by restenosis probability in the design of future studies of restenosis."
-What diagnostic techniques were used to identify the left ventricular aneurysm in the fetus?,"Prenatal diagnosis of fetal left ventricular aneurysm: a case report and review. Fetal echocardiography in a 30-year-old black woman, gravida 4, para 3, demonstrated left ventricular aneurysm. This was confirmed by color flow pulsed Doppler techniques. After delivery, neonatal echocardiography and magnetic resonance imaging further confirmed the diagnosis. The infant was followed closely and underwent surgical correction at 8.5 months of age. Before surgery, cardiac catheterization demonstrated normal hemodynamic function. A review of the literature revealed a paucity of information. Issues of prenatal diagnosis, antenatal surveillance, method of delivery, and neonatal follow-up are not well defined in either the obstetric or pediatric cardiology literature. A rationale for our approach to this complex problem is presented."
-What was the main objective of the study on community obstetric care in West Berkshire?,"Community obstetric care in West Berkshire OBJECTIVE--To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN--Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING--West Berkshire Health District. SUBJECTS--All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES--Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS--Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION--Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife."
-How do the outcomes of psychogenic seizures differ between children/adolescents and adults according to the study?,"Outcome of psychogenic seizures in children and adolescents compared with adults. We compared outcome of psychogenic seizures documented by video-EEG in 18 nonepileptic children and adolescents (ages 8 to 18; median, 14.5 years old) and 20 adults (ages 25 to 56; median, 34.0 years old). Outcome was significantly better for the younger patients at 1 year, 2 years, and 3 years after diagnosis. At these follow-up times, the percentages of children and adolescents free of psychogenic attacks were 73%, 75%, and 81%; at the same follow-up times, the percentages of adults free of psychogenic attacks were only 25%, 25%, and 40%. Factors leading to better outcome for younger patients may have been different psychological mechanisms at different ages of onset and greater effectiveness with earlier intervention."
-What are the proposed criteria for diagnosing migraine without aura in clinical practice?,"Criteria for the diagnosis of migraine in clinical practice. Criteria for the diagnosis of migraine have evolved from generalized descriptions to specific rules designed to ensure the selection of homogenous groups of patients for research studies. For clinical practice, the former are insufficiently specific and the latter are too complex. For care of headache patients by primary care physicians, we propose that the diagnosis of migraine without aura (common migraine) is warranted if any two of the following symptoms are present: unilateral site, throbbing quality, nausea, photophobia or phonophobia. These criteria are derived from a study comparing the features of 100 patients with migraine without aura and 100 patients with chronic daily headache. The proposed criteria for the diagnosis of migraine without aura were highly sensitive and adequately specific in discriminating groups. These simple criteria should facilitate the diagnosis of migraine by primary care physicians."
-What was the main finding regarding secondary prophylactic drug use for patients after myocardial infarction in the study?,"Use of secondary prophylaxis against myocardial infarction in the north of England OBJECTIVE--To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. DESIGN--Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. SETTING--The nine family practitioner committee areas within the Northern Regional Health Authority. PATIENTS--Patients who had had a myocardial infarction and were discharged to their general practitioner. MAIN OUTCOME MEASURE--Whether beta blockers or aspirin, or both, were given on discharge. RESULTS--Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. CONCLUSIONS--Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary."
-How does the MELAS mutation affect mitochondrial RNA transcription termination?,"Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products."
-How do thromboxane A2 synthase inhibition and thromboxane A2/prostaglandin endoperoxide receptor antagonism differently affect occlusive thrombosis in canine coronary arteries with varying degrees of vascular damage?,"Differential effects of thromboxane A2 synthase inhibition, singly or combined with thromboxane A2/prostaglandin endoperoxide receptor antagonism, on occlusive thrombosis elicited by endothelial cell injury or by deep vascular damage in canine coronary arteries. In open-chest dogs, cyclic flow reductions (CFRs, 5.1-6.6/hr in controls; n = 24) caused by platelet deposition/dislodgment at sites of endothelial cell injury in critically stenosed left anterior descending coronary arteries (59% flow reduction) were attenuated to the same extent either by single thromboxane A2 (TXA2) synthase inhibition (0.31 mg/kg i.v. ridogrel; CFR, 0.16 +/- 0.16/hr; n = 6; p less than 0.05) or by a comparatively modest degree of TXA2/prostaglandin endoperoxide receptor antagonism on top of TXA2 synthase inhibition (5 mg/kg i.v. ridogrel; CFR, 0.22 +/- 0.1/hr; n = 10; p less than 0.05). By contrast, occlusive thrombosis on deep vascular damage elicited by intraluminal stimulation (150-microA anodal constant current) in nonpreconstricted canine coronary arteries (time to occlusion, 237.1 +/- 13.9 minutes; n = 7; incidence of occlusion within 300 minutes, six of seven experiments) was not affected by platelet cyclooxygenase inhibition (5 mg/kg i.v. acetylsalicylic acid; n = 7), single TXA2 synthase inhibition (1.25 mg/kg i.v. ridogrel; n = 7), or single TXA2/prostaglandin endoperoxide receptor antagonism (10 mg/kg + 10 mg/kg/hr i.v. sulotroban for 300 minutes; n = 5). However, such an occlusive thrombus formation was significantly reduced by combined TXA2 synthase/prostaglandin endoperoxide receptor inhibition (5 mg/kg i.v. ridogrel; time to occlusion greater than 300 minutes, n = 7; incidence of occlusion within 300 minutes, one of seven experiments; p less than 0.05). This study reveals 1) a differential efficacy of TXA2 synthase inhibition, singly or combined with TXA2/prostaglandin endoperoxide receptor antagonism, depending on the extent of the vessel wall lesion triggering thrombosis and the size of the thrombus required to obstruct the vascular lumen and 2) a significant synergism in preventing occlusive thrombosis of extensively damaged coronary arteries between strong TXA2 synthase inhibition and comparatively modest TXA2/prostaglandin endoperoxide receptor antagonism with ridogrel."
-What were the main outcome measures in comparing dual chamber pacing (DDD) and ventricular rate adaptive pacing (VVIR) in patients with complete heart block?,"Double blind crossover comparison of the effects of dual chamber pacing (DDD) and ventricular rate adaptive (VVIR) pacing on neuroendocrine variables, exercise performance, and symptoms in complete heart block. OBJECTIVE--To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block. DESIGN--Double blind crossover comparison with one month in each pacing mode. PATIENTS--10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers. MAIN OUTCOME MEASURES--Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline. RESULTS--No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes. CONCLUSIONS--In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing."
-How does Epstein-Barr virus infection impact liver transplant patients and their graft function?,"Epstein-Barr virus and persistent graft dysfunction after liver transplantation. Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection."
-What surgical procedure was used to treat scaphoid pseudarthrosis in this long-term review study?,"Pseudarthrosis of the scaphoid treated by the Matti-Russe operation. A long-term review of 77 cases. We report the long-term results of the Matti-Russe operation for pseudarthrosis of the scaphoid in 100 cases, reported previously by Mulder in 1968. Clinical results for 77 patients and radiographic data for 74 were reviewed at 22 to 34.8 years after surgery. In general, there was satisfactory relief of pain and stiffness but some patients had limitation of motion and reduced grip-strength, with usually slight osteoarthritic changes. There was poor correlation between subjective, objective, and radiographic results but 88% of the patients were satisfied with their results."
-What is the significance of the reported case of hydroureteronephrosis secondary to perforated Meckel's diverticulum?,"Hydroureteronephrosis secondary to perforated Meckel's diverticulum. Complications related to Meckel's diverticulum are not unusual. However, involvement of the urinary tract is extremely rare. To our knowledge this is the first reported case of ureteral obstruction due to perforation of Meckel's diverticulum."
-What are the key risk factors that contribute to excess morbidity and mortality from influenza infections in children in developing countries?,"Pathogenesis of respiratory infections due to influenza virus: implications for developing countries. The influenza viruses have an important and distinctive place among respiratory viruses: they change antigenic character at irregular intervals, infect individuals of all ages, cause illnesses characterized by constitutional symptoms and tracheobronchitis, produce yearly epidemics associated frequently with excess morbidity and mortality, and predispose the host to bacterial superinfections. Much is known about influenza viruses, but their role in respiratory infections among children in developing countries is poorly understood, and the risk factors that lead to the excess morbidity and mortality have not been identified clearly. Among the many risk factors that may be important are alterations in host immunity, malnutrition, prior or coincident infections with other microorganisms, inhaled pollutants, and lack of access to medical care. There is a great need for research that can establish more precisely the role these and other unidentified factors play in the pathogenesis of influenza infections in children in the developing world."
-What did the study reveal about the presence of atrial natriuretic factor in the human ventricle in relation to ventricular dilation?,"Expression of atrial natriuretic factor in the human ventricle is independent of chamber dilation This study investigated the presence of atrial natriuretic factor in ventricular tissue obtained from humans with dilated or restrictive heart disease. In 17 patients with ventricular dilation and impaired systolic function and in 8 patients with restrictive heart disease and preserved systolic function, the presence of ventricular atrial natriuretic factor was investigated in tissue obtained by ventricular endomyocardial biopsy. The objective of the study was to determine if the ventricular presence of atrial natriuretic factor is dependent on ventricular dilation. Left ventricular end-diastolic volume index was greater in the group with dilated cardiomyopathy than in the group with restrictive cardiomyopathy (134 +/- 13 versus 78 +/- 5 ml/m2, p less than 0.05); end-diastolic pressure was elevated in the two groups (20 +/- 2 versus 25 +/- 4 mm Hg, p = NS). With the use of immunohistochemical techniques, ventricular atrial natriuretic factor was clearly detected in 15 of the 17 patients with dilated cardiomyopathy and in 6 of the 8 patients with restrictive cardiomyopathy. This study demonstrates the high prevalence of ventricular atrial natriuretic factor in living patients with either systolic or diastolic dysfunction. Whereas in the atria, stretch or dilation may be an important stimulus, atrial natriuretic factor in the ventricular chamber occurs independent of dilation."
-What is the primary purpose of the knowledge-based computer system described in the context?,"Knowledge-based computer system to aid in the histopathological diagnosis of breast disease. A knowledge-based computer system, designed to assist pathologists in the histological diagnosis of breast disease, is described. This system represents knowledge in the form of ""disease profiles"" and uses a novel inference model based on the mathematical technique of hypergraphs. Its design overcomes many of the limitations of existing expert system technologies when applied to breast disease. In particular, the system can quickly focus on a differential problem and thus reduce the amount of data necessary to reach a conclusion. The system was tested on two sets of samples, consisting of 14 retrospective cases and five hypothetical cases of breast disease. Its recommendations were judged ""correct"" by the evaluating pathologist in 15 cases. This study shows the feasibility of providing ""decision support"" in histopathology."
-What changes were observed in the high-frequency peak power of heart rate variability in patients not taking beta blockers during the 24-hour period after acute myocardial infarction?,"Diurnal variations of neurocardiac rhythms in acute myocardial infarction. To determine the diurnal pattern of cardiac autonomic tone in acute myocardial infarction (AMI), this study examined the power spectrum of heart rate (HR) variability in 24 patients during a single 24-hour segment within 4 days of AMI. Patients were nonrandomly allocated to a group (n = 14) without autonomic drugs and to a group (n = 10) already receiving beta blockers at the time of AMI. With use of autoregressive modeling, the power spectrum of HR variability was computed from continuous 1-hour electrocardiographic segments recorded at equally spaced intervals; 7 to 8 A.M., 3 to 4 P.M., and 11 to 12 P.M. All patients were supine, awake and pain free during recordings. There were no differences in HR, HR variance or the low-frequency peak power (0.06 to 0.1 Hz) from one temporal sequence to another. For the patients not taking beta blockers, the high-frequency peak power (0.2 to 0.36 Hz) or vagal component increased significantly from 3 P.M. to 11 P.M. (28 +/- 11 to 45 +/- 20 beats/min2.Hz-1, p less than 0.01). There was a significant decrease in the low- to high-frequency peak power and area ratios from 3 P.M. to 11 P.M. All power spectral parameters in the patients taking beta blockers remained unchanged over 24 hours. There was significantly heightened vagal modulation of sinus node activity in those receiving beta blockers, especially at 7 A.M. and 3 P.M. The data suggest that under steady-state wakeful conditions in the early recovery phase after an AMI, vagal tone is more pronounced during the late evening hours with a possible shift to relative sympathetic dominance during early morning and midafternoon hours."
-What are the three types of adenomatous hyperplasia (AH) identified in the study?,"Argyrophilic nucleolar organizer regions and alpha-fetoprotein in adenomatous hyperplasia in human cirrhotic livers. Recently, adenomatous hyperplasia (AH) of the liver has been suspected as a precancerous lesion in human hepatocarcinogenesis. The authors examined 75 cases of AH from 42 cirrhotic livers, using staining of argyrophilic nucleolar organizer regions (AgNORs). These reflect proliferative cell activity. Findings in AH were compared with those seen in hepatocellular carcinoma (HCC) and other chronic liver diseases. Expression of alpha-fetoprotein (AFP) was also examined immunohistochemically. The authors classified AH into three types: ordinary (OAH), atypical (AAH), and AH with focal malignancy (FM). OAH implies a lack of atypia; AAH represents AH with structural and cellular atypia but without the features of overt carcinoma; and FM denotes AH with foci of overt HCC. Forty of the 75 cases of AH were categorized as OAH, 19 as AAH, and 16 as FM. The noncancerous areas of FM had features of AAH. The mean number of AgNORs in AH was intermediate between that seen in cirrhosis (2.93) and HCC (6.18) and showed a step-wise increase in the following order: OAH (2.95), AAH (3.89), noncancerous areas in FM (4.58), and malignant foci in FM (5.71). There was no significant difference in AgNOR counts between OAH and cirrhosis. AgNOR counts in AAH and FM were significantly higher than those of OAH, and lower than those of HCC. AFP was positive in 12 of 25 HCCs and in malignant foci of 3 FM lesions, but it was absent in OAH and AAH. These data suggest that OAH has a limited capacity for proliferation but that AAH and FM are much more replicative. The latter two conditions are probably preneoplastic lesions or early forms of HCC."
-How does repetition priming differ from explicit memory in patients with depression?,"Explicit memory and repetition priming in depression. Preliminary findings. Explicit memory and repetition priming, a form of implicit memory, were examined in depressed patients and controls. Explicit memory of depressed patients was severely impaired, whereas repetition priming was intact. These results are consistent with the hypothesis that the impairment of memory in depression is linked to a failure of effort-demanding cognitive processes. Repetition priming might be useful in differentiating between depression and dementia."
-How does Lupron affect the cell cycle of the ovarian cancer cell line 2774?,"Lupron retards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment."
-How effective was zidovudine (ZDV) treatment in preventing Friend virus (FV) progression in mice?,"Early-initiated zidovudine therapy prevents disease but not low levels of persistent retrovirus in mice. An F1 hybrid mouse strain containing the Rfv-3r/s genotype was inoculated with Friend virus complex (FV) and treated with zidovudine (ZDV) intraperitoneally three times daily for 20 days beginning as early as 10 min after initial viral exposure. This strain of mice develops FV-specific neutralizing antibodies that aid in reducing viremia and splenic virus titers but do not prevent splenomegaly and eventual FV-associated death. The virally exposed mice treated with ZDV did not develop splenomegaly or have detectable viremia after the last drug treatment. On day 21, a single animal had demonstrable virus in the spleen as determined by a focal immunoenzyme assay; 57% had detectable virus at 5 weeks, but non displayed splenic virus after 35 weeks. None of the animals died after the 35-week holding period, compared to 38% dying in placebo-treated mice. To detect low levels of the virus, or potentially latent virus, splenocytes were cocultivated with a cell line known to readily propagate FV, and the cells were subsequently passaged four times to amplify replication of the virus. After amplification, a significant increase was seen in the number of mice testing positive for virus. Thus, ZDV treatment initiated early after virus exposure was effective in preventing FV-induced splenomegaly and death, but did not prevent low levels of persistent retrovirus in the mice."
-What diagnostic technique was used to detect minute lesions in patients with Crohn's disease during the sigmoidoscopy procedure?,"Minute lesions of the rectum and sigmoid colon in patients with Crohn's disease. Sigmoidoscopy with a spray of 0.1% indigocarmine was performed on 20 patients with Crohn's disease whose main lesions were located proximal to the transverse colon and on 10 age-matched healthy volunteers. Minute lesions such as apthoid lesions, areas of erythema, and small ulcers were found in 90% of patients with Crohn's disease and in 0% of healthy volunteers (p less than 0.001). Among the minute lesions, aphthoid lesions were found in the highest incidence (85%). It was difficult to determine the presence of aphthoid lesions without the spray of indigocarmine, which facilitated detection. Histologically, granulomas were found in 15% of patients with Crohn's disease. Aphthoid lesions were not associated with superficial erosions and lymphoid follicles. The presence of aphthoid lesions in the rectum and sigmoid colon would be a strong indication of the presence of Crohn's disease."
-How did cardiac myocyte size and volume change in different heart regions of rats with aortocaval fistulas after 5 months?,"Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects. Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass."
-What were the main findings of the study regarding the effects of microsurgical DREZ-otomy (MDT) on somatosensory function?,"Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity. The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a ""retuning"" of the dorsal horn as the mode of action of MDT is presented."
-"How do neutrophils, PAF, and thromboxane contribute to the decrease in local blood flow during pulmonary inflammation?","Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane. The intrapulmonary instillation of C5a results in a local inflammatory response that, in this site, is accompanied by a decrease in local blood flow. Reversal of this decrease by vasodilators or the thromboxane synthesis inhibitor dazmegral has been shown to result in enhanced lung inflammation. In the present study the mechanisms underlying the decrease in flow in pulmonary inflammation were investigated in the rabbit in vivo and in the isolated blood-perfused rabbit lung. In vivo, the decrease in local blood flow was shown to be dependent on circulating neutrophils. In the isolated blood-perfused lung, inflammation induced by airway instillation of C5a was similar histologically to that seen in vivo and was also accompanied by a decrease in local blood flow. The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989. Furthermore, no decrease occurred in aspirin-treated lungs perfused with normal blood, suggesting that the source of thromboxane was lung rather than circulating cells. The decrease in blood flow in inflammation did not appear to be a consequence of hypoxic vasoconstriction. Inflammation in the guinea pig lung was also accompanied by a decrease in local blood flow and was also prevented by dazmegral and PAF antagonists. We conclude that local inflammation in the lung is accompanied by a decrease in blood flow that involves neutrophils and the lipid mediators PAF and thromboxane. We suggest that this form of negative feedback by the neutrophil serves to control the inflammatory response."
-What role does echocardiography play in diagnosing and evaluating mitral and tricuspid stenosis?,"Role of echocardiography in the diagnosis and evaluation of severity of mitral and tricuspid stenosis. The presence, severity, and hemodynamic consequences of mitral and tricuspid stenosis can be determined by echocardiographic techniques. In mitral stenosis two-dimensional echocardiographic imaging allows definition of leaflet anatomy and dynamics, subvalvular disease, ventricular function, and involvement of other valves. Spectral and color Doppler echocardiographic techniques permit accurate measurement of transvalvular gradient, determination of functional orifice area, evaluation of associated valvular regurgitation, and assessment of pulmonary artery pressures. These approaches are of recognized clinical value, and they provide additional diagnostic information that is unavailable from clinical assessment alone in a significant number of patients. Compared with available invasive diagnostic standards of reference, echocardiographic data have been found to be comparable in accuracy. In tricuspid stenosis echocardiographic imaging and Doppler techniques provide an assessment of valve morphology and function that should be similarly useful in clinical management decisions, although rigorous comparative studies have not been performed. Currently, carefully done echocardiographic studies are a definitive means of establishing the presence and significance of mitral stenosis and tricuspid stenosis, thereby obviating the need for invasive evaluation in many patients, reducing risk, and potentially decreasing the cost of diagnostic assessment."
-What was the impact of graft diameter on patency in this study of Dacron aortobifemoral bypass grafts?,"Lack of diameter effect on short-term patency of size-matched Dacron aortobifemoral grafts. This study examined the relationship between graft diameter and subsequent patency in 79 patients who received Dacron aortobifemoral bypass grafts for aortoiliac occlusive disease between 1985 and 1989. Sixty-five percent of these patients were men, 25% were diabetic, and 94% were smokers, with an average age of 62 years. Patients were followed for a mean interval of 24 months. Life-table survival was 92% at 3 years. All surviving patients showed ""significant"" postoperative improvement by use of Society for Vascular Surgery/International Society for Cardiovascular Surgery combined clinical and vascular laboratory criteria. There were three early and five late graft thromboses. Primary and secondary life-table patencies were 85% and 92%, respectively, at 3 years. Dacron bifurcation grafts were selected to match the size of native arteries. Patients receiving small diameter grafts, defined as 12 mm (n = 9) and 14 mm (n = 39), were compared with patients receiving large diameter grafts of 16 mm (n = 26) and 18 mm (n = 5). Small diameter grafts were more likely to be used in women (p less than 0.01), but patient groups were otherwise comparable with respect to age, smoking history, diabetes, outflow status, operative indications, type of proximal anastomosis (end-to-end or end-to-side), location of distal anastomosis (common femoral vs deep femoral), type of graft construction (knitted vs woven), and functional result. Graft diameter did not influence life-table patency, which was 84% for small and 87% for large diameter grafts at 3 years (p = 0.74). Furthermore, none of the other variables listed above influenced graft patency."
-How did patients with fornix damage perform on nonverbal memory tests compared to patients with other brain lesions?,"Amnesia following damage to the left fornix and to other sites. A comparative study. Two memory-impaired patients, who had suffered damage to the left or both fornix columns during removal of a ventricular cyst, were compared with 3 others having left-sided hippocampal or thalamic lesions, and with normal controls. The tests used were nonverbal--scene recognition, delayed matching-to-sample and concurrent pattern and object discrimination learning. The last two are differentially sensitive to fornix transection and to hippocampal or thalamic ablations in monkeys; however, the patients with fornix damage did not show a distinctive pattern of impairment. The reasons for this discrepancy are discussed. The study adds to the evidence that fornix transection can cause wide-ranging memory disturbances in man."
-"How did the DNA ploidy status of cervical carcinoma tumors change after radiation therapy, and what was its relationship to tumor response?","DNA ploidy analysis of effectiveness of radiation therapy for cervical carcinoma. Cellular DNA content from 30 patients with cervical carcinoma was determined using flow cytometry before and after radiation therapy (RT). The authors attempted to correlate changes in DNA content, tumor response to RT, and post-RT pathologic findings. Before RT, tumors from eight of 30 patients (26.7%) were diploid or near-diploid; tumors from 22 patients (73.3%) were aneuploid. After RT, diploid or near-diploid tumors were found in 23 patients (76.7%), and aneuploid tumors were observed in seven patients (23.3%). Aneuploidy disappeared in 15 of the patient tumors, and complete tumor response (CR) was observed in 13 of these 15 patients (86.7%). Pathologic examinations were negative in 12 of 15 cases and suspicious in one of 15 cases. Of the seven patients whose tumor aneuploidy did not change after RT, CR was observed in only two (28.7%). Pathologic examinations were positive in five of seven cases and suspicious in one of seven cases. The CR for the 22 patients with pre-RT aneuploid tumors was 15 of 22 (68.2%); the CR for the eight patients with pre-RT diploid tumors was two of eight (25%, P less than 0.01). From these data the authors conclude there is a direct correlation between DNA content and radiosensitivity in cervical carcinoma. Aneuploid tumors from these patients were more radiosensitive than diploid tumors, and they patients had a better clinical tumor response and improved pathologic findings."
-How does enhanced GABAergic inhibition impact neuronal death and cognitive function in an epilepsy model?,"Enhanced GABAergic inhibition preserves hippocampal structure and function in a model of epilepsy. Extensive electrical stimulation of the perforant pathway input to the hippocampus results in a characteristic pattern of neuronal death, which is accompanied by an impairment of cognitive functions similar to that seen in human temporal lobe epilepsy. The excitotoxic hypothesis of epileptic cell death [Olney, J. W. (1978) in Kainic Acid as a Tool in Neurobiology, eds. McGeer, E., Olney, J. W. & McGeer, P. (Raven, New York), pp. 95-121; Olney, J. W. (1983) in Excitotoxins, eds. Fuxe, K., Roberts, P. J. & Schwartch, R. (Wenner-Gren International Symposium Series, Macmillan, London), Vol. 39, pp. 82-96; and Rothman, S. M. & Olney, J. W. (1986) Ann. Neurol. 19, 105-111] predicts an imbalance between excitation and inhibition, which occurs probably as a result of hyperactivity in afferent pathways or impaired inhibition. In the present study, we investigated whether the enhancement of gamma-aminobutyric acid (GABA)-mediated (GABAergic) inhibition of neurotransmission by blocking the GABA-metabolizing enzyme, GABA transaminase, could influence the histopathological and/or the behavioral outcome in this epilepsy model. We demonstrate that the loss of pyramidal cells and hilar somatostatin-containing neurons can be abolished by enhancing the level of synaptically released GABA, and that the preservation of hippocampal structure is accompanied by a significant sparing of spatial memory as compared with placebo-treated controls. These results suggest that enhanced GABAergic inhibition can effectively block the pathophysiological processes that lead to excitotoxic cell death and, as a result, protect the brain from seizure-induced cognitive impairment."
-What percentage of children with acquired cortical blindness had a poor visual outcome in the study?,"Cortical blindness in children: a study of etiology and prognosis. Thirty-four children (20 boys, 14 girls) with congenital and acquired cortical blindness were analyzed for visual outcome in relation to etiology, visual evoked potentials, electroencephalography, and cranial computed tomography. All 7 children with congenital cortical blindness remained blind on subsequent examination. Of the 27 children with acquired blindness, 16 (59%) had poor visual outcome. Poor visual outcome occurred in those with cardiac arrest, hypoxia, status epilepticus, intracranial hemorrhage, cerebral thrombosis, and head trauma. Good visual outcome occurred in children with hypotensive episodes after cardiac surgery. Of the 12 children with recovery of vision, the interval from acute loss of vision to partial or total recovery was 2 weeks to 5 months. Seven children had complete recovery of vision with no residual visual field defect. The majority of children (87%) had focal or multifocal spike-and-waves and slow sharp-wave discharges on electroencephalography. None had photic recruitment response or occipital spike-and-wave discharges. Flash visual evoked potential studies performed during acute episodes of cortical blindness documented 11 with absent response, 10 with bilateral increases in latency, and 6 with normal responses. There was no correlation between normal visual evoked potentials and a good visual outcome. Only 2 of 6 children with normal responses had normal vision. Abnormal or absent responses are more predictive of a poor recovery of vision because only 3 of 21 (14%) had normal vision on subsequent examination. Abnormal electroencephalographic findings with focal or multifocal spike-and-wave discharges or cerebral atrophy on cranial computed tomography are also poor prognostic signs."
-What factors beyond physical swallowing ability influence a patient's capacity to resume oral nutrition in oropharyngeal dysphagia?,"Factors affecting ability to resume oral nutrition in the oropharyngeal dysphagic individual. Successful oral intake of nutrition depends not only on the patient's ability to swallow efficiently and safely but also a number of cognitive, neurolinguistic, and behavioral variables. This paper reviews these competencies as they are integrated into the act of oral feeding and describes the types of disorders that affect these abilities. Methods of evaluating and treating the abilities needed for successful oral intake are described."
-What is the significance of screening for Wilson disease in cases of unexplained recurrent abortion?,"Recurrent abortion and the diagnosis of Wilson disease. We describe the first patient with Wilson disease and recurrent abortion who was effectively treated with oral zinc for both conditions. Between the ages of 21-26, this patient experienced seven successive unexplained abortions. At age 27, neurologic signs and liver function disturbances appeared. Wilson disease was diagnosed when Kayser-Fleischer rings were detected in the cornea. Decoppering therapy was instituted with zinc sulfate per os. By the age of 31, hepatic and neurologic signs had vanished. The patient conceived, and after an uncomplicated eighth pregnancy she delivered her first healthy child. Two years later, a ninth pregnancy was equally successful. The chance that Wilson disease may be the cause of recurrent abortion is small. However, because the disease is fatal if left untreated and because it is an underdiagnosed disease, we recommend screening for Wilson disease in cases of unexplained recurrent abortion when family history demonstrates consanguinity or neurologic, psychiatric, and/or liver disorders. A strategy to this end is proposed."
-How does Ki-67 immunostaining correlate with nuclear grade and clinical outcome in node-negative breast carcinoma?,"Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Prognostic predictors for node-negative breast carcinoma have not been clearly established. Immunostaining with Ki-67 antibody was performed on frozen sections of histologically proved node-negative breast carcinomas from 42 patients to examine its prognostic value and its association with other clinicopathologic and biochemical parameters, i.e., patient age and tumor size, histologic type, nuclear grade, mitotic rate, presence of vascular or lymphatic invasion, DNA ploidy, percentage of cells in S-phase, estrogen content, and c-erbB-2 amplification. Thirty-seven of the 42 tumors showed immunoreactivity with Ki-67 antibody in 1% to 55% of the tumor cells. A strongly significant correlation was observed between Ki-67 staining percentage and, respectively, nuclear grade, age, and mitotic rate. Nuclear grade 1 (the most anaplastic) tumors showed a significantly higher median percentage of cells stained (median, 14; range, 3 to 40) compared with nuclear grade 3 tumors (median, 0.5; range, 0 to 8). Thirteen patients developed recurrence; six of them died of disease. On univariate analysis, both 5-year disease-free and overall survivals were strongly associated with percentage of cells stained with Ki-67 antibody. Our results suggest that Ki-67 immunostaining correlates well with nuclear grade and clinical outcome in node-negative breast carcinoma. Because of small sample size analyzed in this study we were unable to do multivariate analysis. Therefore, further studies with larger number of cases are needed to determine whether tumor proliferative activity determined by Ki-67 immunostaining is an independent prognostic parameter or it merely reflects histopathologic features such as nuclear grade or mitotic activity."
-How was DNA typing used to determine paternity in the case of a putrefied fetus during a forensic investigation?,"A forensic application of DNA typing. Paternity determination in a putrefied fetus. Using minisatellite DNA probes that hybridize to a variable number of tandemly repeated loci, an individual-specific DNA fingerprint can be determined. In the case reported here, we succeeded in extracting high-molecular-weight DNA from a 3-month-old fetus discovered during the autopsy of a murdered 28-year-old pregnant woman reported missing 10 days earlier. The results of analysis of restriction-fragment-length polymorphisms showed that all bands present in the fetus's pattern, but absent in the mother's, matched only those of the putative father. Thus, the paternity of the victim's husband was ruled out."
-What drugs showed the greatest influence on clinical outcomes in the treatment of metastatic neuroblastoma?,"Chemotherapy dose intensity correlates strongly with response, median survival, and median progression-free survival in metastatic neuroblastoma We examined the efficacy of five commonly used drugs, teniposide (VM26), cisplatin (CDDP), cyclophosphamide (CPM), doxorubicin (DOXO), and vincristine (VCR) in a retrospective analysis of 44 clinical trials of induction chemotherapy for stage IV neuroblastoma patients newly diagnosed at older than 1 year of age. Dose intensity (DI) of each drug was calculated as milligrams per square meter per week. Linear regression analyses showed that the Dls of VM26 and CDDP had the greatest influence on clinical outcomes (ie, proportion of major response, median survival, and median progression-free survival [PFS]), while those of CPM and DOXO were less significant. VCR had no influence on the three clinical end points. Although many protocols extended treatment to more than 1 year, none of these end points correlated positively with the duration of therapy. Twenty-one weeks appeared adequate for achieving superior response, median survival, and median PFS. These results suggest that maximal dose intensification of selective drugs over a short duration may improve the outcome of patients with poor-risk neuroblastoma."
-What was the primary purpose of performing palliative amputations in this study?,"Major amputations done with palliative intent in the treatment of local bony complications associated with advanced cancer. Palliative amputations were performed on 11 patients (7 men, 4 women) with disseminated disease to control local bony complications. The average patient age was 54 years (range 14-78 years). The primary diseases were melanoma/sarcoma (seven patients) and carcinoma (four patients). All had pain; eight had intractable pain that could not be controlled by analgesics. All 11 patients had additional severe local complications, which included recurrent pathological fracture (4), sepsis (2), hemorrhage (2), radiation necrosis (2), and iliofemoral thrombosis secondary to tumor (1). Previous attempts of palliation had been made in all 11 patients, and 8 had undergone previous operative procedures (5 had undergone two or more) prior to amputation. Three anterior hemipelvectomies, five posterior hemipelvectomies, two hip disarticulations, and one forequarter amputation were performed. All patients survived the surgery, and there were no intraoperative complications. All patients received dramatic relief of pain. Postoperative complications included two cases of flap necrosis and two infections; all resolved satisfactorily. The six patients who were nonambulatory before surgery ambulated postoperatively, and two eventually ambulated with a prosthesis. Six of 11 patients survived 1 year or longer, with a median postoperative survival period of 13 months (average 16 months). Although major amputations are viewed at times as offering little to already-compromised patients, they can improve dramatically the quality of life in selected patients."
-What did the confirmatory factor analysis reveal about the theoretical structure of the McGill Pain Questionnaire in acute pain scenarios?,"Confirming the theoretical structure of the McGill Pain Questionnaire in acute clinical pain. Based upon a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. Although a number of exploratory factor analytic studies have failed to consistently support the theoretical structure of the instrument, one previous confirmatory factor analytic study of chronic pain did statistically support the a priori model. Because it has been suggested that acute pain may not involve the same dimensions as chronic pain, this study provided a direct test of the theoretical structure of the MPQ through multi-sample confirmatory factor analysis (CFA) using data provided by women experiencing pain during labor (n = 185) and women experiencing acute postoperative pain (n = 192). Results of the LISREL CFA analysis indicated that the a priori, 3-factor, oblique model originally proposed by Melzack provided the most parsimonious representation of the data across the 2 samples of acute pain."
-What specific areas of medical knowledge must cardiologists possess when treating adults with congenital heart disease?,"The physician's responsibilities: residua and sequelae. Cardiologists assuming responsibility for adults with congenital heart disease must have knowledge of electrophysiologic, valvular (native valves), prosthetic (valves, patches and conduits), ventricular (especially chamber function), vascular (especially elevated pulmonary vascular resistance) and noncardiovascular residua and sequelae. Acquired cardiac and noncardiac diseases coexist in older adults with postoperative congenital heart disease and add to the physician's responsibilities."
-"How did the Mini Shah grommet compare to the conventional Shah grommet in terms of extrusion, effusion recurrence, and tympanosclerosis?","The mini-grommet and tympanosclerosis. One hundred and sixteen children with otitis media with effusion underwent myringotomy and insertion of a conventional pattern of Shah grommet in one ear and the much smaller Mini Shah grommet in the other. Close observation post-operatively determined the comparative rate of extrusion, recurrence of effusion, and of onset and degree of tympanosclerosis. At one year review, the Mini Shah shows a significantly earlier extrusion and a greater tendency to recurrence of otitis media with effusion. However, this is compensated by a decreased incidence of tympanosclerosis and reduced severity in those affected. This tends to support the view that shear forces produced by heavier patterns of ventilation tube promote tympanosclerosis."
-What is the rare complication observed in this patient with mixed connective tissue disease?,Hemobilia due to vasculitis of the gall bladder in a patient with mixed connective tissue disease. A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of the gall bladder wall. Hemobilia has not been described before as a complication in mixed connective tissue disease.
-What unique medical findings were discovered in the autopsy of this 62-year-old world record marathon runner?,"A world record marathon runner with silent ischemia without coronary atherosclerosis. A 62-year-old world record marathon runner was found to have silent ischemia manifested by a very abnormal stress test, whereas at autopsy nine months later, there was virtually no coronary atherosclerosis nor other disease of the coronary microvasculature. However, there was focal fibrosis of the papillary muscles consistent with remote ischemia secondary to possible CV. It is postulated that endurance-related high catecholamine levels might have been responsible."
-What were the findings of the study regarding the potential ototoxic effects of ciprofloxacin when applied ototopically?,Lack of ciprofloxacin ototoxicity after repeated ototopical application. The possible side effects of ototopically applied ciprofloxacin on inner ear function were investigated. The hearing function of pigmented guinea pigs was evaluated by daily frequency-specific evoked response audiometry after repeated application of the drug to both ears. Ciprofloxacin appeared to have no statistically significant effect on the hearing thresholds of the experimental animals.
-What are the key risk factors for tunnel infections in continuous peritoneal dialysis?,"Risk factors for tunnel infections in continuous peritoneal dialysis. Little data are available about risk factors for peritoneal catheter subcutaneous tunnel infection. Therefore, we analyzed tunnel infections occurring in our program over a 10.5-year period. One hundred twenty-nine tunnel infections occurred in 92 of 411 patients (22%) on peritoneal dialysis for a mean of 19 +/- 19 months. Tunnel infection rate was 0.19 per year. By 1 year, 15% of patients had a tunnel infection, and by 2 years, 23%. Tunnel infection rates decreased with increasing time on peritoneal dialysis: 2.4 per year for patients on peritoneal dialysis less than 1 year, 0.8 per year for patients on dialysis 1 to 2 years, and 0.4 per year for patients on dialysis greater than 2 years (all different at P less than 0.01). Organisms were cultured in 109 tunnel infections: gram-positive cocci in 77 episodes (71%) [Staphylococcus aureus 57, 52%], and gram-negative bacilli in 24 episodes (22%). Tunnel infection rates were higher in diabetics than in nondiabetics (0.27 per year v 0.16 per year, respectively; P less than 0.001 by life-table analysis of time to first infection) and also higher in women than in men (0.23 per year v 0.17 per year, P less than 0.001). Tunnel infection rates were 0.35 per year for diabetic women, 0.20 per year for diabetic men, 0.18 per year for nondiabetic women, and 0.15 per year for nondiabetic men (groups different, P less than 0.001). Race and age were similar in patients with and without tunnel infections. Catheter loss was 80% when tunnel infection was associated with peritonitis and 40% when tunnel infection alone was present (P less than 0.001). We conclude that the risk of tunnel infection is highest early in the course of peritoneal dialysis and that diabetic women, for unclear reasons, are at the highest risk."
-How does color Doppler flow sonography help in assessing erectile function in normal and abnormal cases?,"Assessment of normal and abnormal erectile function: color Doppler flow sonography versus conventional techniques. The penile arteries were studied with color Doppler flow sonography in 10 subjects with normal and 39 patients with abnormal erectile function. The relationships of systolic and diastolic velocities to spectral waveform changes in the penile arteries in response to tumescence were studied before and after intracorporal injection of vasoactive medications that induce erection. In normal subjects, a characteristic spectral waveform pattern corresponded to increasing intracorporal pressure. Patients with abnormal arterial inflow and/or abnormal venous sinusoidal leakage demonstrated deviation from the patterns noted in normal subjects. Patients with abnormal arterial inflow had lower mean peak systolic velocities than normal subjects. Patients with severe venous sinusoidal incompetence had an arrest of waveform progression with evolution to but not beyond phases 1 or 2 (diastolic flow remained positive). Patients with abnormal arterial inflow and abnormal venous sinusoidal outflow had waveform changes that reflected both processes. Systolic/diastolic velocity and waveform relationships can be used to define the integrity of both the cavernosal artery inflow and venous sinusoidal outflow occlusion mechanisms."
-What percentage of women with metastatic breast cancer develop eye metastases?,"Breast cancer metastatic to the eye is a common entity. Breast cancer metastatic to the eye is a common entity occurring in up to 30% of women with metastatic disease. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs. The diagnosis should be suspected in any women with a history of breast cancer and any visual symptoms, particularly metamorphopsia and scotomata. A thorough ophthalmologic evaluation, aided by ultrasonography, computed tomography, or magnetic resonance scanning, usually confirms the diagnosis. Early treatment with radiation therapy can alleviate symptoms and control local disease. The recognition and treatment of this disorder is important in maximizing the quality of life in patients with metastatic breast cancer, especially because newer treatment regimens prolong survival and thereby increase the chances for ocular metastasis."
-What are the two major types of cystic pancreatic neoplasms mentioned in the context?,"Incidental detection of a microcystic adenoma of the pancreas. Cystic neoplasms of the pancreas are uncommon. The two major types of cystic pancreatic neoplasms are microcystic (serous) cystadenoma and mucinous cystic lesions (mucinous cystadenoma and mucinous cystadenocarcinoma). The two types differ substantially in the long-term mortality. Symptoms and signs do not distinguish between the two types, and small lesions are often asymptomatic. The neoplasms may be discovered during imaging procedures for unrelated complaints. Computerized tomography may suggest the diagnosis of microcystic adenoma or mucinous cystic neoplasm when the features are typical, but the final diagnosis must be established by surgical biopsy. Characteristic gross findings, light microscopic findings, and immunohistochemical staining patterns distinguish between the two types. When preliminary open biopsy confirms microcystic adenoma, extensive unnecessary surgery can be avoided."
-How does dobutamine affect left ventricular isovolumic relaxation in patients with congestive heart failure compared to normal subjects?,"Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle. BACKGROUND. We tested the hypothesis that beta-adrenergic receptor-stimulated acceleration of left ventricular (LV) isovolumic relaxation (i.e., positive lusitropic response) is attenuated in patients with severe congestive heart failure (CHF) compared with patients without LV dysfunction or CHF. METHODS AND RESULTS. The beta-adrenergic agonist dobutamine was infused by the intracoronary route in 14 subjects (normal group, six; CHF patients, eight) and by the intravenous route in a second group of 14 subjects (normal group, four; CHF patients, 10). The positive inotropic response to intracoronary or intravenous dobutamine was substantially and significantly reduced in the patients with CHF. LV isovolumic relaxation rate was determined by the methods of Weiss (TL), Mirsky (T1/2), and by a nonlinear regression technique (TNL). LV isovolumic relaxation assessed by all three methods was significantly prolonged in CHF patients compared with normal subjects. Intracoronary and intravenous infusions of dobutamine caused significant acceleration of LV isovolumic relaxation in both normal subjects and patients with CHF. The magnitude of the dobutamine-stimulated acceleration of isovolumic relaxation in patients with CHF was comparable with that in normal subjects. CONCLUSIONS. These data demonstrate that beta-adrenergic receptor stimulation causes significant acceleration of LV isovolumic relaxation in both normal subjects and patients with severe CHF. Coronary to our hypothesis, the lusitropic response to beta-adrenergic stimulation is well preserved in patients with severe CHF despite substantial attenuation of the beta-adrenergic positive inotropic response. These findings have potentially important implications regarding the physiology and pharmacology of adrenergically mediated LV relaxation in humans."
-What is the significance of dystrophin-positive fibers (revertants) in Duchenne muscular dystrophy patients?,"Dystrophin expression and somatic reversion in prednisone-treated and untreated Duchenne dystrophy. CIDD Study Group. The mechanism by which prednisone improves muscle strength and function in Duchenne muscular dystrophy (DMD) is unknown. We addressed the possibility that clinical improvement was related to prednisone-induced alterations in skeletal muscle dystrophin. We performed muscle biopsies on patients at the conclusion of a randomized, double-blind, 6-month trial of prednisone and analyzed dystrophin content using Western blots and antibody staining of tissue sections. These studies demonstrated no significant differences in dystrophin content between treatment (prednisone 1.5 mg/kg/d, n = 12; prednisone 0.75 mg/kg/d, n = 9) and placebo (n = 12) groups. Of interest, however, was the presence of varying numbers of dystrophin-positive fibers (revertants) occurring individually or in clusters in antibody-stained tissue sections of more than one-half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions half of the Duchenne patients. Mutation analysis revealed that revertants occurred in DMD patients with identifiable deletions or duplications, and in nondeletion patients. Prednisone treatment did not influence the prevalence of revertants. Revertants are most likely due to a second-site mutation occurring in a somatic cell allowing for restoration of the translational reading frame of the dystrophin transcript."
-What is the relationship between dimethylformamide (DMF) exposure and liver enzyme levels among synthetic leather workers?,"Dimethylformamide-induced liver damage among synthetic leather workers. Prevalence of liver injury associated with dimethylformamide (DMF) exposure was determined. Medical examinations, liver function tests, and creatine phosphokinase (CPK) determinations were performed on 183 of 204 (76%) employees of a synthetic leather factory. Air concentrations of solvents were measured with personal samplers and gas chromatography. The concentration of DMF in air to which each worker was exposed was categorized. High exposure concentrations of DMF (i.e., 25-60 ppm) were significantly associated with elevated alanine aminotransferase (ALT) levels (ALT greater than or equal to 35 IU/l), a result that did not change even after stratification by hepatitis B carrier status. Modeling by logistic regression demonstrated that exposure to high concentrations of DMF was associated with an elevated ALT (p = .01), whereas hepatitis B surface antigen (HBsAg) was slightly but independently associated with an elevated ALT (p = .07). In those workers who had normal ALT values, there occurred still significantly higher mean ALT and aspartate aminotransferase (AST) activities, especially among those who were not HBsAg carriers. A significant association existed between elevated CPK levels and exposure to DMF. However, an analysis of the CPK isoenzyme among 143 workers did not reveal any specific damage to muscles. This outbreak of liver injury among synthetic leather workers is ascribed to DMF. It is recommended that the occupational standard for DMF and its toxicity among HBsAg carriers be evaluated further."
-What is Parathyroid Hypertensive Factor (PHF) and how does it contribute to hypertension?,"Parathyroid hypertensive factor, a circulating factor in animal and human hypertension. A new circulating hypertensive factor (parathyroid hypertensive factor; PHF) was shown to exist in the plasma of spontaneously hypertensive rats (SHR) but not in that of normotensive rats. PHF produced a delayed increase in blood pressure with a peak response at 45 min (bolus injection) or 60 to 90 min (continuous infusion). This increase in blood pressure was coupled with an in vitro increase in calcium uptake in rat tail artery with a similar time course. The involvement of calcium in the mechanism of action was supported by the inhibitory effect of calcium antagonists on the vascular action of PHF. Furthermore, PHF increased the intracellular free calcium concentration in cultured smooth muscle cells from rat tail artery. Parathyroidectomy and parathyroid transplant experiments indicated the parathyroid origin of PHF. A culture of parathyroid glands from SHR, but not from normotensive rats, produced in the medium a factor which has the same biological property and HPLC retention time as plasma PHF. A novel cell type was described in the parathyroid gland of SHR, but not normotensive rats, and the percent of these cells correlated significantly with plasma PHF level and blood pressure. In some hyperparathyroid patients, plasma PHF and hypertension were found, both of which disappeared after surgical removal of the parathyroid gland. In both animal models and human studies, PHF seems to be associated with low or normal plasma renin and salt-sensitive type of hypertension."
-How accurately can radiographers triage x-ray films in accident and emergency departments?,"How well can radiographers triage x ray films in accident and emergency departments? [published erratum appears in BMJ 1991 Mar 23;302(6778):696] OBJECTIVE--To assess the ability of radiographers to identify abnormal radiographs of patients attending accident and emergency departments. DESIGN--Prospective study over six weeks. SETTING--Teaching hospital casualty x ray department. PATIENTS--3394 consecutive patients referred for radiography. INTERVENTIONS--Radiographs were assessed by radiographers who were offered a four point triage scheme: normal, abnormal, insignificantly abnormal, or further advice required. MAIN OUTCOME MEASURES--Comparison of radiographers' assessments with an assessment made independently by the reporting radiologists. RESULTS--Overall disagreement between the radiographers and radiologists was 9.4%. There were 7% false positives and 14% false negatives. Most errors occurred in assessing radiographs of the skull, facial bones, chest, abdomen, and soft tissues. CONCLUSION--Unselected radiographers can offer useful advice on radiographs to casualty officers, but their high rate of false positive diagnoses indicates that they cannot triage casualty radiographs sufficiently accurately to allow them to extend their current reporting role."
-What was the primary objective of the nicardipine study in ischemic stroke patients?,"Early treatment of ischemic stroke with a calcium antagonist. We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified."
-Is intravenous immunoglobulin G recommended as a first-line treatment for acute thrombotic thrombocytopenic purpura?,"Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature. Acute thrombotic thrombocytopenic purpura (TTP) is a rare and serious disease. Treatment with prednisone, anticoagulation, antiplatelet drugs, splenectomy, exchange transfusions, vincristine, and plasmapheresis may be effective in some patients, but the response to these therapies is inconsistent and all carry the potential for serious side effects. We, and others, have recently seen dramatic responses to intravenous (IV) immunoglobulin G (IgG) when other treatments have failed. Although IV IgG is expensive, its costs are low compared with those extended plasmapheresis regimens. Since the response to treatment can usually be evaluated within a few days and the side effects appear less than with other treatments, we believe a strong case can be made for the use of IV IgG as first-line therapy for acute TTP. Continued multicenter studies are necessary to finally solve the problem of competing and confusing treatment attempts and synergism of treatment in acute TTP."
-What were the key findings regarding the prognostic value of tumor grade and DNA ploidy status in stage D2 prostate cancer patients?,"The prognostic value of deoxyribonucleic acid flow cytometric analysis in stage D2 prostatic carcinoma. This study was designed to compare the prognostic potential of tumor grade and ploidy status in patients with stage D2 prostate cancer. Two outcome groups were selected on the basis of survival after orchiectomy: a bad outcome group consisting of 66 patients who died of the disease within 12 months and a good outcome group comprising 37 patients who survived beyond 5 years. Tumors were classified histologically as well (17%), moderately (17%) or poorly (66%) differentiated. Tumor grade was a significant predictor of outcome, with 76% of poorly differentiated tumors in the bad outcome group and 65% of well differentiated tumors in the good outcome group (p less than 0.005). Deoxyribonucleic acid (DNA) ploidy analysis was performed on formalin fixed, paraffin embedded samples of the primary tumor to yield 97 final tracings that were classified using set criteria for DNA ploidy status. Over-all, 54% of the tumors were nondiploid (33% aneuploid and 21% tetraploid) and the remaining 46% were diploid. DNA ploidy status was a significant indicator of outcome (p less than 0.001), with 64% of diploid tumors in the good outcome group and 88% of the nondiploid tumors in the poor outcome group. Tetraploid tumors behaved no differently from other nondiploid tumors. We conclude that DNA ploidy status and tumor grading are significant independent predictors of outcome after orchiectomy and when combined yield important additional prognostic information."
-How does milrinone affect left ventricular remodeling after an acute myocardial infarction in rats?,"Effects of milrinone on left ventricular remodeling after acute myocardial infarction. BACKGROUND. Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS. Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION. Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation."
-What percentage of women with chronic pelvic pain were found to have occult somatic pathology after a negative laparoscopy?,"Nongynecologic somatic pathology in women with chronic pelvic pain and negative laparoscopy. One hundred eighty-three women with chronic pelvic pain were referred to a multidisciplinary chronic pelvic pain clinic after negative laparoscopy. One hundred twenty-two of them completed a thorough medical and psychologic evaluation and were followed for a minimum of six months after completion of therapy. Occult somatic pathology was diagnosed in 57 women (47%), including 19 in whom coexistent psychopathology was diagnosed. Myofascial pain was the most common somatic diagnosis, followed by atypical cyclic pain (dysmenorrhea or mittelschmerz); gastroenterologic, urologic and infectious diseases; and pelvic vascular congestion. No plausible somatic etiology was apparent in the remaining 65 (53%) of the 122 referrals. Nongynecologic somatic pathology accounted for 34 (29%) and gynecologic pathology for 23 (19%) of the referrals, only 6 (5%) of whom ultimately required hysterectomy. Women with a somatic diagnosis were found to be significantly older than the remainder of the referral population. Long-term symptomatic improvement or resolution of pain was obtained in 43 (75%) of the 57 patients with somatic diagnoses. Coexistent psychopathology was found to correlate with a poorer long-term prognosis. Our findings underscore the importance of a multidisciplinary approach to evaluating and treating chronic pelvic pain in women and confirm that hysterectomy is indicated in this setting only rarely."
-What was the efficacy of teicoplanin in treating osteomyelitis and vascular-access-associated bacteremias in this study?,"Treatment of bone, joint, and vascular-access-associated gram-positive bacterial infections with teicoplanin. Teicoplanin, a glycopeptide antibiotic, was evaluated for safety and efficacy in the treatment of vascular-access-associated bacteremias and of bone and joint infections due to susceptible gram-positive organisms. Of 35 patients enrolled, 26 had osteomyelitis, 8 had vascular-access-associated bacteremias, and 1 had a joint infection. A total of 38 gram-positive isolates were identified: 23 Staphylococcus aureus and 6 coagulase-negative staphylococcus and 9 streptococcus isolates. After at least 6 months of follow-up, 17 patients were evaluable for efficacy: 10 of 14 (71%) with osteomyelitis and 3 of 3 with vascular-access-associated bacteremias had full resolution of their infections. Inadequate debridement, the presence of metal, and inadequate dosing were likely causes of two failures and two relapses in patients with osteomyelitis. For all but two organisms, teicoplanin MICs were less than or equal to 2 micrograms/ml. Patients who responded had median peak and trough serum bactericidal levels at serum dilutions of 1:64 and 1:16; trough levels of teicoplanin in serum were greater than 30 micrograms/ml. Patients did not respond as expected to daily doses of 4 mg/kg of body weight, which consequently were increased to greater than or equal to 15 mg/kg. Audiology testing of 20 patients found 2 with a mild loss of high-frequency hearing; 1 patient complained of tinnitus. Patients tolerated peak levels in serum as high as 127 micrograms/ml and trough levels of 49 micrograms/ml. However, 5 of 18 patients (28%) whose daily dose was greater than or equal to 12 mg/kg developed drug fever and rash and had teicoplanin discontinued. Further study of the antibiotic at such higher doses is needed."
-"How did nicardipine affect glucose tolerance, insulin secretion, and blood lipid levels in the study?","Effect of the calcium antagonist nicardipine hydrochloride on glucose tolerance and insulin secretion. The calcium antagonist nicardipine was administered to 42 patients at a dose of 60 or 120 mg/day for an average of 7.8 weeks to determine its effects on glucose tolerance and insulin secretion. Glucose tolerance and immunoreactive insulin levels were essentially unchanged by nicardipine regardless of the preexisting level of glucose tolerance. Mean systolic and diastolic blood pressures decreased in all patients. Concentrations of triglycerides decreased and high-density lipoprotein cholesterol levels increased significantly (p less than 0.05) in association with nicardipine administration. Therefore it is concluded that, regardless of the preexisting level of glucose tolerance, nicardipine exerted hypotensive effects without significant adverse effects on glucose tolerance or insulin secretion."
-How did the monitoring of somatosensory evoked potentials (SEPs) help predict and potentially prevent neurological deficits during middle cerebral artery aneurysm surgeries?,"Monitoring of somatosensory evoked potentials during surgery for middle cerebral artery aneurysms. Somatosensory evoked potentials (SEPs) were monitored during 53 procedures for aneurysms of the middle cerebral artery (MCA). ""Significant"" changes were reported to the surgeon, who took corrective action when possible. Changes in the SEPs were categorized as follows: Type I, no change; Type II, significant change with complete return to baseline; Type III, significant change with incomplete return to baseline; Type IV, complete loss with no return; and Type V, no response at baseline. Only 1 of 37 patients with a Type I SEP had a new neurological deficit, and this was a patient who could not be examined for several days after surgery because he was in a pentobarbital coma. All 4 patients with Type III and IV changes had new postoperative neurological deficits. Perhaps of greater importance, 4 of 5 patients with Type II changes had no new deficit. These patients all had changes in SEPs that were completely reversible by clip adjustment (2), prompt removal of temporary clips (1), and inducing hypertension after aneurysm trapping (1). These cases may, therefore, represent instances in which SEP monitoring allowed the clinicians to prevent a neurological deficit. The MCA supplies the area of the somatosensory cortex that controls the hand. Median nerve SEPs are, therefore, a theoretically ideal monitor during surgery for MCA aneurysms. This study suggests that the results of MCA aneurysm surgery may be accurately predicted and improved with SEP monitoring."
-What diagnostic values were studied in patients with spinal metastasis from adenocarcinoma of unknown origin?,"Clinical diagnosis for metastatic adenocarcinoma of spine of unknown origin. A comparative study. The diagnostic values of the presence of Virchow's node (VN) or rectal shelf (RS) in spinal metastasis from adenocarcinoma of unknown origin were studied prospectively in 60 patients during 1986-1988. These were compared with 14 cases with other malignancies of the spine and 37 controls with nonneoplastic spinal lesions. The diagnosis was confirmed by histologic study in all malignant cases. The results were analyzed by diagnostic test analysis and McNemar chi 2 testing. This yields 18.3-21.6%, 97.2-100%, and 92.8-100% sensitivity, specificity, and predictive value, respectively, for a positive test for VN and RS to differentiate significantly adenocarcinoma from other malignancies and control patients (P less than 0.005). These findings may thus be considered as a simple and economic guide for physicians to determine the proper approach to patients with a spinal lesion suspected to be malignant."
-What is the primary purpose of using botulinum toxin in the treatment of spasmodic dysphonia?,"Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia. Spasmodic dysphonia is a focal dystonia that causes a loss of the fine control of intrinsic laryngeal muscles and produces a strained staccato voice. Temporary relief from symptoms has been reported in patients treated with botulinum toxin percutaneously injected into the thyroarytenoid muscle. A newly developed method of treatment differs from reported methods by increasing the accuracy of botulinum toxin placement, reducing soft tissue trauma, and applying basic scientific information about the functional histology of intrinsic laryngeal musculature. Sixteen patients with primarily adductor spasmodic dysphonia were treated. Initial assessment included laryngeal examination by indirect laryngoscopy, videoendoscopy, and stroboscopy, neurology examination (including laryngeal EMG), and vocal function studies with acoustic analysis and aerodynamic studies. A device originally designed for collagen injection allowed the precise microdelivery of toxin to the thyroarytenoid muscle. Indirect laryngoscopy was used to direct the needle, in an attempt to cover a broad area of motor end plates. The minimally effective dose was titrated for each patient, to avoid paralysis and preserve laryngeal function. All patients showed improved voices after treatment. There were no major complications. The basic technique can be performed in the otolaryngologist's office and does not require electromyography equipment or expertise."
-What is the main purpose of the new approach described in the study for differentiating between supraventricular tachycardia with aberrant conduction and ventricular tachycardia?,"A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. BACKGROUND. In the differential diagnosis of a tachycardia with a wide QRS complex (greater than or equal to 0.12 second) diagnostic mistakes are frequent. Therefore, we investigated the reasons for failure of presently available criteria, and we identified new, simpler criteria and incorporated them in a stepwise approach that provides better sensitivity and specificity for making a correct diagnosis. METHODS AND RESULTS. A prospective analysis revealed that current criteria had a poor specificity for the differential diagnosis. The value of four new criteria incorporated in a stepwise approach was prospectively analyzed in a total of 554 tachycardias with a widened QRS complex (384 ventricular and 170 supraventricular). The sensitivity of the four consecutive steps was 0.987, and the specificity was 0.965. CONCLUSIONS. Current criteria for the differential diagnosis between supraventricular tachycardia with aberrant conduction and ventricular tachycardia are frequently absent or suggest the wrong diagnosis. The absence of an RS complex in all precordial leads is easily recognizable and highly specific for the diagnosis of ventricular tachycardia. When an RS complex is present in one or more precordial leads, an RS interval of more than 100 msec is highly specific for ventricular tachycardia. This new stepwise approach may prevent diagnostic mistakes."
-What percentage of patients in the study experienced otolaryngic complications during cancer chemotherapy?,"The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed."
-How did rice bran treatment affect stone formation rates in hypercalciuric patients?,"Results of long-term rice bran treatment on stone recurrence in hypercalciuric patients. A series of 182 calcium stone formers with idiopathic hypercalciuria underwent treatment with rice bran for 1 to 94 months. Urinary calcium excretion was considerably reduced, but there was some increase in urinary phosphate and oxalate. Urinary excretion of magnesium and uric acid, serum calcium, magnesium, phosphate, uric acid, parathyroid hormone (PTH) and ALP was unaffected. There were no obvious changes in serum iron, zinc and copper even when patients were treated for long periods. Rice bran was well tolerated in almost all cases and there were no serious side effects; 49 patients have undergone treatment for more than 3 years (average duration of administration 5.09 years). The frequency of new stone formation was drastically reduced (individual stone formation rate (no./year) from 0.720 +/- 0.533 to 0.125 +/- 0.204; group stone formation rate (no./patient-year) from 0.721 to 0.120) compared with the 3-year period before treatment. During treatment, 61.2% of patients remained in remission. Although rice bran therapy should be effective in correcting absorptive hypercalciuria, there may be limits to the overall ability of rice bran monotherapy to prevent recurrence."
-What was the primary objective of this Phase II trial involving intraperitoneal mitoxantrone in epithelial ovarian cancer?,"Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer. Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was less than or equal to 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation)."
-How does the presence of the S-allele in Dahl rats affect their alcohol consumption?,"The influence of the renin gene on alcohol consumption in Dahl rats. A rat renin allele (the S-allele) has been identified in Dahl rats which cosegregates with increases in blood pressure. Rats with a double dose of the allele--the salt-sensitive hypertensive rats--have low renin activity compared with the salt-resistant hypertensive rat that does not have this S-allele. Alcohol consumption in rats has also been shown to vary with renin activity, and the possible involvement of renin activity in the genetics of alcohol consumption was suggested by previous work showing that the alcohol-preferring P line of selected rats had low renin levels. In the present study we examined alcohol consumption in a group of inbred Dahl rats, which have a double dose of the S renin allele, and in a group of selected Dahl rats, which have only a single dose of this S-allele. After an initial acclimation period, these two groups were first given daily 1-hr access to ascending concentrations of alcohol (3%, 6%, 8% w/v) over a 34-day period followed by continuous access to alcohol for a further 10 days. Water and food were always available. Regardless of whether alcohol was rationed or continuously available, the rats with the double dose of the S-allele drank significantly more alcohol than the rats that had only a single dose of this allele. These findings suggest that genetically mediated alterations in the renin gene may exert a significant influence on alcohol consumption and may be a component in the etiology of alcoholism."
-What was the clinical outcome of treating 15 patients with high-risk intracranial saccular aneurysms using electrolytically detachable coils?,"Electrothrombosis of saccular aneurysms via endovascular approach. Part 2: Preliminary clinical experience. Fifteen patients with high-risk intracranial saccular aneurysms were treated using electrolytically detachable coils introduced via an endovascular approach. The patients ranged in age from 21 to 69 years. The most frequent clinical presentation was subarachnoid hemorrhage (eight cases). Considerable thrombosis of the aneurysm (70% to 100%) was achieved in all 15 patients, and preservation of the parent artery was obtained in 14. Although temporary neurological deterioration due to the technique was recorded in one patient, no permanent neurological deficit was observed in this series and there were no deaths. It is believed that this new technology is a viable alternative in the management of patients with high-risk intracranial saccular aneurysms. It may also play an important role in the occlusion of aneurysms in the acute phase of subarachnoid hemorrhage."
-"How did the National Health Service Corps physicians contribute to reducing perinatal mortality rates in Dade County, Florida between 1987 and 1989?","The impact of National Health Service Corps physicians in the lowering perinatal mortality rate in Dade County, Florida. In some parts of Dade County, Florida, perinatal mortality rates have revealed serious problems in the delivery of health care to poor pregnant women. From 1982-1985, the reported perinatal mortality rates varied from 32-36 per 1000 live births, more than double the national average. Under the leadership of the Primary Health Care Consortium of Dade County (a federation of community health centers and other primary care providers), National Health Service Corps obstetricians and pediatricians served inner-city, medically needy patients as part of a coordinated perinatal plan from 1987-1989. Data on fetal and neonatal deaths, collected from census tracts adjacent to the community health centers, were used to study the impact of Corps obstetrician and pediatrician placement. The respective perinatal mortality rates were compared with those of 1986 as historic controls. Within a year, the overall perinatal mortality rate was reduced by 45%. As a result, an estimated 320 lives were saved between 1987-1989. This public health achievement represents a measurable impact due to assignment of National Health Service Corps physicians and can be used as a working model to reduce perinatal mortality in medically underserved communities in the United States."
-How does smoking affect ambulatory systolic blood pressure in hypertensive patients over 50 years old?,"Elevation of ambulatory systolic blood pressure in hypertensive smokers. A case-control study. Although smoking raises blood pressure, the office blood pressure measurements of smokers are the same as, or lower than, those of nonsmokers. To resolve this paradox, we compared the office and 24-hour ambulatory blood pressures of 59 untreated hypertensive smokers with 118 nonsmoking hypertensives matched for age, sex, and race. The office blood pressures of the smoking and nonsmoking groups were 141/93 and 142/93 mm Hg, respectively. The awake ambulatory systolic blood pressure was significantly higher in the smokers (145 vs 140 mm Hg). This difference was greater among patients over the age of 50 years (153 vs 142 mmHg), and absent among patients under 50 years (140 vs 139 mm Hg). Blood pressures during sleep did not differ between the two groups (121/76 vs 123/77 mm Hg). We conclude that, among white hypertensives above the age of 50 years, smokers maintain a higher daytime ambulatory systolic blood pressure than nonsmokers even though blood pressure measured in the office is similar."
-What rare underlying condition was found in a 46-year-old obese and mildly hypertensive patient with bilateral central retinal vein occlusions?,"Bilateral central retinal vein occlusion as an initial manifestation of pseudotumor cerebri. Pseudotumor cerebri, or benign intracranial hypertension, is known to produce visual symptoms. Central retinal vein occlusion has been linked with pseudotumor cerebri but rarely as an initial manifestation. We describe a 46-year-old patient--who was obese and mildly hypertensive with bilateral central retinal vein occlusions--who was subsequently diagnosed as having pseudotumor cerebri. In patients with simultaneous bilateral central retinal vein occlusions, unusual underlying systemic conditions such as pseudotumor cerebri should be considered in the diagnostic evaluation."
-What were the outcomes of laser laparoscopic management for patients with endometriomas in terms of fertility and pelvic pain?,"Laser laparoscopic management of large endometriomas. Forty-seven patients underwent laser laparoscopic management of endometriomas from 3 to 12 cm in diameter. Eighteen patients had infertility, 15 had pelvic pain, and 14 had both. The types of laser used were the carbon dioxide, argon, and potassium-titanyl-phosphate. There were no surgical complications. Twelve of 32 patients with infertility achieved pregnancy after the initial procedure. Subsequently, 2 patients conceived after a second-look procedure. Twenty-three of 30 patients with pelvic pain reported improvement or resolution. We confirm the efficacy of operative laparoscopy using lasers in the management of large ovarian endometriomas."
-What were the key findings regarding family practice residents' attitudes and behaviors towards serum cholesterol screening and management?,"Serum cholesterol: attitudes and behavior of family practice residents BACKGROUND. Given the current health promotion efforts regarding coronary artery disease, more information is needed about residents' attitudes and behaviors that relate to identification and management of patients with elevated serum cholesterol levels. METHODS. Family practice residents from eight US programs (N = 128) were surveyed in 1989 to assess their attitudes and reported practice patterns. Resident survey data were compared, when feasible, to published data from 1986 and 1990 surveys of practicing physicians performed by the National Heart, Lung, and Blood Institute. RESULTS. The use of faculty ""key contacts"" resulted in a 90% response rate (N = 115). Both residents and practicing physicians attributed a high degree of importance to cholesterol as a risk factor. Residents reported more frequent routine screening of middle-aged men than the routine screening rate of practicing physicians in 1986 (P less than .01). Residents reported less frequent screening of younger and older adults than of middle-aged men (P less than .001). Residents' threshold for the use of cholesterol-lowering medication was lower than that of practicing physicians surveyed in 1986, but higher than that of physicians surveyed in 1990. Compared with practicing physicians, residents did not believe they were as well prepared to counsel patients about dietary change or as successful when they tried to help patients make changes; residents reported a significantly higher rate of referral to dietitians (P less than .01). CONCLUSIONS. Residents may need more education regarding screening guidelines for children and young adults. A health promotion skills gap may exist that explains reported discrepancies between self-report and actual behavior and indicates that residency educators may need to pay more attention to fostering dietary assessment and counseling skills in their residents."
-What were the key findings regarding the relationship between calcitonin gene-related peptide (CGRP) concentrations and blood pressure in patients with mild to moderate essential hypertension?,"Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension. Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease."
-How does interleukin-1 (IL-1) contribute to the autocrine growth regulation of the B1 leukemic cell line?,"Constitutive expression and role in growth regulation of interleukin-1 and multiple cytokine receptors in a biphenotypic leukemic cell line. A cell line (B1) was established from the bone marrow of a patient with a relapse of acute leukemia characterized by a 4;11 chromosomal translocation and biphenotypic features of early B and myeloid lineages. Analysis of the growth requirements of this cell line showed density-dependent growth and secretion of an autostimulatory growth factor, suggesting an autocrine mechanism. Several lines of evidence implicate the participation of interleukin-1 (IL-1) in the autocrine growth regulation of B1 cells. These cells constitutively express the messenger RNA (mRNA) for IL-1 and IL-1 receptor and secrete IL-1; recombinant IL-1 stimulated the growth of colonies when cells were seeded at low density, and anti-IL-1 antibodies inhibited the growth of colonies with cells seeded at higher density. B1 cells do not express detectable levels of mRNA for any of the other cytokines tested, and other cytokines failed to support the growth of B1 cells at low density. In addition, B1 cells express multiple cytokine receptor genes, including the receptors for IL-6, IL-7, tumor necrosis factor and gamma-interferon. Addition of the respective cytokines to the B1 cells resulted in inhibition of the growth of leukemic cells in vitro. The multiplicity of growth-inhibitory cytokine receptors on this leukemic cell line might be due to its biphenotypic lineage and may suggest new therapeutic possibilities in controlling leukemic cell proliferation."
-"How do cephalometric measurements differ between patients with sleep apnoea, non-apnoeic snorers, and non-snoring control subjects?","Cephalometric measurements in snorers, non-snorers, and patients with sleep apnoea. Cephalometry is often used to assess patients with sleep apnoea but whether these measurements differ from those in non-apnoeic snorers and how they are influenced by age is not clear. Cephalometric radiographs of patients with sleep apnoea were compared with those of snorers without sleep apnoea and those of non-snorers. Fifty two snorers with suspected sleep apnoea had a conventional sleep study and were divided into two groups: those with an apnoea-hypopnoea index greater than 10/h (n = 40, sleep apnoea group) and those whose apnoea-hypopnoea index was 10/h or less (n = 12, snorer group). The cephalometric measurements in these patients were compared with those of 34 non-snoring control subjects. Controls were subdivided into two groups: control group 1 included 17 subjects similar in age to the sleep apnoea and snorer groups (mean (SD) age 50.0 (10.9), 50.7 (9.4), and 50.6 (9.7) years); control group 2 included 15 young men (25.4 (2.6) years). The distance from the mandibular plane to the hyoid bone (MP-H) and the length of the soft palate were greater in the patients with sleep apnoea (28.7 (7.8) and 43.6 (5.0) mm) than in the snorers (23.7 (4.2) and 40.3 (4.9 mm). The MP-H was similar in snorers and age matched control subjects, but was significantly greater in the older than in the younger control subjects (22.1 (6.1) vs 17.0 (6.8]. The soft palate was longer in subjects who snored (both sleep apnoea patients and snorers) than in control subjects. The MP-H distance significantly correlated with age for all subjects (snorers and controls) and for the control subjects alone. This study shows that non-apnoeic snorers have cephalometric abnormalities that differ from those of patients with sleep apnoea and that cephalometric values are influenced by the subject's age."
-What were the four major sources of artifactual staining identified in the study of intermediate filament antibodies in human brain and brain tumors?,"Unexpected immunoreactivities of intermediate filament antibodies in human brain and brain tumors. Immunoreactivities of 35 different monoclonal antibodies (MAbs) that detect intermediate filaments were studied systematically on serial cryostat sections of 14 well-defined human gliomas (five astrocytomas, three oligodendrogliomas, six glioblastomas) and on normal brain. Glial fibrillary acidic protein (GFAP), vimentin, desmin, neurofilaments, and broad-specificity keratin MAbs, as well as MAbs that recognize several or only single keratin polypeptides, were used. Unexpected reactivities were surprisingly frequent. As these may lead to diagnostic confusion and misinterpretation on this material, the authors investigated these phenomena more thoroughly. Four major sources of artifactual staining were found: 1) positive staining attributable to the rabbit gamma G immunoglobulins used in the alkaline phosphatase anti-alkaline phosphatase technique; 2) certain desmin and keratin MAbs cross-reacted with astrocytic glia and with other brain-specific epitopes; 3) technical difficulties; 4) some MAbs directed against neurofilaments and keratins showed unexpected reactivities only on individual anaplastic gliomas. The implications of these findings for intermediate filament typing of neuropathologic material are discussed."
-What behavioral and sensory changes were observed in rats after partial sciatic nerve injury?,"A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Partial nerve injury is the main cause of causalgiform pain disorders in humans. We present here a novel animal model of this condition. In rats we unilaterally ligated about half of the sciatic nerve high in the thigh. Within a few hours after the operation, and for several months thereafter, the rats developed guarding behavior of the ipsilateral hind paw and licked it often, suggesting the possibility of spontaneous pain. The plantar surface of the foot was evenly hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized. There was a sharp decrease in the withdrawal thresholds bilaterally in response to repetitive Von Frey hair stimulation at the plantar side. After a series of such stimuli in the operated side, light touch elicited aversive responses, suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a companion report, we show that these abnormalities critically depend on the sympathetic outflow. Based on the immediate onset and long-lasting perpetuation of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the resemblance of the contralateral phenomena to 'mirror image' pains in some humans with causalgia, we suggest that this preparation may serve as a model for syndromes of the causalgiform variety that are triggered by partial nerve injury and maintained by sympathetic activity."
-Which viruses demonstrated the most significant ability to infect and persist in human joint tissue according to the research?,"Susceptibility of normal human joint tissue to viruses. A model system has been developed to investigate the comparative ability of different viruses to replicate and persist intraarticularly. The viruses chosen for study were rubella, mumps, Coxsackie B4, adenovirus and varicella zoster, a selection of viruses with different degrees of association with joint symptoms in clinical studies. Our results showed that these viruses demonstrated a range of abilities to infect and persist in human joint tissue cultured in vitro. The most arthritogenic viruses, rubella, and to a lesser extent mumps, replicated and penetrated deeply into the synovial membrane. In contrast, the other 3 viruses were much less arthrotropic, and may only induce arthritis by immunopathological mechanisms."
-What is the relationship between intermittent claudication and silent myocardial ischemia in the study?,"Intermittent claudication as a manifestation of silent myocardial ischemia: a pilot study. One hundred consecutive patients with intermittent claudication were screened noninvasively with electrocardiography chest wall mapping stress test and transcutaneous aortovelography during bicycle ergometry. Electrocardiographic chest wall stress testing indicated three-vessel coronary disease in 25 patients and left anterior descending plus circumflex (left main stem equivalent) disease in seven. In these 32 patients transcutaneous aortovelography demonstrated a decrease in stroke distance (an index of cardiac stroke volume) (median, -28%; 90% range, +5% to -48%), and coronary angiography confirmed the presence and severity of the disease. The claudication distance ranged between 50 and 250 meters. After myocardial revascularization or medical therapy a significant increase occurred in the stroke distance after exercise (median, +20; 90% range, +40% to -25%); also a significant increase in the postexercise pressure index and a reduction in the recovery time (p less than 0.01). No change occurred in the ankle/pressure index at rest. Twelve patients were able to walk without being limited by claudication; 15 reported improvement with a two to tenfold increase in claudication distance. No change occurred in three. The results indicate that silent myocardial ischemia is a common finding in patients with intermittent claudication. It produces left ventricular dysfunction and a decrease in stroke volume leading to a large fall in ankle pressure and early onset of claudication during exercise. Niltrates and myocardial revascularization tend to reverse this."
-What unique characteristics were observed in the five children with intractable ulcerating enterocolitis of infancy?,"Intractable ulcerating enterocolitis of infancy. Five children (three boys, two girls) presenting in the first year of life with intractable diarrhoea had a number of features in common. All had ulcerating stomatitis, four had partial villous atrophy on small intestinal biopsy, all had colitis characterised by large ulcers with overhanging edges, and four had severe perianal disease; no stool pathogens were detected. Treatment with steroids, sulphasalazine, and azathioprine was unsuccessful. All five required subtotal colectomy. Four were children of consanguinous marriages, two were siblings of Pakistani origin, two were cousins of Arab origin, and the fifth was Portuguese. Although the diagnoses of Behcet's disease and Crohn's disease were considered, it appears that these children represent a distinct inherited condition affecting the whole gastrointestinal tract, particularly the colon."
-What trend was observed in operative mortality rates for gastric cancer surgery from 1970 to 1990?,"Improving survival in gastric cancer: review of operative mortality in English language publications from 1970. In this review of English language publications from 1970, operative mortality following surgery for gastric cancer has been analysed. Operative mortality has declined in series reporting operations in successive decades to 1970, 1980 and 1990. Series reporting patients having surgery for gastric cancer in the decade to 1990 show a mean operative mortality rate of 7.8 per cent (median 4.6 per cent). This improvement may have contributed to the declining mortality rates for gastric cancer in the face of unchanging surgical workload. Results of operations for gastric cancer should be reported in a standard manner."
-What evidence suggests a potential link between anal cancer and cervical cancer in this study?,"Aetiological parallel between anal cancer and cervical cancer. It has been postulated that an infectious agent and/or specific sexual behaviour is involved in the aetiology of anal cancer, in analogy with the aetiology established for cancer of the cervix. A case-control study of 29,648 women with cancers registered in the Danish Cancer Registry during 1968-87 tested the hypothesis that anal cancer patients were more likely than patients with colon, stomach, or vulva cancer to have had a previous diagnosis of cervical intraepithelial neoplasia (CIN) or invasive cervical cancer. The odds ratio of CIN, adjusted for age and year of diagnosis, for anal vs colon cancer was 5.2 (95% confidence interval [CI] 3.3-8.3), that for anal vs stomach cancer 3.6 (2.1-6.0), and that for anal vs vulva cancer 1.6 (0.9-2.9). The median time from diagnosis of CIN to diagnosis of the registered cancer was 151 months for anal, 112 months for vulva, 114 months for colon, and 126 months for stomach cancer. The association with previous invasive cervical cancer was also investigated; no patient with cervical cancer in this second analysis had been included in the CIN analysis. The odds ratios were similar. In addition, anal cancer patients were significantly more likely to have had cervical cancer than were patients with vulva cancer (odds ratio 1.8 [1.0-3.9]). The strong association between anal cancer and CIN/invasive cervical cancer suggests that these cancers share common risk factors. The association is at least as strong as that between cervical and vulva cancer."
-How did two-dimensional echocardiography and continuous-wave Doppler help diagnose the pseudo-tricuspid stenosis in this case?,Reversible tricuspid stenosis. Demonstration with two-dimensional echocardiography and continuous-wave Doppler. We report a case of pseudo-tricuspid stenosis as a result of extrinsic compression of the tricuspid valve by a large right-sided pericardial effusion. Two-dimensional echocardiography and continuous-wave Doppler enabled accurate noninvasive diagnosis and hemodynamic assessment.
-What did the study reveal about the relationship between Helicobacter pylori antibodies and tissue staining in subjects with atrophic body gastritis?,"Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophic body gastritis. Helicobacter pylori is rarely found in gastric biopsy specimens from individuals with atrophic gastritis of the body mucosa. To determine if subjects with atrophic body gastritis have evidence of previous infection with H. pylori, immunoglobulin G antibody to H. pylori was measured by enzyme-linked immunosorbent assay in sera of 399 Finnish subjects. In 124 subjects, multiple biopsy specimens from body and antrum had been evaluated for the presence of H. pylori by Giemsa staining. Antibody correlated well with H. pylori staining except in the subgroup with atrophic body gastritis, in whom the prevalence of seropositivity (86%) was significantly greater than the prevalence of positive staining (33%) (P less than 0.001). Twenty-five subjects had positive antibody and negative staining. This group had a significantly higher prevalence of atrophic body gastritis (80%), lower maximal acid output, lower serum pepsinogen I levels, and higher serum gastrin concentrations than did seropositive subjects with H. pylori. These data suggest that most patients with atrophic body gastritis, despite having a low incidence of current overt infection, have been infected with H. pylori at some point in their lives."
-How does the superoxide anion production of neutrophils in Crohn's disease patients differ from that of healthy subjects when stimulated by PMA1 and PMA2?,"Superoxide production by Crohn's disease neutrophils. Neutrophil superoxide anion production was measured in healthy subjects and in patients with quiescent and active Crohn's disease using superoxide dismutase inhibitable cytochrome C reduction. Three stimuli were used: phorbol 12-myristate 13-acetate (PMA1), phorbol 20-oxo-20-deoxy 12-myristate 13-acetate (PMA2), and Candida albicans in serum. Normal neutrophils produced significantly more superoxide anion than Crohn's disease neutrophils with both PMA1 (mean (SD) 9.6 (2.2) v 8.6 (1.8) nmol/10(6) cells/5 minutes, p = 0.04) and PMA2 (1.8 (0.8) v 0.8 (0.77) nmol/10(6) cells/5 minutes, p = 0.00004). With C albicans in serum, normal and Crohn's disease neutrophils produced similar amounts of superoxide anion (4.4 (1.5) v 4.3 (1.7) nmol/10(6) cells/30 minutes, not significant). Results were independent of disease activity. Superoxide anion production by PMA-stimulated Crohn's disease neutrophils is significantly lower than by normal neutrophils."
-What changes were observed in the circulating levels of the N-terminus of the atrial natriuretic factor (ANF) prohormone in patients with pheochromocytomas?,"Increased circulating concentration of the N-terminus of the atrial natriuretic factor prohormone in persons with pheochromocytomas. To investigate the possible relationship of hypertension and the N-terminus of the atrial natriuretic factor (ANF) prohormone which contains two peptides [i.e. pro ANF-(1-30) and pro-ANF-(31-67)] with blood pressure-lowering effects, we examined the circulating levels of the N-terminus of the ANF prohormone in three patients with pheochromocytomas before surgery, during an increase in their blood pressure with surgical manipulation of their tumors, and after surgery when their blood pressures returned to normal. The circulating levels of the whole N-terminus [amino acids 1-98; pro-ANF-(1-98)] and pro-ANF-(31-67) from the midportion of the N-terminus of the ANF prohormone were increased 2-fold in patients with both extraadrenal and intraadrenal pheochromocytomas. In both the intraadrenal and extraadrenal patients N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) circulating levels increased further during surgical manipulation and returned to normal after surgical removal of their respective tumors. Each of these pheochromocytomas was found to have pro-ANF-(1-30) and -(31-67)-binding sites that were functional, since they could enhance the guanylate cyclase-cGMP system 2-fold in these pheochromocytomas. The entire 126 amino acids of the prohormone were present within each of the pheochromocytomas, since both the whole N-terminus and C-terminus (i.e. ANF) of the prohormone were present. Examination of the pheochromocytomas by electron microscopy revealed electron-dense granules similar to those in the heart, which have been associated with the synthesis and storage of the ANF prohormone. We conclude that 1) the whole N-terminus [pro-ANF-(1-98)] and pro-ANF-(31-67) of the ANF prohormone circulate at higher concentrations in persons with pheochromocytomas and return to normal with removal of the tumors; 2) pheochromocytomas contain specific binding sites for pro-ANF-(1-30) and -(31-67); 3) these binding sites are functional, since pro-ANF-(1-30) and -(31-67) could enhance the enzyme guanylate cyclase within these tumors; and 4) the entire 126 amino acids of the ANF prohormone are present within these tumors, which have electron-dense granules associated with polypeptide hormone synthesis, suggesting that the ANF prohormone is being synthesized within the pheochromocytomas."
-What is the purpose of using human recombinant erythropoietin in the preoperative setting described in this case report?,"Use of human recombinant erythropoietin to correct severe preoperative anemia. The risks of homologous blood transfusion are well known. Herein, we describe the successful preoperative use of human recombinant erythropoietin to correct severe anemia in a patient refusing transfusion. This case report emphasizes the important perioperative role human recombinant erythropoietin may play in the future."
-How do staging procedures and tumor stage differ between academic and community hospitals for lung cancer patients?,"Cancer staging may have different meanings in academic and community hospitals. We investigated differences in lung cancer care and outcome between academic and community settings for all lung cancer patients diagnosed during 1973-1976 in New Hampshire and Vermont. Trained abstracters reviewed hospital charts to record personal, diagnostic, and clinical information, and survival was determined for all patients through the end of 1979. Patients diagnosed in university hospital cancer centers underwent more staging procedures and tended to be assigned to a higher stage than similar patients diagnosed in community hospitals. When tumor stage was considered as a covariable in a survival analysis, these patients appeared to have a lower mortality rate both for non-small cell tumors (mortality rate ratio, 95% confidence interval = 0.81, 0.71-0.91) and for small cell tumors (0.71, 0.55-0.91). When functional status rather than tumor stage was used to adjust for disease severity, there was no apparent survival advantage for university patients with non-small cell cancer (0.96, 0.85-1.09) and the lower mortality for small cell cancers (0.76, 0.59-0.97) was attenuated, although still statistically significant. We conclude that inconsistently-collected data on clinical stage can complicate comparisons of prognosis between cancer patients from different types of hospitals and that measures of performance status may be more useful indicators of disease severity in population based studies."
-How does lumbar puncture affect intracranial cerebrospinal fluid (CSF) volume and its relationship to post-lumbar puncture headache?,"Changes in intracranial CSF volume after lumbar puncture and their relationship to post-LP headache. Post-lumbar puncture (LP) headache may be due to ""low CSF pressure"", leading to stretching of pain sensitive intracranial structures. The low intracranial pressure is secondary to net loss of intracranial CSF. It has, however, not been possible to measure intracranial CSF volume accurately during life until recently. Intracranial CSF volume can now be measured non-invasively by a MRI technique. The changes in intracranial CSF volume were studied in 20 patients who had LP. Total intracranial CSF volume was reduced in 19 of the 20 patients 24 hours after LP (range -1.8 mls to -158.6 mls). Most of the CSF was lost from the cortical sulci. Very large reductions in intracranial CSF volume were frequently related to post-LP headache but some patients developed headache with relatively little alteration in the intracranial CSF volume. There was not a measurable change in position of the intracranial structures following LP."
-What is the prognostic significance of proliferating cell nuclear antigen (PCNA) in gastric carcinoma according to the study?,"Prognostic value of proliferating cell nuclear antigen in gastric carcinoma. A new monoclonal antibody to proliferating cell nuclear antigen (PCNA), PC10, which can be used on routinely processed tissue, was applied to 93 cases of gastric carcinoma. Significant intra-tumoural variation in staining occurred. In addition to a PCNA index (percentage of positive cells per 1000 tumour cells), a semiquantitative PCNA grading system was devised, based on estimates of less than or more than 50% of positive tumour cells in whole sections. Neither PCNA index nor PCNA grade showed any correlation with established histological variables, tumour stage, or the presence of lymph node metastases. No significant correlation was observed between PCNA index and S + G2M phase fraction measured by flow cytometric analysis. To analyse survival tumours with PCNA indices above and below the median level (41%) were compared. Those with a higher index tended to have a worse prognosis, but when PCNA grade was considered, it was found to have definite independent prognostic value, tumours of low grade surviving better than those of high grade. The ability of semiquantitative PCNA grading to allow for intra-tumoural variation suggests it may have advantages over absolute counting, which is prone to sampling error when tumour heterogeneity is a major factor. The prognostic value of PC10 staining in gastric carcinoma is therefore promising."
-What is the recommended approach for treating renal oncocytomas based on the Australian experience described in the context?,"Renal oncocytomas--an Australian experience. A review was made of 24 cases of renal oncocytoma seen between 1978 and 1989. There was considerable overlap between the clinical presentation of renal oncocytomas and renal carcinomas. Although pre-operative radiological, cytological and pathological investigations may suggest the presence of an oncocytoma, these studies cannot make a definitive diagnosis. We recommend that these tumours be treated as potential renal carcinomas until post-operative microscopic evaluation proves otherwise."
-What were the key findings of the study comparing the effectiveness of metoprolol and nifedipine in patients with mixed angina?,"Transient myocardial ischemia during daily life in rest and exertional angina pectoris and comparison of effectiveness of metoprolol versus nifedipine. The clinical characteristics of 65 patients with mixed angina were classified by means of (1) a questionnaire investigating the proportion of symptoms occurring at rest and on effort, (2) an exercise stress test, (3) 24-hour ambulatory Holter monitoring, and (4) coronary arteriography. According to the questionnaire, the proportion of effort-induced anginal episodes ranged from 1 to 99%. The ischemic threshold during exercise testing ranged from 110 x 10(2) to 350 x 10(2) mm Hg x beats/min. At least 1 episode of ST-segment depression was observed in 29 of the 65 patients during Holter monitoring. Ischemic episodes during Holter monitoring were more frequent (p less than 0.05) in patients reporting greater than or equal to 50% of anginal attacks on effort, with moderate to severe limitation of exercise capacity and with multivessel coronary artery disease. The effect on ambulatory ischemia of a 6-week treatment with a beta blocker (metoprolol CR, 200 mg once daily) or a dihydropyridine calcium antagonist (nifedipine retard 20 mg twice daily) were then compared according to a double-blind, parallel group design. Metoprolol significantly reduced the number and duration of the ischemic episodes during daily life (p less than 0.05) irrespective of the patients' clinical characteristics. Nifedipine was ineffective, particularly in patients with angina predominantly on effort and with a moderate to severe reduction in exercise tolerance. It is concluded that in patients with mixed angina, ischemic episodes during daily life are more likely to occur in patients with a clinical presentation suggesting poor coronary reserve."
-What are the primary indications for liver transplantation according to the context?,"Liver transplantation for alcoholic liver disease, viral hepatitis, and hepatic neoplasms. In closing, it is important to note that the indications for liver transplantation are not static but rather are remarkably dynamic and capable of change over time. Thus yesterday's major indications can become relative contraindications, while yesterday's absolute contraindications have become today's nuisances. The goal for physicians who care for individuals with problems such as alcoholic liver disease, viral hepatitis, and hepatic cancer should be to develop new strategies of care that will ultimately eliminate these diseases as problems, rather than eliminating individuals with such health problems from currently available health options. In other words, physicians who accept the responsibility for a patient's life should be searching for the best form of therapy available for their patient rather than examining the reasons that exist for limiting one's choice in health care."
-Which drug was more effective in converting paroxysmal atrial fibrillation to sinus rhythm: propafenone or flecainide?,"The value of class IC antiarrhythmic drugs for acute conversion of paroxysmal atrial fibrillation or flutter to sinus rhythm. In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainide (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p less than 0.02). If atrial fibrillation was present less than or equal to 24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p less than 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS). Mean time to conversion was 16 +/- 10 min in the propafenone group versus 18 +/- 13 min in the flecainide group (p = NS). QRS lengthening (83 +/- 15 to 99 +/- 20 ms) was observed only in the patients treated with flecainide (p less than 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p less than 0.01). In conclusion, at a dose of 2 mg/kg in 10 min, flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter."
-What potential complication can tissue plasminogen activator (t-PA) cause during treatment of acute myocardial infarction?,"Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable."
-What are the primary early mechanical features observed in cemented femoral components of hip arthroplasties?,"The initiation of failure in cemented femoral components of hip arthroplasties. We studied 16 femora retrieved at post-mortem from symptomless patients who had a satisfactory cemented total hip arthroplasty from two weeks to 17 years earlier, with the aim of delineating the initial mechanisms involved in loosening. Only one specimen showed radiographic evidence of loosening; the other 15 were stable to mechanical testing at 17.0 Nm of torque. In all 16 specimens, the cement-bone interface was intact with little fibrous tissue formation. By contrast, separation at the cement-prosthesis interface and fractures in the cement mantle were frequent. The most common early feature was debonding of the cement from the metal, seen at the proximal and distal ends of the prosthesis. Specimens which had been in place for longer also showed circumferential fractures in the cement, near the cement-metal interface, and radial fractures extending from this interface into the cement and sometimes to the bony interface. The most extensive cement fractures appeared to have started at or near sharp corners in the metal, or where the cement mantle was thin or incomplete. Fractures were also related to voids in the cement. The time relationship in this series suggested that long-term failure of the fixation of cemented femoral components was primarily mechanical, starting with debonding at the interface between the cement and the prosthesis, and continuing as slowly developing fractures in the cement mantle."
-"What was the purpose of studying the vasomotor response of coronary artery segments in patients with syndrome X, chronic stable angina, and control subjects?","Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X) The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments."
-What is Henoch-Schonlein purpura and how does it affect children according to the surgical evaluation in this study?,"Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived."
-What were the key findings of the study regarding peritoneal factors in rabbits with surgically induced endometriosis?,"Surgically induced endometriosis does not alter peritoneal factors in the rabbit model. OBJECTIVE: It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN: Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS: There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS: These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue."
-What are the two distinct patterns of venous pulse observed in patients with dilated cardiomyopathy?,"Jugular venous 'a' wave in dilated cardiomyopathy: sign of abbreviated right ventricular filling time. OBJECTIVE--To study the mechanisms underlying the high venous pressure often seen in patients with dilated cardiomyopathy. DESIGN--Retrospective and prospective examination of the pattern of flow in the superior vena cava, cardiac echo-Doppler studies, and recordings of the jugular venous pulse. SETTING--A tertiary referral cardiac centre. PATIENTS PARTICIPANTS--23 patients with dilated cardiomyopathy, all with functional mitral and tricuspid regurgitation. RESULTS--Two patterns of venous pulse were seen: a dominant 'a' wave and 'x' descent, with systolic flow in the superior vena cava (group 1, n = 11), and a dominant 'v' wave with 'y' descent and diastolic flow in the superior vena cava (group 2, n = 12). A comparison of group 1 and group 2 showed: age (mean (SD] 58 (12) v 61 (6) years, left ventricular end diastolic dimension 7.0 (0.7) cm in both groups, right ventricular short axis 3.3 (0.6) v 3.6 (0.5) cm and long axis 7.3 (0.5) v 7.1 (0.7) cm, and duration of tricuspid regurgitation 350 (65) v 370 (50) ms. The RR interval (550 (100) v 680 (80) ms) and right ventricular filling time (150 (30) v 290 (50) ms) were significantly shorter in group 1. In all patients in group 2 right ventricular filling time was more than 200 ms with separate E and A waves on the tricuspid Doppler echocardiogram, while in all group 1 patients it was less than 200 ms with a single summation peak. In nine patients in group 1, the right ventricular filling time was limited by prolonged tricuspid regurgitation and in the remaining two by prolonged isovolumic relaxation time (215 (80) ms), so that it was consistently significantly less than that of the left ventricle. CONCLUSION--In patients with dilated cardiomyopathy, right ventricular filling time may be so short that it limits stroke volume. Such patients can be recognised by a dominant 'a' wave on the jugular venous pulse. Patients in whom the right ventricular filling time was longer showed a dominant 'v' wave. Both groups can present as ""congestive heart failure""."
-How does the response of atrial natriuretic factor (ANF) differ between patients with and without right ventricular (RV) infarction after volume expansion?,"Impaired response of atrial natriuretic factor to blood volume expansion in acute right ventricular infarction. To assess the role of atrial natriuretic factor (ANF) in right ventricular (RV) infarction, 30 patients with inferior wall acute myocardial infarction (15 with RV involvement) and normal left heart filling pressures were studied 39 +/- 12 hours after the onset of symptoms. Serial measurements of cardiac output, right atrial, pulmonary artery and pulmonary wedge pressures, as well as plasma ANF, plasma renin activity, plasma aldosterone and vasopressin were obtained before and 30 minutes after acute volume expansion to raise wedge pressure greater than or equal to 20 mm Hg. Baseline mean right atrial pressure and plasma ANF levels were greater in patients with than without RV infarction (8 +/- 3 vs 5 +/- 2 mm Hg; p less than 0.0001, and 4.6 +/- 2.9 vs 2.7 +/- 1.5 fmol/ml; p less than 0.05, respectively). There were no differences in other baseline hemodynamic or humoral parameters between both groups. After volume expansion, pulmonary wedge pressure was similar in both groups, but right atrial pressure increased to higher levels in patients with RV infarction (19 +/- 2 vs 14 +/- 2 mm Hg; p less than 0.0001). Despite this greater stimulus for ANF secretion, the increase in plasma ANF was less pronounced in patients with RV infarction (63 +/- 81 vs 455 +/- 417%; p less than 0.002), especially among those with paroxysmal supraventricular tachyarrhythmias. Thus, despite higher baseline plasma levels of ANF, response to volume loading is markedly attenuated in patients with RV infarction complicating an inferior wall acute myocardial infarction."
-Which virulence characteristics were independently associated with Escherichia coli strains causing acute pyelonephritis according to the multivariate statistical analysis?,"Relative importance of eight virulence characteristics of pyelonephritogenic Escherichia coli strains assessed by multivariate statistical analysis. We have previously reported univariate statistical analysis of the prevalences of putative virulence determinants in Escherichia coli isolated from children and adults with acute pyelonephritis. The expression of P-fimbriae, cell surface hydrophobicity, mannose resistant haemagglutination, haemolysin synthesis, cytotoxic necrotizing factor production and aerobactin mediated iron uptake occurred more often in a collection of 115 Escherichia coli strains isolated from children and women with acute non-obstructive pyelonephritis compared to 96 strains isolated from the commensal fecal flora. With the aim to study which of these virulence markers were independently associated with strains causing infection we performed a multivariate statistical analysis with the data from these strains. The previously proposed virulence factors, expression of type 1 fimbriae and adhesion to HeLa cells were also included in the analysis. P-fimbriae, mannose resistant haemagglutination and the production of haemolysin were, in the multivariate analysis, associated with strains isolated from patients with acute pyelonephritis."
-What was the mean time to sensation of warmth in the spinal and extradural groups during the study?,"Sensitivity, specificity and predictive value of the sensation of warmth as a method of detecting inadvertent subarachnoid injection of local anaesthetic when performing extradural blocks. In order to test if the rate of onset of sensation of warmth in the legs after the injection of 0.5% bupivacaine might discriminate between subarachnoid and extradural injection, 150 urological patients were allocated randomly to receive either spinal anaesthesia with isobaric (IS) or hyperbaric (HS) 0.5% bupivacaine, or extradural anaesthesia with isobaric 0.5% bupivacaine. The volume of the local anaesthetic for spinal anaesthesia and for the extradural test dose was 3-4 ml. The patients were asked to report at once if they had a sensation of warmth in the legs during or after injection of local anaesthetic. The mean time to the sensation of warmth was significantly shorter in the spinal groups (80 (SEM 10) s in IS and 76 (8.0) s in HS) than in the extradural group (558 (38) s). However, six patients in the IS and two in the HS group had no sensation of warmth."
-What is the purpose of the document developed by the Centers for Disease Control (CDC) regarding HIV and hepatitis B virus transmission?,Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. This document has been developed by the Centers for Disease Control (CDC) to update recommendations for prevention of transmission of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in the health-care setting. Current data suggest that the risk for such transmission from a health-care worker (HCW) to a patient during an invasive procedure is small; a precise assessment of the risk is not yet available. This document contains recommendations to provide guidance for prevention of HIV and HBV transmission during those invasive procedures that are considered exposure-prone.
-What was the main purpose of the study regarding pancreatic pseudocyst amylase concentration?,"The value of pancreatic pseudocyst amylase concentration in the detection of pseudocyst communication with the pancreatic duct. The aims of the study were to compare the results of endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous cystopancreatography (PCP) in the detection of the communication between the pancreatic pseudocyst and the pancreatic duct, and to assess the reliability of the increased amylase concentration in the pseudocyst content as an indicator of the existence of communication between the pancreatic pseudocyst and the pancreatic duct system. Forty-three patients were included in the study. Pseudocystic fluid content was obtained by percutaneous aspiration. Twenty-four patients had pseudocyst amylase concentrations above 64 Wolgemuth units (WU), and 19 patients had less than 64 WU. The communication between pseudocyst and the pancreatic duct was determined in 22 patients by ERCP and in 13 patients by PCP, all in the group with increased pseudocyst amylase concentration. Due to high sensitivity and specificity of pseudocyst amylase concentration for the existence of pseudocyst communication with the pancreatic duct, we conclude that guided percutaneous aspiration of the pancreatic pseudocyst with the determination of amylase concentration in the fluid can replace ERCP as a method of choice for the detection of pseudocyst communication with the pancreatic duct."
-What are the key findings from the review of lumbar discectomies regarding intestinal injury?,"Intestinal injury after lumbar discectomy. In a review of 5,200 lumbar discectomies performed from 1974 to 1989, two patients sustained a ventral perforation of the disc space followed by isolated small intestinal injury. Both patients underwent lumbar discectomy at the lumbosacral junction and presented with signs and symptoms of acute abdominal distress within three days after the operation. At surgical laparotomy, small tears were noted in the ileum, which were closed primarily. The patients had an uneventful recovery. The results of a review of 11 instances reported in the literature suggest that isolated intestinal injuries usually occur postoperatively at the lumbosacral junction and involve the small intestine. Factors, such as body habitus, surgical experience, patient positioning and types of instruments, as well as the use of a surgical microscope, do not appear to modify the risk of intestinal injury. After discectomy, patients may present with acute abdominal signs and symptoms or chronic wound infections. Work-up studies include evaluation of vascular structures and ureters either roentgenographically or at abdominal exploration. A high index of suspicion and adequate disc space visualization during discectomy may reduce the incidence of this complication."
-What percentage of patients achieved union in the salvage operations for nonunion following total ankle arthrodesis?,"Salvage of nonunion following ankle arthrodesis for failed total ankle arthroplasty. Revision operations for nonunion following total ankle arthrodesis for total ankle arthroplasty (TAA) were reviewed in ten patients. Operations averaged 2.0 years after prior arthrodesis attempts and featured external fixation in seven, internal fixation in one, percutaneous pin fixation in one, and cast immobilization only in one. Bone graft was used in seven. Union was achieved in 78%. The one complication was an infection in a patient with prior sepsis. The results were considered excellent in three, good in one, fair in three, and poor in two of the nine patients with adequate follow-up evaluation (average, 7 years). Despite successful arthrodesis, residual symptoms were common because of factors such as hindfoot degenerative arthritis and malalignment."
-What was the main finding of the study regarding the effects of low to moderate lead exposure on vitamin D metabolism and bone mineral content in young children?,"Serum vitamin D metabolites and bone mineralization in young children with chronic low to moderate lead exposure. One hundred five children (49 male, 99 black) with known lead exposure indices from birth and adequate nutrient intake of calcium, phosphorus, and vitamin D were studied at 1 of 3 ages (21, 27, or 33 months) to determine the effects of chronic low to moderate lead exposure on circulating concentrations of vitamin D metabolites and bone mineral content as determined by photon absorptiometry. Univariate multiple regression analyses showed no direct relationship of blood lead levels to vitamin D metabolites or bone mineral content. Structural equation analyses which took into account potential covariates of age, season, race, and sex showed estimated declines in serum concentrations of total calcium (from 9.72 to 9.61 mg/dL), phosphorus (from 5.4 to 4.67 mg/dL), and 25-hydroxyvitamin D (from 27.24 to 25.8 ng/mL) and estimated increases in concentrations of parathyroid hormones (from 73.03 to 83.14 microL Eq/mL), 1,25-dihydroxyvitamin D (from 62.39 to 62.69 pg/mL), and bone mineral content (from 222.66 to 234.91 mg/cm) over the observed range of average lifetime blood lead concentrations (4.76 to 23.61 micrograms/dL, geometric mean 9.74 micrograms/dL). However, the only statistically significant effect of average lifetime blood lead concentration was that for phosphorus, and the multivariate test of the combined effects of lead on these six outcomes was not statistically significant (P = .2). It is concluded that significant alterations in vitamin D metabolism, calcium and phosphorus homeostasis, and bone mineral content are not present in children whose nutritional status is adequate and who experience low to moderate lead exposure."
-What was the overall response rate and median survival time in this Phase II pilot study of weekly cisplatin-based induction regimen for extensive non-small cell lung cancer?,"A weekly cisplatin-based induction regimen for extensive non-small cell lung cancer. A Southwest Oncology Group study. The purpose of this Phase II pilot study was to determine whether a dose-intensive regimen of weekly cisplatin combined with other active non-cross-resistant agents would improve the response rate and survival time of patients with extensive non-small cell lung cancer. Patients received cisplatin (50 mg/m2/wk) on days 1, 8, 15, 22, 36, 43, 50, and 57 combined with mitomycin C (8 mg/m2) on days 1 and 36, vinblastine (3 mg/m2) on days 8 and 43, and 5-fluorouracil (5-FU) (1 g/m2) by continuous infusion over 24 hours on days 15 and 50. Responding patients received consolidation therapy with cisplatin and etoposide (VP-16). Of 82 registered patients, 80 were eligible and 77 were evaluable for response. The overall response rate was 23% with 1 patient achieving a complete response (CR) and 17 patients achieving a partial response (PR). The median survival time was 4.6 months. The toxicity profile was not different from that described for standard-dose regimens. Although this regimen does not offer any benefit over standard-dose cisplatin regimens for patients with extensive non-small lung cancer, the weekly schedule permits a dose-intensive regimen with acceptable toxicity for tumors that may benefit from this approach."
-What is the significance of intercellular adhesion molecule 1 expression in primary biliary cirrhosis and primary sclerosing cholangitis?,"Increased expression of intercellular adhesion molecule 1 on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis. It has been suggested that immunological mechanisms involving lymphocyte-mediated damage are important in the characteristic bile-duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function-associated antigen 1 in the liver of patients with primary biliary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium-sized ducts, which are spared by the disease, were negative. Minimal bile-duct staining was seen in conditions in which bile-duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy. The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile-duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver-cell damage and fibrosis that occur during the development of cirrhosis."
-What technique is described for salvaging thrombosed forearm polytetrafluoroethylene (PTFE) vascular access grafts?,"Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting. A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction."
-How did dopexamine compare to dopamine in preventing renal impairment in patients undergoing orthotopic liver transplantation?,"A comparison of dopexamine and dopamine to prevent renal impairment in patients undergoing orthotopic liver transplantation. The efficacy of low-dose dopamine as a renal protective agent was compared with that of dopexamine in patients who underwent orthotopic liver transplantation. Twelve patients who received a continuous infusion of dopexamine (1-3 micrograms/kg/minute) were matched for age, diagnosis, pre-operative creatinine clearance and blood loss with 12 patients who received a low-dose infusion of dopamine (2 micrograms/kg/minute). The catecholamine infusion was started after induction of anaesthesia and continued for 48 hours after surgery. Patients in the dopexamine group had less evidence of renal impairment and failure than those in the dopamine group during 7 days after the operation, although the differences between groups did not achieve statistical significance. Similarly there were no significant differences between the two groups in peri-operative urine output, urine/plasma osmolality ratio or creatine clearance. Dopexamine is at least as effective as dopamine for renal protection in patients who undergo liver transplantation."
-How does sodium benzoate administration affect the urinary carnitine profile?,"Alteration of urinary carnitine profile induced by benzoate administration. To study the effect of sodium benzoate on carnitine metabolism, the acylcarnitine profile in the urine of five normal volunteers and two patients with urea cycle disorders was examined with fast atom bombardment-mass spectrometry. The volunteer subjects were given 5 g of sodium benzoate orally and the two patients with urea cycle disorders (carbamyl phosphate synthetase deficiency type I and ornithine transcarbamylase deficiency) were already undergoing treatment with sodium benzoate and L-carnitine. The amount of benzoylcarnitine excretion depended on the dose of both sodium benzoate and L-carnitine in a reciprocal relation. Increased excretions of acetylcarnitine and propionylcarnitine were also noted after sodium benzoate administration. The alteration of the urinary aclycarnitine profile was consistent with the change of mitochondrial CoA profile predicted by in vitro studies of an animal model. It is suggested that urinary acylcarnitine analysis is important to assess the effect of benzoate administration on mitochondrial function in vivo. Supplementation with carnitine may be necessary to minimise the adverse effects of sodium benzoate treatment in hyperammonaemia."
-What are the key findings of magnetic resonance imaging (MRI) in patients with spinal trauma within 3 weeks and more than 3 weeks after injury?,"Magnetic resonance imaging of spinal trauma. A retrospective series of 118 magnetic resonance examinations of 110 patients who had sustained previous spinal trauma is reported. Examinations performed within 3 weeks of trauma showed extraspinal soft tissue (including ligamentous) injury in 48% and intraspinal lesions in 61% (mostly consisting of extradural haematoma and spinal cord contusion). In examinations performed more than 3 weeks after injury intraspinal abnormalities were shown in 51% and these represented spinal cord compression, atrophy, myelomalacia and syringohydromyelia. Magnetic resonance imaging has the unique capability of displaying non-invasively the late sequelae of spinal trauma permitting simultaneous evaluation of the extra-spinal soft tissues, vertebral column and spinal cord. It is therefore recommended as the technique of choice in the investigation of patients who have sustained previous spinal injury, particularly those with neurological deficit. In the acute phase potentially remediable causes of neurological impairment such as disc herniation or extradural haematoma can be identified. Signal changes in the cord may allow the prognosis for neurological recovery to be established. In the later stages sequelae such as cord atrophy, myelomalacia and syringohydromyelia are accurately identified and surgical therapy may be guided, where appropriate."
-What changes were observed in the density of glomerular atrial natriuretic factor binding sites in bile duct-ligated rats with ascites?,"Altered density of glomerular binding sites for atrial natriuretic factor in bile duct-ligated rats with ascites. The renal response to atrial natriuretic factor is blunted in cirrhosis with ascites. This might be due to alterations of renal receptors for atrial natriuretic factor. Therefore density and affinity of glomerular atrial natriuretic factor binding sites of bile duct-ligated rats with ascites (n = 10) and of sham-operated controls (n = 10) were determined. Glomerular atrial natriuretic factor binding sites were identified to be of the B-(""biologically active"") and C-(""clearance"") receptor type. Discrimination and quantitative determination of B and C receptors for atrial natriuretic factor were achieved by displacement experiments with atrial natriuretic factor(99-126) or des(18-22)atrial natriuretic factor(4-23), an analogue binding to C receptors only. Density of total glomerular atrial natriuretic factor binding sites was significantly increased in bile duct-ligated rats (3,518 +/- 864 vs. 1,648 +/- 358 fmol/mg protein; p less than 0.05). This was due to a significant increase of C-receptor density (3,460 +/- 866 vs. 1,486 +/- 363 fmol/mg protein; p less than 0.05), whereas density of B receptors was not significantly different in bile duct-ligated rats (58 +/- 11 vs. 162 +/- 63 fmol/mg protein). Affinity of atrial natriuretic factor to its glomerular binding sites did not differ significantly between both groups. These data suggest that an altered glomerular atrial natriuretic factor receptor density could be involved in the renal resistance to atrial natriuretic factor in cirrhosis with ascites."
-"How did the treatment approach for medulloblastoma change between 1970-1983 and 1984, and what impact did this change have on patient outcomes?","The change in patterns of relapse in medulloblastoma. The authors reviewed 89 patients treated for cerebellar medulloblastoma between 1970 and 1989 to determine the impact of changing treatment (high-dose posterior fossa radiation therapy and chemotherapy) on the pattern of failure in medulloblastoma. Between 1970 and 1983, 50 patients (median follow-up, 110 months) were treated with surgery and postoperative craniospinal irradiation (CSI). Nineteen of the 50 (38%) recurred in the central nervous system (CNS). Isolated systemic (bone) metastases occurred in six. The median time to the development of bone metastases was 12 months. Since 1984, 39 patients (median follow-up, 27 months) were treated with preradiation chemotherapy consisting of cisplatin and vincristine for 9 weeks before initiation of CSI. Nine of the 39 (23%) patients recurred in the CNS. There were no systemic failures in this cohort. The actuarial 5-year disease-free survival was 55 +/- 7% for the earlier cohort and 72 +/- 8% for the later cohort (P equals 0.3). Posterior fossa recurrence was associated with radiation therapy to this area. The cumulative incidence of posterior fossa relapse was 50 +/- 13% in patients who received less than 5300 cGy and 18 +/- 7% in those who received 5300 cGy or more (P equals 0.005). All six bone relapses were in patients treated with CSI alone and 5300 cGy or more to the posterior fossa for a 5-year cumulative incidence of bone metastases of 18 +/- 7% compared with 0% for patients treated with 5300 cGy or more and chemotherapy (P equals 0.03). The authors concluded that high-dose radiation therapy has altered the pattern of relapse with an increase in systemic recurrence after radiation therapy alone that is now equivalent to the risk of recurrence in the posterior fossa. Chemotherapy may be indicated in an attempt to decrease this high risk of systemic metastases."
-What type of graft was used for venous reconstruction in the superior vena cava replacement during mediastinal and pulmonary tumor resections?,"Long-term follow-up after prosthetic replacement of the superior vena cava combined with resection of mediastinal-pulmonary malignant tumors. The contraindication to curative excision of mediastinal and pulmonary cancers because of invasion of the superior vena cava is now challenged by the existence of vascular prostheses that are suitable for venous replacement. Between 1979 and 1990 22 patients underwent resection of lung cancer (n = 6) or malignant mediastinal tumors (n = 16) involving the superior vena cava. Resection was done with concomitant venous reconstruction, and polytetrafluorethylene grafts were used. All bronchogenic carcinomas necessitated right pneumonectomy, whereas the excision of mediastinal tumors had to include pulmonary resections in nine patients (five lobectomies and four sublobar resections) and the right phrenic nerve in 12 patients. Venous reconstruction was performed by interposition of a large polytetrafluoroethylene graft between the proximal and cardiac ends of the superior vena cava (n = 8), or between one (n = 10) or both brachiocephalic veins (n = 4) and the right atrium. One patient died postoperatively (4.5%), and another had mediastinitis that was successfully treated by omentopexy. Chemotherapy was administered preoperatively to five patients and postoperatively to seven patients; radiotherapy was administered to two and 10 patients, respectively. The overall actuarial survival rate is 48% at 5 years, with 11 patients presently alive. The survival rate of patients with mediastinal tumors is 60% at 5 years. Among the patients with lung cancer, two with N1 disease are alive at 16 and 51 months, and one died at 38 months; the two patients with N2 disease died at 6 and 8 months. Only one graft occlusion occurred in the postoperative period; another occurred 14 months after operation and was precipitated by insertion of a central venous catheter. The patency of all remaining grafts was demonstrated after an average time of 23 (1 to 98) months. On the basis of these results, polytetrafluoroethylene graft replacement of the superior vena cava should be part of the planning and execution of radical excision with curative intent of mediastinal and right pulmonary malignant tumors that are not present with other contraindications, such as pleural or distant metastasis and severe systemic disease."
-"What is the purpose of using a free gastric mucosal flap with microvascular transfer in the reconstruction of malignant lesions in the oral cavity, base of tongue, and oropharynx?","Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered."
-What was the purpose of the study on intravenous heme-albumin in acute intermittent porphyria?,"Intravenous heme-albumin in acute intermittent porphyria: evidence for repletion of hepatic hemoproteins and regulatory heme pools. The purpose of this study was to assess effects of heme administered intravenously, complexed to human serum albumin, on activities of the hepatic hemoproteins, cytochrome(s) P-450, and tryptophan pyrrolase, and on the size of the heme pool that regulates activity of 5-aminolevulinate synthase. Effects were compared in six normal women and four women with acute intermittent porphyria. All porphyric subjects over-excreted heme precursors and had histories of acute neurovisceral porphyric attacks. All subjects were placed on a constant daily diet that included at least 3 g carbohydrate/kg body weight and sufficient total intake to provide 1.4 times the estimated resting energy expenditure. Urinary excretions of 5-aminolevulinate, porphobilinogen, porphyrins, and metabolites of tryptophan were measured daily before, during, and after infusions of heme-albumin. In the porphyric subjects, intravenous heme [4 mg (6.1 mumol)/kg body weight (BWt) with equimolar albumin], given daily for 4 days, markedly reduced overexcretion of 5-aminolevulinate, porphobilinogen, and porphyrins, indicating repletion of the regulatory heme pool. The heme infusions also decreased mean urinary excretion of 5-hydroxyindoleacetic acid from 4.9 to 2.9 mg/g creatinine per day, suggesting increased activity of hepatic tryptophan pyrrolase, the rate-controlling enzyme for metabolism of tryptophan to products not in the serotonin-5-hydroxyindoleacetic acid pathway. Heme-albumin infusions were without detectable effects on excretions of heme precursors or tryptophan metabolites in normal subjects. In contrast, in both normals and porphyrics, heme-albumin infusions significantly increased rates of antipyrine metabolism (by 159% and 330%, respectively), suggesting increased activities of cytochrome(s) P-450 were produced by the infusions. The infusions were well tolerated; no subject developed thrombophlebitis or bleeding. We conclude that such infusions are safe and effective in repleting deficient heme pools and hemoproteins in patients with acute porphyria, and that activities of cytochrome(s) P-450 in normal subjects may also be increased by heme administration. The therapeutic effect of heme in acute porphyria probably relates to its ability to decrease overproduction of precursors of heme or serotonin, as the result of its increasing critical cellular heme pools."
-How did the researchers use anti-V region antibodies to study cutaneous T cell lymphomas and leukemias?,"Anti-V region antibodies as ""almost clonotypic"" reagents for the study of cutaneous T cell lymphomas and leukemias. Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an ""almost clonotypic"" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL."
-What was the effect of recombinant human erythropoietin (rHuEPO) on anemia correction in predialysis patients with chronic renal failure?,"Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group [published erratum appears in Am J Kidney Dis 1991 Sep;18(3):420] One hundred seventeen patients with anemia related to chronic renal failure not severe enough to require maintenance dialysis were randomly assigned to receive recombinant human erythropoietin (rHuEPO; 50, 100, or 150 U/kg body weight) or placebo intravenously (IV) three times a week for 8 weeks or until their anemia was corrected. Correction of anemia (hematocrit of 40% for males, 35% for females) occurred in 87% of those given 150 U/kg, 64% of those given 100 U/kg, 46% of those given 50 U/kg rHuEPO and in 3% of the placebo group. Energy levels and work capacity improved significantly in the group with corrected anemia compared with the group with uncorrected anemia. rHuEPO appeared to be well tolerated. There was no evidence that rHuEPO therapy accelerated the deterioration of renal function as measured by serum creatinine and reciprocal of serum creatinine compared with placebo treatment. However, it is essential that blood pressure and hematocrit be carefully monitored, particularly in hypertensive patients, to prevent the development of complications associated with hypertension."
-How has the understanding and diagnosis of preeclampsia changed over time according to the given context?,"Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased."
-What is the relationship between non-cirrhotic portal hypertension and IgA nephropathy in the reported case?,IgA nephropathy in non-cirrhotic portal hypertension. Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease.
-What are the four types of diarrheal illnesses identified in rural Bangladesh according to folk terminology?,"Folk terminology for diarrhea in rural Bangladesh. Diarrhea, a descriptive term used in medical science for a variety of clinical diseases, denotes an illness that is categorized differently and known by numerous terms in various cultures. These diversified classifications and terminologies are based on the symptoms of diarrheal disorders, their perceived etiology, and their treatment. In Bangladesh, four types of illnesses with names derived from folk terminology have been identified for which the clinical symptoms resemble those of diarrhea. These include dud haga, which is due to ingestion of breast milk by infants; ajirno, which is due to overeating; amasha, a mucoid diarrhea; and daeria, which is severe watery diarrhea or cholera. Use of the word diarrhea in epidemiologic evaluations was discovered to be problematic; people confused this term with daeria, which accounted for only 5% of all episodes of diarrhea. The implications of such epidemiologic information for a large-scale program of oral rehydration therapy are also discussed."
-What is the significance of using 31P localized magnetic resonance spectroscopy in the assessment of head and neck tumors?,"31P localized magnetic resonance spectroscopy of head and neck tumors--preliminary findings. Magnetic resonance imaging (MRI) is a powerful tool for accurate assessment of the anatomic extent of head and neck neoplasms. The development of methods for spatial localization by use of multiply tuned radio frequency coils that permit the measurement of multiple nuclear MR spectra (1H and 31P) from precisely defined volumes of interest has provided a basis for integrating spectroscopy into the clinical MRI examination. This offers a means for noninvasive monitoring of relative concentrations of mobile metabolites within a tumor. With the use of imaging to determine proper coil placement, a test-retest variance of about 17% is seen on MR spectroscopy. Data are presented from MRI/MRS studies for four head and neck lesions: (1) a squamous cell carcinoma of the lip; (2) a juvenile angiofibroma extending into the nasal cavity; (3) a massive chondrosarcoma of the nasal septum; and (4) a cervical nodal metastasis of a squamous cell carcinoma of the pharynx. Spectra are evaluated by comparison of relative concentrations of phosphorus compounds. The concentrations of phosphomonoesters and phosphodiesters are significantly higher in the neoplasms studied than in normal skeletal muscle. The developing role of integrated MRI/MRS to monitor the response of malignant neoplasm to radiation therapy is discussed."
-How did Streptococcus pneumoniae infection affect the metabolic responses and performance capacity of rats during swimming exercise?,"Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats. The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection."
-What are the current challenges in treating congestive heart failure and its high mortality rate?,"Congestive heart failure. New frontiers. Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome."
-How was leuprolide acetate used to manage symptoms of severe fibrocystic breast disease in the study?,Management of severe fibrocystic disease of the breast with leuprolide acetate. Symptoms of severe fibrocystic disease of the breast were successfully ameliorated in two patients as a result of treatment with daily subcutaneous LA without adverse effects. A state of drug-induced hypogonadotropic hypogonadism appears to be responsible for the clinical effect and is further suggestive of the hormonal dependence of this common disorder.
-Are surgical procedures performed by residents as safe as those performed by attending staff?,"Safety of surgical procedures performed by residents. The outcome of surgical procedures on the gallbladder performed by surgical residents in a university hospital was compared with the outcome of those performed by the attending staff. More than 60% of the operations (643/1084) were done by residents under the direct supervision of the attending surgeon. We found no differences in the rate of technical complications, postoperative morbidity and mortality, or length of hospitalization between the two groups. Thus, resident surgery under appropriate guidance is safe and does not compromise the quality of patient care or operative outcome."
-What complications did the patients with chickenpox pneumonia experience in this case report?,"Chickenpox pneumonia, its complications and management. A report of three cases, including the use of extracorporeal membrane oxygenation. We report three cases of chickenpox pneumonia in adults, all of whom required intermittent positive pressure ventilation. One patient developed a variety of complications, and another, a pregnant woman, required extracorporeal membrane oxygenation."
-How does acetylcholine influence pancreastatin secretion in the QGP-1N cell line?,"Acetylcholine regulates pancreastatin secretion from the human pancreastatin-producing cell line (QGP-1N). Studies were made of pancreastatin (PST) secretion from a human PST-producing cell line (QGP-1N) in response to various secretagogues. Cells with immunoreactivity for PST were observed in monolayer cultures of QGP-1N cells. Carbachol stimulated PST secretion and the intracellular Ca2+ mobilization concentration dependently in the range of 10(-6)-10(-4) M. The PST secretion and Ca2+ mobilization induced by carbachol were inhibited by atropine. The calcium ionophore (A23187) stimulated PST secretion. However, cholecystokinin and gastrin-releasing peptide did not stimulate either PST secretion or Ca2+ mobilization. Secretin also did not stimulate PST secretion. The glucose concentration in the culture medium had no effect on PST secretion. These results suggest that PST secretion is mainly regulated by acetylcholine through a muscarinic receptor, and that an increase in intracellular Ca2+ plays an important role in stimulus-secretion coupling in QGP-1N cells."
-What are the potential causes of delayed visual loss following head trauma according to the study?,"Delayed visual loss due to trauma of the internal carotid artery. The group of six patients in this study experienced delayed visual loss following head trauma. Visual loss occurred from 1 day to 13 years after the initial injury. All patients suffered indirect trauma to the internal carotid artery resulting in formation of either an aneurysm or pseudoaneurysm or a carotid-cavernous fistula. Review of the radiologic and clinical findings was performed in six patients. The diagnosis was established by computed tomography, magnetic resonance imaging, and angiography. All patients had follow-up clinical evaluation and imaging studies. Treatment by neurosurgical or interventional neuroradiologic procedures resulted in significant visual improvement in five patients. Different pathophysiologic mechanisms could be correlated with the delayed visual loss produced by the two types of lesions. The pathologic changes associated with the aneurysms/pseudoaneurysms included direct compression of optic nerves and/or chiasm and intracranial hematoma. A carotid-cavernous fistula caused delayed visual loss by either hematoma at the orbital apex or compression of the chiasm and/or optic nerves by saccular dilatation of the cavernous sinus. The delayed onset of decreased vision following head trauma should alert the physician to the possibility of a traumatic aneurysm/pseudoaneurysm or a carotid-cavernous fistula. Different neuro-ophthalmologic symptoms can usually be correlated with the pathologic changes demonstrated by neuroimaging procedures."
-What were the key findings regarding exercise-related sudden ischemic death in the study of 17 resuscitated victims?,"Clinical and angiographic observations on resuscitated victims of exercise-related sudden ischemic death. The clinical and angiographic findings of 17 resuscitated victims of exercise-related sudden ischemic death are reported in an attempt to elucidate the mechanism(s) of these deaths. Ten survivors developed cardiac arrest during or after sporting activities (group A) and 7 others during or after an exercise stress test (group B). There were 15 men and 2 women. The mean age of group A was 46 years and of group B 55 years. Coronary risk factors, as well as previous angina and myocardial infarction, were more frequent in group B. Only 3 of the 17 survivors had anginal symptoms before sudden death. Sudden death in group A was associated with acute myocardial infarction in 8 and unstable angina in 2 and was associated in group B with acute myocardial infarction in 2, unstable angina in 3 and silent ischemia in 2. Coronary angiography was acutely performed in 15 patients. In most patients the ischemia-related coronary artery was totally or subtotally occluded. Clinical and angiographic findings indicate that exercise-related sudden ischemic death was due to an acute coronary event--in most cases unexpected and unpredictable. It is suggested that exercise-induced intracoronary changes were probably responsible for the development of acute coronary (sub)occlusion and sudden death."
-What is the significance of the Shope papilloma-carcinoma complex in rabbits for understanding human papillomavirus-associated malignancies?,"Establishment from Shope carcinoma induced in an inbred rabbit of culture cell lines with various potentials for differentiation and tumorigenicity. Shope papillomas induced by cottontail rabbit papilloma-virus (CRPV) in domestic rabbits frequently regress spontaneously or, failing to do so, convert into squamous cell carcinomas at a high rate. This papilloma-carcinoma complex in rabbits provides an experimental model for human papillo-mavirus-associated malignancies. The aim of this study was to prepare an experimental system in inbred rabbits by establishing culture cell lines of the tumor. Squamous cell carcinoma developed from a Shope papilloma that had been induced 6 months previously by inoculating CRPV into an inbred B/J rabbit. By in vitro culturing of the tumor cells, cell lines with potentials for terminal differentiation and tumorigenicity were established. Cloning yielded sublines that varied in these potentials and possessed episomal and integrated CRPV genomes as revealed by Southern hybridization in both one- and two-dimensional electrophoresis. Major CRPV-specific transcripts were similarly observed both in well-differentiated and in poorly differentiated sublines. Immunofluorescence with syngeneic rabbit antibody against tumor-specific antigens localized such antigens mainly in the nuclei of the cells of these sublines. This experimental system allows experiments that were not feasible in randomly bred rabbits."
-How do limited access to healthcare and cultural barriers impact neurological care for minority populations in the United States?,"Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies."
-What is xeroderma pigmentosum (XP) and how does it affect patients neurologically?,"Neurological disease in xeroderma pigmentosum. Documentation of a late onset type of the juvenile onset form. Xeroderma pigmentosum (XP) is an autosomal recessive, neurocutaneous disorder characterized by sunlight-induced skin cancers and defective DNA repair. Many XP children develop a primary neuronal degeneration. We describe 2 unusual XP patients who had a delayed onset of XP neurological disease. Somatic cell genetic studies indicated that they have the same defective DNA repair gene and are both in XP complementation group A. These 2 patients, together with a group A patient previously reported from London, establish as a distinct clinical entity the late onset type of the juvenile onset form of XP neurological disease. The functional capacity of these patients' cultured fibroblast strains to survive after treatment with ultraviolet radiation indicates that their DNA repair defect is less severe than that of typical group A patients who have a more severe neurodegeneration with an earlier symptomatic onset. The premature death of nerve cells in XP patients (which is presumably due to their inherited defects in DNA repair mechanisms) suggests that normal repair of damaged DNA in neurons is required to maintain integrity of the human nervous system."
-What morphometric findings were observed in the brain stems of patients with Joseph disease using computed tomography?,"Brain stem atrophy in Joseph disease: a morphometric study using two-dimensional (area) measurement by computed tomography. Eight Japanese patients with Joseph disease were studied using computed tomography (CT). Morphometric analysis using the two-dimensional (area) measurement by CT was performed in the infratentorial region. The brain-stem index, an index of brain-stem atrophy or pontine atrophy, revealed a significant decrease (P less than 0.01), with a mean of 66.7% when compared with 16 control subjects. The patients showed a significant increase (P less than 0.01), with a mean of three times that of the controls in the fourth ventricular index, an index of fourth ventricular dilatation. There were no differences in the cerebellar index, an index of cerebellar atrophy, between these patients and the controls, although the patients had an increased number of visible cerebellar vermian (2.0, SD 0.7) and hemispheric sulci (2.6 SD 0.6) as compared with the controls (vermian sulci: 0.4, SD 0.7: hemispheric sulci: 0). These data indicate severe pontine atrophy, fourth ventricular dilatation with mild involvement of the cerebellum and correlate well with the common pathological features of Joseph disease. The present morphometric evaluation by CT may be useful in the clinical diagnosis of Joseph disease."
-How does the day of the menstrual cycle affect the incidence of postoperative nausea and vomiting in women undergoing laparoscopy?,"The incidence of postoperative nausea and vomiting in women undergoing laparoscopy is influenced by the day of menstrual cycle. Postoperative nausea and vomiting is a major cause of postoperative morbidity. It can lead to increased recovery time, delaying patient discharge and an increase in hospital costs. Past studies have shown that postoperative nausea and vomiting is more frequent in women than men, appears to elevate around the time of menarche and is reduced around the time of menopause. This retrospective review of a one-year experience of laparoscopic tubal ligation at our institute examined the effect of menstrual cycle on postoperative nausea and vomiting. The anaesthetic and surgical techniques were consistent for all patients. Patient data included age, weight, last day of menstrual cycle, the length of anaesthetic, the dose of inhalational agent, the dose of narcotic, emesis on emergence and whether or not droperidol was used. Of the the 235 patients in the study, the incidence of nausea and vomiting was 28%. One hundred fifty-eight had had no preoperative antiemetic and 77 had received droperidol. These two groups were analyzed separately. The incidence in the group not receiving droperidol was 33.5% and in the droperidol group, 16.9% (P less than 0.01). The incidence of nausea and vomiting was higher on the first eight menstrual days (51.6 vs 21.6, P less than 0.001), was highest on day five of the menstrual cycle and lowest on days 18, 19, and 20 where there was no nausea and vomiting. Droperidol reduced the incidence of postoperative nausea and vomiting but the variation in postoperative nausea and vomiting during the cycle persisted."
-What percentage of patients survived long-term after receiving the Bio-Medicus ventricular assist device during cardiac surgery?,"Bio-medicus ventricular assist device for salvage of cardiac surgical patients Over a 5-year period, 41 (1%) of 4,193 patients undergoing cardiac operations underwent intraoperative or early postoperative insertion of a Bio-Medicus ventricular assist device when it became apparent that the patient could not otherwise survive. Fourteen patients were in cardiogenic shock and 7 were in cardiac arrest at the time of initiation of their primary cardiac surgical procedure, and in no instance was the device planned as a bridge to cardiac transplantation. Bleeding, sepsis, and thromboembolism were frequent postoperative complications. Central nervous system deficits were observed in 16 patients during their postoperative course. Eight patients (19.5%) were long-term survivors. Of the preoperative risk factors evaluated only age was significantly associated with survival, with 7 (33%) of the 21 younger (39 to 63 years) patients surviving. Blood product usage and hospital cost were analyzed in an attempt to assess cost/effectiveness of use of this device for attempted salvage of such desperately ill patients."
-What are the key applications of PET scanning in clinical oncology?,"The applications of PET in clinical oncology. With the advent of a new generation of PET scanners that have introduced whole-body PET to the clinical setting, there is now more interest in developing protocols for the evaluation of both intracranial and somatic cancers. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumors, head and neck tumors, primary and metastatic brain tumors, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. A summary of current clinical applications of PET in oncology is presented with special attention to colorectal, lung, and intracranial neoplasms since the majority of clinical trials have focused on these cancers. A variety of radiopharmaceuticals are described that are currently included in clinical tumor-imaging protocols, including metabolic substrates such as fluorine-18-fluorodeoxyglucose and carbon-11-methionine, and analogs of chemotherapeutic agents such as fluorine-18-fluorouracil and fluoroestradiol. An attempt is also made to include examples of clinical trials that demonstrate response to therapeutic intervention. The increasing number of oncologic PET studies reflects the growing interest in functional imaging in oncology."
-What were the key findings regarding the response of patients with systemic sclerosis to nifedipine and captopril in this study?,"Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril. PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed ""borderline"" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder."
-How did oral administration of myelin antigens affect the progression of experimental autoimmune encephalomyelitis in Lewis rats and strain 13 guinea pigs?,"Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the Lewis rat and strain 13 guinea pig. Oral administration of proteins is a long-recognized method of inducing antigen-specific peripheral immune tolerance. We previously showed that oral administration of myelin basic protein suppresses monophasic experimental autoimmune encephalomyelitis in the Lewis rat when it is given in association with immunization and prior to disease onset. As a potential therapy for human autoimmune disease, it is crucial to determine whether oral tolerance can ameliorate an ongoing immune response. We therefore asked whether oral administration of myelin antigens, after sensitization and disease expression has occurred, could affect immunological, clinical, or pathological features of experimental autoimmune encephalomyelitis. Chronic relapsing experimental autoimmune encephalomyelitis was induced in the Lewis rat and strain 13 guinea pig by immunization with whole guinea pig cord homogenate, complete Freund's adjuvant, and Mycobacterium tuberculosis. Following recovery from the first attack, animals were orally given bovine myelin, guinea pig myelin, or guinea pig myelin basic protein three times per week for up to 3 months. Animals receiving myelin products orally had decreased severity and frequency of clinical relapses, decreased delayed-type hypersensitivity responses to myelin antigens, diminished inflammation in the central nervous system (CNS), and decreased areas of CNS demyelination. In the rat, guinea pig myelin basic protein was as effective as guinea pig myelin in ameliorating the disease and also resulted in decreased serum anti-myelin basic protein antibody levels. No exacerbation of disease or worsening of pathological findings occurred in the animals given myelin products. These results demonstrate that oral administration of myelin antigens can suppress chronic relapsing experimental autoimmune encephalomyelitis and have direct relevance to therapy of human demyelinating disorders such as multiple sclerosis."
-What diagnostic techniques were used to identify and confirm the intrahepatic arterioportal fistula in this patient?,"Intrahepatic spontaneous arterioportal fistula: duplex ultrasound diagnosis and angiographic treatment. A 54-yr-old male with portal hypertension received ineffective medical therapy for the diagnosis of portal hepatic cirrhosis. Duplex ultrasound (US) revealed pulsatile arterial flow in the right main portal vein. The correct diagnosis of intrahepatic arterioportal fistula was established and confirmed by angiography. Right hepatic artery embolization with three coils was performed. The patient is alive for 16 months after the embolization, and his complaints have disappeared. There has been full resorption of ascites and absence of varices. Nine previously reported similar cases are reviewed."
-What characteristics of focal hepatic lesions can help differentiate between benign and malignant tumors using MR imaging?,"Focal hepatic lesions: differentiation with MR imaging at 0.5 T. Magnetic resonance (MR) examinations of 43 patients with 95 focal hepatic lesions (diameter, greater than 1 cm) were analyzed for lesion shape, homogeneity, and relative signal intensity compared with normal liver parenchyma, spleen, and skeletal muscle. On T1-weighted, balanced, and T2-weighted images, most metastases (74%), cavernous hemangiomas (76%), and cysts (82%) were smooth and round or oval, while the hepatocellular carcinomas all had irregular borders (40%) or were lobulated (60%). All lesions with irregular borders were malignant. Seventy percent of metastatic lesions, 85% of cavernous hemangiomas, and 100% of simple hepatic cysts were of homogeneous signal intensity, while 60% of hepatocellular carcinomas were inhomogeneous. Logistic regression analysis of multiple lesion characteristics showed that inhomogeneous lesions had a high likelihood of malignancy, while markedly hyperintense lesions had a very low probability of being malignant, regardless of other traits. Homogeneous lesions that were isointense or hyperintense compared with spleen on balanced images but were not markedly hyperintense on T2-weighted images also had a high likelihood of malignancy."
-What percentage of stage I testicular cancer patients experienced recurrence in the Testicular Cancer Intergroup Study?,"Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study. The Testicular Cancer Center Intergroup Study entered surgically staged patients with nonseminomatous tumor and metastases limited to the regional lymph nodes into a previously reported cooperative trial of immediate versus delayed therapy for positive retroperitoneal node disease. Patients with negative nodes (stage I) were placed in an observation registry with specified treatment strategy upon relapse. Of 264 stage I cancer patients 27 (10.2%) had recurrence: 5 of these 27 patients died after recurrence of the testicular malignancies, while 4 other nontumor-related deaths have occurred. Pre-lymphadenectomy staging characteristics observed to predict significantly node positivity are the results of radiological examinations, presence of tumor invasion, vascular invasion and tumor histology. In a multiple logistic regression analysis with these variables, misclassification still occurs in more than a fourth of the patients. Future refinements in diagnosis may allow for better prediction of these patients at risk to have positive lymph nodes and ultimately recurrence. Presently, if assessment of nodal involvement is the objective, noninvasive procedures are not an adequate substitute for surgical staging with modified lymphadenectomy."
-What distinctive features of crackling lung sounds were found in patients with different respiratory conditions?,"Crackles in patients with fibrosing alveolitis, bronchiectasis, COPD, and heart failure. We have studied the crackling lung sounds of ten patients with cryptogenic fibrosing alveolitis, ten with bronchiectasis, ten with chronic obstructive pulmonary disease, and ten with heart failure by analyzing frequency, waveform, and timing of crackles. The upper frequency limit of inspiratory sounds was higher in CFA than in COPD or in HF. The period of crackling was shorter in COPD than in CFA or BE. Inspiratory crackling terminated significantly earlier in COPD than in CFA, BE, or HF. The initial deflection width and the two-cycle duration of the expanded waveforms of crackles were smaller in CFA than in BE, COPD, or HF. The largest deflection width was smaller in CFA than in BE, HF, or COPD and smaller in BE than in HF. The results indicate that crackling lung sounds in different diseases have distinctive features and that their analysis can be of diagnostic value."
-What novel treatment strategies have been explored for Parkinson's disease?,"Parkinson's disease: new treatment strategies. Recent interest has focused on two novel approaches to the treatment of Parkinson's disease-medications to slow or arrest disease progression, and cerebral transplantation. Two recent studies have demonstrated that selegiline can slow, although not halt, the progression of recent-onset Parkinson's disease. The data are sufficiently compelling to justify the use of this drug in most new patients. It also seems reasonable to extrapolate from the data and offer this medication to all patients but those with the most advanced Parkinson's disease. The current focus on excessive oxidative stress as a causative factor has led some investigators to recommended treating patients with the antioxidant tocopherol (vitamin E). There is no clinical evidence demonstrating its effectiveness, but a current multicenter study is being conducted, with the results expected within the next 2 years. High-dose vitamin E (such as 800 to 2000 U/d), taken for a number of months, is probably harmless. It is probably reasonable, therefore, to allow patients to take this over-the-counter compound until more definitive evidence is available. Another antioxidant, vitamin C, has also been advocated as a means of slowing the progression of Parkinson's disease. There are no studies that demonstrate any clinical effectiveness, and there are also no ongoing studies investigating this issue in patients with Parkinson's disease. The excitement surrounding the initially favorable results of adrenal-brain transplantation has waned with the failure of numerous institutions to replicate the original dramatic success. While mild or occasionally moderate improvement has been noted in subsequent patients undergoing adrenal-brain transplantation, the improvement has not been sufficient to justify the risk and expense of this surgery."
-What was the impact of switching from body ventilators (BVs) to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP) on patients with obstructive sleep apnea?,"Obstructive sleep apnea complicating negative-pressure ventilatory support in patients with chronic paralytic/restrictive ventilatory dysfunction. The purpose of this study was to determine the incidence and severity of obstructive events and oxyhemoglobin desaturation (dSaO2) in 37 patients with paralytic/restrictive ventilatory insufficiency during use of nocturnal ventilatory assistance provided by means of negative-pressure body ventilators (BVs). Thirteen of the 37 patients had mean oxyhemoglobin saturation (SaO2) less than 95 percent and a mean of ten or more episodes per hour when the dSaO2 was greater than or equal to 4 percent (4%dSaO2/h). In all, 26 of the 37 patients had evidence of significant multiple episodes of dSaO2 while asleep on BVs. Polysomnography performed on three of these patients substantiated the obstructive nature of the dSaO2. Twenty-two of the 37 patients who had a mean SaO2 of 90.6 +/- 7.2 percent and a mean of 17.7 +/- 16.1 4%dSaO2/h on BVs were switched to noninvasive ventilatory assistance by intermittent positive airway pressure (NV-PAP). Their mean SaO2 improved to 96.0 +/- 2.2 percent, and the 4%dSaO2/h decreased to 1.2 +/- 1.8 per hour. All symptoms similar to those of obstructive sleep apnea were relieved. We conclude that BV use is associated with significant dSaO2 in over 50 percent of patients. The dSaO2 is predominantly obstructive in nature but may be due to chronic underventilation in patients using less effective BVs. Patients with a mean SaO2 less than 95 percent or 10 or more 4%dSaO2/h may benefit from conversion to NV-PAP via the nose, the mouth, or an oral-nasal interface."
-What significant changes have occurred in rehabilitation approaches for patients with rheumatic diseases over the past decade?,"Rehabilitation in rheumatic diseases. What's new. In the past decade, considerable change has occurred in concepts of rehabilitation in patients with rheumatic diseases. This includes approaches to functional assessment and outcome, new concepts in exercise, and new orthotics."
-How does a family history of coronary artery disease affect hemodynamic responses to exercise in young black boys?,"Family history of myocardial infarction and hemodynamic responses to exercise in young black boys. The influence of family history of coronary artery disease on children's hemodynamic responses to exercise was examined with 25 black boys aged 7 to 10 years. Blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance were evaluated during preexercise, peak exercise, and recovery stages. Children with a family history of CAD exhibited greater systolic blood pressure and total peripheral resistance during preexercise and peak exercise stages than did those without a family history of coronary artery disease. After controlling for preexercise differences, the group with a family history of coronary artery disease exhibited greater increases in systolic blood pressure and less attenuation of total peripheral resistance to peak exercise than the group without a family history of coronary artery disease. Cardiac output indexed by body surface area and stroke volumes were higher at all times in the group without a family history compared with the group with a family history of coronary artery disease. Findings are compared with those of adult studies in terms of influence of family history of coronary artery disease on cardiovascular reactivity to stress."
-What evidence suggests that the chronic lymphocytic leukemia and lymphoblastic lymphoma in this patient originated from the same malignant cell?,"Emergence of a B-cell lymphoblastic lymphoma in a patient with B-cell chronic lymphocytic leukemia: evidence for the single-cell origin of the two tumors. A patient is described who presented with a chronic lymphocytic leukemia (CLL) and later developed a lymphoblastic lymphoma. The cells from the CLL were typical mature B lymphocytes as could be assessed by morphologic, cytochemical, and surface marker analyses. The cells from the lymphoblastic lymphoma were immature B cells that expressed CD10, CD20, and HLA-DR markers, but not surface Ig or cytoplasmic mu chains, and were negative for terminal deoxynucleotidyl transferase (TdT). The cells of two continuous cell lines, obtained from the bone marrow and the peripheral blood of the patient, had the same phenotype as the lymphoblastic lymphoma cells, did not contain the Epstein-Barr virus genome, and displayed malignant features in vitro, including the capacity to form colonies in agar. The two cell lines also shared identical chromosomal abnormalities, a finding which suggests that they derived from the same malignant cell already present in vivo. Such chromosomal abnormalities were not seen in the karyotype of the peripheral blood cells at the onset of the disease. Analysis of the Ig heavy chain genes using a DJ-specific probe showed the very same monoclonal rearrangement in the cells from the B-CLL, the lymphoblastic lymphoma and the two cell lines, thus demonstrating their common clonal origin. By contrast, a monoclonal rearrangement of the lambda chain gene locus was found in the B-CLL cells only, a finding consistent with their exclusive capacity to express surface IgM lambda. This patient represents a rare case in whom a chronic lymphoproliferative disorder with mature malignant cells transforms into a lymphoblastic lymphoma characterized by cells frozen at a very early maturational stage. The possible mechanisms leading to such transformation within the same cell clone are discussed."
-How does the degree of headache relief impact psychological changes in chronic headache patients?,"Psychological changes accompanying non-pharmacological treatment of chronic headache: the effects of outcome. Several prior studies suggest that non-drug treatment for chronic headache is accompanied by concomitant reductions in patients' anxiety, depression and somatization. It is currently unclear, however, whether such beneficial side effects are a function of degree of headache relief or are due simply to receiving treatment. Most work to date in this area has treated outcome as a dichotomous variable. The present report employed a regression approach which treats outcome (degree of headache relief) as a continuous variable in the study of 149 chronic headache patients and their accompanying psychological changes. Anxiety and depression were significantly reduced for headache patients regardless of degree of headache relief. With somatization, however, degree of headache relief had a significant effect; the greater the reduction in headache, the fewer somatic concerns were expressed, especially for mixed headache."
-What was the main purpose of the study on exocrine pancreatic function in children with coeliac disease?,"Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal."
-What is the significance of left atrial spontaneous echo contrast in patients undergoing transesophageal echocardiography?,"Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement."
-What was the main finding regarding resting energy expenditure (REE) in patients with newly detected gastric and colorectal cancers?,"Resting energy expenditure in patients with newly detected gastric and colorectal cancers. Resting energy expenditure (REE) was measured in 104 patients with newly detected gastric or colorectal (GCR) cancer and was compared with two groups of control subjects without cancer: healthy subjects (H control subjects) and patients with nonmalignant diseases of the gastrointestinal tract (GI patients). REE in GCR-cancer patients was not significantly different from REE in GI patients or H control subjects. Comparison of measured REE with predicted REE obtained from prediction equations may erroneously suggest that increased REE is a contributing factor in the development of cancer cachexia. No significant differences in REE were found when patients with liver metastases were compared with patients without metastases. There were no differences in REE between gastric and colorectal cancer patients. The decrease in energy expenditure, which normally occurs during starvation and weight loss in healthy men and women, could not be demonstrated in weight-losing, GCR-cancer patients. In conclusion, elevation of REE contributes little to the pathogenesis of cancer cachexia in GCR-cancer patients."
-What was the main finding of the study comparing short-term and long-term cefoxitin prophylaxis after radical hysterectomy?,"Comparative efficacy of short-term versus long-term cefoxitin prophylaxis against postoperative infection after radical hysterectomy: a prospective study. We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy."
-What was the response rate and median time to progression for patients with recurrent malignant glioma treated with intravenous carboplatin?,"Intravenous carboplatin for recurrent malignant glioma: a phase II study. Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate."
-What are the bactericidal properties of fibrin gel against different bacterial species in a contaminated hepatic injury model?,"Autologous fibrin gel: bactericidal properties in contaminated hepatic injury. Fibrin glue is an effective hemostatic agent in a variety of clinical situations; its utility is limited by potential transmission of viral infection. We studied the bactericidal properties of fibrin gel (FG) in a murine contaminated hepatic injury model and in vitro by agar plate culture method. Intra-abdominal abscess formation and adhesion rate were assessed following controlled liver injury in association with abdominal contamination with 10(7) Bacteroides fragilis and hepatorrhaphy (H, n = 15) or FG (n = 12). Animals treated by hepatorrhaphy had a significantly greater intra-abdominal abscess rate (15/15 vs. 4/12, p less than 0.05) and adhesion rate (14/15 vs. 6/12, p less than 0.05) than animals treated with FG. Fibrin gel is bactericidal to Bacteroides fragilis, Enterobacter faecium, Escherichia coli, and Staphylococcus aureus but has no effect against Klebsiella pneumoniae or Pseudomonas aeruginosa; the plasma component appears active. Fibrin gel demonstrates significant improvement in adhesion formation and intra-abdominal abscess rate when compared with suture hepatorrhaphy. Fibrin gel appears protective in contaminated hepatic injury."
-What rare ictal phenomenon was investigated in two patients with epilepsy?,"Blindness as an ictal phenomenon: investigations with EEG and SPECT in two patients suffering from epilepsy. Blindness is a rare ictal phenomenon in epileptic seizures. It can occur as an aura, as the seizure itself, or postictally. We investigated two such patients, in one of whom blindness manifested as an aura prior to tonic clonic seizures; the interictal EEG exhibited a spike-wave focus bioccipitally. In the second patient blindness occurred postictally. An ictal SPECT, carried out at the onset of the seizure demonstrated marked hyperperfusion in both occipital regions."
-What medical condition was observed in a 16-month-old infant with congenitally-acquired HIV infection?,Acute hemiplegia associated with HIV infection. An acute hemiplegia secondary to a large cerebral infarct is described in a 16-month-old infant with congenitally-acquired human immunodeficiency virus infection. Serial imaging studies during the next year documented improvement in his hemiplegia and a static underlying human immunodeficiency virus encephalopathy. Acquired immunodeficiency syndrome should be included in the differential diagnosis of children with acute hemiplegia.
-What is moricizine hydrochloride and what is its primary medical application?,"Moricizine: a new agent for the treatment of ventricular arrhythmias. Over the last several years, a number of new antiarrhythmic agents have come into use. One of these promising new drugs, moricizine hydrochloride (Ethmozine), is now available for use in this country. Although similar in some aspects to both quinidine and lidocaine, Moricizine hydrochloride is in many ways unique. The purpose of this review is to summarize the pharmacologic and physiologic effects of moricizine and to outline its clinical use."
-What was the mortality rate during the initial admission for neonates with oesophageal atresia and/or tracheo-oesophageal fistula in this surgical study?,"Success and failure with neonatal tracheo-oesophageal anomalies. In seven and a half years, one surgical team treated 67 consecutive neonates with oesophageal atresia and/or tracheo-oesophageal fistula. According to Waterston's classification, 28 were in group A, 12 in group B and 27 in group C. The mortality rate during the initial admission was 10 per cent, all seven deaths being unavoidable in infants in group C with multiple anomalies. Birthweight alone had no bearing upon the chances of survival. Primary oesophageal repair, including one suture-fistula procedure and one delayed primary repair, was attempted in 54 (84 per cent) of the 64 patients with atresia and was successful in 46 (85 per cent). All three H-type tracheo-oesophageal fistulae were successfully divided in infants in group A. Recurrent tracheo-oesophageal fistula developed in four (7 per cent) infants, one of whom (group A) underwent successful repair. One disrupted anastomosis was successfully resutured (group A), so an intact oesophagus was finally achieved in 51 patients, of whom six (12 per cent) developed anastomotic strictures and 21 (41 per cent) underwent surgery for gastro-oesophageal reflux. Of the 60 early survivors, 10 (17 per cent) underwent aortopexy for tracheomalacia. Whenever possible, primary repair is advocated in all infants. Even for those in group C with multiple, severe associated anomalies, the combined early and late mortality was no greater following primary repair (7 died of 12 operated) than after staged repair (4 died of 7 operated), but major anastomotic complications were more common in infants in group C (5 out of 19) than in those in groups A and B (3 out of 38)."
-How did the quality of life differ between patients taking atenolol and nifedipine GITS during the 20-week antihypertensive therapy trial?,"Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system. To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation."
-What was the significance of culturing the calcified lymph nodes in this patient's case?,"Esophagobronchial fistula and mediastinal tuberculosis. A 59-year-old man was seen with what preoperatively was thought to be an acquired esophagobronchial fistula secondary to an old burned-out infection with tuberculosis. At operation the gross and microscopic findings were most compatible with a congenital H-shaped esophagobronchial fistula. However, cultures of calcified lymph nodes grew Mycobacterium tuberculosis. The need for culturing calcified tissue to assure proper treatment is emphasized."
-How does acute appendicitis present differently in patients with AIDS/HIV infection compared to immunocompetent patients?,"Acute appendicitis in patients with AIDS/HIV infection. Nine patients known to have acquired immunodeficiency syndrome (AIDS) and/or human immunodeficiency virus (HIV) infection and operated on for acute appendicitis are presented. Six of the nine patients did not have an elevation in the white blood cell count preoperatively. Two patients underwent diagnostic laparoscopy prior to exploration. In four cases, a perforated appendix was removed. Seven patients had persistent postoperative fever, while all nine had a significant lack of leukocytosis after surgery. Other than the absence of a preoperative increase in white blood cell count, the presenting characteristics of this group were similar to those expected in immunocompetent patients. However, concern for a possible opportunistic infection etiology and a desire to avoid operating on these patients resulted in an undue delay prior to exploration. The use of diagnostic laparoscopy aided in earlier and more accurate diagnosis. Despite persistent postoperative fever, appendectomy was performed in patients with AIDS/HIV infection without significant increase in morbidity and mortality."
-What was the success rate of antitachycardia pacing in treating tachycardia episodes in this study?,"Reduction in defibrillator shocks with an implantable device combining antitachycardia pacing and shock therapy. Implantable defibrillators reduce the risk of sudden death in patients with malignant ventricular arrhythmias, but significant restriction in quality of life can occur as a result of frequent device activation. To determine if a device that provides both antitachycardia pacing and shock therapy can safely reduce the frequency of shocks after implantation, 46 consecutive patients undergoing initial implantation of a defibrillator were studied. In all patients, the implanted device provided antitachycardia pacing and shock therapy. Detected tachycardia characteristics and the results of therapy were stored in the device's memory. There were 42 men and 4 women, aged 26 to 71 years (mean 58.7 +/- 13.5). Left ventricular ejection fraction ranged from 13% to 67% (mean 32.2 +/- 13.4%) and 31 patients had experienced one or more episodes of cardiac arrest. Induced arrhythmias included sustained monomorphic ventricular tachycardia in 38 patients, nonsustained polymorphic ventricular tachycardia in 2 and ventricular fibrillation in 4. Over a total follow-up period of 255 patient-months (range 1 to 13, mean 6.1), 25 patients experienced spontaneous arrhythmic events. In 22 patients, 909 episodes of tachycardia were treated by antitachycardia pacing, which was successful on 840 occasions (92.4%). Acceleration of ventricular tachycardia by pacing therapy was estimated to have occurred 39 times. Syncope occurred once during pacing-induced acceleration of ventricular tachycardia. Forty-four episodes of tachycardia in seven patients were treated directly by shocks because of short tachycardia cycle length; 88% of all detected tachycardias were treated without the need for shocks. Four patients died from cardiorespiratory failure and one patient died suddenly without any detected tachyarrhythmia."
-What are the primary methods for treating active esophagogastric variceal bleeding and preventing its recurrence?,"Bleeding esophagogastric varices. Ways to treat active episodes and prevent recurrence. Bleeding from esophagogastric varices carries a high mortality rate. Active variceal bleeding can usually be temporarily controlled medically with a combination of intravenous vasopressin and nitroglycerin, with balloon tamponade, or with endoscopic sclerotherapy. Because of the high likelihood of recurrence, long-term treatment, such as repeated sclerotherapy, propranolol therapy, or shunt surgery, is necessary. The proper selection of such measures requires consideration of the site of variceal bleeding, local availability of specialized techniques, and patient factors. Only liver transplantation reverses the liver damage and offers hope of improved long-term survival. As success at identifying high-risk patients by endoscopic features improves, propranolol or other pharmacologic prophylaxis may become an acceptable treatment."
-What method is described for reorienting the left ventricular long-axis from myocardial transaxial tomographic data?,"Reorientation of the left ventricular long-axis on myocardial transaxial tomograms by a linear fitting method. A method is described for reorientating the left ventricular (LV) long-axis from myocardial transaxial tomographic data. On a midventricular transverse slice and on a midventricular sagittal slice, the apical and basal limits are selected successively by the operator. The linear activity profiles between these two limits are plotted line by line. In each profile, the two points with the maximum counts in the septal and lateral walls on the transverse slice, or in the anterior and inferior walls on the sagittal slice, are detected. The intermediate point with the minimum counts is then determined. The set of points with minimum counts are fitted by a straight line using the least squares method. This line is taken as the LV long-axis. In a series of 15 cases with stress-delayed 201Tl SPECT, the reproducibility of the reorientation with this semi-automatic method was compared with manual selection of the LV long-axis. In all patients, a successful reorientation was obtained with the present method. The reproducibility was significantly better with the semi-automatic method than with the manual selection of the LV long-axis."
-What was the primary finding of the study regarding nocturnal airflow obstruction in children with allergic asthma?,"Nocturnal airflow obstruction, histamine, and the autonomic central nervous system in children with allergic asthma. A study was carried out to investigate whether an imbalance in the autonomic nervous system or release of histamine, or both, is responsible for the nocturnal increase in airflow obstruction in asthmatic children. The study comprised 18 children with allergic asthma, nine with (group 1) and nine without (group 2) nocturnal airflow obstruction, and an age matched control group. All drugs were withheld for three days before and during the study. On day 4 each child was admitted to hospital and a series of measurements was made every four hours for 24 hours. These included measurements of the forced expiratory volume in one second (FEV1), heart rate and sinus arrhythmia gap from an electrocardiogram (an indirect measure of parasympathetic activity) and urine sampling for determination of catecholamine and N'-methylhistamine concentrations (measures of sympathetic activity and histamine release respectively). Urinary N'-methylhistamine excretion was significantly higher over the 24 hours in children in group 1 than in children in group 2, and overnight values were also significantly higher in children in group 1 than those in group 2. Mean (SEM) values (mumol/mol creatinine) were 154.6 (11.2) in group 1 and 110 (11.2) in group 2 for 2400-0400 hours samples and 139.2 (13.1) and 101.2 (10.6) 0400-0800 hours samples. There was no evidence of decreased sympathetic or increased parasympathetic activity in association with the nocturnal airflow obstruction; noradrenaline concentrations were increased in group 1. These observations indicate that nocturnal airflow obstruction is associated with increased release of histamine overnight."
-What was the main finding regarding regional cerebral blood flow in patients after cardiac arrest?,"Regional cerebral blood flow after human cardiac arrest. A hexamethylpropyleneamine oxime single photon emission computed tomographic study. We studied 30 patients 24 hours after out-of-hospital cardiac arrest and 13 age-matched normal controls with the use of technetium Tc 99m-hexamethylpropyleneamine oxime single photon emission computed tomography. All patients were followed up for 12 months or until death. Frontal hypoperfusion (anteroposterior perfusion ratio, less than 0.90) was observed in 23 patients (77%). In eight patients who remained comatose and died, the total size of perfusion defects was larger (38% +/- 20%) than in the 21 patients who recovered consciousness (24% +/- 14%), but the anteroposterior ratio was similar in both of these patient groups (0.83 +/- 0.09) and significantly lower than in the controls (0.96 +/- 0.03). During follow-up, both the anteroposterior perfusion ratio and the relative defect size improved, but frontal hypoperfusion was still observed in seven of 13 patients. After cardiac arrest, regional cerebral blood flow is characterized by frontal hypoperfusion that tends to improve over time but that persists in most patients."
-How do nitrendipine and removal of extracellular calcium ions affect tetanic responses in frog toe muscles?,"Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle. The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the ""late negative afterpotential"" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers."
-What percentage of splenic lesions were found to be hypoechoic in the sonographic study?,"Sonography of focal lesions of the spleen. The sonographic appearances of benign and malignant splenic lesions in 154 patients are illustrated. Sixty-six of the 154 patients had malignant splenic lesions; 55 of these had malignant lymphoma and 11 had splenic metastatic lesions. The lesions were hypoechoic in 64 cases (97%), including all cases of malignant lymphoma, and were hyperechoic in two. Eighty-eight patients had benign splenic lesions; findings included cysts, infarcts, abscesses, hemangiomas, and calcifications."
-What was the outcome of the prospective assessment of the rebound tenderness test in patients with abdominal pain?,Rebound tenderness test. The usefulness of the rebound tenderness test in indicating peritonitis was prospectively assessed in 142 unselected patients admitted as emergencies with abdominal pain and tenderness. It was found to be of no predictive value.
-What rare complication can occur after local steroid injection of a ganglion cyst on the hand?,"Localized depigmentation after steroid injection of a ganglion cyst on the hand. Presented is the case of a man who had localized depigmentation after local injection of triamcinolone diacetate. Search of the literature indicates that this is a rare complication of such therapy. Localized depigmentation may have important cultural implications for dark-skinned patients. There is some experimental evidence that less-potent and shorter-acting steroid preparations have a lower likelihood for depigmenting side effects, and such agents may be more appropriate when injecting subcutaneous structures to prevent this complication."
-What are the key diagnostic challenges associated with identifying Enterobius egg granuloma in medical pathology?,"Enterobius egg granuloma of the vulva and peritoneum: review of the literature. Two cases of Enterobius granuloma containing eggs only are reported. The first case involved the vulva, where no such granuloma has been reported previously. The coexistence of peritoneal granuloma and rectal adenocarcinoma in the second case suggests the possibility of direct penetration of the damaged colonic wall by the parasite, as emphasized by several previous reports of neoplastic involvement and perforation of the intestinal wall in cases of ectopic infections. The diagnostic criteria of Enterobius eggs granuloma, which might be a diagnostic dilemma for pathologists who are not familiar with such criteria, are described herein."
-What is the significance of thiamine deficiency in chronic hemodialysis patients according to the case report?,"Acute encephalopathy due to thiamine deficiency (Wernicke's encephalopathy) in a chronic hemodialyzed patient: a case report. We report the case of a patient with terminal renal disease on chronic hemodialysis who developed acute thiamine deficiency as confirmed by erythrocyte transketolase determinations. The patient presented with a confusional state and severe memory disturbances, but other classical features of Wernicke's encephalopathy were absent. Almost all central nervous system symptoms rapidly disappeared after thiamine therapy. Therefore the possibility of thiamine deficiency must be considered in patients on chronic dialysis who present with central nervous system disturbances, even if all of the classical features of Wernicke's encephalopathy are not present."
-What was the primary objective of the study on transjugular intrahepatic portosystemic shunt?,"Percutaneous transjugular portosystemic shunt. OBJECTIVE.--To determine the effectiveness of the Palmaz balloon expandable stent for the creation of a transjugular intrahepatic portosystemic shunt. The device is designed to achieve portal decompression in patients with variceal hemorrhage secondary to portal hypertension. DESIGN.--Transjugular intrahepatic portosystemic shunting was performed in eight patients during a 9-month period. Mean follow-up was 5 months. PATIENTS.--All patients had cirrhosis with portal hypertension and varices. Bleeding occurred in seven patients from esophageal varices and in one patient from hemorrhoids. MAIN OUTCOME MEASURES.--Shunt patency and recurrent variceal hemorrhage. RESULTS.--Shunts created from a transjugular approach between a hepatic and a portal vein (diameters of 8 to 12 mm) lowered the average portosystemic pressure gradient from 36 to 11 mm Hg. Mean postoperative hospital stay was 7.7 days. Complete variceal decompression after transjugular intrahepatic portosystemic shunt placement was identified endoscopically in all eight patients. The patient treated for hemorrhoids rebled and was treated successfully by transfemoral balloon expansion of the shunt diameter from 8 to 12 mm. All shunts were patent at 1 to 9 months (mean, 5 months) of follow-up. CONCLUSION.--Initial results suggest that transjugular intrahepatic portosystemic shunt is a safe and effective method of portal decompression for the treatment of variceal hemorrhage."
-What was the percentage of true histiocytic neoplasias found among malignant lymphoma and related conditions in this Japanese study?,"Histiocytic neoplasias: immunohistochemical evaluation of their frequencies among malignant lymphoma and related conditions in Japan. Through histologic review of 1,766 cases with malignant lymphoma and related conditions, 35 cases (2%) were selected as probable histiocytic neoplasias. Proliferating cells in these cases had voluminous, granulated cytoplasm, and round to irregularly shaped nuclei often with bi- or multinucleated forms showing monomorphous or polymorphous proliferation accompanying small lymphocytes, plasma cells, and, less frequently, eosinophils. Cases showing proliferation of convoluted cells with numerous benign-appearing histiocytes or large cells with clear cytoplasm were excluded under a diagnosis of T-cell lymphoma. To evaluate the immunologic character of proliferating cells, immunohistochemistry using antibodies Mx-Pan B, MB-1, MT-1, UCHL-1, lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 alpha, S-100 beta, Leu M1, epithelial membrane antigen, and Ki-1 were carried out in 23 cases. Naphthol-ASD-chloracetate reaction and toluidine blue stain were also performed. These procedures revealed that 12 cases (52%) were B-cell type, three cases (13%) T-cell type, six cases (26%) true histiocytic type, and two cases null type. Therefore, the frequency of cases with true histiocytic neoplasias among cases with malignant lymphoma and related conditions in Japan may be 0.5%."
-What factors in childhood can predict future high blood pressure?,"Childhood predictors of future blood pressure. Blood pressure in infants and children is much lower than that in adults. It is suspected that children whose blood pressures are greatest for their age or body size may be destined for future hypertension. However, it is apparent that some children with lower blood pressures are also destined for hypertension as adults. Children with a family history of hypertension demonstrate greater blood pressure and heart rate responses to mental challenge. These responses are enhanced when a high salt diet is consumed. Increased maximal exercise systolic blood pressure and increased left ventricular wall mass in childhood add significantly to the prediction of future high blood pressure. In addition, the acquisition of excess weight for height from childhood to young adult life adds to the prediction of future blood pressure elevations. Both children and adults who are obese have significantly higher blood pressures than those who are lean. Approximately 34% of the variability in body mass index is explained by genotype differences at a single recessive locus, 41% by genotype differences at polygenic loci, and 25% by nongenetic factors. Thus, the genetic influence of obesity may be an important factor responsible for elevated blood pressure in both children and adults."
-What is the relationship between anemia and postoperative apnea in former preterm infants undergoing inguinal hernia repair?,"Anemia and postoperative apnea in former preterm infants. To examine the association between anemia and postoperative apnea in former preterm infants, 24 former preterm infants of less than 60 weeks postconceptual age undergoing inguinal hernia repair were studied. A hematocrit of at least 25% was required for study participation. General endotracheal inhalational anesthesia, supplemented with neuromuscular blockade and controlled ventilation, was used. No barbiturates or opioids were administered. Respiratory pattern and heart rate were recorded for at least 12 h postoperatively using an impedance pneumograph. Tracings were analyzed for evidence of apnea, periodic breathing, and/or bradycardia by a pulmonologist unaware of the hematologic profile of the infant. Nineteen patients had a hematocrit of 30% or greater (group 1). Their mean (+/- standard deviation [SD]) gestational age was 33.5 +/- 2.7 weeks and postconceptual age 45.5 +/- 4.6 weeks. Five infants had a hematocrit less than 30% (group 2). Their mean gestational age (+/- SD) was 32.4 +/- 3.2 weeks and postconceptual age 43.6 +/- 5.5 weeks. Anemic infants had an 80% incidence of postoperative apnea versus 21% in infants with a normal hematocrit (P less than .03). In the infants who developed postoperative prolonged apnea and/or bradycardia, a prior history of apnea was equally present in both groups (21% in group 1 and 20% in group 2). This study shows that anemia in former preterm infants can be associated with an increased incidence of postoperative apnea."
-What are the general characteristics and treatment approaches for haemangiomas in different parts of the urinary tract?,"Haemangioma of the urinary tract: review of the literature. General features. Haemangiomas are benign vascular tumours. They can regress spontaneously as a result of fibrosclerosis, suggesting a conservative approach wherever possible. Asymptomatic haemangiomas do not require treatment. Renal haemangioma. In all, 198 cases have been reported. The lesion is usually solitary and unilateral and occurs most often in the pyramid, and in the mucosa or subepithelial tissue of the pelvis. In some cases a tentative diagnosis of haemangioma has been made by means of selective renal angiography and pre- or per-operative renoscopy. Partial nephrectomy is recommended in cases of minor haemangioma. Ureteric haemangioma. Six cases have been described. When haemangioma is suspected a conservative operation is recommended. Bladder haemangioma. A total of 106 cases have been reported. Many of the tumours had the characteristics of an iceberg, with considerable extravesical extension making endoscopic management less suitable because of the possibility of massive haemorrhage or recurrence. Consequently, many authors prefer local excision. In the case of endoscopic treatment the patient should be prepared for open surgery. Urethral haemangioma. Twenty cases have been described. The lesions often extend further than is immediately apparent. Endoscopic management is recommended for small lesions and, in the case of more extensive lesions, open exploration is advised followed by appropriate urethral reconstruction."
-What was the most common gastrointestinal complication in patients who underwent cardiopulmonary bypass surgery?,"Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group."
-What is the key finding in the histologic examination of the small intestine in this case of familial enteric neuropathy?,"Familial enteric neuropathy with pseudoobstruction. We report a case of autosomal dominant chronic intestinal pseudoobstruction secondary to a familial enteric neuropathy. Esophagogastrointestinal manometry studies in the index case showed decreased postprandial contractile frequency with normal amplitude of pressure activity in the stomach and small bowel. Pupillary function and autonomic reflexes were all normal, excluding an extrinsic autonomic neuropathy of the viscera. Histologic examination of the small intestine by hematoxylin and eosin stains revealed normal smooth muscles but a reduced number of neurons in the myenteric plexus without inflammatory cells or neuroNal intranuclear inclusions. Histologic examination of the myenteric plexus using the sections taken along the longitudinal axis of the intestine, stained with silver by the Smith technique, disclosed decreased numbers of argyrophilic neurons and degeneration of neurons and axons; however, there was no reactive increase in the number of glial cell nuclei. The patient's mother had suffered from chronic intestinal pseudoobstruction, which did not abate following extensive small bowel resection. This is the third family reported with an autosomal dominant enteric neuropathy unassociated with evidence of extrinsic autonomic or peripheral neuropathy. Subtotal resection of the small bowel was followed by recurrence of the pseudoobstruction syndrome in both affected members of the family."
-Does the anatomical position of the vermiform appendix impact the clinical presentation and outcomes of acute appendicitis?,"Does the retrocecal position of the vermiform appendix alter the clinical course of acute appendicitis? A prospective analysis. Ninety-four adult patients undergoing appendectomy for acute appendicitis were prospectively studied during a 2-year period. Patients were divided into retrocecal (group 1; n = 27 [29%]) and anterior (group 2; n = 67 [71%]) groups according to the position of the appendix. There was no statistical difference between the two groups in duration of symptoms, presenting signs and symptoms, and initial white blood cell count. Furthermore, retrocecal appendicitis was not associated with a higher rate of perforation or increased morbidity. We conclude that the retrocecal position of the appendix does not alter the presentation of appendicitis."
-What was the healing rate of transmetatarsal amputations in different patient groups based on revascularization?,"Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized."
-What was the purpose of the isotopic examination of the stomach in patients with chronic nausea and/or vomiting?,"Idiopathic gastroparesis in patients with unexplained nausea and vomiting. Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for at least 6 hr were given 0.5 mCI of [99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of the T1/2 emptying time was used. In normal controls T1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation."
-How did the researchers correct the human beta S-globin gene in the mouse-human hybrid cell line BSM?,"Correction of a human beta S-globin gene by gene targeting. As a step toward using gene targeting for gene therapy, we have corrected a human beta S-globin gene to the normal beta A allele by homologous recombination in the mouse-human hybrid cell line BSM. BSM is derived from a mouse erythroleukemia cell line and carries a single human chromosome 11 with the beta S-globin allele. A beta A-globin targeting construct containing a unique oligomer and a neomycin-resistance gene was electroporated into the BSM cells, which were then placed under G418 selection. Then 126 resulting pools containing a total of approximately 29,000 G418-resistant clones were screened by PCR for the presence of a targeted recombinant: 3 positive pools were identified. A targeted clone was isolated by replating one of the positive pools into smaller pools and rescreening by PCR, followed by dilution cloning. Southern blot analysis demonstrated that the isolated clone had been targeted as planned. The correction of the beta S allele to beta A was confirmed both by allele-specific PCR and by allele-specific antibodies. Expression studies comparing the uninduced and induced RNA levels in unmodified BSM cells and in the targeted clone showed no significant alteration in the ability of the targeted clone to undergo induction, despite the potentially disrupting presence of a transcriptionally active neomycin gene 5' to the human beta A-globin gene. Thus gene targeting can correct a beta S allele to beta A, and the use of a selectable helper gene need not significantly interfere with the induction of the corrected gene."
-"What was the relationship between DNA ploidy, N-myc gene amplification, and clinical outcome in stage IVS neuroblastoma?","N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required."
-What were the long-term surgical outcomes for patients who underwent lateral cranial base surgery between 1970 and 1987?,"Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis."
-How does the intracerebral temperature compare to the rectal temperature in neurosurgical patients?,"Intracerebral temperature in neurosurgical patients. Recent laboratory results have indicated that the ischemic brain is very sensitive to minor variations in temperature. This has created new interest in hypothermia and brain temperature. There is, however, very little information available regarding human intracerebral temperature and its relation to body core temperature during normal and pathological circumstances. We therefore made continuous measurements of the temperature of the lateral ventricle in 15 neurosurgical patients utilizing a newly developed technique with copper-constantan thermocouples introduced through a plastic catheter also used for monitoring intracranial pressure. The intraventricular temperature was higher than the rectal temperature during approximately 90% of all measurements. The largest temperature gradient measured was 2.3 degrees C. Usually the difference between the temperature of the rectum and the brain was much smaller, the mean value being 0.33 degrees C. For the patients in the most severe condition, the rectal temperature was sufficiently close to the brain temperature to afford a reliable basis for adequate clinical judgment."
-What are the three processes related to leukotrienes that are observed during the immediate reaction in bronchial asthma?,"The potential roles of leukotrienes in bronchial asthma. Leukotrienes (LTs), in particular LTC4, LTD4, and LTE4, have been shown to be capable of participating in the induction of three related processes observed during the immediate reaction in bronchial asthma: edema formation, mucus secretion, and muscle contraction. Despite impressive evidence potentially implicating the LTs, the role of LTs in asthma is still unproved, and a positive answer to their critical actions in causing airflow obstruction will require studies with specific antagonists."
-What is the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft (CABG) surgery?,"Functional recovery of hibernating myocardium after coronary bypass surgery: does it coincide with improvement in perfusion? To determine the relationship between functional recovery and improvement in perfusion after coronary artery bypass graft surgery (CABG), 49 patients were studied. Radionuclide angiography was performed before, 1 month after, and 6 to 12 months after CABG to evaluate regional wall motion. Exercise thallium-201 myocardial perfusion imaging was done before and 1 month after CABG to assess regional perfusion. Preoperative asynergy was observed in 108 segments, and 74 of them showed an improvement in wall motion 1 month after CABG (segment A). Sixty-six of these segments (89%) were associated with an improvement in perfusion. Eight segments that had not improved 1 month after CABG demonstrated a delayed recovery of wall motion 6 to 12 months after CABG (segment B). However, seven of eight segments (88%) already showed an improvement in perfusion 1 month after CABG. A total of 82 segments exhibited functional recovery after CABG and were considered hibernating segments. In the preoperative study segment B more frequently had areas of akinesis or dyskinesis than segment A (75% vs 34%, p less than 0.05). The mean percent thallium-201 uptake in segment B was lower than that in segment A (74% +/- 9% vs 83% +/- 8%, p less than 0.05). Functional recovery of hibernating myocardium usually coincided with an improvement in perfusion. However, delayed functional recovery after reperfusion was observed in some instances. Severe asynergy and severe thallium-201 defects were more frequently observed in these segments with delayed recovery. Hibernating myocardium might remain stunned during those recovery periods."
-What are the key challenges patients with HIV infection face in rehabilitation medicine?,"Human immunodeficiency virus infection and diffuse polyneuropathy. Implications for rehabilitation medicine. Patients at various stages of human immunodeficiency virus (HIV) infection require rehabilitation services. These patients present problems for each of the disciplines in a rehabilitation team, and all team members must confront the psychosocial and ethical issues involved with the disease. Patients with HIV infection may have polyneuropathy with multisystem involvement, including dysphagia, autonomic dysfunction, respiratory failure, bowel and bladder dysfunction, generalized weakness, a painful sensory neuropathy, and depression. Guidelines are presented for determining if inpatient rehabilitation or other settings are appropriate. Case management is a valuable strategy for the rehabilitation of patients with this complicated disorder."
-How does the extent of small bowel resection in Crohn's disease patients affect the absorption of cholecalciferol and 25-hydroxycholecalciferol?,"Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn's disease and intestinal resection. We compared the intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with Crohn's disease and resections of the small bowel. Patients were subgrouped into those with small (less than 100 cm), intermediate (100-300 cm), and large (greater than 300 cm) resections. [3H]cholecalciferol or [3H]25-hydroxycholecalciferol were given orally and serial blood samples were taken for measurement of plasma radiolabeled vitamin. Absorption of both forms of the vitamin decreased with extent of resection but 25-hydroxycholecalciferol absorption was always greater than that of cholecalciferol. When compared with normal control subjects, 25-hydroxycholecalciferol absorption in these patients was better maintained than that of cholecalciferol. These data indicate that vitamin D malabsorption reflects the extent of distal small-bowel resection in Crohn's disease. Treatment with oral cholecalciferol is sufficient in those with small or moderate resections but oral 25-hydroxycholecalciferol supplementation may be preferred in those with a severe short-bowel syndrome."
-What alternative treatment was used for the patient with Wilson's disease when low-dose D-penicillamine caused severe neurological deterioration?,"Zinc sulphate therapy for Wilson's disease after acute deterioration during treatment with low-dose D-penicillamine. A 30-year-old woman with Wilson's disease was treated with low-dose D-penicillamine. After 12 days, treatment was changed to zinc sulphate because of severe neurological deterioration. The patient subsequently improved within a few days. During a follow-up period of 20 months, the effectiveness of therapy was evaluated by measuring copper and zinc levels in plasma and urine, and by 64Cu-loading tests. We conclude that sulphate therapy may be a satisfactory alternative, even when rapid deterioration occurs in the early stages of D-penicillamine treatment."
-What were the key findings of the 15-year follow-up study on cardiovascular risk factors in primary hyperparathyroidism?,"Cardiovascular risk factors in primary hyperparathyroidism: a 15-year follow-up of operated and unoperated cases. The need for treatment of mild and apparently asymptomatic primary hyperparathyroidism (HPT) is questioned, but a raised incidence of cardiovascular disease has been regarded as evidence in favour of surgery. While it is well known that several risk factors for cardiovascular disease (hypertension, hyperlipidaemia and diabetes mellitus/impaired glucose tolerance) are overrepresented in HPT, it is not known whether surgery provides long-term normalization in these respects and reduces the risk of premature death. In a 15-year follow-up of a cohort of 172 subjects in whom mild hypercalcaemia was initially detected during a health screening, it was found that 56 subjects had died. 17 individuals had been operated on for HPT, 47 individuals were persistently hypercalcaemic, while 45 subjects had serum calcium within the normal range (seven individuals were lost to follow-up). There had been no significant differences in blood pressure between these groups of mildly hypercalcaemic patients and age- and sex-matched controls at the initial screening, but at follow-up blood pressure was significantly higher not only in subjects with persistent hypercalcaemia, but also in those who had been successfully operated on for HPT. Neither of the hypercalcaemic groups showed any significant deviations from the controls with regard to indices of lipid or glucose metabolism. These findings suggest that there is no simple cause-and-effect relationship to account for the propensity toward high blood pressure in primary HPT. Consequently it cannot be assumed that surgery for HPT will eliminate the increased risk of cardiovascular disease in patients with mild HPT."
-How do the reflex responses of airway smooth muscle in piglets change between 2 and 10 weeks of age?,"Maturation of respiratory reflex responses in the piglet. Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation."
-What complication occurred after platelet transfusion following a successful PTCA procedure?,Abrupt vessel closure following platelet transfusion post-PTCA. A successful PTCA was complicated by abrupt closure following a platelet transfusion which was given for control of local bleeding. Possible mechanisms of abrupt closure are discussed. Recommendation is made to avoid giving platelet transfusion following PTCA.
-What is a porencephalic cyst and how can it potentially occur during fetal intravascular transfusion?,"Porencephalic cyst: a complication of fetal intravascular transfusion. A case of unilateral porencephalic cyst as a result of intravascular intrauterine transfusion is reported. Although other factors may have contributed, fetal bradycardia and relative hyperviscosity as a result of increased fetal hematocrit value were considered to be related to this event. Because some authors recommend direct intravascular transfusion to supraphysiologic hematocrits to prolong the interval between procedures, we would caution the use of this approach on the basis of theoretic considerations and the occurrence of this complication."
-What was the 5-year patency rate for different types of grafts used in infrapopliteal bypass surgery?,"Infrapopliteal bypass for severe ischemia: comparison of autogenous vein, composite, and prosthetic grafts. Results of 253 consecutive bypass grafts to infrapopliteal arteries were reviewed. Most (92%) were placed for rest pain (103) or tissue loss (130). Autogenous veins were used in 175 (69%) cases, composite vein-prosthetic grafts were used in 45 (18%), and prosthetic grafts alone were used in 33 (13%). Follow-up ranged from 0 to 101 months (mean, 19 months); 37 grafts (15%) were lost to follow-up. The operative mortality rate was 4%, and 5-year patient survival rate was 44%. Limb salvage was 82% at 5 years. The 5-year patency of vein grafts (63%) exceeded that of both composite (28%) and prosthetic (7%) grafts (p = 0.005 and p = 0.00007, respectively); but the patency of composite and prosthetic grafts did not differ significantly (p = 0.29). The patency of reversed vein (59%) and in situ vein grafts (74%) was not significantly different at 5 years (p = 0.34). Patency was also not affected by the site of the proximal or distal anastomoses or diabetes. The major determinant of long-term patency in infrapopliteal reconstructions continues to be graft material. Composite grafts offered no clear advantage over prosthetic grafts, and both should be used only when there is no other alternative to amputation."
-What were the common problems and rehabilitation interventions encountered in patients with AIDS?,"Experience with rehabilitation in the acquired immunodeficiency syndrome. Patients with the acquired immunodeficiency syndrome (AIDS) represent a novel referral population for rehabilitation services. Limited information about the rehabilitation needs of individuals with human immunodeficiency virus infection is available. We reviewed 51 consecutive patients with AIDS referred to a rehabilitation consult service. Common problems encountered included generalized deconditioning (27%) and neurologic dysfunction (45%). Neurologic presentations were diverse and included hemiparesis, diffuse cognitive dysfunction and dementia, myelopathy, myopathy and peripheral neuropathy. Other patients were referred for wound care as well as the management of the local effects of Kaposi's sarcoma, various musculoskeletal syndromes and new onset blindness. Problems identified included impaired mobility (76%), difficulty with self-care (57%), impaired cognition (29%) and uncontrolled pain (37%). Among the rehabilitation interventions utilized were therapeutic exercise (73%), gait aids (45%), bathroom and safety equipment (45%), orthotics (29%), vocational counseling (4%), pain management (29%) and whirlpool treatments (10%). Five patients were too ill or refused treatment. We conclude that AIDS patients referred for rehabilitation have a wide variety of physical deficits, demonstrate a considerable degree of functional impairment and may require multiple rehabilitation interventions."
-What are the typical symptoms and diagnostic challenges of adnexal torsion in postmenopausal women?,"Adnexal torsion. An unusual cause of abdominal pain in postmenopausal women. Adnexal torsion is a rare cause of abdominal pain in older women. Because the presenting symptoms and signs are vague, the diagnosis is not often considered. Lower abdominal pain with nausea and vomiting are usual in patients with torsion. Ultrasonography or computed tomography are useful diagnostic tests. Two case reports of older patients with adnexal torsion are presented to emphasize the diagnostic features of this entity, including lower abdominal pain, nausea and vomiting, and abdominal mass. Although the condition is uncommon, adnexal torsion should be considered in the differential diagnosis of acute abdominal pain."
-Which two genes have been identified as influencing the onset of autoimmune type 1 diabetes in nonobese diabetic mice?,"Genetic analysis of autoimmune type 1 diabetes mellitus in mice Two genes, Idd-3 and Idd-4, that influence the onset of autoimmune type 1 diabetes in the nonobese diabetic mouse have been located on chromosomes 3 and 11, outside the chromosome 17 major histocompatibility complex. A genetic map of the mouse genome, analysed using the polymerase chain reaction, has been assembled specifically for the study. On the basis of comparative maps of the mouse and human genomes, the homologue of Idd-3 may reside on human chromosomes 1 or 4 and Idd-4 on chromosome 17."
-Does Helicobacter pylori infection increase the severity of mucosal injury caused by naproxen or aspirin?,"Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin."
-What is the origin of the extra chromosome 21q in Down syndrome cases with de novo Robertsonian translocation t(14q;21q)?,"Down syndrome due to de novo Robertsonian translocation t(14q;21q): DNA polymorphism analysis suggests that the origin of the extra 21q is maternal. Down syndrome is rarely due to a de novo Robertsonian translocation t(14q;21q). DNA polymorphisms in eight families with Down syndrome due to de novo t(14q;21q) demonstrated maternal origin of the extra chromosome 21q in all cases. In seven nonmosaic cases the DNA markers showed crossing-over between two maternal chromosomes 21, and in one mosaic case no crossing-over was observed (this case was probably due to an early postzygotic nondisjunction). In the majority of cases (five of six informative families) the proximal marker D21S120 was reduced to homozygosity in the offspring with trisomy 21. The data can be best explained by chromatid translocation in meiosis I and by normal crossover and segregation in meiosis I and meiosis II."
-What are the key differences in oxygen transport patterns between cardiogenic and septic shock patients in this study?,"Oxygen transport in cardiogenic and septic shock. OBJECTIVE: To review clinical studies of oxygen transport in cardiogenic and septic shock. DESIGN: Descriptive and prospective studies. SETTING: University hospital multi disciplinary ICU. PATIENTS: Critically ill cardiogenic and septic shock patients greater than 18 and less than 80 yrs of age. INTERVENTIONS: The responses to volume loading with colloid or crystalloid and infusion of catecholamines are documented with baseline hemodynamic and oxygen transport measurements before and after administration of catecholamines. MEASUREMENTS AND MAIN RESULTS: Nineteen patients in cardiogenic shock were studied. In three patients, invasive systemic mean arterial pressure was greater than 80 mm Hg and cardiac index was greater than 2.0 L/min.m2. In all patients, there were increases in oxygen extraction ratio that averaged 48 +/- 18 (SD) %. However, in 30 septic shock patients, extraction ratio was 24 +/- 2%. In both groups, the response to therapy was an increase in mixed venous oxygen saturation from 54 +/- 16% to 69 +/- 8% in cardiogenic patients (p less than .001) and from 75 +/- 2% to 80 +/- 1% in septic shock (p less than .01). CONCLUSIONS: There are widely differing oxygen transport patterns in cardiogenic and septic shock that may have implications for therapy."
-"What medical condition did the 35-year-old man have, and how was it treated?","Repair of a cerebrospinal fluid perilymph fistula primarily through the middle ear and secondarily by occluding the cochlear aqueduct. A 35-year-old man had a 5-year history of fluctuating hearing loss in his only hearing ear. History and diagnostic tests indicated a perilymph fistula, a diagnosis subsequently confirmed by exploration. Primary and secondary repairs temporarily ameliorated symptoms. A spinal fluid to middle ear fluid pathway was identified by radioactive tracer. A patent cochlear aqueduct indicated on computed tomography scan was found and repaired through a posterior cranial fossa approach. Hearing was preserved, remaining relatively stable during the 2-year follow-up period."
-What are the new therapies for gallstone management that have been developed in the past decade?,New trends in gallstone management. Many new therapies for the management of gallstone disease have been pioneered in the past decade. The object of this review is to equip the surgeon with the answers to all of the questions a patient will ask about gallstone therapy; the review is therefore didactic as well as comprehensive.
-What was the main finding regarding pulmonary artery wedge pressure (PAWP) and cardiac performance in patients with aneurysmal subarachnoid hemorrhage?,"Cardiac performance indices during hypervolemic therapy for cerebral vasospasm. The effect of hypervolemic preload enhancement on cardiac performance was systematically analyzed in nine patients following aneurysmal subarachnoid hemorrhage. The patients ranged in age from 34 to 63 years, and none had a history of cardiac disease. Each patient underwent placement of a flow-directed balloon-tipped catheter and the following measurements were taken during hypervolemic therapy: pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), cardiac index (CI), stroke volume index (SVI), and left ventricular stroke work index (LVSWI). After baseline measurements were recorded, hetastarch or plasmanate was infused intravenously at 300 cc/hr. Thermal output determination and pressures were measured every 15 minutes. The PAWP did not correlate in a statistically significant fashion with the CVP in the ranges recorded; however, a statistically significant correlation did exist between PAWP increases and increases in CI, SVI, and LVSWI (p less than 0.01). There was no statistical correlation between PAWP increases above 14 mm Hg and improvement in cardiac performance as evidenced by CI, SVI, and LVSWI measurements. It is concluded that CVP is an unreliable index of cardiac performance during hypervolemic therapy and that, in previously healthy individuals, a PAWP of 14 mm Hg is associated with maximum cardiac performance."
-What were the key histologic and ultrastructural findings observed in the Leeds-Keio prosthetic anterior cruciate ligament after 18 months of implantation?,"Histologic and ultrastructural findings of tissue ingrowth. The Leeds-Keio prosthetic anterior cruciate ligament. A light and electron microscopy investigation was performed on a Leeds-Keio ligament removed because of rupture 18 months after implantation to repair an anterior cruciate ligament. The investigation showed fibrous connective tissue on the plane of the main stress force. There was elastin and adequate vascularization interspersed with Type I collagen fibrils in the area most distant from the ligament. The tissue near the Dacron fibers was highly cellular with a matrix of infrequent, thin collagen fibrils and abundant fine granular material. The growth of the host tissue occurred in and around a Leeds-Keio ligament in response to tensile stresses."
-What surgical technique was used to treat syndactyly with osseous fusion of the distal phalanges?,"Surgical method for treatment of syndactyly with osseous fusion of the distal phalanges. For the interdigital space plasty to correct a syndactyly with fusion of the distal phalanges, we adopted a new operative procedure, covering the exposed distal bone with local rectangular flaps designed transversely on both dorsal and volar surfaces. A full-thickness skin graft from the groin region covers the remaining raw surface. The procedure was performed in six patients, and the flaps measured 6 mm (width) x 12 to 16 mm (length) in four patients, 5 x 15 mm in one patient, and 5 x 18 mm in one patient. Partial necrosis was observed in only one patient, in whom a narrow flap of 5 x 18 mm was used. In the other five patients, however, the results were satisfactory on both external appearance and function during the follow-up period of 3 to 6 years."
-How many patients preferred ultrasound over flexible cystoscopy in the detection of recurrent bladder tumours?,"Flexible cystoscopy compared with ultrasound in the detection of recurrent bladder tumours. A combination of transrectal and transabdominal ultrasound was compared with flexible cystoscopy as a means of detecting recurrent bladder tumours. The study group comprised 50 patients who had previously had rigid cystoscopy. They underwent combination ultrasound in the out-patient department 1 week before flexible cystoscopy. Combination ultrasound identified 25 patients with recurrent tumours and flexible cystoscopy identified 26. Thirty-four patients (68%) preferred ultrasound, 10 (20%) preferred flexible cystoscopy, 3 (6%) preferred general anaesthesia and rigid cystoscopy and 3 (6%) had no preference. The main objection to ultrasound was the use of the transrectal probe."
-What is the key advantage of stab evulsion phlebectomy for treating truncal varicose veins compared to traditional surgical methods?,"Ambulatory stab evulsion phlebectomy for truncal varicose veins. The management of primary varicose veins is evolving. Recovery time, cost, recurrence rate, and cosmesis are critical determinants. Classic ""high ligation"" and ankle-to-groin stripping is expensive, results in a long convalescence, and may produce unacceptable scarring and possible permanent nerve injury. This report describes the technique of stab evulsion phlebectomy performed in an outpatient setting. Under loco-regional anesthesia, and after high ligation, existing tributary and trunk varicosities are evulsed with specially designed hooks. The multiple stab incisions, 1.5- to 3-mm long, are closed with adhesive strips. Fifty-six patients, with 69 involved limbs, have been operated on during the past 9 months. Postoperative pain and complications were minimal. Convalescence was eliminated and all patients immediately resumed normal daily activities. Cosmesis was excellent. This technique is based on hemodynamically accurate principles. It effectively removes all varicosities, eliminates the proximal source of reflux, and disconnects potentially outflowing perforators, yet leaves in situ undamaged trunk veins, which may be used as potential vein grafts."
-What imaging features help distinguish between primary central nervous system lymphoma and toxoplasmosis in AIDS patients?,Primary central nervous system lymphoma versus toxoplasmosis in AIDS. The imaging studies of 16 patients with acquired immunodeficiency syndrome (AIDS) and proved primary central nervous system (CNS) lymphoma were reviewed. All studies included computed tomography (CT); six also included magnetic resonance (MR) imaging. A periventricular lesion was seen in 50% of patients. At least one such lesion exhibited subependymal spread or ventricular encasement in 38%. One-third of lesions in three of five patients who underwent nonenhanced CT were hyperattenuating. Five lesions were at least in part hypointense on T2-weighted MR images. The specificity of these findings was evaluated with a similar review of the imaging studies in 28 patients with AIDS and proved toxoplasmosis. Only 3% of lesions were periventricular. None exhibited subependymal spread or encasement. None were hyperattenuating on nonenhanced CT scans. Similar findings in other CNS lesions in AIDS patients could not be found in the literature. A focal enhancing mass with subependymal spread on CT or MR images and hyperattenuation at nonenhanced CT were the most reliable features in distinguishing between primary CNS lymphoma and toxoplasmosis in AIDS patients.
-What was the predictive accuracy of electrophysiologic localization for single and multiple accessory pathways in this study?,"Predictive accuracy of electrophysiologic localization of accessory pathways. Operative ablation of accessory pathways depends critically on preoperative localization when technical limitations preclude complete intraoperative mapping. To assess the accuracy of localization, 345 patients undergoing operative ablation were studied; 316 (91.6%) had a single accessory pathway and 29 (8.4%) had multiple accessory pathways. The electrophysiologic study was diagnostically complete and accurate in 294 patients (93%) with a single accessory pathway and 19 (61%) with multiple accessory pathways. A left lateral accessory pathway was most accurately localized with excellent sensitivity (99%) and positive predictive value (98.5%). Diagnostic errors occurred in 33 patients because of 1) incorrect localization (n = 16), 2) failure to detect a second pathway (n = 9), and 3) diagnosis of a second pathway not verified intraoperatively (n = 8). Multiple pathways were more prevalent in the group with errors (33.3% vs. 5.8%, p = 0.0001), as were unidirectional pathways (48.5% vs. 24.3%, p = 0.003). It is concluded that preoperative localization of accessory pathways is sufficiently accurate to allow intraoperative mapping to be brief and focused."
-What method is proposed for estimating the optimum ventricular catheter length when intraoperative ultrasound is not available?,Index for optimum ventricular catheter length. Technical note. The optimum length of a ventricular catheter to be placed in a particular patient may be difficult to determine when either intraoperative ultrasound is not available or considerable time has elapsed between the diagnostic computerized tomography scan and the operation. An index for estimating ventricular length based on the head circumference of the individual is described. This method was tested clinically and proved to be successful.
-What did the population-based study reveal about the influence of gender on multiple sclerosis susceptibility in sibling pairs?,"The influence of gender on the susceptibility to multiple sclerosis in sibships. A population-based study of pairs of relatives (siblings, second- and third-degree) concordant for multiple sclerosis did not show an excess of like-sexed pairs. In addition, data on human lymphocyte antigen typing for sibling pairs concordant for multiple sclerosis did not find an increase in haplotype sharing for like-sexed pairs. These data do not support the notion that sex-related factors influence multiple-sclerosis susceptibility in families."
-How did intermittent negative pressure ventilation (INPV) affect oxygen and carbon dioxide levels in COPD patients with severe hypercapnic respiratory failure?,"Intermittent short-term negative pressure ventilation and increased oxygenation in COPD patients with severe hypercapnic respiratory failure. With the aim of testing a method that allows increasing concentrations of oxygen to be administered to patients with severe hypoxemia and hypercapnia while avoiding the risk of increasing respiratory acidosis, we studied 17 male patients with advanced chronic obstructive pulmonary disease (COPD) and severe hypercapnic respiratory failure. During 6 h and on one day only, all patients were given intermittent negative pressure ventilation (INPV) together with oxygenation starting at a concentration of 24 percent and increasing to 30 percent. Using this procedure, it was possible to raise arterial PaO2 to safe levels (from 47.2 +/- 3 mm Hg to 61.5 +/- 6 mm Hg, p less than 0.001) without increasing hypercapnia, and a significant drop in PaCO2 levels (from 74.4 +/- 9 mm Hg to 65.6 +/- 12 mm Hg, p less than 0.005) was even observed. One hour after INPV ended, the mean values of PaO2, PaCO2, oxygen saturation, and pH were also significantly better than prestudy values. We conclude that INPV and oxygen therapy with increasing oxygen flow could constitute an alternative option to intubation and mechanical ventilation in cases of severe hypercapnic respiratory failure due to advanced COPD."
-What are the key findings regarding ventricular tachycardia in patients with sarcoidosis based on this study?,"Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device. The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin."
-How did the researchers detect DNA sequence polymorphisms in the retinoblastoma susceptibility locus?,"Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. The discovery of RFLPs and their utilization as genetic markers has revolutionized research in human molecular genetics. However, only a fraction of the DNA sequence polymorphisms in the human genome affect the length of a restriction fragment and hence result in an RFLP. Polymorphisms that are not detected as RFLPs are typically passed over in the screening process though they represent a potentially important source of informative genetic markers. We have used a rapid method for the detection of naturally occurring DNA sequence variations that is based on enzymatic amplification and direct sequencing of genomic DNA. This approach can detect essentially all useful sequence variations within the region screened. We demonstrate the feasibility of the technique by applying it to the human retinoblastoma susceptibility locus. We screened 3,712 bp of genomic DNA from each of nine individuals and found four DNA sequence polymorphisms. At least one of these DNA sequence polymorphisms was informative in each of three families with hereditary retinoblastoma that were not informative with any of the known RFLPs at this locus. We believe that direct sequencing is a reasonable alternative to other methods of screening for DNA sequence polymorphisms and that it represents a step forward for obtaining informative markers at well-characterized loci that have been minimally informative in the past."
-"What were the age-adjusted incidence rates of amyotrophic lateral sclerosis for males and females in Harris County, Texas, during the period 1985-1988?","Incidence and prevalence of amyotrophic lateral sclerosis in Harris County, Texas, 1985-1988. The incidence of amyotrophic lateral sclerosis was determined in Harris County, Texas, for the period 1985 through 1988. Amyotrophic lateral sclerosis cases were ascertained from four sources: area neurologists, hospitals, death certificates, and the Muscular Dystrophy Association. The age-adjusted incidences of 1.27 per 100,000 person-years in males and 1.03 per 100,000 person-years in females were lower than recent rates in the northern US, Canadian, and northern European studies but higher than rates in southern European studies. Comparisons with other recent incidence studies show less uniformity in occurrence of amyotrophic lateral sclerosis, in both the overall rates and in the age- and sex-specific patterns, than was suggested by mortality studies. The incidence of amyotrophic lateral sclerosis among blacks and whites was similar. Hispanic males had incidences similar to white males, although a deficit of female Hispanic cases was found in Harris County. The prevalence of amyotrophic lateral sclerosis peaked in the 65- to 74-year age group at 33 per 100,000 population among males and 19 per 100,000 population for females."
-What unique histological feature was observed in the liver of this peripheral T-cell lymphoma case?,"Extensive hepatic granulomas associated with peripheral T-cell lymphoma. A case of T-cell lymphoma presenting with marked hepatosplenomegaly and extensive hepatic granulomas is described. A 55-yr-old female experienced long-term liver damage showing histological triaditis with atypical lymphoid cell infiltration and erythrophagocytosis. The patient developed marked hepatosplenomegaly and eventually died of respiratory failure. Neither systemic lymphadenopathy nor hematological disorder was noted until her death. Autopsy revealed small atypical lymphoid cells positive for T-cell marker, as well as extensive infiltration of generalized organs, including the liver, spleen, and lungs. As a result of diffuse proliferation of atypical lymphoid cell admixed with variable reactive cells, mainly at the T-zone, the lymph nodes underwent effacement of normal architecture; however, the peripheral sinuses and the fibrous capsule remained relatively well preserved. These histological features were consistent with a diagnosis of peripheral T-cell lymphoma (PTL). It is interesting to note that there were numerous epithelioid granulomas admixed with a small number of atypical lymphoid cells within the hepatic parenchyma. The atypical lymphoid cells may be responsible for the granulomatous reaction in the liver. To our knowledge, there have been no other reported cases of PTL that presented with numerous epithelioid granulomas confined to the liver."
-What are the most practical and useful techniques for diagnosing perivalvular extension of infection in patients with infectious endocarditis?,"Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review."
-What is microvascular angina and how does it differ from traditional coronary artery disease?,"Microvascular angina. Cardiovascular investigations regarding pathophysiology and management. A significant minority of patients with chest pain who undergo cardiac catheterization are found to have angiographically normal coronary arteries. Over the past 25 years, several studies have shown that a subset have demonstrable abnormalities in coronary flow and cardiac function; however, only a minority of these patients have convincing evidence for myocardial ischemia during stress, and alternative mechanisms have been explored to explain the frequent and debilitating symptoms of pain experienced by the majority of these patients undergoing study. Abnormal visceral nociception appears to be a fundamental abnormality in this population, whether or not demonstrable abnormalities in coronary flow or cardiac function can be demonstrated."
-What is Bazex syndrome and what are its key characteristics?,"Bazex syndrome (acrokeratosis paraneoplastica). An analytic review. Bazex syndrome (acrokeratosis paraneoplastica) is characterized by a psoriasiform eruption that favors acral sites and has been associated with an underlying malignancy in all reported cases. Of the 93 patients in this series, 89 were male with a mean age of 60 +/- 8.5 years. Squamous cell carcinomas of the head and neck and squamous cell tumors of unknown primary with cervical lymph node metastases were the most commonly associated neoplasms, suggesting that the factor(s) responsible for the development of the syndrome are relatively specific for tumors of the upper aerodigestive tract. The cutaneous lesions were erythematous to violaceous in color and had associated scale; the most frequently observed sites of involvement were the ears, nose, hands, and feet, including the nails. In 63% of the cases, the cutaneous lesions preceded the initial symptoms or diagnosis of the tumor by an average of 11 months (range, 1-72) and, in general, the eruption was resistant to a variety of topical treatments. Occasionally, a reappearance of the papulosquamous lesions signaled the recurrence of the tumor (6 cases) or the appearance of skin lesions coincided with the development of metastatic disease (3 cases). In 91% (64/70) of the patients, the skin eruption either improved significantly following treatment of the underlying malignancy or did not improve in the setting of persistent tumor. However, even when all of the skin lesions cleared, the nail dystrophy often persisted. Fifteen of the patients developed vesicles, bullae, and crusts in addition to papulosquamous lesions. Possible explanations include the formation of an epidermal-dermal split via a bullous lichen planus-like mechanism, or the coexistence of two diseases; i.e., acrokeratosis paraneoplastica plus either porphyria cutanea tarda, bullous pemphigoid, or epidermolysis bullosa acquisita. One possible explanation for the development of the characteristic cutaneous eruption is an immune reaction, humoral or cellular, directed against a common antigen present on the tumor and the normal skin. Alternatively, tumor production of a keratinocyte growth factor such as TGF-alpha may be involved in the induction of the psoriasiform skin lesions."
-How do phalloidin and antamanide help mitigate the side effects of interleukin-2 (IL-2) in rats?,"Attenuation of IL-2-induced multisystem organ edema by phalloidin and antamanide. Interleukin 2 (IL-2) is a potent cytokine with diverse effects, including the ability to stimulate lymphocyte differentiation into cells capable of lysing tumor. Its therapeutic efficacy is limited because of side effects such as breakdown of the microvascular barrier and edema. Control of the microvascular barrier is in part regulated by endothelial cell cytoskeletal contractile proteins. This study tests whether the cyclopeptides that maintain actin filament organization and distribution and reduce macromolecular flux across the endothelial cell junction in vitro would similarly maintain barrier tightness and prevent early edema produced by IL-2 in vivo. Anesthetized rats were treated at 30-min periods with intravenous saline (0.5 ml, n = 41), phalloidin (20 micrograms in 0.5 ml, n = 21), or antamanide, (20 micrograms in 0.5 ml, n = 21), starting 30 min before the 1-h infusion of 10(6) U of recombinant human IL-2 or saline. Six hours after the start of IL-2, there was edema in the saline/IL-2 group, as measured by increased wet-to-dry ratios (W/D) in the lungs, heart, and kidney. With saline/IL-2, bronchoalveolar lavage (BAL) fluid contained an elevated protein concentration and higher plasma thromboxane levels compared with controls. The number of neutrophils sequestered in the lungs was more than twice that of saline controls. Phalloidin significantly attenuated edema in lung and reduced BAL protein leak. Antamanide treatment was as effective in limiting lung and heart edema, but, in contrast to phalloidin, antamanide prevented kidney edema and did not lead to an alteration in the liver W/D. Antamanide also prevented BAL fluid protein leak."
-What is telangiectatic osteosarcoma and how has its prognosis changed over time?,"Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy."
-How do the contractile responses to norepinephrine and caffeine differ in mesenteric arteries from normotensive and hypertensive rats?,"Agonist-sensitive calcium stores in arteries from steroid hypertensive rats. The present study characterizes cellular calcium stores that are sensitive to norepinephrine and caffeine in arteries from deoxycorticosterone acetate hypertensive rats. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. In calcium-free solution, phasic contractile responses to norepinephrine (5.9 x 10(-9) to 5.9 x 10(-6) M), but not caffeine (0.3-30 mM), were greater in hypertensive arteries. D-600, a calcium channel blocker, or removal of the endothelium did not alter phasic contractions to norepinephrine or caffeine. In contrast, contractions to both norepinephrine and caffeine were inhibited by ryanodine, a drug that depletes calcium from intracellular stores. An inhibitor of phospholipase C (2-nitro-4-carboxyphenyl N,N-diphenylcarbamate) attenuated contractions to norepinephrine but not those to caffeine. The augmented response to norepinephrine in hypertensive rats did not occur early after implantation of the mineralocorticoid, suggesting that this vascular change may not play a role in the development of high blood pressure in this experimental model. The augmented response to norepinephrine was reduced in mineralocorticoid-treated rats maintained on a low sodium diet, and these rats had blood pressures in the normotensive range. Because contractile responses to caffeine were not enhanced in arteries from hypertensive rats, we conclude that the cellular store for calcium is not enlarged compared with that in normotensive arteries. In contrast, the mobilization of calcium from cellular stores by norepinephrine is augmented in mineralocorticoid hypertension. This augmented response may be linked to altered phospholipase C activity and thus to an augmented action of inositol trisphosphate that releases calcium from intracellular sites."
-What were the key differences observed between patients with Hodgkin's disease above the diaphragm (ADHD) and below the diaphragm (BDHD) in this study?,"Stage I and II subdiaphragmatic Hodgkin's disease. From January 1971 to December 1986, 521 patients with Hodgkin's disease were evaluated and treated at the Yale University School of Medicine or one of its close affiliates. A total of 258 patients had pathologic stage (PS) I or II disease, with 239 patients having Hodgkin's disease above the diaphragm (ADHD) and 19 patients having Hodgkin's disease below the diaphragm (BDHD). A comparison of patients with BDHD versus patients with ADHD showed that patients with BDHD were older (mean age, 42 versus 28 years of age, P = 0.005), were initially seen less often with nodular sclerosis subtype (32% versus 77%, P = 0.00001), and had a higher male: female ratio (2.8 versus 1.2, P = 0.12). Ten patients with BDHD (53%) had positive findings at staging laparotomy (0 of 4 clinical stage [CS] IA patients and 10 of 15 (67%) CS II patients). Radiation therapy alone was the initial treatment of choice for 74% of patients with BDHD versus 94% of the patients with ADHD. There was no statistical difference in the overall survival or relapse-free survival rates for patients with BDHD versus ADHD (10-year survival rates, BDHD = 73% and ADHD = 81%). However, patients with BDHD who initially had intra-abdominal disease had a statistically significant increase in death rate (60%) due to Hodgkin's disease compared with patients with BDHD who initially had only peripheral nodal disease (0%). Treatment recommendations for patients with BDHD should be tailored to the specific clinical presentation of each patient. For most PS IA/IIA patients initially seen with peripheral nodal disease, radiation therapy alone is a successful treatment program. However, combined modality therapy should be the treatment of choice for patients with BDHD initially seen with intra-abdominal disease."
-How does high-resolution contact B-scan echographic imaging help in diagnosing and assessing anterior hyaloidal fibrovascular proliferation?,"Echographic diagnosis of anterior hyaloidal fibrovascular proliferation. High-resolution contact B-scan echographic imaging of the ciliary body and peripheral retina was performed on five eyes with anterior hyaloidal fibrovascular proliferation and media opacity by means of a wide (58 degrees) scanning arc. This technique determined the circumferential and anteroposterior extent of peripheral traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation, which correlated highly with findings at subsequent vitrectomy. Final visual acuity of 20/400 or better was achieved in the two eyes (50%) with more limited peripheral traction detachment. In the presence of media opacity, anterior echographic imaging may allow early detection of traction retinal detachment associated with anterior hyaloidal fibrovascular proliferation and may be useful in characterizing the severity of this condition."
-How reliable is pulse oximetry in assessing collateral blood flow to the hand compared to Doppler ultrasound?,"Pulse oximetry compared with Doppler ultrasound for assessment of collateral blood flow to the hand. Ischaemic injury to the hand after arterial cannulation is a rare but well documented complication and routine testing of the adequacy of collateral circulation is widely advocated. The widespread availability of the pulse oximeter in the operating theatre. its applicability in circumstances where the patient is unable to cooperate, and its dependence on pulsatile blood flow suggest that this device could potentially be usefully applied to the assessment of collateral blood flow. The reliability of the pulse oximeter to detect the presence or absence of collateral circulation was prospectively compared to Doppler ultrasound in 109 hands from 64 adult patients. Nine hands demonstrated inadequate ulnar collateral flow, one hand demonstrated inadequate radial collateral flow and a persistent median artery was found in one hand. In all patients the results of pulse oximeter testing (probe placed on the thumb correlated precisely with the results obtained with the Doppler device (probe located over the lateral aspect of the superficial palmar arch). These results demonstrate pulse oximetry to be a reliable method of assessing collateral blood flow to the hand before arterial cannulation."
-What was the range of ionized calcium levels observed in patients with chronic lung disease?,"Ionized calcium in blood: studies on patients with pulmonary disease. A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01-1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults."
-"What were the key findings regarding macrophages, microglia, and HLA-DR antigens in the fetal and infant brain tissue samples?","Macrophages, microglial cells, and HLA-DR antigens in fetal and infant brain. Immunohistochemical reactions for macrophages, microglia, and HLA-DR antigens were tested on frozen sections of necropsy brain tissue from 20 fetuses and infants ranging in age from 18 weeks' gestation to 8 months post term. No primary central nervous system disease was present but there were four cases of sudden infant death syndrome (SIDS). Macrophages were detected in all the samples studied and were located in the germinal matrix zone, in perivascular spaces throughout the brain, and in the leptomeninges and subependymal layer. Well differentiated microglia were present in all cases examined after 35 weeks' gestation and less well ramified forms were seen at earlier stages of gestation. HLA-DR antigens were detected on a small number of macrophages, chiefly in a perivascular location, in all but three cases. The fewest reactive cells and the weakest reactions occurred in the youngest fetuses. One case of SIDS showed increased foci of microglia in perivascular white matter: this case and one other case of SIDS were the only cases with well ramified microglia that expressed HLA-DR antigens. These findings may be relevant to an understanding of local immune responses in fetal brain infections, including human immunodeficiency virus infection."
-What are the advantages of using mandibular reconstruction plates for jaw reconstruction?,"Immediate mandibular replacement using reconstruction plates. Mandibular reconstruction at the time of tumor resection remains a surgical dilemma. Primary reconstruction allows for immediate reconstitution of mandibular form and function. Various methods have been attempted, but none enjoys uniform success. With advances in the field of microvascular surgery have come numerous options in replacing these defects. These procedures, however, require special surgical teams and are associated with an increase in operative time as well as morbidity at the donor site. An alternative method involves the use of mandibular reconstruction plates to bridge the defect between segments. This review focuses on 19 patients whose jaws were reconstructed in this fashion. Although not free of complications, mandibular plate reconstruction offers the advantages of (1) lack of donor site morbidity, (2) expediency, (3) excellent mandibular contour, and (4) the ability to reconstruct the condyle when necessary. The technique, results, and complications associated with this procedure are discussed."
-What is the key advantage of the modified craniofacial approach described in the context for ethmoid and anterior skull base surgery?,"Modified approach for ethmoid and anterior skull base surgery. The use of combined craniofacial resection is well established for tumors of the ethmoid bone and the anterior aspect of the base of the skull. Mobilization of the medial fronto-orbital ridge improves the transbasal approach and can be performed with a monobloc bone flap. We describe an en bloc bifrontal craniotomy including the supraorbital ridges and the nasal bones. This provides a wider angle of approach to the anterior aspect of the base of the skull than any other method and avoids retraction of the frontal lobes. This type of bone flap procedure can be performed after a wide periosteal dissection in the coronal area of the scalp alone, without facial skin incision."
-What were the hemodynamic effects of a 24-hour milrinone infusion in patients with severe heart failure?,"Effects of a twenty-four-hour milrinone infusion in patients with severe heart failure and cardiogenic shock as a function of the hemodynamic initial condition. The systemic and pulmonary arterial hemodynamics of 40 patients with severe congestive heart failure were determined during a 24-hour infusion of milrinone (0.5 micrograms/kg/min) after a loading dose of 50 micrograms/kg. A subgroup (n = 18) with severe cardiac pump dysfunction and three patients in cardiogenic shock were analyzed separately; their hemodynamic response was compared with that of the total group (n = 40). After 15 minutes of intravenous therapy with milrinone, the total group (n = 40) showed an increase of 65% in cardiac index; in the subgroup (n = 18) cardiac index increased by 94% after 15 minutes and by 106% after 30 minutes. Likewise, pulmonary capillary wedge pressure decreased after 30 minutes in both the total group (n = 40) and the subgroup (n = 18). The heart rate showed an overall tendency to decrease. The systolic blood pressure tended upward and remained statistically unchanged in the total group, whereas in the subgroup in which pressure was initially low, there was an increase in the systolic pressure after 1 hour and a further increase after 24 hours. Mean arterial pressure also rose in this subgroup. The early improvement in all measured hemodynamic parameters was sustained throughout the 24-hour infusion period. Development of tolerance was not observed, nor were any clinically symptomatic side effects or symptomatic arrhythmias. Thus intravenous milrinone is a safe medication for the rapid and prolonged improvement in hemodynamics, specifically in patients with severely restricted cardiac pumping function."
-How do different antihypertensive agents impact serum lipid profiles?,"Antihypertensive therapy: taking lipids into consideration. Several antihypertensive agents have been found to influence serum lipid profiles. Thiazide diuretics increase total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and slightly reduce high-density lipoprotein (HDL) cholesterol. Most beta-blockers substantially increase triglycerides and lower HDL cholesterol. Angiotensin-converting enzyme inhibitors, calcium channel antagonists, alpha- and beta-blockers, and beta-blockers with intrinsic sympathomimetic activity are lipid neutral. alpha 1-Antagonists (e.g., terazosin and prazosin) lower total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improve total cholesterol/HDL ratios. Observational epidemiologic studies indicate that the lipid effects of antihypertensive agents are large enough to account for substantial differences in the predicted incidence of coronary heart disease. Combination therapy with the alpha 1-antagonist terazosin plus either thiazides or beta-blockers also ameliorates the adverse lipid effects of these agents used alone. A reasonable approach to managing the lipid problems often associated with hypertension is to advise a cholesterol-lowering, low-sodium diet and weight reduction and to select drugs that alone or in combination do not adversely affect lipid profiles."
-What is the dissociation index (DI) and how does it help in assessing brainstem maturation in infants with cyanosis during feeding?,"Phasic sleep components in infants with cyanosis during feeding. Although brainstem immaturity has been postulated as one of the pathogenesis underlying cyanosis during feeding (CDF), there has been no widely accepted physiologic parameter that reflects brainstem function. We recently proposed that the dissociation index (DI), one of the phasic sleep parameters, is a reliable and quantitative sleep parameter for assessing brainstem maturation during early infancy. In the present study, we evaluated brainstem impairment in infants with CDF using phasic sleep components. Polysomnographies were obtained for 12 infants with CDF who were equally divided into 2 groups: one had or subsequently experienced apparent life-threatening events or sudden infant death syndrome (ALTE-SIDS group) and the other did not (CDF group). Rapid eye movement density and the number of gross movements (body movements, including the trunk, lasting greater than or equal to 2 sec) in the patients were identical to those in the controls. In the CDF group, the decrease of the average DI value from the controls was significantly less than the decrease in the ALTE-SIDS group. CDF may be a mild expression of brainstem immaturity. DI appears to be useful when evaluating infants with cyanosis during feeding."
-What was the surgical success rate for patients with and without asthma in this study of intranasal ethmoidectomy?,"The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present."
-Does chronic triamterene therapy lead to folate deficiency in humans?,"Chronic diuretic therapy with moderate doses of triamterene is not associated with folate deficiency. The diuretic drug triamterene has previously been shown to be a competitive inhibitor of folate absorption in the rat intestine (J Lab Clin Med 1986;108:272-6). We therefore investigated whether human subjects who are taking the drug on a long-term basis are at increased risk of folate deficiency. In each of two free-living populations, a study was performed to compare the folate status of triamterene users with those not taking the drug. The first population consisted of 272 elderly individuals not living in institutions who were participants in a nutrition status survey and who were taking a variety of antihypertensive medications; 32 of these individuals were daily users of triamterene. The hemoglobin concentration, red blood cell (RBC) count, and mean corpuscular volume (MCV) values were not significantly different between the triamterene users and nonusers. The female triamterene users had a slightly higher serum folate level than the female nonusers (p less than 0.04); a similar pattern was observed among the men, although the difference was not statistically significant. The second population consisted of 27 individuals attending a hypertension clinic; 18 subjects were taking 50 to 150 mg of triamterene per day and nine were taking antihypertensive drugs other than triamterene. The hemoglobin concentration, RBC count, MCV, serum folate values, and RBC folate values were found to not differ significantly between the triamterene users and the hypertensive controls (p greater than 0.05). These data suggest that chronic triamterene administration in individuals not living in institutions, at the doses examined in this study, is not associated with indications of folate deficiency."
-What is the relationship between left atrial myxoma and pulmonary haemosiderosis in the given medical case?,Pulmonary haemosiderosis associated with left atrial myxoma. A patient with features suggesting pulmonary haemosiderosis was found to have a myxoma. The pulmonary lesion cleared after excision of the tumour.
-How effective was hematoporphyrin derivative (HPD) in identifying early colonic cancer in rats?,"Fluorescence localization of early colonic cancer in the rat by hematoporphyrin derivative. Laser excitation of hematoporphyrin derivatives (HPD) localizing in tumors of the tracheobronchial tree and bladder is useful in the identification and treatment of those tumors. A comparable utility for HPD in the endoscopic localization of colonic tumors may be possible. In this study the ability of HPD to identify 1,2 dimethylhydrazine (DMH) induced colon cancer in rats is evaluated. A total of 111 rats were studied with HPD. Sixty-nine rats received weekly injections of DMH (20 mg/kg) and 42 received injections of the vehicle alone. Twenty-four hours after the intravenous injection of 5 mg/kg of HPD, 18 DMH-induced tumors were identified by visual fluorescence using excitation by either a blue light (390-436 nm) or an argon laser (488 and 514 nm). This represented 100% of the visually or microscopically detected tumors. Seventy-five fluorescent areas were noted that did not contain evidence of cancer. The majority (63) of false positive areas contained lymphoid follicles. All but 2 false positive areas (73/75, 97%, p less than .001) were seen in DMH-treated animals, suggesting that they were an artifact of DMH treatment. HPD fluorescence did not identify microscopic dysplasia. We conclude that HPD fluorescence is an effective method of identifying early colonic cancer and may have a potential clinical role in patients at high risk for colorectal cancer."
-Does preoperative and postoperative anticoagulant medication improve the short-term outcomes of lower-limb arterial thromboembolectomy?,"Acute lower limb ischemia: failure of anticoagulant treatment to improve one-month results of arterial thromboembolectomy. A prospective randomized multi-center study. The value of short-term anticoagulant treatment in improving the early outcome in patients operated on for acute lower-limb ischemia has been debated and so far unproven. In this prospective randomized multi-center study, 188 such patients were randomized on admission, either to preoperative and postoperative anticoagulant medication (AC group, n = 94) or no anticoagulant treatment during the first month after surgery (O group, n = 94). Background factors were evenly distributed in the two groups, and 89% of the cases were considered as embolic. Analysis on an intention-to-treat basis showed no differences in outcome after 30 days. Good results, survivors who had amputation, and patients who died in the two groups are given respectively: AC group, 61%, 9%, 30%; O group, 65%, 11%, 24%. The results were similar in the two treatment groups also if only patients with a cardiac source of embolism were analyzed. Local bleeding complications were more common in the AC group (17% vs 2%, p less than 0.01). It is concluded that preoperative and early postoperative anticoagulant medication should not be routinely administered since such treatment is unlikely to improve the short-term results of lower-limb arterial thromboembolectomy while bleeding complications increase. The possible value of late (beyond 1 month) long-term anticoagulant treatment remains to be studied."
-How does intraperitoneal contrast material improve the detection of peritoneal metastases compared to standard CT examinations?,"Intraperitoneal contrast material improves the CT detection of peritoneal metastases. The preoperative detection of peritoneal metastases from gynecologic malignancies is difficult; in particular, CT often fails to detect peritoneal implants. This study was designed to determine if the administration of intraperitoneal iodinated contrast media would increase the CT detection of such peritoneal metastases. Prospectively, both standard and intraperitoneal contrast-enhanced CT studies of the abdomen and pelvis were performed in 16 patients with suspected gynecologic tumors. All patients then underwent operative staging, with the location and number of metastases documented. The intraperitoneal enhanced CT studies were more sensitive in the detection of peritoneal metastases than standard CT examinations. Whereas routine CT detected peritoneal metastases in seven (64%) of 11 patients with surgically proved implants, the intraperitoneal enhanced CT studies detected peritoneal metastases in all 11 patients. Depending on the specific intraperitoneal compartments involved, the sensitivity of intraperitoneal enhanced CT in the detection of peritoneal metastases was two- to fourfold greater than that of standard CT examinations. Our results suggest that intraperitoneal enhanced CT is superior to standard CT in the detection of peritoneal metastases."
-What was the restenosis rate for patients with unstable angina pectoris compared to those with stable angina pectoris after percutaneous transluminal coronary angioplasty (PTCA)?,"Higher recurrence rate after coronary angioplasty in unstable angina pectoris. PURPOSE: Recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA) is a significant problem, requiring repeat dilation in about one-third of all treated patients. Various clinical and procedure-related predictors have been proposed. Between 1983 and 1987, 257 patients underwent 322 procedures, where 380 stenoses were attempted. Indications were: stable angina pectoris 73%, unstable angina pectoris 22%, other indication 5%. The primary success rate was defined as a less than 50% remaining postprocedure stenosis. FINDINGS: Repeat angiograms were done for 88% of the initially successful cases, either six months after PTCA or if there was a clinical recurrence. Restenosis was defined as a recurrence of a more than 50% diameter stenosis. The restenosis rate was 33% and was significantly higher (p less than 0.05) for unstable (46%) than for stable angina pectoris (29%). There was a nonsignificant tendency to a higher restenosis rate in the left anterior descending artery than in the other coronary vessels. IMPLICATIONS: The increased restenosis rate seen after PTCA for unstable angina pectoris could be caused by a higher activity in systems affecting the proliferative processes in the smooth muscle cells of the arterial wall, which is thought to form the pathophysiologic basis for restenosis after PTCA."
-How did the nutritional status of patients with left ventricular assist device (LVAD) support change from implantation to cardiac transplantation?,"Nutritional assessment of patients with extended left ventricular assist device support. The nutritional status of nine patients with end-stage heart disease who were supported by a left ventricular assist device (LVAD) for more than 30 days while awaiting cardiac transplantation was evaluated. Nutritional status was indicated by the following scale: 0-2, adequate nourishment; 3-5, moderate malnourishment; greater than 5, severe malnourishment. This scale was based on serial assessments of albumin, transferrin, total lymphocyte count, percentage of ideal body weight, midarm circumference, triceps skinfold, and arm muscle circumference. Each variable was compared with established standards before implantation and before transplantation times and assessed 1 point if less than the normal value and 0 points if within the normal range. At the time of LVAD implantation, 5 patients had a score of 0-2, 3 patients had a score of 3-5, and 1 patient had a score greater than 5. At the time of cardiac transplantation, 7 patients had a score of 0-2, 2 patients had a score of 3-5, and no patients had a score greater than 5. The patients who were able to meet at least 50% of their daily caloric and protein requirements by oral intake alone were noted. At LVAD implantation, only 2 patients (22%) met this requirement; however, 6 patients (67%) met this requirement at the time of cardiac transplantation. All 9 patients underwent cardiac transplantation, and 8 survived. Thus, it appears that extended LVAD support and maintenance of hemodynamic stability allow patients to regain the desire and ability to achieve adequate nutritional status, which may considerably reduce their perioperative transplant risks."
-What rare combination of vascular conditions was observed in the patient described in the context?,"Congenital arteriovenous communications and the development of two types of leaking retinal macroaneurysms. We treated a patient with a rare combination of congenital arteriovenous communications and the development of leaking macroaneurysms of different types. Initially, leaking macroaneurysms developed in the shunt area of the arteriovenous communication; later, a preexistent fusiform macroaneurysm in the afferent arteriole of the congenital communication started leaking. Because exudates and fluid from the leaking macroaneurysms reached the fovea, laser treatment was performed to obliterate the macroaneurysms. We assume that after obliteration of the macroaneurysms with laser in the shunt area, the increase of hydrostatic pressure on the thin wall of the fusiform aneurysm of the afferent artery led to its leaking. We saw no signs of vascular occlusion after laser treatment."
-What is post-traumatic syringomyelia and how can it develop after a spinal fracture?,"Post-traumatic syringomyelia following uncomplicated spinal fracture. Two cases of post-traumatic syringomyelia presenting 10 and 41 years after spinal injuries that had caused lumbar vertebral fractures but no lasting neurological deficits are reported. In both patients the caudal end of the syrinx cavities, as shown by MRI, corresponded to the level of the previous vertebral fractures. Patients presenting with post-traumatic syringomyelia after uncomplicated spinal fracture are very rare, and the significance of the past history of spinal trauma may be overlooked."
-How effective was epidermal growth factor in treating chronic wounds in this study?,"Stimulation of healing of chronic wounds by epidermal growth factor. We evaluated the effect of topical epidermal growth factor treatment on healing of chronic wounds in a prospective, open-label, crossover trial. Five males and four females who ranged in age from 40 to 72 years (average 57 +/- 9 years) were enrolled. Four patients had adult-onset diabetes mellitus, two had rheumatoid arthritis, two had old burn scars, and one had a failed abdominal incision. The average duration of the ulcers prior to treatment with epidermal growth factor was 12 +/- 5 months (range 1 to 48 months). Following failure of the wounds to heal with conventional therapies, including debridement, skin graphs, and vascular reconstruction, wounds were treated twice daily with Silvadene alone for periods ranging from 3 weeks to 6 months. No evidence of healing was observed in any of the patients' wounds during Silvadene treatment, and patients were crossed over to twice a day treatment with Silvadene containing 10 micrograms epidermal growth factor per gram. Wounds of eight patients healed completely with epidermal growth factor-Silvadene treatment in an average of 34 +/- 26 days (mean +/- SD, range 12 to 92 days) and did not reoccur for periods ranging from 1 to 4 years. One patient failed therapy. These results suggest that topical treatment of chronic wounds with epidermal growth factor may stimulate healing."
-What were the cognitive outcomes for elderly patients with major depression after receiving tricyclic antidepressants or electroconvulsive therapy (ECT)?,"Cognitive outcome following tricyclic and electroconvulsive treatment of major depression in the elderly. OBJECTIVE: This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. METHOD: Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months. RESULTS: Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified. CONCLUSIONS: The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population."
-What were the main findings of the study comparing different anesthetic regimens in pediatric strabismus surgery?,"Effect of propofol on the incidence of postoperative vomiting after strabismus surgery in pediatric outpatients. Vomiting is a common problem after strabismus surgery in pediatric outpatients. We compared the effects of propofol with and without N2O and droperidol to the effects of a conventional regimen consisting of halothane-N2O-droperidol on the recovery characteristics and the incidence of postoperative emesis after strabismus surgery in 120 ASA physical status 1 or 2 children. After induction of anesthesia with halothane-N2O, patients were randomly assigned to one of four groups. Group A (control) received halothane, 66% N2O, and droperidol 75 micrograms.kg-1; group B, propofol 2 mg.kg-1 bolus followed by infusion of 160 microgram.kg-1.min-1; group C, propofol (as in group B) and 66% N2O; and group D, propofol (as in group B), 66% N2O (as in group C), and droperidol 75 micrograms.kg-1. Patients in group B had more episodes of intraoperative oculocardiac reflex responses than patients in group A, but had shorter times to extubation, oral intake, ambulation, and discharge, as well as a lower incidence of postoperative emesis (P less than 0.05). The addition of N2O to the propofol anesthetic regimen (group C) was associated with an increased incidence of emesis (P less than 0.05), whereas the addition of droperidol to the propofol-N2O regimen (group D) did not affect the incidence of emesis compared to the other three groups. We conclude that maintenance of anesthesia with a total intravenous regimen using propofol results in a more rapid recovery and less postoperative emesis than with a halothane-N2O-droperidol regimen."
-What surgical technique was used to address a persistent filtration bleb leak?,Donor scleral graft patching for persistent filtration bleb leak. We report effective and efficient sealing of a persistent leak in a cystic filtration bleb by applying a full-thickness donor scleral patch.
-What is the significance of finding occult submucosal duodenal-wall microgastrinomas in patients with Zollinger-Ellison syndrome?,"Zollinger-Ellison syndrome. A new look at regression of gastrinomas. Of 44 patients with the Zollinger-Ellison syndrome treated at our institution, nine appeared to have undergone ""regression"" of their gastrinomas. Six of the nine patients had sporadic gastrinomas and became permanently eugastrinemic following excision of nodal metastases and total gastrectomy (n = 4), antrectomy (n = 1), or pancreatoduodenectomy (n = 1) (mean survival, 13 years). The other three patients had Zollinger-Ellison syndrome as part of the multiple endocrine adenopathy type 1 syndrome and became temporarily eugastrinemic after total gastrectomy (mean survival, 11 years). Occult submucosal duodenal-wall microgastrinomas (mean size, 3.0 mm) were found to have been serendipitously excised in four patients. Long-term follow-up of these nine patients, as well as of six other patients described in the literature, demonstrates that excision of occult duodenal-wall gastrinomas provides a plausible explanation for the phenomenon of apparent regression of primary gastrinomas and the eugastrinemia that may follow total gastrectomy."
-How do neonates respond hormonally and metabolically to operative stress?,"Hormonal and metabolic response to operative stress in the neonate. It is evident from this review that newborns, even those born prematurely, are capable of mounting an endocrine and metabolic response to operative stress. Unfortunately, many of the areas for which a relatively well-characterized response exists in adults are poorly documented in neonates. As is the case in adults, the response seems to be primarily catabolic in nature because the combined hormonal changes include an increased release of catabolic hormones such as catecholamines, glucagon, and corticosteroids coupled with a suppression of and peripheral resistance to the effects of the primary anabolic hormone, insulin."
-What was the main finding of the study regarding neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities?,"Continuation of normal neurobehavioural development in fetuses with absent umbilical arterial end diastolic velocities. Detailed serial observations of behaviour were made in four singleton fetuses who were very small for dates and who had persistently absent umbilical artery end diastolic velocities for 2 to 9 weeks duration. All were born preterm for deteriorating maternal disease, and in two there were additional fetal indications for delivery. Behavioural comparison with 45 low risk singleton fetuses, at comparable gestations, revealed no significant differences in the development of behavioural cycles, the proportion of time spent in quiet cycles, or the amount of fetal breathing. None of the fetuses developed an abnormal heart rate pattern. We conclude that prenatal neurobehavioural development may continue apparently unimpaired in the presence of absent umbilical artery end-diastolic velocity of several weeks duration. Long term data of infant outcome are necessary before the clinical significance of this can be assessed."
-What are the potential complications of untreated abdominal aortic thrombosis?,"Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function."
-What were the most common neuro-ophthalmologic signs observed in AIDS patients in this study?,"Neuro-ophthalmologic signs of AIDS: 50 patients. In 50 hospitalized patients with acquired immunodeficiency syndrome, signs of central eye movement limitation (28 cases) were most common. Peripheral eye movement limitations (18), abnormalities of vision (18), and abnormal spontaneous eye movements (15) occurred with about equal frequency. Meningitis (17), usually due to lymphoma (8) or Cryptococcus (8), was the usual cause of peripheral nervous system involvement, while toxoplasmosis (18) was more common than lymphoma (4) or presumed viral causes (8) in producing CNS dysfunction. The midbrain and pretectal (8) were affected about as often as the pontine tegmentum (9), but rostral brainstem lesions appeared to be the result of toxoplasmosis (4) or lymphoma (3), whereas a viral etiology was the presumed cause of most caudal stem involvement."
-What specific changes in medullary catecholaminergic neurons were observed in Parkinson's disease brains compared to normal human brains?,"Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease. Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation."
-What was the main objective of the study comparing ivermectin and diethylcarbamazine (DEC) in patients with bancroftian filariasis?,"Efficacy of ivermectin for control of microfilaremia recurring after treatment with diethylcarbamazine. I. Clinical and parasitologic observations. We compared the efficacy of a single dose of ivermectin with that of a standard course of diethylcarbamazine (DEC) for the control of microfilaremia in 60 patients with bancroftian filariasis who had developed recurrent microfilaremia after each of three or more prior treatments with DEC. The study was done as a randomized, double-blind trial. Complete, but in some cases, transient clearance of microfilaremia was observed in both treatment groups. At one year, recurrent microfilaremia was present in seven patients treated with ivermectin and in five treated with DEC. Pretreatment levels of microfilaremia were significantly higher in patients who relapsed within one year after treatment than in those who remained amicrofilaremic. Side effects with both treatments were common, but mild. Febrile reactions were more frequent in the ivermectin group; localized reactions consistent with a flare-up of acute filarial disease occurred mostly in the DEC group. We conclude that ivermectin is an effective and practical alternative to DEC for treatment of recurrent microfilaremia due to bancroftian filariasis."
-Does using a drain after cholecystectomy improve patient outcomes?,"Cholecystectomy is safer without drainage: the results of a prospective, randomized clinical trial. Drainage after cholecystectomy remains routine despite the lack of scientific supportive data. Numerous clinical studies in the past have attempted to address this controversy but have failed to resolve the issue for different reasons. These include retrospective design, inclusion of only selected cases, and randomization before surgery. In this study 479 patients undergoing cholecystectomy were randomly allocated to a drainage group (a high-pressure suction drain in Morison's pouch for 48 hours) or a nondrainage group. Randomization was performed at the time of peritoneal closure. All patients undergoing cholecystectomy, both elective and urgent, were included and the operations were performed by all grades of surgeons. There were two deaths from cardiopulmonary causes, both in the drainage group. No patient required reoperation in either group. The incidence of both wound infections (15 vs 5; p less than 0.05) and chest infections (56 vs 19, p less than 0.02) was significantly higher in the drainage group. Three hundred fifty-six patients underwent abdominal ultrasonography 72 hours after surgery. The number of subhepatic fluid collections thus detected was significantly higher in the patients who received a drain (17 vs 6, p less than 0.05). None of these collections was clinically significant. The postoperative hospital stay was longer in the patients with drains (10.3 vs 9.1 days), but this difference failed to reach statistical significance. We conclude from this study that the use of a drain after cholecystectomy serves no useful purpose and is potentially harmful. This practice should be abandoned."
-How can striae of Retzius in dental enamel help in identifying an individual in forensic anthropology?,"Individualization and enamel histology: a case report in forensic anthropology. The cranium of a native Indian child about six years old was found in 1979 near Taseko River, British Columbia, Canada. While the remains matched the report of a child missing for eight years in terms of race, age at death, locale, and elapsed time since death, the cranium and dentition were basically unidentifiable because of the claimed lack of medical or dental history. There was no dental work, and the parents were unknown or dead. We report the presence, in the dental enamel of the primary and secondary dentition, of stress markers, termed striae of Retzius, whose locations correspond well with anecdotal reports and recently discovered medical records which describe the timing of specific episodes of stress. The enhanced probability of personal identification from dental histological stress markers is evaluated."
-What medication was used to manage hypotension during the perioperative period for a patient with idiopathic orthostatic hypotension undergoing coronary artery bypass grafting?,"Idiopathic orthostatic hypotension, midodrine, and anaesthesia. A patient with idiopathic orthostatic hypotension receiving chronic oral midodrine therapy required anaesthesia for coronary artery bypass grafting. A perioperative infusion of phenylephrine was substituted for midodrine, an alpha-2 agonist, enabling hypotension resulting from low systemic vascular resistance to be controlled easily. Anticipated adrenergic receptor denervation hypersensitivity was noted. The only significant perioperative problem was one episode of syncope from orthostatic hypotension during the reambulation period."
-"What medical condition did the patient initially present with, and how was it resolved?","Hemidystonia due to a contralateral parieto-occipital metastasis: disappearance after removal of the mass lesion. A patient presented with left-sided hemidystonia. CT revealed a contralateral parieto-occipital mass lesion compressing the basal ganglia, which were spared by the mass. After microsurgical resection of the tumor, which was verified histologically as a metastasis of a large-cell anaplastic carcinoma, the movement disorder dissolved completely."
-What was the primary finding of this study regarding bradycardia in children with leukemia after sepsis?,"Postsepsis bradycardia in children with leukemia. OBJECTIVE: We observed sinus bradycardia in a small number of children with hematologic malignancies who were recovering from sepsis. Our objective was to define this symptom complex and attempt to delineate its etiology. DESIGN: Retrospective chart review. SETTING: A pediatric ICU in a children's oncology hospital. PATIENTS: Children admitted to the ICU over a 24-month period who developed persistent bradycardia (heart rate less than 5% for age for greater than 1 hr) after an episode of sepsis. MEASUREMENTS AND MAIN RESULTS: Seven children developed postsepsis bradycardia. Six patients had a primary diagnosis of acute myelogenous leukemia and one patient had acute lymphocytic leukemia. All patients had positive blood cultures (Streptococcus mitis, n = 4; Escherichia coli, n = 2; and Klebsiella pneumoniae, n = 1). All seven children were clinically recovering from sepsis when the bradycardia developed. Neither hypotension nor other symptom was associated with the bradycardia. No therapy was given for the bradycardia. Echocardiograms and ECGs were normal in all patients, except for the presence of bradycardia. Bradycardia persisted for 24 to 72 hrs. After that time, heart rates slowly increased to the normal range for age. CONCLUSIONS: We speculate that this syndrome may result from alterations in beta-adrenergic receptor function or an unidentified humoral factor produced by the invading organism or as part of the host's response to sepsis. Prior drug therapy or the underlying illness may predispose to this condition, since all the patients had acute leukemia. As the bradycardia was clinically insignificant, invasive therapeutic or diagnostic strategies were not indicated."
-What potential complication can occur to the pancreas during extracorporeal shock wave lithotripsy (ESWL) for renal calculus fragmentation?,"Shock wave-induced pancreatic trauma. A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury after ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed."
-What was the purpose of the study on recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers?,"The protective efficacy of recombinant hepatitis B vaccine in newborn infants of hepatitis B e antigen-positive-hepatitis B surface antigen carrier mothers. Recombinant hepatitis B vaccine has been shown to be as safe and effective as plasma-derived vaccines. However, its efficacy in the prevention of perinatal infection has not been fully evaluated in an endemic area. We recruited 110 high risk infants born to hepatitis B e antigen-positive-hepatitis B surface antigen (HBsAg) carrier mothers in a study of recombinant vaccine efficacy. They were randomized into 2 groups, A (54 infants) and B (56 infants), to receive 4 doses of vaccine, containing 20 or 10 micrograms of surface antigen, respectively, at 0, 1, 2 and 12 months of age. An additional 60 high risk infants were recruited later (Group C) and received three 20-micrograms doses of vaccine at 0, 1 and 6 months of age. All infants also received a dose (145 IU) of hepatitis B immunoglobulin soon after birth. Sera were collected at 0, 1, 2, 3, 6, 12 and 14 months of age to assay HBsAg and anti-HBs. At 12 months of age the HBsAg carrier rates were 7.4 and 1.8%, in Groups A and B, respectively. In Group C the HBsAg-positive rate was 3.3%. HBsAg was invariably first observed between 0 and 2 months of age. Virtually all noncarrier infants developed substantial titers of anti-HBs at 12 months of age. No serious adverse effect was observed after vaccination."
-What association was found between HLA-DR1 and the development of multiple basal cell carcinomas in southern Australia?,"Multiple basal cell carcinomas and HLA frequencies in southern Australia. An association between HLA-DR1 and the development of multiple basal cell carcinomas was detected in southern Australia. A reduction in HLA-DR4 was found in patients with basal cell carcinoma compared with a local control group. The relative risk for HLA-DR1 was 2.1, which was lower than that for persons in farther countries from the equator."
-What is a coronary arteriovenous fistula and how rare is it?,Successful operation on a coronary arteriovenous fistula in a 74 year old woman. Coronary arteriovenous fistulas are rare and are usually diagnosed in children or young adults. Most are believed to be congenital. A right coronary arteriovenous fistula was first diagnosed in a patient of 74. Despite her age the fistula was successfully operated on and her symptoms were relieved.
-"What were the effects of different interferons (alpha, beta, and gamma) on human melanoma cell lines in terms of proliferation, differentiation, and cell surface markers?","Antitumor activities of interferon alpha, beta, and gamma and their combinations on human melanoma cells in vitro: changes of proliferation, melanin synthesis, and immunophenotype. The antitumor activities of human interferon (IFN) alpha, beta, and gamma alone or in combination were studied on four human melanoma cell lines (StML-11, StML-12, StML-14, and SKMel-28) in various concentrations (1-50,000 IU/ml IFN alpha, 0.1-1000 IU/ml IFN beta, 1-10,000 IU/ml IFN gamma) in vitro. In all experiments IFN beta exhibited the most potent antiproliferative effect of all IFN tested. After 3 d of incubation a 50% growth inhibition was achieved with 20-40 IU/ml for natural IFN beta and with 600-1200 U/ml for recombinant IFN gamma. Substantially higher doses (7,000 to more than 50,000 IU/ml) of recombinant IFN alpha 2a were required to achieve a 50% growth inhibition. A strong synergistic antiproliferative activity resulted from the combination of IFN alpha with IFN gamma and IFN beta with IFN gamma. None of the IFN tested induced terminal differentiation of melanoma cells in vitro. The formation of dendrites was inhibited, and the portion of differentiated cells in vitro was reduced after treatment with IFN in comparison to the untreated controls (untreated controls: 100%; portion of differentiated cells after treatment with IFN alpha: 58%-74%, IFN beta: 48%-96%, IFN gamma: 10%-33%). The melanin synthesis was slightly elevated after treatment with IFN alpha (untreated controls: 100%; after treatment with IFN alpha: 103%-157%, ns.) and decreased significantly after treatment with IFN beta (49%-71%, p less than 0.05) as well as with IFN gamma (80%-88%, ns.). Cell surface markers were modulated varyingly by the IFN: HLA-I antigens were enhanced by all IFN, with IFN beta emerging as the most potent inducer. Only IFN gamma, however, induced a de novo expression of HLA-DR and -DQ antigens and increased the expression of the ICAM-1 molecule and of the melanoma progression marker A.1.43. Possibly, these findings indicate a biologically more aggressive phenotype of melanoma cells."
-What diagnostic technique was used to identify cor triatriatum and pulmonary venous stenosis in this adult case?,Cor triatriatum with isolated pulmonary venous stenosis in an adult: diagnosis with transesophageal two-dimensional echocardiography. The diagnosis of cor triatriatum in an adult was made from routine two-dimensional transthoracic echocardiography. The findings of aliasing and turbulence in the roof of the left atrium suggested pulmonary venous stenosis. A transesophageal echocardiogram defined both the hemodynamic features of nonobstructing cor triatriatum and the presence of isolated pulmonary venous stenosis. The clinical use of transesophageal echocardiography with color flow Doppler in the elucidation of complex anatomic substrate is demonstrated.
-What percentage of mastoid surgeries in children were performed for chronic otomastoiditis in this study?,"Mastoid surgery in childhood. The presenting features and operative findings in 105 patients aged 16 years or less undergoing mastoid surgery are reviewed. In 94% surgery was for chronic otomastoiditis, usually acquired, and associated with cholesteatoma in 64%. Post-operative otorrhoea persisted beyond 6 months in 44% and contralateral disease required some form of surgical procedure in 20%. Post-operative hearing thresholds were improved or unchanged in the majority of patients, most of whom underwent cortical or modified radical mastoidectomy. An improvement in the therapeutic results of mastoid surgery in childhood is clearly necessary, but requires a greater understanding of the aetiology of chronic middle ear disease."
-How does Doppler echocardiography help in monitoring cardiac transplant recipients compared to traditional cardiac biopsy?,"Doppler echocardiography for rejection surveillance in the cardiac allograft recipient. Echocardiography is noninvasive, allows real-time visualization of the heart, and can be performed serially without harmful biologic effects. It is also relatively inexpensive compared with other diagnostic modalities used for cardiac transplant rejection surveillance, such as cardiac biopsy, computed tomography, and magnetic resonance imaging. It is free of the potential complications associated with cardiac biopsy, such as accidental disruption of cardiac valves or chordae tendineae, ventricular septal perforation, introduction of bacteria, and the difficulty of obtaining adequate sampling for effective diagnosis as a result of formation of scar tissue. Unlike biopsy, echocardiography does not cause the patient anxiety and discomfort or use many physician and instrument or laboratory resources. Because the results of echocardiography are available within minutes compared with the hours usually needed for biopsy results, it allows prompt decisions regarding patient clinical care and treatment. In our work to date, echocardiography has not replaced the cardiac biopsy in surveillance of rejection in the cardiac transplant patient, but rather has become a useful adjunct to it. When echocardiographic findings indicate changes characteristic of rejection, biopsies are performed earlier, leading to earlier diagnosis and treatment. Furthermore, when echocardiographic findings are stable and negative for rejection, the number of routine cardiac biopsies performed can be reduced. This article discusses the use of echocardiography in surveillance of the cardiac transplant patient and the ability of echocardiography to augment the biopsy and clinical regimens in assessing cardiac allograft rejection."
-How do different alpha 1-adrenergic receptor blockers affect the incidence of abnormal automaticity in ischemic Purkinje fibers?,"Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype. BACKGROUND. Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101. METHODS AND RESULTS. In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment. CONCLUSIONS. Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment."
-What complications did the 12-year-old girl develop after receiving chemotherapy for osteogenic sarcoma?,"Secondary myelodysplastic syndrome complicating therapy for osteogenic sarcoma. A 12-year-old girl with nonmetastatic osteogenic sarcoma received treatment with doxorubicin, methotrexate, cisplatin, cyclophosphamide, bleomycin, and dactinomycin. She developed unexplained persistent pancytopenia after completion of chemotherapy. Twenty-three months after the initial diagnosis of osteosarcoma an evaluation revealed a bone marrow pattern consistent with the diagnosis of refractory anemia with excess blasts, and karyotype analysis showed characteristic findings of therapy-related myelodysplasia (loss of chromosomes 5 and 7, as well as 12p and 17p deletions). Bone marrow transplantation from an human leukocyte antigen (HLA)-compatible sibling donor was performed 26 months after the diagnosis of the primary malignancy. Although it is unproven that the alkylating agents administered to this patient were responsible for the myelodysplastic syndrome, careful follow-up of osteosarcoma patients who receive alkylating agents is warranted."
-What was the most common gastrointestinal complication in patients who underwent cardiopulmonary bypass surgery?,"Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Thirty-nine gastrointestinal complications occurred in 35 of 4473 patients (0.78 per cent) who underwent surgery involving cardiopulmonary bypass during an 8-year period. The mortality rate when one of these complications occurred was 22 (63 per cent) representing 11.5 per cent of the 191 deaths from all causes in the series. The relative risk of developing a gastrointestinal complication was 1:249 when the heart was not opened, 1:66 when it was and 1:5 after cardiac transplantation. Gastrointestinal bleeding (n = 20) was the most common complication of whom nine (45 per cent) died, followed by intestinal infarction (n = 12) with eight (67 per cent) deaths and acute pancreatitis (n = 6) all of whom died. There was one death after surgery for gastrointestinal bleeding (n = 7). No patient survived bowel infarction without operation but resection was possible in five of the eight who underwent surgery, four of whom survived. The results demonstrate that surgical intervention is not associated with undue mortality but inappropriate conservative therapy is poorly tolerated in this high-risk group."
-How does the pH level affect gastrin secretion from antral G-cells?,"Much ado about gastrin [editorial; comment] The regulation of gastrin secretion from antral G-cells is of major importance in the physiologic control of acid secretion. Gastrin secretion is highly dependent upon gastric intraluminal pH and is inhibited significantly by a pH of less than 3.0. Acute gastric alkalinization greater than pH 6.0 with antisecretory agents such as H2-receptor antagonists or H+/K+ ATPase inhibitors has little impact on fasting serum gastrin levels but promotes an enhanced sustained rise in meal-stimulated gastrin release. Courses of standard therapy with both H2-antagonists and H+/K+ inhibitors cause a significant rise in 24 h integrated plasma gastrin levels that is inversely correlated to the 24-h integrated gastric acidity. The rise in fasting or integrated plasma gastrin levels observed in patients treated with H2-antagonists is small and of unclear clinical significance. Therapy with antisecretory agents leads to earlier ulcer relapse than with other agents. A variety of factors have been proposed to explain the earlier ulcer relapse rate, including secondary hypergastrinemia with rebound acid hypersecretion after discontinuation of the drug. Secondary hypergastrinemia may also lead to tolerance to prolonged courses of H2-antagonists therapy with a decrease in acid inhibition. This may contribute to break-through ulcer recurrence during maintenance H2-antagonist therapy. However, the relative importance of hypergastrinemia and tolerance to H2-antagonists compared with other factors such as baseline gastric acid secretion, smoking status, nonsteroidal anti-inflammatory drug use, and Helicobacter pylori status is difficult to assess."
-What was the purpose of using Indium-111-leukocyte imaging in conjunction with 99mTc-iminodiacetic derivative (IDA) scintigraphy for detecting acute cholecystitis?,"Indium-111-leukocyte imaging in acute cholecystitis. Eleven patients with suspected acute cholecystitis underwent sequential 99mTc-iminodiacetic derivative (IDA) and 111In-white blood cell (WBC) imaging to determine if 111In-WBCs accumulate within an acutely inflamed hemorrhagic gallbladder wall and, thus, could be employed as a reasonable alternative to 99mTc-IDA scintigraphy in detecting acute cholecystitis. Seven patients had surgically confirmed acute cholecystitis. Of these cases, five had a true-positive 99mTc-IDA and 111In-WBC, one an indeterminate 111In-WBC and true-positive 99mTc-IDA, and one a true-positive 111In-WBC and false-negative 99mTc-IDA scan. The remaining four patients did not have acute cholecystitis. All visualized their gallbladder within 1 hr after 99mTc-IDA administration and none had 111In-WBC gallbladder wall uptake. Both 111In-WBC and 99mTc-IDA scintigraphy accurately detected acute cholecystitis: hepatobiliary scintigraphy demonstrated a cystic duct obstruction and 111In-WBC imaging detected the inflammatory infiltrate within the gallbladder wall. The sensitivity and specificity of each was 86% and 100%, respectively."
-What was the overall response rate in the study of recurrent and/or metastatic head and neck squamous cell carcinoma treated with cisplatin-based chemotherapy?,"Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy. One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What was the main objective of the study on visual evoked potentials in migraine patients?,"Visual evoked potentials and background EEG activity in migraine. To investigate whether quantification of the background EEG during a visual evoked potential (VEP) study is of value for the diagnosis of migraine we studied 8 unmedicated migraineurs between attacks, and 10 age-matched controls. Three paradigms were used: the first two concerned pattern-reversal VEPs with different analysis times (500 and 1500 ms), and in the third paradigm the pattern did not reverse. Power spectra were calculated for individual responses, and the delta, theta, alpha and beta areas of the averaged spectra were noted as indicators of background reactivity. Alpha and beta powers were consistently but not significantly higher in the migraine group. The difference was too small to be of value as a diagnostic test. Alpha power was (not significantly) lower in the presence of photic stimulation than in its absence. As this was the case in both groups photic stimulation does not explain the higher alpha powers in the migraine group. We conclude that EEG background activity during the VEP does not distinguish reliably between migraineurs and controls."
-How does interferon-gamma affect the bone marrow response to lipopolysaccharide after hemorrhagic shock?,"Interferon-gamma reverses bone marrow inhibition following hemorrhagic shock. Hemorrhagic shock has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide. Interferon-gamma has been shown to improve the immune response following experimental shock and injury; however, its effect on myelopoiesis is controversial. This study was performed to determine whether treatment with interferon-gamma will improve the bone marrow response to lipopolysaccharide after hemorrhagic shock. Rats subjected to either shock or a sham procedure were allocated into three groups: (1) control rats received no further treatment; (2) lipopolysaccharide-treated rats received saline for 3 days and then were challenged with lipopolysaccharide to stimulate myelopoiesis; and (3) interferon-treated rats received interferon-gamma (7500 U subcutaneously 1 hour after shock and then every day for 3 days) and lipopolysaccharide as in group 2. Serum colony-stimulating factor levels were measured 6 hours and bone marrow white blood cell count and granulocyte-macrophage colony-forming units (CFU-GM) were measured 24 hours following lipopolysaccharide administration. In sham-treated rats, lipopolysaccharide increased CFU-GM 77% compared with controls. In contrast, treatment with lipopolysaccharide decreased CFU-GM 43% following shock. Treatment with interferon-gamma increased CFU-GM in all animals and reversed the decline in CFU-GM seen in shocked lipopolysaccharide-treated animals. Serum colony-stimulating factor levels were unaffected by either shock or interferon-gamma administration. These data demonstrate that interferon-gamma exerts a stimulatory effect on bone marrow following shock and restores the myelopoietic response to lipopolysaccharide."
-What methods were used to study the proliferative activity of neuroendocrine tumours in this research?,"Proliferative activity of neuroendocrine tumours of the gastroenteropancreatic endocrine system: DNA flow cytometric and immunohistological investigations. The proliferative activity of 16 tumour specimens from 13 patients with neuroendocrine tumours of the gastroenteropancreatic endocrine system was studied by DNA flow cytometry and immunohistology for the nuclear Ki67 proliferation antigen. Equivalent results were obtained with both methods, which showed the proliferative activity of gastroenteropancreatic neuroendocrine tumours to be heterogeneous. In four malignant small intestinal carcinoids and one extravisceral carcinoid localised in the retroperitoneum the percentage (index) of proliferating tumour cells as measured by DNA flow cytometry ranged from 2.9 to 36.2% corresponding to low, moderate, or high proliferative activity. In four malignant pancreatic endocrine tumours and their metastases indices ranged from 8.7 to 18.3%, corresponding to low, moderate, or high proliferative activity. In four benign pancreatic endocrine tumours indices ranged from 4.3 to 7.7%, all corresponding to low proliferative activity. This heterogeneity of proliferative activity may in part explain the heterogeneous results reported of chemotherapy treatment. As chemotherapy of tumours is largely affected by favourable cell cycling kinetics, individual diagnostic investigations of the proliferative activity of these neuroendocrine tumours may be of value for identifying patients suitable for this treatment."
-What were the survival rates for different groups of patients undergoing hepatic resection for hepatocellular carcinoma?,"Experience with 225 hepatic resections for hepatocellular carcinoma over a 4-year period. During the past 4 1/2 years, we have performed hepatic resection on 225 patients with hepatocellular carcinoma (HCC). These patients included 171 men and 54 women, whose ages ranged from 29 to 84 years with an average of 60 years. Underlying cirrhosis of the liver was found in 67% of the patients and chronic hepatitis in 27%. Patients undergoing hepatic resection were classified into five groups according to curability as follows: Group A, resection of the tumor-bearing segment and one additional segment; Group B, complete resection of the tumor with more than 1.0 cm free surgical margin; Group C, complete resection of the tumor with less than 1.0 cm free surgical margin; Group D, incomplete resection of the tumor; Group E, surgical approach for advanced HCC with tumor thrombi in the main trunk or the first branch of the portal vein and/or the inferior vena cava, with multiple daughter nodules in both lobes and with tumor recurrence. The number of patients in Groups A, B, C, D, and E was 12 (5%), 83 (37%), 58 (26%), 14 (6%) and 58, (26%), respectively. There were 4 deaths (2.4%) among the 167 patients in Groups A to D within 30 days after operation and 12 deaths (20.7%) in Group E. The 3-year survival rate of Groups A, B, C, D, and E was 100%, 74%, 21%, 0%, and 35%, respectively."
-How did tamoxifen therapy affect the incidence of contralateral breast cancer in postmenopausal breast cancer patients during the randomized trial?,"Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer."
-What are the key differences between B-cell and T-cell types of clear-cell immunoblastic lymphoma (IBLC) in terms of morphologic and clinical characteristics?,"Immunoblastic lymphoma with abundant clear cytoplasm. A comparative study of B- and T-cell types. The morphologic, phenotypic, molecular genetic, and clinical features of 34 cases of clear-cell immunoblastic lymphoma (IBLC) are described. Sixteen cases were of B-cell type (IBLC-B) and 18 cases were of T-cell type (IBLC-T). There were no significant differences in the morphologic characteristics of the neoplastic cells in the two types, although IBLC-B was less likely to be polymorphic than IBLC-T. Interfollicular proliferation, a higher mitotic rate, infiltration by eosinophils, and an increase in capillary-sized blood vessels were also features of IBLC-T, whereas necrosis and fibrosis were more extensive in IBLC-B. Patients with IBLC-B were predominantly female, whereas those with IBLC-T were predominantly male. The mean age was 62 years for those with IBLC-B and 46 years for those with IBLC-T. Patients with IBLC-B usually had lower-stage disease, but there was no significant difference in survival rate between those with IBLC-B and those with IBLC-T. Although most cases of IBLC have been considered to be of peripheral T-cell origin, the authors conclude that IBLC-B is more common than previously considered and that clear-cell morphologic characteristics are not a reliable indicator of T-cell type."
-What was the estimated reduction in death rate and recurrence rate for patients treated with levamisole in this melanoma study?,"Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guerin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma."
-How do the intrarenal hemodynamic parameters differ between the stenotic and contralateral kidneys in patients with renovascular hypertension?,"Glomerular hypertension in renovascular hypertensive patients. Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Forty patients with essential hypertension and 40 patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for effective renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as afferent arteriolar resistance (RA), efferent arteriolar resistance (RE) and glomerular hydrostatic pressure (PG) in each kidney. Normal values of intrarenal hemodynamic parameters were obtained in 24 normotensive subjects without ureteral catheterization, assuming each kidney had the half function of both kidneys. Systemic mean arterial pressure did not differ between essential and renovascular hypertension (141 +/- 3 vs. 148 +/- 3 mm Hg). Effective renal plasma flow and glomerular filtration rates were decreased in the stenotic kidney of RVH (98 +/- 8, 24 +/- 2 ml/min/m2), while increased in the contralateral kidney (195 +/- 11, 48 +/- 2), compared with the right kidney of essential hypertension (162 +/- 8, 33 +/- 1). Although effective renal plasma flow rate was not different from normal (191 +/- 8), glomerular filtration rate was significantly higher in the contralateral kidney of RVH than in normal (38 +/- 1). RA was elevated due to the stenotic lesion in the stenotic kidney (28,500 +/- 1,900 dyns.sec.cm-5), while the elevation in the contralateral kidney (10,800 +/- 600) was less than in the right kidney of essential hypertension (14,900 +/- 1,200). RE (5,800 +/- 300) in both kidneys of RVH was higher than in the right kidney of essential hypertension (4,500 +/- 200)."
-What is the significance of recognizing graft-vs-host disease-like histology in small intestinal biopsy specimens from patients with common variable immunodeficiency?,Small intestinal lesion resembling graft-vs-host disease. A case report in immunodeficiency and review of the literature. We report graft-vs-host disease-like histology in a small intestinal biopsy specimen that was obtained from a patient with common variable immunodeficiency and related T-cell defect. We include findings from immunohistochemical studies and follow-up information. Review of the literature yielded only a small number of histologically documented cases of this lesion without previous bone marrow transplantation. Awareness of this clinicopathologic entity is important in the interpretation of gastrointestinal biopsy specimens.
-What was the maximum tolerated dose of CPT-11 in this Phase I study of non-small-cell lung cancer treatment?,"Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance."
-How did the number of preoperative chemotherapy courses affect tumor necrosis and surgical outcomes in patients with osteosarcoma?,"Increased survival, limb preservation, and prognostic factors for osteosarcoma. Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery."
-What is a mesenchymoma of the chest wall and how rare is it in children?,"Mesenchymoma of the chest wall in children. Benign chest wall mesenchymoma in children is an extremely rare disease. Only 20 patients have been reported in the world literature. We report a chest wall mesenchymoma in a 2-year-old boy who was admitted to the hospital after a routine chest roentgenogram showed a mass in the right upper chest wall. The patient was asymptomatic. Clinical examination was negative, but chest roentgenograms and computed tomography showed a mass in the right upper chest wall involving the third rib. A 2 x 2 x 1.5-cm tumor was excised totally with partial resection of the third rib. The histology of the lesion corresponded to a mesenchymoma (hamartoma) of the chest wall. Our patient has been followed up for 8 years without recurrence."
-What was the primary treatment approach for chiasmal and hypothalamic gliomas in infants and children during the study period?,"Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease."
-What is the significance of the prolonged postischemic ventricular dilatation observed in the 99mTc MIBI scan?,"Transient prolonged postischemic ventricular dilatation documented by 99mTc MIBI scan. We describe two cases of prolonged postischemic ventricular dilatation during myocardial scintigraphy with 99mTc MIBI, the new perfusion tracer that has only negligible redistribution. Ventricular dilatation, caused by true chamber dilatation and/or subendocardial ischemia, was still present over two hours after the induced ischemic episode, suggesting a prolonged duration of such a commonly believed fleeting scintigraphic finding."
-What was the main purpose of the clinical study involving lidoflazine in cardiac arrest survivors?,"A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. Brain Resuscitation Clinical Trial II Study Group BACKGROUND. Abnormalities of cellular calcium homeostasis have been implicated in the pathophysiology of postischemic encephalopathy. Calcium-entry-blocking drugs inhibit the influx of calcium into cells and have been shown to mitigate postischemic encephalopathy in animal models. METHODS. Five hundred twenty patients with cardiac arrest who remained comatose after the restoration of spontaneous circulation were randomly assigned to receive three doses of lidoflazine, an experimental calcium-entry blocker, or a placebo and were followed for six months. Four patients were lost to follow-up. Treated patients received an intravenous loading dose (1 mg per kilogram of body weight) of lidoflazine and two subsequent doses (0.25 mg per kilogram) 8 and 16 hours after resuscitation. The investigators were blinded to treatment assignment. RESULTS. There was no statistically significant difference between the lidoflazine group (n = 259) and the placebo group (n = 257) in the proportion of patients who died during the six-month follow-up (82 vs. 83 percent), who survived with good cerebral recovery (15 vs. 13 percent), or who survived with severe neurologic deficit (1.2 vs. 1.9 percent). Analysis of the best level of recovery achieved at any time during follow-up also did not show a difference between the treatment groups: 24 percent of those given lidoflazine and 23 percent of those given placebo recovered good cerebral function (normal or only moderately disabled cerebral performance) at some time. CONCLUSIONS. The administration of lidoflazine after cardiac arrest was not found to be beneficial. Our data do not support the routine use of this calcium-entry-blocking drug in comatose survivors of cardiac arrest."
-What is an ileal neobladder and what makes it an optimal bladder substitution technique?,"The ileal neobladder. The ileal neobladder in many respects approximates the theoretically ideal continent urinary diversion. The technique, while more technically demanding than the performance of the standard ileal loop diversion, is not difficult, particularly for surgeons used to performing radical retropubic prostatectomies. The ileal neobladder appears to approximate most closely the optimal bladder substitution. Although currently feasible only in males, future considerations could conceivably involve urologists working with their colleagues in gynecology and colorectal surgery to extend the benefits of bladder substitution using the ileal neobladder to selected patients having cystectomy for associated gynecologic or colorectal malignancies."
-What was the surgical success rate for patients with and without asthma in this study of intranasal ethmoidectomy?,"The intranasal ethmoidectomy: an experience with 1,077 procedures. A series of 1,077 intranasal ethmoidectomies (825 with sphenoid sinusotomies) was performed in 600 patients over a 15-year period at The Mount Sinai Medical Center. The technique is a modification of the classical operation originally proposed by Yankauer. The rate of significant complications was 1.1%. A subset of 90 patients underwent 166 procedures and were followed an average of 3.5 years. The patients were analyzed according to whether the disease was focal or diffuse, infectious or polypoid, and whether asthma was present. The surgical success rate was 88% in nonasthmatics, but dropped to 50% in asthmatic patients despite total sphenoethmoidectomy. This underscores the importance of this condition as a biological modifier of surgical prognosis. Accordingly, a system of classification of sinus diseases is proposed based upon disease extent and type and whether asthma is present."
-What conservative treatment method was used to manage vesicovaginal fistulas in the described cases?,Conservative treatment of vesicovaginal fistulas by bladder drainage alone. We describe 4 cases of conservative management of vesicovaginal fistulas occurring as a complication of abdominal and vaginal hysterectomy. In all cases treatment involved simple bladder drainage for periods ranging from 19 to 54 days. At follow-up all patients remained dry. Such spontaneous closure of vesicovaginal fistulas following adequate bladder drainage has not been previously reported.
-How did early captopril administration affect infarct expansion and left ventricular segment length in patients with acute myocardial infarction?,"Effects of early captopril administration on infarct expansion, left ventricular remodeling and exercise capacity after acute myocardial infarction. In a double-blind study, 99 patients (82 men, age range 40 to 75 years) with acute myocardial infarction (AMI) were randomly assigned to receive captopril or placebo. Treatment began within 24 hours of admission. Serial echocardiographic measurements of endocardial segment lengths and left ventricular (LV) volumes, and ejection fractions were obtained. The 2 groups were matched at baseline except for an excess of previous AMI in the placebo group (13 of 50 vs 2 of 49 patients, p = 0.002). The increase in anterior segment length, from baseline to 2 months, was significantly less in the captopril than in the placebo group (2.8 +/- 1.6 vs 10.4 +/- 2.4mm, 95% confidence interval [CI] -13.5 to -1.7, p = 0.01). The increase in posterior segment length was also less in the captopril group, but the difference was not significant (3.2 +/- 1.2 vs 7.0 +/- 1.8mm, 95% CI -8.0 to 0.5, p = 0.08). Fewer patients in the captopril group demonstrated increases in segment length greater than 2 standard deviations of the measurement error (14 of 70 [20%] vs 29 of 72 [40%] patients, p = 0.009). In patients with anterior AMI, the infarct-containing anterior segment length increased by 4.5 +/- 2.3 mm in the captopril versus 12.4 +/- 3.1 mm in the placebo group (95% CI -15.7 to -0.2, p = 0.046), and fewer patients in the captopril group demonstrated infarct expansion (6 of 20 [30%] vs 13 of 21 [62%] patients, p = 0.04)."
-How can AIDS prevention programs help in controlling the spread of hepatitis B virus in sub-Saharan Africa?,"How AIDS forces reappraisal of hepatitis B virus control in sub-Saharan Africa For developing countries the cost-benefit of vaccination in the control of hepatitis B virus (HBV) infection is great since the acute infection is generally subclinical and the benefit is the prevention of small numbers of cases of cirrhosis and hepatocellular carcinoma. Since the pattern of HBV infection in Africa is such that, compared with south-east Asia, infection occurs later in childhood and spread is horizontal rather than vertical, investigation of the method of spread of HBV may result in a means of control other than by vaccination. In the meantime, because of the overlap in the means by which HBV and human immunodeficiency virus (HIV) are spread, it could be worthwhile taking advantage of existing AIDS prevention programmes to educate people about how to avoid both HBV and HIV infections."
-What are the key characteristics of pulmonary angiitis and granulomatosis syndromes in terms of clinical presentation and radiologic features?,"Pulmonary angiitis and granulomatosis. The presentation of a patient with multiple pulmonary nodules with or without cavitation and often with signs of a multisystemic vasculitis should suggest one of the pulmonary angiitis and granulomatosis syndromes. The five conditions traditionally considered together in the category of pulmonary angiitis and granulomatosis differ widely in their cause and pathogenesis and are more appropriately considered as variants or relatives of other processes. The radiologic features of this group of diseases, however, are similar, and it is useful to still consider them together. Table 1 summarizes the radiologic features of these conditions."
-How does core temperature affect splanchnic sympathetic nerve activity in rats during environmental heating?,"Splanchnic sympathetic nerve activity and circulating catecholamines in the hyperthermic rat. The mechanisms responsible for the initial rise in splanchnic vascular resistance with environmental heating are controversial, and those responsible for the subsequent fall in splanchnic resistance in the severely hyperthermic animal are unknown. Thus we examined the effect of environmental heating on plasma catecholamine concentration, splanchnic sympathetic nerve activity (SNA), and select blood chemistries. In one study, 25 male Sprague-Dawley rats (270-300 g) were assigned to one of five groups on the basis of their core temperature (Tc, 37, 39, 41, 43, or 44 degrees C) at death. Heart rate (HR), mean arterial pressure (MAP), and Tc were monitored during heat stress under alpha-chloralose anesthesia (12.5 mg.ml-1.h-1). At each predetermined Tc, an aortic blood sample was drawn and analyzed for mean plasma concentration of norepinephrine (NE), epinephrine (E), Na+, K+, and lactate. From 41 to 43 degrees C, NE and E rose significantly, and the animals became hyperkalemic and lactacidemic. In a separate study, we quantitated SNA from the greater splanchnic nerve during heat exposure of artificially respired animals anesthetized with pentobarbital sodium (50 mg/kg). MAP, splanchnic SNA, and Tc were recorded. Tc was elevated from 37.0 +/- 0.12 to 41.3 +/- 0.18 degrees C in 70 min by increase of ambient temperature to 38 degrees C in an environmental chamber. Splanchnic SNA was 54 +/- 8 spikes/s at a Tc of 37 degrees C and increased significantly as Tc exceeded 39 degrees C (P less than 0.05)."
-How does clonidine affect blood pressure and hemodynamic responses differently in normal subjects compared to tetraplegic patients?,"Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action. BACKGROUND. Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated. METHODS AND RESULTS. The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors. CONCLUSIONS. Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension."
-What were the treatment methods used for prostatic cancer in the study involving 63 patients?,"Morbidity of modified pelvic lymphadenectomy and radiotherapy for prostatic cancer. The records of 63 patients treated by pelvic lymphadenectomy and radiotherapy at the University of Tennessee, Memphis, Baptist Memorial Hospital of Memphis, and the Memphis Veterans Affairs Hospital were reviewed. Of those patients, 45 received external beam radiation therapy to the prostate while 16 were treated by Iodine-125 implantation. Two patients had only staging lymphadenectomy. The incidence of postoperative and late complications were analyzed."
-How did the application of a smooth Teflon clip to the inferior vena cava affect the incidence of pulmonary embolism in patients undergoing radical cystectomy?,"Application of smooth Teflon clip to inferior vena cava during radical cystectomy to prevent postoperative pulmonary embolism. Between 1976-1986, a smooth Teflon clip was applied to the inferior vena cava of 56 patients who underwent radical cystectomy for bladder cancer. The purpose of the clip is to narrow the lumen of the inferior vena cava so that large emboli will be trapped and thus prevented from reaching the lungs. These 56 patients were compared with a group of 26 historical controls who underwent radical cystectomy without application of such a clip between 1967-1976. One patient (1.8%) whose vena cava was clipped had a pulmonary embolus which was fatal. Four (15.4%) of the 26 control patients had postoperative pulmonary emboli, the embolic event being fatal in 3 (11.5%). Application of the smooth Teflon clip to the inferior vena cava significantly lessens the incidence of pulmonary embolism following radical cystectomy."
-Who was Paul Broca and what significant medical procedure did he perform in 1871?,"Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization."
-What makes coronary restenosis a significant challenge in interventional cardiology?,"Coronary restenosis: what have we learned from angiography? Coronary restenosis remains a major problem for interventional cardiology not only by virtue of its frequency, but also because of the current inability to prevent it. Symptomatic status and non-invasive evaluation have been used to study restenosis, but both lack specificity and sensitivity, particularly in patients with multivessel disease. Angiography remains the reference standard. Several arbitrary definitions have been used, some related to visual estimates of coronary stenosis and others to quantitative angiographic techniques. In another approach, linear modeling is used to assess minimal luminal diameter of lesions on restudy. Although angiographic studies have been essential in the study of restenosis, questions concerning the underlying mechanism and pathophysiology remain. The development of animal models that closely resemble human restenosis should allow evaluation of pathophysiologic mechanisms and development of new strategies to prevent the problem."
-What are the main sources of mortality data for shigellosis in developing countries?,"Mortality due to shigellosis: community and hospital data. Almost all fatal cases of shigellosis occur in developing countries, and data on mortality are generally compiled from three sources: investigations of epidemics caused by Shigella dysenteriae type 1, surveillance of endemic diarrheal disease, and reports from hospitals. Attack rates during epidemics of dysentery due to infection with S. dysenteriae type 1 have ranged from 1% to 33%, and case-fatality rates have ranged from 1% to 7%. In Matlab, a rural district in Bangladesh, most diarrhea-related deaths and approximately 25% of all deaths among children 1 through 4 years of age are attributable to dysentery. In 1984, an epidemic of dysentery was associated with a 42% increase in the death rate in that age group. At the Dhaka Treatment Centre of the International Centre for Diarrhoeal Disease Research, Bangladesh, the fatality rate for 970 inpatients with shigellosis was 11% in 1988, with most deaths occurring among malnourished children who were infected with Shigella flexneri. Control of mortality from shigellosis will require prevention of epidemic S. dysenteriae type 1 disease and endemic S. flexneri infections in children who live in countries with a high prevalence of malnutrition."
-How does diclofenac affect the healing of gastroduodenal mucosal lesions according to the study?,"Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. The effects of the water-soluble and delayed-release formulations of a nonsteroidal antiinflammatory drug, diclofenac, on the healing of gastroduodenal mucosal lesions were compared in a double-blind, double cross-over, placebo-controlled endoscopic study conducted in 14 healthy volunteers. Severe endoscopic lesions (petechiae, erosions, ulcers, and esophageal candidiasis) were found only in the group taking the soluble formulation of diclofenac (P less than 0.05 vs placebo). The endoscopic healing of biopsies at one week was delayed by both preparations in comparison to placebo (P less than 0.05 vs placebo). Neither formulation produced significantly more histological inflammation or minor endoscopic lesions (erythema, red striae) than placebo. Both formulations were equally well tolerated and produced no more symptoms than placebo. This study suggests that soluble diclofenac acts topically to delay gastroduodenal healing and produce gastroduodenal injury; it thus provides a model for future studies of the production, perpetuation, and healing of peptic lesions."
-What is auriculotemporal syndrome (ATS) and how does it relate to temporomandibular joint (TMJ) surgery?,"Auriculotemporal syndrome following the preauricular approach to temporomandibular joint surgery. Forty-seven joints in 28 patients were examined 4 months to 10 years after temporomandibular joint (TMJ) surgery via a modified preauricular approach. Many patients had undergone multiple procedures. None of the patients had any subjective or objective evidence of auriculotemporal syndrome (ATS), although patients in previous studies with more extensive incisions have demonstrated ATS. It was concluded that ATS is an unlikely complication following TMJ surgery. A small incision without an oblique superior extension may further reduce the risk."
-How does left ventricular hypertrophy (LVH) impact cardiovascular health and what role do calcium channel blockers play in managing this condition?,"Left ventricular hypertrophy: impact of calcium channel blocker therapy. Left ventricular hypertrophy (LVH) of the concentric type is the classic cardiac adaptation to sustained arterial hypertension. Data from the Framingham cohort have shown that patients with LVH have a severalfold higher risk of sudden death, acute myocardial infarction, and other cardiovascular morbidity than those with normal hearts. Common sequelae of LVH are ventricular ectopy, impaired ventricular contractility, myocardial ischemia, and decreased left ventricular filling. The benefits of antihypertensive therapy should not be limited to lowering arterial pressure, but should extend to preventing or reducing target organ damage. A variety of antihypertensive agents, such as calcium channel blockers, angiotensin-converting enzyme inhibitors, antiadrenergic drugs, and, to a lesser extent, beta blockers, have been shown to reduce LVH and to improve left ventricular filling. We have shown that calcium channel blockers diminish ventricular ectopy in parallel with the reduction of LVH, whereas antihypertensive therapy with diuretics neither reduced LVH nor suppressed ventricular ectopy, although it lowered arterial pressure to a similar extent. Whether or not these cardiac changes with antihypertensive therapies will improve cardiovascular morbidity and mortality in patients with LVH remains to be documented."
-What was the unusual finding in this patient's case that led to a pathological confirmation during nephrectomy?,"Intrarenal pancreatic cyst. A case report of intrarenal true cyst of the pancreas is presented. The patient presented with flank pain. Her diabetes and hypertension were well-controlled. The cause of the pain was presumed to be a cystic renal mass, which proved to be of pancreatic origin only after the pathologic confirmation from the nephrectomy specimen."
-How has the understanding and diagnosis of preeclampsia changed over time according to the given context?,"Preeclampsia as the great impostor. In contrast with a generation ago when preeclampsia was misdiagnosed as medical or surgical disease unrelated to pregnancy, today's diagnostic errors are those that consider surgical and medical problems as either pregnancy-induced hypertension or as the hemolysis, elevated liver enzymes, and low platelet count syndrome. Eleven case histories are presented of significant medical or surgical problems that were initially diagnosed as hemolysis, elevated liver enzymes, and low platelet count syndrome or pregnancy-induced hypertension. The incorrect diagnosis of medical-surgical cases during pregnancy often meant that appropriate therapy was delayed and that the rate of iatrogenic prematurity was increased."
-What unique medical technique was used to manage a through-and-through knife injury of the aortic arch in this case report?,"Artificially induced ventricular fibrillation in the management of through-and-through penetrating wounds of the aortic arch: a case report. Case report of a 28-year-old woman in whom a through-and-through knife injury of the aortic arch is presented. The hemorrhage could not be brought under control by conventional means and was handled by artificially induced temporary electric fibrillation of the heart, direct suture, and immediate defibrillation. The patient made an uneventful recovery."
-How does profound cerebral hypothermia (Ttm less than 10 degrees C) compare with deep hypothermia (15 degrees C) in terms of neurologic outcomes after circulatory arrest in dogs?,"Profound hypothermia (less than 10 degrees C) compared with deep hypothermia (15 degrees C) improves neurologic outcome in dogs after two hours' circulatory arrest induced to enable resuscitative surgery. Deaths from uncontrollable hemorrhage might be prevented by arresting the circulation under protective hypothermia to allow resuscitative surgery to repair these injuries in a bloodless field. We have shown previously that in hemorrhagic shock, circulatory arrest of 60 minutes under deep hypothermia (tympanic membrane temperature, Ttm = 15 degrees C) was the maximum duration of arrest that allowed normal brain recovery. We hypothesize that profound cerebral hypothermia (Ttm less than 10 degrees C) could extend the duration of safe circulatory arrest. In pilot experiments, we found that the cardiopulmonary system did not tolerate arrest at a core (esophageal) temperature (Tes) of less than 10 degrees C. Twenty-two dogs underwent 30-minute hemorrhagic shock (mean arterial pressure 40 mm Hg), rapid cooling by cardiopulmonary bypass (CPB), blood washout to a hematocrit of less than 10%, and circulatory arrest of 2 hours. In deep hypothermia group 1 (n = 10), Ttm was maintained at 15 degrees C during arrest. In profound hypothermia group 2 (n = 12), during cooling with CPB, the head was immersed in ice water, which decreased Ttm to 4 degrees-7 degrees C. The Tes was 10 degrees C in all dogs during arrest. Reperfusion and rewarming were by CPB for 2 hours. Controlled ventilation was to 24 hours, intensive care to 72 hours. In the 20 dogs that followed protocol, best neurologic deficit scores (0% = normal, 100% = brain death) at 24-72 hours were 23% +/- 19% in group 1 and 12% +/- 8% in group 2 (p = 0.15). Overall performance categories and histologic damage scores were significantly better in group 2 (p = 0.04 and p less than 0.001, respectively). We conclude that profound cerebral hypothermia with CPB plus ice water immersion of the head can extend the brain's tolerance of therapeutic circulatory arrest beyond that achieved with deep hypothermia."
-How does the location of the sample volume affect the transmitral filling measurements in pulsed Doppler echocardiography?,"Dependency of the pulsed Doppler-derived transmitral filling profile on the sampling site. In previous reports that evaluated pulsed Doppler transmitral filling, the sampling site has varied; we examined the effect of the sample volume location on Doppler measurements. Studied were 97 patients: 58 with normal echocardiograms, 20 with mitral regurgitation, and 19 with miscellaneous cardiac diseases. Transmitral filling was recorded at the mitral anulus and at the left atrial and left ventricular (LV) sides of the mitral tips. As the sample volume was moved from the mitral anulus to the LV side, the peak velocity and time-velocity integral of early diastole increased (40.6 +/- 13.8 versus 59.0 +/- 19.0 cm/sec, 5.26 +/- 1.65 versus 8.35 +/- 2.37 cm; p less than 0.001) as did those of late diastole (48.7 +/- 11.5 versus 57.5 +/- 17.0 cm/sec, 3.48 +/- 0.97 versus 4.59 +/- 1.39 cm; p less than 0.001). The late-to-early diastolic peak velocity and time-velocity integral ratios and the late-to-total diastolic time-velocity integral ratio decreased (1.33 +/- 0.51 versus 1.06 +/- 0.41, 0.71 +/- 0.24 versus 0.58 +/- 0.19, 0.40 +/- 0.09 versus 0.36 +/- 0.08; p less than 0.001). The dependency of these indices on the sampling site was in the same degree in all three groups. However, the peak filling rate normalized to mitral stroke volume (4.71 +/- 1.43 versus 4.63 +/- 1.32 l/sec; p = NS) was not influenced by the sample volume location; thus this parameter may be more reliable for assessing LV filling."
-Is anticoagulation completely contraindicated in hemorrhagic cardioembolic stroke?,"Hemorrhagic cardioembolic stroke: is anticoagulation absolutely contraindicated? Hemorrhagic cerebral embolism should not be considered an absolute contraindication to immediate low-dose systemic anticoagulation. Low levels of anticoagulation may give some protection from recurrent embolism while minimizing the risks of intracranial bleeding. Until further studies are available, these decisions must be made on a case-by-case basis, supported by limited scientific information."
-What are the key advantages of laparoscopic cholecystectomy compared to conventional cholecystectomy?,"Laparoscopic cholecystectomy: 111 consecutive cases. Laparoscopic cholecystectomy removes the gallbladder through three or four puncture wounds in the abdominal wall. The technique reduces the recuperative time to full activity, from as long as 4 wk to as little as 3 days, compared with conventional cholecystectomy. We herein present our initial experience with this procedure. In this series of 111 laparoscopic cholecystectomies, there were no mortalities and only one morbidity. Thirty-nine patients (35%) had a history of prior abdominal surgery. Fourteen underwent laparoscopic lysis of adhesions. Intraoperative cholangiograms were performed in 24 patients (21%), demonstrating choledocholithiasis in three. Two of the three patients underwent postoperative endoscopic retrograde cholangiopancreatography (ERCP); in the other, laparoscopic common bile duct exploration was performed. In each case, the common bile duct (CBD) was completely cleared of stones. Incidental laparoscopic appendectomy was also performed in three patients. The average time for completion of laparoscopic cholecystectomy in cases of chronic cholecystitis was 40 min. If the gallbladder was acutely inflamed, the procedure took a mean of 126 min. This series had a higher percentage of patients (19%) with acute cholecystitis then previously reported; therefore, the 2% conversion rate in this series emphasizes the broad applicability of the technique. The average length of stay in the hospital was 1.4 days, and patients returned to work in about 7 days."
-How did infection and malnutrition affect liver glutathione and cytochrome P450 levels in the experimental rat study?,"Liver glutathione and cytochrome P450 activity in experimental infection: study of the relative effects of infectious stress and malnutrition. OBJECTIVE: To study the effects of infection and malnutrition on liver glutathione and cytochrome P450 (P450) in rats. DESIGN: Controlled experimental groups (12 groups). ANIMALS: Adult male Sprague-Dawley rats. INTERVENTIONS: Experimental endocarditis, pyelonephritis, or peritonitis were caused. Controls included free-fed rats and sham-operated rats, pair-fed to infected animals. Infection was verified by tissue culture. Rats were killed 3 days (acute infection) or 10 days (chronic infection, except endocarditis) after the induction of infection. RESULTS: Sham rats had lower liver weights, liver/body weight, and liver glutathione values than controls. Infected rats had larger liver weights and liver/body weight ratios and liver glutathione content than shams, and larger liver/body weight ratios than controls (acute infection). Infected rats had lower P450 values than both shams and controls. CONCLUSION: The malnutrition associated with infection caused decreased liver weight and glutathione content. Infection increased the liver weight, and liver glutathione content, but caused severe reduction in liver P450. If the same finding is true in infected patients, it could have consequences for the management of such patients."
-"What is the significance of the ""Metsovo lung"" phenomenon in Greece?","Metsovo lung outside Metsovo. Endemic pleural calcifications in the ophiolite belts of Greece. Endemic PCs and high incidence of malignant mesothelioma from household use of asbestos have been reported in Metsovo in northwestern Greece (""Metsovo lung""). In the present study, we present similar findings in six more areas of Greece. Like Metsovo, all these areas are located within ophiolite belts. Like Metsovo, material similar to ""Metsovo whitewash"" has been used for various domestic uses. Asbestos fibers (chrysotile, antigorite and tremolite) were found in three of the six areas. Also, in two, MPM has been diagnosed. These findings suggest that ""Metsovo lung"" occurs in several areas of Greece and has similar etiology and epidemiology."
-How does the radionuclide technique (VEST) help in detecting silent myocardial ischemia during balloon angioplasty?,"Validation of continuous radionuclide left ventricular functioning monitoring in detecting silent myocardial ischemia during balloon angioplasty of the left anterior descending coronary artery. Silent myocardial ischemia has been inferred from transient ST-segment depression during continuous electrocardiographic monitoring. Recently, continuous ambulatory monitoring of left ventricular (LV) function using a radionuclide technique (VEST) has demonstrated episodes of significant silent LV dysfunction in the absence of electrocardiographic changes. To validate the demonstration of silent LV dysfunction with this technique, 12 men were studied during percutaneous transluminal coronary angioplasty. A total of 18 left anterior descending coronary artery balloon inflations were performed. Balloon inflations at 8 +/- 2 atm (4 to 10 atm) lasted 70 +/- 16 seconds. Seventeen of 18 inflations were associated with a decrease in LV ejection fraction greater than 0.10. Mean LV ejection fraction decreased from 0.53 +/- 0.08 to 0.28 +/- 0.11 (p less than 0.0001). In contrast, there was pain in only 10 inflations and ST-segment changes in 7. LV dysfunction was associated with a minimal increase in end-diastolic volume (4 +/- 3%, p less than 0.003), and a major increase in relative end-systolic volume (69 +/- 43%, p less than 0.001). These data suggest that continuous monitoring of LV function with the VEST can sensitively detect silent ischemic decreases in LV function occurring during angioplasty, and provide further validation of the use of this technique for detecting silent myocardial ischemia."
-What is the relationship between primary sclerosing cholangitis and bone mineral density?,"The metabolic bone disease of primary sclerosing cholangitis. The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis."
-How do propofol and methohexital differ in their effects on left ventricular performance and hemodynamic parameters?,"Left ventricular performance during propofol or methohexital anesthesia: isotopic and invasive cardiac monitoring. Using gated radionuclide ventriculography and invasive cardiac monitoring, the effects of propofol and methohexital on left ventricular volumes and function were investigated in 22 unpremedicated patients (ASA physical status III, 50-78 yr) with chronic coronary artery disease (NYHA class II-III). Anesthesia was induced with either propofol or methohexital (2 mg/kg), followed by a maintenance infusion of 100 micrograms.kg-1.min-1. Vecuronium (0.05 mg/kg) was administered and ventilation (FIO2, 1.0) was manually controlled (FECO2, 0.04-0.05). Data acquisitions were serially obtained over 15 min. Propofol and methohexital anesthesia caused an average 15% decrease in mean arterial pressure, associated with a 20% decrease in cardiac index without a decrease in systemic vascular resistance index. It is interesting that the determinants of these hemodynamic effects were different. Heart rate did not change during propofol infusion despite the decrease in mean arterial pressure, whereas heart rate increased during methohexital infusion. In the propofol group, the decrease in cardiac index was associated with decreases in indicators of preload (end-diastolic volume and pulmonary capillary wedge pressure), whereas end-systolic volume and global ejection fraction did not change statistically. In the methohexital group, the decrease in cardiac index was associated with a decrease in global ejection fraction and an increase in end-systolic volume, whereas indicators of preload remained unchanged. It is concluded that methohexital reduces left ventricular performance. In contrast, propofol preserves left ventricular performance despite a likely negative inotropic effect."
-How does the orientation of a lipid-water interface affect the chemical shift artifact in magnetic resonance imaging?,"Chemical shift artifact: dependence on shape and orientation of the lipid-water interface. On magnetic resonance images, chemical shift artifact (CSA) can be seen at a planar lipid-water interface oriented within the plane of the phase-encoding and section-select directions (ie, perpendicular to the frequency-encoding direction). Phantoms and a clinical case were used to demonstrate that when a lipid-water interface is curvilinear (eg, spherical) or planar but not oriented along the section-select direction, CSA may be absent or diminished. This effect can be seen at interfaces of normal structures (kidneys, bladder) as well as at interfaces with pathologic lesions such as lipid-containing dermoids. Not only is this effect dependent on section thickness, field of view, matrix size, and receiver bandwidth, but it is also strongly dependent on the orientation of the interface with respect to the section-select direction. Knowledge of the factors that can alter CSA is important since it is used to distinguish lipid-containing from nonlipid-containing structures of similar signal intensities."
-How does exercise echocardiography compare to electrocardiography as a screening test for coronary artery disease?,"Exercise echocardiography as a screening test for coronary artery disease and correlation with coronary arteriography. We evaluated exercise echocardiography as a screening test for coronary artery disease in 228 patients, all of whom underwent subsequent coronary angiography. After an echocardiogram at rest was obtained, each patient performed maximal, symptom-limited, upright treadmill exercise, immediately after which repeat imaging was performed. The exercise echocardiogram was abnormal if any segment failed to become hypercontractile with exercise, and these regional wall motion abnormalities were used to predict the extent and distribution of coronary disease. At subsequent angiography, coronary stenosis was defined as significant if luminal diameter was reduced greater than or equal to 50%. Compared with electrocardiography, exercise echocardiography was more sensitive (97 vs 51%) and specific (64 vs 62%), and had higher positive (90 vs 82%) and negative (87 vs 28%) predictive accuracies. Exercise echocardiography was also highly predictive of the extent (no, 1-, 2- or 3-vessel disease) and distribution (which vessel) of coronary stenoses. It is concluded that exercise echocardiography is an excellent screening test for the presence, extent and distribution of coronary artery disease."
-How can nutrition therapy potentially help in managing immune dysfunction in critically ill patients?,Potential of parenteral and enteral nutrition in inflammation and immune dysfunction: a new challenge for dietitians [published erratum appears in J Am Diet Assoc 1991 Aug;91(8):913] Advances in the understanding of the interrelationship between immunology and nutrition indicate that immune dysfunction in critically ill patients is linked with nutrient deficiency and abnormal acute-phase response to illness. Immune dysfunction requires special nutrition therapy and metabolic support; immunoregulation by nutrition manipulation may lead to specific immunotherapies for defined groups of patients. The success of dietary strategies must be measured not only by metabolic indexes but also by effects on immune function. The health profession must combat immune dysfunction and inflammation for the sick and frail patients under its care.
-What were the main risk factors for cerebrovascular events in patients with acute myocardial infarction according to the GISSI trial?,"Cerebrovascular events after myocardial infarction: analysis of the GISSI trial. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). OBJECTIVES--To describe the epidemiology of cerebrovascular events in patients given or not given fibrinolytic treatment and to assess the prognostic implications and risk factors. DESIGN--Case series derived from the GISSI randomised trial. SETTING--176 coronary care units in Italy giving various levels of care. PATIENTS--5860 patients with acute myocardial infarction treated with 1.5 million units of intravenous streptokinase and 5852 patients not given fibrinolytic treatment. MAIN OUTCOME MEASURES--Cerebrovascular event, sex, age, blood pressure, history of previous infarct, site of infarction, and Killip class. RESULTS--99 of 11,712 patients (0.84%) had a cerebrovascular event. Older age, worse Killip class, and anterior location of infarction seemed to be risk factors for cerebrovascular events (40/3201 aged 65-75 v 42/7295 aged less than 65, odds ratio 2.18; 9/437 class 3 v 55/8277 class 1, 1.81; and 57/4878 anterior v 24/4013 posterior, 1.96). No significant difference was found in the rate of cerebrovascular events between patients treated with streptokinase and controls (45/5852 (0.92%) streptokinase v 54/5860 (0.77) control). More patients in the streptokinase group than in the control group had cerebrovascular events (especially haemorrhagic strokes) on day 0-1 after randomisation (27 streptokinase v 7, control), although this was balanced by late events in control patients (54 streptokinase v 45 control at one year). The mortality of patients who had a cerebrovascular event was higher than that of those who did not (47% (47/99) v 11.6% (1350/11,613]. CONCLUSIONS--Although the incidence of cerebrovascular events complicating myocardial infarction was low, they increased morbidity and mortality. Treatment with streptokinase did not significantly alter the incidence, but age and poor haemodynamic state were associated with an increased risk."
-"What surgical approach was used for treating orbital floor and rim fractures in this study, and what were its advantages?","Treatment of 813 zygoma-lateral orbital complex fractures. New aspects. A 10-year experience with surgical treatment of 813 zygomalateral orbital complex fractures is reviewed. Regardless of the type or severity of the fracture pattern, concomitant fractures of the orbital floor and rim were approached exclusively through the transconjunctival approach without a lateral canthotomy. The advantages of this approach compared with the subciliary access are the avoidance of a visible scar and markedly reduced incidence of postoperative lower eyelid complications such as ectropion and edema. Implants of lyophilized dura or cartilage and autogenous bone were used to reconstruct orbital floor defects. Malar asymmetry is a frequent complication of zygoma fractures resulting from inadequate three-dimensional reduction. Methods for accurate reduction and stabilization, indications for closed and open reduction, and management of the fractured infraorbital rim are emphasized. The indications for miniplates vs wire ligatures for the infraorbital rim are discussed. Long-term follow up and evaluation of the results with regard to the fracture pattern, complications, maxillary sinus dysfunction, and facial and orbital symmetry are presented."
-What was the key finding regarding lymphocyte response to group A haemolytic streptococcal antigens in patients with chronic plaque psoriasis?,"Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis. The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed."
-What is the prevalence of celiac or superior mesenteric artery stenoses among male veterans evaluated for peripheral vascular disease?,"Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. The prevalence of unsuspected renal artery stenosis among patients with peripheral vascular disease has been reported to be as high as 40%, but the prevalence of asymptomatic celiac and superior mesenteric artery stenoses in these patients is not known. The biplane aortograms of 205 male patients who were military veterans and had aneurysms or occlusive disease were independently reviewed, and medical records were studied to determine associated coronary disease, risk factors, and patient outcome. Fifty-six patients (27%) had a 50% or greater stenosis in the celiac or superior mesenteric artery, and seven patients (3.4%) had significant stenoses in both mesenteric arteries. Patients with celiac or superior mesenteric artery stenoses were older (p = 0.002) and had a higher prevalence of hypertension (p = 0.029) than those without significant mesenteric stenoses. Fifty of the 205 patients had significant renal artery stenoses, and 20 had advanced (greater than 75% diameter loss) renal stenoses. Ten of the 20 patients (50%) with advanced renal stenoses had a concomitant celiac artery stenosis, compared to 40 of the 185 patients (22%) who did not have advanced renal stenoses (p = 0.011). In the present study asymptomatic celiac or superior mesenteric artery stenoses were common among male veterans evaluated for peripheral vascular disease, but the prevalence of significant stenoses in both the celiac and superior mesenteric arteries was low. The prevalence of significant celiac stenosis was higher in patients with advanced (greater than 75%) renal artery stenoses who might be considered for prophylactic renal revascularization. Lateral aortography with evaluation of the celiac artery is always appropriate in these patients."
-What medical treatments were used for lichen sclerosus and squamous hyperplasia in this clinical study?,"Lichen sclerosus and squamous hyperplasia of the vulva. A clinical study of medical treatment. One hundred thirty-eight cases of nonneoplastic epithelial disorders of the vulva treated with medical therapy from 1984 to 1988 were evaluated at the University of Florence, Florence, Italy. The 67 cases of lichen sclerosus were treated with testosterone propionate or progesterone ointment for 32 weeks. The 31 cases of squamous hyperplasia were treated with corticosteroid ointment for 16 weeks. The 40 patients with lichen sclerosus associated with squamous hyperplasia were treated with corticosteroid ointment for 12 weeks and then with testosterone propionate ointment for another 20. To evaluate the efficacy of the treatments, the patients were examined before and after therapy. The evaluation took into account the symptoms and gross appearance of the lesions, which were given a score of 1-3. Considering all the cases evaluated, a total regression of symptoms occurred in 82 patients (59.4%), while a partial regression occurred in 37 (26.8%). Furthermore, there was a total regression of gross changes in 68 cases (49.3%) and a partial one in 43 (31.1%). The best results were obtained with squamous hyperplasia, which lichen sclerosus, alone or associated with squamous hyperplasia, yielded less successful results."
-What were the key findings of the study on the Duhamel operation for treating idiopathic megarectum and megacolon?,"Results of the Duhamel operation in the treatment of idiopathic megarectum and megacolon. The results of the Duhamel operation in patients with idiopathic megarectum and megacolon have been reviewed. Twenty patients (14 males, six females) underwent the Duhamel operation over a 17-year period for this condition. The mean age at operation was 25 years; the mean age of onset of constipation was 3 years; and the mean follow-up period was 4.5 years. All the resected colons were of enlarged diameter. There was agreement between the preoperative radiographs and the operative specimens with regard to which parts of the rectum and colon were dilated. Subjective feelings of well-being were generally improved by surgery, as was bowel frequency in ten patients. Soiling, straining, abdominal pain and distension were, however, common after operation. Early complications were also common and five patients required further surgery for constipation. The Duhamel operation for megarectum and megacolon is characterized by an improved sense of well-being and improved bowel frequency, but it is associated with the persistence of many symptoms and further surgery is often required."
-What are the key clinical considerations when managing cocaine-induced thrombocytopenia and hypertension during early pregnancy?,"Acute transient thrombocytopenia associated with cocaine abuse in pregnancy. A case is described of cocaine-induced severe transient thrombocytopenia associated with a hypertensive crisis at 21 weeks' gestation. Liver function tests and coagulation studies were all within normal ranges. Blood pressure was controlled with hydralazine. This clinical presentation, similar to severe preeclampsia, should be considered in the differential diagnosis of acute hypertension and low platelet count, especially in early gestations when preeclampsia is relatively rare. Unlike severe preeclampsia, for which active intervention and delivery are usually selected, cocaine-related hypertension-thrombocytopenia, especially in very premature gestations, may warrant conservative management."
-What treatment was found effective for adult patients with severe abdominal complications of Henoch-Schonlein purpura?,"Successful treatment of adult Henoch-Schonlein purpura with factor XIII concentrate. We report the cases of three adult patients with severe abdominal complications of Henoch-Schonlein purpura who had low activity of factor XIII during the acute phase of the disease. In all three cases, abdominal symptoms and purpura immediately responded to heat-treated, placenta-derived factor XIII concentrate. No adverse effects were experienced. Factor XIII concentrate replacement should be considered as the initial treatment for severe abdominal symptoms in adult Henoch-Schonlein purpura associated with a decreased level of factor XIII activity."
-What percentage of patients in the study experienced a decrease in arterial oxygen saturation levels during colonoscopy?,"An evaluation of multiple clinical variables for hypoxia during colonoscopy. One hundred consecutive patients undergoing routine colonoscopy were evaluated for changes in arterial oxygen saturation levels. All of the patients were monitored with the Nellcor N-200 pulse oximeter (Nellcor Incorporated) by finger probe and received supplemental oxygen when SaO2 levels decreased below 90 per cent. Forty patients demonstrated a decrease in SaO2 to less than 90 per cent after intravenous sedation but prior to colonoscopy, 14 patients demonstrated a decrease in SaO2 to less than 90 per cent during colonoscopy, and 46 patients maintained SaO2 levels greater than 90 per cent at all times. No statistical differences were found when these three groups were compared for age, body surface area, drug dosage, smoking history and a history of pre-existing hypertension, diabetes, arrhythmias, angina or myocardial infarction and pulmonary disease. These data indicate that all patients undergoing colonoscopy should be placed on supplemental oxygen. We further recommend continuous cardiac and pulse oximetry monitoring when available."
-What unusual cause of pneumoperitoneum was revealed in this case report?,"Recurrent pneumoperitoneum following vaginal insufflation. The authors report a case of a 24-year-old nulligravida woman who presented to the hospital with complaints of severe abdominal pain and radiographic evidence of pneumoperitoneum. She had two prior nondiagnostic laparotomies for similar complaints and radiographic findings. After a careful sexual history was taken the patient revealed that she had sexual intercourse preceding every similar episode including this one, during which her partner forcefully blew air into her vagina. Pneumoperitoneum associated with vaginal insufflation has been previously reported in two multigravida patients with and without anatomic abnormalities. When pneumoperitoneum is present in the absence of gastrointestinal symptoms or trauma, a meticulous sexual history should be made to avoid unnecessary laparotomies."
-What were the key findings of the study regarding the performance of the new radiopaque balloon-expandable coil stent in pigs?,"Coronary stenting with a new, radiopaque, balloon-expandable endoprosthesis in pigs. BACKGROUND. Intracoronary stents may be effective when used as ""bail-out"" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs. METHODS AND RESULTS. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressure-fixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 microns (range, 42-88 microns) after 1 week and 139 microns (range, 84-250 microns) after 4 weeks. CONCLUSIONS. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited."
-What unique characteristics were found in the promoter region of the human platelet-derived growth factor A-chain gene?,"Promoter region of the human platelet-derived growth factor A-chain gene. The platelet-derived growth factor (PDGF) A- and B-chain genes are widely expressed in mammalian tissues and their homodimeric gene products appear to regulate the autocrine growth of both normal and transformed cells. In this study, we analyzed the 5' flanking sequences of the human PDGF A-chain gene to seek elements important to regulating its transcription. The promoter region was exceptionally G + C-rich and contained a ""TATA box"" but no ""CAAT box."" The transcription start site was identified 845 base pairs 5' to the translation initiation site by S1 nuclease mapping and by primer extension. Both in vitro transcription and transient expression of the chloramphenicol acetyltransferase gene linked to the PDGF A-chain 5' flanking sequences established that the putative promoter region was active, and RNase H mapping established that the three characteristic mRNAs (1.9, 2.3, and 2.8 kilobases) used the same transcription start site, which was used in normal endothelial cells and in two human tumor cell lines that express high levels of A-chain transcripts. The results established an exceptionally G + C-rich promoter region and a single transcription start site active for each of the three mRNAs of the PDGF A-chain gene. DNA sites of potential importance in mediating the activation of the PDGF A-chain gene in normal cells and in transformed cell lines expressing high levels of PDGF A chain were identified."
-"What was the primary objective of the multicenter, prospective trial involving the Nd:YAG laser in treating endometriosis and pelvic adhesions?","Operative laparoscopy with the Nd:YAG laser in the treatment of endometriosis and pelvic adhesions. A multicenter, prospective trial was initiated to test the effectiveness and safety of the Nd:YAG laser equipped with artificial sapphire contact tips for the laparoscopic treatment of pelvic pain. Ninety-three women were enrolled in the study, 37 with endometriosis alone, 47 with endometriosis complicated by pelvic adhesions, and 9 women with adhesions alone. In over 90% of adhesions and 96% of endometriotic implants the Nd:YAG laser could be delivered to the site and be used to restore normal anatomy. The exception was deep bowel involvement with endometriosis, which was not treated. The majority of women had marked reduction or resolution of their symptoms for up to 12 months postoperatively. We conclude that the use of the Nd:YAG laser is an appropriate method to laparoscopically treat pelvic pain resulting from endometriosis or pelvic adhesions."
-What challenges do physicians face when treating patients who have used designer drugs?,"'Designer drugs'. Treating the damage caused by basement chemists. Use of ""designer drugs"" has created a new dilemma for physicians. Generally, it is possible to recognize symptoms and signs of intoxication that fit a specific class of substances, such as amphetamine-like effects for the phenylethylamines and opioid effects for the fentanyl analogues. Designer compounds have crossed these boundaries, and toxicology laboratories cannot readily identify them. For now, physicians must rely on clinical presentation and treat accordingly."
-What percentage of patients with high-energy midface fractures experienced orbital dislocations in the study?,"High-energy orbital dislocations: the possibility of traumatic hypertelorbitism. In a 4-year period from 1983 to 1987, 7160 patients with blunt injuries were admitted to the Maryland Institute of Emergency Medical Services Systems Shock Trauma Center. Facial injuries occurred in 10 percent of this population. High-energy fractures (characterized by computed tomography) were seen in approximately 10 percent of these patients. In this high-energy group, five cases of high-energy orbital dislocations, some representing examples of traumatic hypertelorbitism, were observed. They represent 1.5 percent of the 342 midface fractures observed and 4.8 percent of the naso-orbital ethmoid fractures observed (105 patients). One additional patient is described who was seen at the UCLA Medical Center for late repair of the condition. High-energy impacts of the upper midface created fractures of both orbits, zygomas, and nasoethmoidal regions permitting lateral transposition, enlargement, and divergence of the orbits. Interorbital, intercanthal, and interpupillary distances were increased, criteria that confirm the diagnosis of hypertelorbitism. Fifty percent of the patients were bilaterally blind, and one patient sustained unilateral blindness."
-How does the combination of hemorrhage and intracranial hypertension affect thromboxane A2 production in the brain?,"Hemorrhage and intracranial hypertension in combination increase cerebral production of thromboxane A2. BACKGROUND AND METHODS: To determine the effects of reduced cerebral perfusion pressures produced by hemorrhage alone or in combination with intracranial hypertension on thromboxane A2 (TxA2) production, we undertook a randomized study in 38 anesthetized, mongrel dogs. Animals were subjected to 30 mins of hemorrhagic shock with normal (group 1) or increased (group 2) intracranial pressure (ICP). Group 1 animals (n = 22) were hemorrhaged to reduce cerebral perfusion pressure to 40 mm Hg for 30 mins. In group 2 (n = 16), cerebral perfusion pressure was reduced by the combination of less severe hypotension and intracranial hypertension (20 mm Hg). Cerebral and systemic hemodynamic measurements were recorded, including cerebral blood flow (sagittal sinus outflow method); ICP; cerebral perfusion pressure; and arterial and cerebral venous concentrations of TxB2 (double-antibody radioimmunoassay technique), the major metabolite of TxA2. Data were obtained at baseline and at the beginning and end of the 30-min shock period. RESULTS: Hemorrhagic shock significantly (p less than .05) decreased cerebral blood flow in both groups. At the beginning of the shock period, cerebral blood flow was higher in group 1 than in group 2 (p less than .05) and venous-arterial differences in TxB2 increased significantly (p less than .05) in group 2, but not in group 1. At the end of the 30-min shock period, venous-arterial levels of TxB2 remained significantly (p less than .05) higher in group 2. CONCLUSIONS: Increased cerebral production of TxA2 during hypotension accompanied by intracranial hypertension may contribute to the severity of neural damage produced by the combination of head trauma and shock."
-How do oxygen-derived free radicals impact myocardial injury during coronary microvascular embolization?,"Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization BACKGROUND. Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization. METHODS AND RESULTS. To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization. CONCLUSIONS. We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization."
-What percentage of heart failure patients die suddenly before reaching New York Heart Association class IV symptoms?,"Genesis of arrhythmias in the failing heart and therapeutic implications. Between 50 and 70% of patients with heart failure die suddenly and unexpectedly before they have deteriorated to New York Heart Association class IV symptoms. It has long been known that ventricular ectopy predicts sudden cardiac death in coronary heart disease, and this has also been shown in dilated cardiomyopathy. It is less certain whether antiarrhythmic drugs reduce this risk and improve prognosis. Supraventricular arrhythmias frequently develop in heart failure of all causes. They nearly always cause symptoms, and the establishment of atrial fibrillation may mark a permanent deterioration. Except for sustained ventricular tachycardia, ventricular arrhythmias are often occult. Hypokalemia and digitalis toxicity may have been precipitated by diuretics or interaction with antiarrhythmic drugs. In coronary heart failure, arrhythmias may be related to scar tissue or ischemia, which may also be responsible in dilated cardiomyopathy. Use of inotropes and inodilators may precipitate arrhythmias, whereas drugs that conserve energy or potassium, such as beta blockers and angiotensin-converting enzyme inhibitors, may prevent them. Since suppression of ventricular arrhythmias has not been shown to prevent sudden death or prolong life in patients with heart failure, it may be that such arrhythmias do not directly presage ventricular fibrillation except in so far as they are markers of a poor prognosis with a risk of sudden death. If so, such arrhythmias are most likely to be suppressed by agents that result in improvement of left ventricular function and, through that, prolongation of life."
-How did the perceived beliefs of others and attitudes impact regimen compliance among myocardial infarction patients two years after the intervention?,"Regimen compliance two years after myocardial infarction. Two-years postinfarction, the effect of a nursing intervention at 30 days postinfarction, and intentions, attitudes, and perceived beliefs of others on regimen compliance of myocardial infarction patients was investigated. The sample was comprised of 51 patients (E = 29, C = 22) who participated in a five-phase study over 2 years. No differences were found between experimental and control groups for regimen compliance to activity, stress, and medication prescriptions. The experimental group was significantly more compliant to the diet prescription than the control group. The control group was significantly more compliant than the experimental group with cessation from smoking. Perceived beliefs of others were predictive of compliance for all regimen prescriptions at 2 years. Attitude was also predictive of compliance with the diet, smoking, and stress regimens."
-What was the overall response rate of the high-dose cisplatin with dacarbazine and tamoxifen treatment in patients with metastatic melanoma?,"High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine."
-What are the key diagnostic modalities used for accurately classifying subtypes of lymphoma and leukemia?,"Cytologic diagnosis of leukemia and lymphoma. Values and limitations. The value and limitations of the cytologic diagnosis of lymphoma and leukemia using a multiparameter approach, including cytomorphology, immunocytochemistry, and flow cytometry, are discussed. Using these diagnostic modalities, most subtypes of lymphoma and leukemia can be classified accurately. The differential diagnoses of the different disease entities also are presented."
-How does left ventricular mass relate to symptoms and cardiac function in childhood dilated cardiomyopathy?,"Left ventricular mass in childhood dilated cardiomyopathy: a possible predictor for selection of patients for cardiac transplantation. To determine the relationship of left ventricular hypertrophy (as assessed by mass) to symptoms and cardiac function in chronic childhood dilated cardiomyopathy, 17 long-term survivors (12 asymptomatic, 5 symptomatic) were studied at a median follow-up of 6.25 years (1.25 to 16.8 years). Left ventricular mass, dimension, wall stress, and contractility (relationship between velocity of circumferential fiber shortening and end-systolic wall stress) were assessed by echocardiography. These data were compared to measurements at the onset of disease. At follow-up, mass decreased significantly from the onset in the asymptomatic patients but remained elevated in the symptomatic patients (101 +/- 35 gm/m2 to 54 +/- 12 gm/m2, p = 0.001; 122 +/- 55 gm/m2 to 198 +/- 115 gm/m2, p = 0.23, respectively). Shortening fraction and contractility were both significantly lower in the symptomatic group compared with the asymptomatic group at follow-up (shortening fraction = 21 +/- 7% vs 29 +/- 5%, p = 0.02; contractility = -0.24 +/- 0.14 circ/sec vs -0.05 +/- 0.11 circ/sec, p = 0.01). Follow-up wall stress was slightly higher in symptomatic patients compared with asymptomatic patients. Three symptomatic patients had progressive hypertrophy and either died or required transplantation. Higher left ventricular mass is associated with the presence of symptoms, depressed contractility, and slightly higher wall stress. Persistence or progression of hypertrophy may be a poor prognostic sign in survivors of childhood dilated cardiomyopathy. Measurement of mass may be useful to indicate the necessity for closer follow-up to select patients for cardiac transplantation before hemodynamic decompensation."
-How do immune complexes modulate granuloma formation in patients with chronic schistosomiasis?,"Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. Granulomatous hypersensitivity to parasite eggs of Schistosoma mansoni is an important factor in the development of morbidity in chronic schistosomiasis. It has been demonstrated previously that the chronic, well-tolerated, intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms. We have used an in vitro model of granuloma formation for the purpose of studying the regulation of granulomatous hypersensitivity to S. mansoni egg antigens, mediated by immune complexes (IC). Our results show that the peripheral blood mononuclear cells (PBMCs) from patients with active schistosome infections, when treated with sera from chronic schistosomiasis patients, were able to induce an inhibitory activity on in vitro granuloma formation. Significant modulation of the in vitro granuloma reaction remained after treatment of PBMCs with isolated IC or manufactured IC with soluble egg antigen (SEA) and purified IgG from pooled chronic schistosomiasis sera. In contrast to granuloma modulation stimulated with whole molecule IgG-SEA IC, the incubation of PBMCs with F(ab')2 IgG-SEA IC did not induce any suppression of the granulomatous hypersensitivity to SEA. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating macrophages to release suppressive mediators. We have demonstrated this possibility by inhibition of prostaglandin activity using indomethacin. The addition of indomethacin to the granuloma culture significantly reduced in vitro granulomatous hypersensitivity to S. mansoni eggs in patients with chronic intestinal schistosomiasis and do so by inducing macrophages to secrete prostaglandins."
-How did the patient's Cushing's disease potentially contribute to the development of cutaneous alternariosis?,"Cushing's disease and cutaneous alternariosis. Alternaria species are common plant pathogens, but a rare cause of human infection. We present a patient with cutaneous alternariosis that revealed a relapse of an old case of Cushing's disease. Immunosuppression following the excessive glucocorticoid production seemed to contribute to the development of dermatosis. We also present a review of the literature on the association of Cushing's disease and cutaneous alternariosis. Our case is unique because the ketoconazole therapy that we used was successful in the treatment of both diseases."
-What surgical technique was used to successfully treat the esophagocutaneous fistula in this case report?,"Esophagocutaneous fistula after anterior cervical spine surgery and successful treatment using a sternocleidomastoid muscle flap. A case report. An esophagocutaneous fistula following anterior cervical fusion is rare. A 61-year-old man had cervical myelopathy because of ossification of the posterior longitudinal ligament of the cervical spine. Anterior decompression of the cervical spine and anterior fusion with strut bone grafting were performed. A second anterior fusion was done because the graft was dislodged after the patient fell out of bed one month after surgery. An esophagocutaneous fistula occurred three months after the second anterior surgery. One of the causes of this esophagocutaneous fistula was considered to be a pressure necrosis of the esophagus because of to projection of the bone graft. Conservative treatment, which consisted of wound drainage and intravenous administration of antibiotics, was tried but was unsuccessful. A good result was achieved by cancellous bone grafting, closure of the esophageal fistula, and transposition of a sternocleidomastoid muscle flap to the interspace between the esophagus and the cervical spine."
-How does diazepam binding inhibitor (DBI) affect mitochondrial steroidogenesis in Y-1 adrenocortical and MA-10 Leydig cell lines?,"Diazepam binding inhibitor and its processing products stimulate mitochondrial steroid biosynthesis via an interaction with mitochondrial benzodiazepine receptors. A recognition site for benzodiazepines structurally different from that linked to various gamma-aminobutyric acid A (GABAA) receptor subtypes is located on the outer mitochondrial membranes of steroidogenic cells. This protein has been signified to be important in the regulation of steroid biosynthesis. Because of its location it is designated herein as the mitochondrial benzodiazepine receptor (MBR). A putative endogenous ligand for MBR is the peptide diazepam binding inhibitor (DBI), previously shown to displace drugs from MBR and to be expressed and stored in steroidogenic cells rich in MBR. The two model systems used to study steroidogenic regulation by DBI were the Y-1 adrenocortical and MA-10 Leydig cell lines previously shown to be applicable in studies of mitochondrial steroidogenesis. Both cell lines contain DBI as well as DBI processing products, including the DBI fragments that on reverse phase HPLC coelute with the naturally occurring triakontatetraneuropeptide [TTN; DBI-(17-50)] and octadecaneuropeptide [DBI-(33-50)]. When DBI purified from rat brain was added to mitochondria prepared from Y-1 and MA-10 cell lines, it increased the rates of pregnenolone formation in a dose-related manner. In both cell lines, maximal stimulation (3-fold) of mitochondrial steroidogenesis was obtained with 0.33 microM DBI, with an EC50 of approximately 0.1 microM. However, DBI concentrations higher than 1 microM caused a smaller increase in pregnenolone formation. Flunitrazepam, a benzodiazepine that binds with high nanomolar affinity to MBR, was recently shown to act as an antagonist of ACTH and LH/hCG-induced steroidogenesis and was found in the present studies to inhibit DBI-stimulated mitochondrial steroidogenesis. During the incubation with mitochondria, DBI was partially processed to different peptide fragments, including octadecaneuropeptide and TTN. To determine whether DBI processing products influence mitochondrial steroid biosynthesis, several DBI fragments and other peptides structurally unrelated to DBI were tested. Among these, only TTN stimulated mitochondrial steroid synthesis in a dose-dependent manner similar to DBI."
-What are the advantages of centrally acting sympatholytic agents in managing hypertension?,"Use of centrally acting sympatholytic agents in the management of hypertension. Considerable evidence suggests that hyperactivity of the sympathetic nervous system is implicated not only in the pathogenesis of essential hypertension but also in several blood pressure-independent complications of essential hypertension. Even with the advent of newer antihypertensive agents, including angiotensin-converting enzyme inhibitors and calcium antagonists, the centrally acting sympatholytics (alpha 2-adrenoceptor agonists) remain a valuable group of medications for the management of hypertension of all grades of severity. Their advantages include efficacy; rarity of contraindication; absence of most metabolic and serious side effects; favorable effects on systemic hemodynamics; lack of true tolerance and infrequency of volume expansion-related pseudotolerance; suitability in the elderly, in isolated systolic hypertension, and in patients with various concomitant conditions, such as diabetes mellitus; ability to reverse left ventricular hypertrophy; and relative low cost. The long duration of action of guanfacine hydrochloride, the most recently marketed agent, and of the transdermal formulation of clonidine is an especially commendable feature. The principal disadvantages of this class of medications are an overlap between the therapeutic dosage and that producing sedation and dry mouth and the potential to cause the discontinuation syndrome and sexual dysfunction."
-What was the main finding of the Medical Research Council Vitamin Study regarding the prevention of neural tube defects?,"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. A randomised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid (one of the vitamins in the B group) or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects (anencephaly, spina bifida, encephalocele). A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups--namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect; 27 of these had a known neural tube defect, 6 in the folic acid groups and 21 in the two other groups, a 72% protective effect (relative risk 0.28, 95% confidence interval 0.12-0.71). The other vitamins showed no significant protective effect (relative risk 0.80, 95% Cl 0.32-1.72). There was no demonstrable harm from the folic acid supplementation, though the ability of the study to detect rare or slight adverse effects was limited. Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy, and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid."
-What are the key findings of the study regarding the distribution of neurofilament protein epitopes in cortical Lewy bodies?,"Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. A subset of demented elderly patients exhibit large numbers of cortical intraneuronal inclusions similar to the neurofilament (NF)-rich Lewy bodies (LB) found in pigmented subcortical neurons of patients with Parkinson's disease (PD). Because these cortical inclusions may contribute to the emergence of cognitive impairments in afflicted individuals, the authors mapped the distribution of NF epitopes in these so-called cortical LBs. This was done using ethanol-fixed tissues and a large library of monoclonal antibodies (MAbs) with well-characterized binding specificities to various regions of each NF triplet protein. Cortical LBs were examined by light, confocal, and electron microscopy, and they were compared with the subcortical LBs of PD and LBs in the peripheral nervous system (PNS). Monoclonal antibodies specific for the rod regions of each of the three NF subunits, or for phosphate-dependent and independent antigenic sites in the tail region of the high- (NF-H) and middle- (NF-M) molecular weight (Mr) NF subunits as well as other MAbs to the extreme COOH terminus of NF-L and NF-M or the head region of NF-M labeled a variable number of cortical LBs. Remarkably one of these anti-NF MAbs, RMO32, which recognized a phosphorylated epitope in the tail region of NF-M, immunolabeled nearly all cortical LBs, whereas each of the other anti-NF MAbs never labeled more than 10% of ubiquitin- or RMO32-positive cortical LBs. Further LBs in the PNS resembled those in the central nervous system (CNS) in their immunologic properties, and LBs in both sites were dominated by filamentous aggregates at the ultrastructural level. These findings suggest that NF proteins are profoundly altered during their incorporation into cortical and PNS LBs. Further the authors here identified immunologic and ultrastructural properties common to cortical LBs, PNS LBs, and classic substantia nigra LBs in PD. The accumulation of filamentous, perikaryal inclusions rich in NF proteins at diverse sites in the CNS and PNS of patients with a variety of neurodegenerative disorders suggests a widespread disruption of NF metabolism or transport."
-How can sexually transmitted diseases impact the reproductive health of women and their offspring?,"Preventing fetal damage from sexually transmitted diseases. The STDs threaten the reproductive health of women in many ways, ranging from premature births through congenital infections and death. An understanding of the natural history of these diseases permits timely interventions which can mitigate the perinatal damage caused by these infections substantially. Ideally, primary prevention or safer sex will be adopted by sexually active women, thereby reducing the morbidity not only for their offspring but for themselves as well. Antiviral therapy is not yet available for minimizing any hazard of fetal exposure to HPV, HSV, HIV, and hepatitis B viral infections. Early antibiotic therapy should reduce the risk of congenital syphilis and any perinatal hazards associated with chlamydial and gonococcal infections."
-What are the two main groups of drugs used in migraine therapy?,"Pharmacology of antimigraine drugs. The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT1-like receptors, beta-adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT1-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine."
-What are the most practical and useful techniques for diagnosing perivalvular extension of infection in patients with infectious endocarditis?,"Perivalvular extension of infection in patients with infectious endocarditis. Perivalvular extension of infection is a not-infrequent and potentially fatal complication of bacterial endocarditis. Because the efficacy of various modalities in the diagnosis of such complications is not well established, a selective review of the published literature on this issue is worthwhile. The electrocardiogram is the easiest study to obtain. It is quite specific in identifying perivalvular extension of infection when conduction system disease is demonstrated but has a low degree of sensitivity overall. Transthoracic two-dimensional echocardiography, transesophageal echocardiography, and color-flow Doppler echocardiography are the most practical and useful techniques for diagnosis of perivalvular extension of infection. Magnetic resonance imaging also appears to be an effective tool in this setting; however, because of a paucity of clinical data, its precise utility has not yet been determined. Nuclear medicine studies and computed tomography play a minimal role. Cardiac catheterization is as useful as the echocardiographic techniques but is invasive, not as readily available, and significantly riskier in terms of complications. An approach to the diagnosis of perivalvular extension of infection is proposed on the basis of the literature review."
-What are the primary aims of treatment for patients with heart failure?,"Assessing drugs for the treatment of heart failure. The aims of treatment in patients with heart failure, as with any other condition, are to relieve symptoms and prolong life. A secondary objective is to do so at the lowest possible economic cost. When treatment of the cause of heart failure is possible--which usually means some form of surgery, but could include treatment of a primary disease, such as thyrotoxicosis--then this is obviously the treatment of choice. In patients for whom there is no such definitive treatment, a wide and increasing variety of drugs are available. When new antifailure drugs are to be developed there are therefore two problems: first, to ensure that they are more effective than placebo treatment, and second, to compare them with existing drugs. Both of these tests can present ethical difficulties, for it is unreasonable to withhold established effective treatment in order to conduct a placebo-controlled trial, and when drugs are being compared, it is unlikely that any new medication will be dramatically superior to an old one. The more effective the treatments already available, the harder it becomes to evaluate a new drug."
-How quickly do motor units diminish in muscles affected by amyotrophic lateral sclerosis (ALS) during the first year of disease progression?,"The extent and time course of motoneuron involvement in amyotrophic lateral sclerosis. The numbers and relative sizes of motor units have been estimated in 373 muscles of 123 patients with ALS: 74 of the muscles were examined on more than one occasion. The median duration between the onset of symptoms and the initial examination was 12 months; by this time, approximately 90% of the tested muscles showed losses of motor units. The evoked motor unit potentials continued to enlarge in most, but not all, muscles as the disease progressed. Once a muscle became affected by the disease process, the average time-course was such that the motor unit population halved in each 6-month period of the first year and diminished more slowly thereafter. A small proportion of patients was encountered in whom the disease progressed much more slowly and there were occasional large fluctuations in the motor unit estimates suggestive of reversible motoneuron dysfunction."
-How does prolonged hypoxia affect prostacyclin production and adenylate cyclase activity in rat pulmonary arteries?,"Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat. Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta-adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia."
-How was the treadmill score calculated in this study of outpatients with suspected coronary artery disease?,"Prognostic value of a treadmill exercise score in outpatients with suspected coronary artery disease BACKGROUND. The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients. METHODS. We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk). RESULTS. Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent). CONCLUSIONS. The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment."
-How did iodine-131-3F8 radioimmunoscintigraphy compare to other diagnostic methods in detecting neuroblastoma sites?,"Radioimmunodetection of neuroblastoma with iodine-131-3F8: correlation with biopsy, iodine-131-metaiodobenzylguanidine and standard diagnostic modalities. Iodine-131-3F8, a murine IgG3 monoclonal antibody specific for ganglioside GD2 was evaluated by radioimmunoscintigraphy in 42 patients with neuroblastoma. Comparison was made with 131I-metaiodobenzylguanidine (MIBG), 99mTc-methylene diphosphonate (MDP) bone scans, as well as computed axial tomography (CT) or magnetic resonance imaging (MRI). Iodine-131-3F8 detected more abnormal sites (283) than [131I] MIBG (138) or 99mTc-MDP (69), especially in patients with extensive disease. In 20 patients with soft-tissue tumors demonstrated by CT/MRI, 131I-3F8 detected the disease in 18. Upon surgical resection, two tumors interpreted as negative with 131I-3F8 imaging revealed ganglioneuroma, one showing microscopic foci of neuroblastoma. In contrast, 131I-3F8 imaging identified tumors that were confirmed histologically as neuroblastomas. In 26 patients with evidence of marrow disease by antibody scans, 14/26 had confirmation by iliac crest marrow aspirate/biopsy examinations. We conclude that 131I-3F8 scintigraphy has clinical utility in the management of patients with neuroblastoma by improving the sensitivity of tumor detection."
-How does the number of metastatic lymph nodes affect the 5-year survival rate in patients with gastric cancer?,"Prognostic significance of the number of metastatic lymph nodes in patients with gastric cancer. To confirm the prognostic significance of the number of the metastatic lymph nodes (MLN) in cases of gastric cancer, the results of surgical treatment of 668 patients with primary gastric cancer were analyzed retrospectively. Five-year survival rates were calculated with reference to the number of MLN, namely, none (89.2%), one to three (77.4%), four to six (55.8%), and seven or more (36.2%). Furthermore, even when the cancer had invaded the serosa, 5-year survival was significantly more frequent in patients with one to three MLN (71.7%) than in those with four to six (35.5%) or more than six (31.5%) (P less than 0.01), and the 5-year survival was close to that of patients with no MLN (70.5%). Not only qualitative but also quantitative evaluation of lymph node metastasis is essential for estimating the prognosis of patients with gastric cancer."
-How does the biopsychosocial model fall short in understanding the role of culture in the experience of illness?,"Culture, illness, and the biopsychosocial model. Family medicine has appropriated the biopsychosocial model as a conceptualization of the systemic interrelationships among the biological, the psychological, and the social in health and illness. For all its strengths, it is questionable whether this model adequately depicts the centrality of culture to the human experience of illness. Culture (as meaning system) is not an optional factor that only sometimes influences health and illness; it is prerequisite for all meaningful human experience, including that of being ill. A more adequate model of the relationship between culture and illness would demonstrate the preeminence of culture in the experience of illness among all people, not just members of ""exotic"" cultures; would view healers as well as patients as dwellers in culture; would incorporate the role of culture as meaning system in linking body, mind, and world; and would promote the significance of the cultural context as a resource for research and therapy."
-How did the levels of von Willebrand factor (vWF) and factor VIII (FVIII) change in renal transplant recipients during the first 4 months after transplantation?,"von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients. In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment."
-What are the key clinical manifestations of liver involvement in Alpers disease?,"Liver involvement in Alpers disease. Alpers disease consists of diffuse cerebral degeneration manifested as developmental delay, seizures, vomiting, and progressive neuromuscular deterioration, with liver disease and death. We report the clinical course of the liver disease, histologic progression of the hepatic lesions, and etiologic investigations in five patients (four girls, three kinships). All had grown and developed normally until seen at 6 to 36 months of age (mean 20 months), with vomiting (n = 5), progressive hypotonia (n = 3), or seizures (n = 2). All had been given anticonvulsants, including valproic acid in three. Liver disease was noted at a mean age of 35 months (range 9 to 67 months), with hepatomegaly (two patients), abnormal hepatic synthetic function (three) or transaminase values (three), and cirrhosis in one. Patients survived for a mean of 4.6 weeks (range 1 to 8 weeks) after the identification of liver disease; all died of hepatic failure. Results of evaluation for infectious and metabolic causes of liver disease and causes of degenerative neuromuscular disease were negative in all patients. Premortem liver biopsy specimens (n = 3) demonstrated an early lesion consisting of lobular disarray, microvesicular steatosis, periportal acute and chronic inflammation, and individual hepatocyte necrosis. Autopsy findings (n = 5) consisted of macrovesicular steatosis, massive hepatocyte dropout, and proliferation of bile ductular elements, with almost complete replacement of hepatocytes by proliferating bile ductular elements in two patients. Brain showed characteristic neuronal degeneration. We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction."
-How does ischemia affect the density and regeneration of nerve fibers?,"Vulnerability of nerve fibres to ischaemia. A quantitative light and electron microscope study. In order to learn more about the vulnerability of nerve fibres to ischemia, a quantitative study of nerve fibre abnormalities was performed on biopsy specimens of the superficial branch of the peroneal nerve from 26 patients with vasculitic neuropathy: 20 had necrotizing arteritis, 5 a lymphocytic, and 1 a leucocytoclastic vasculitis on nerve and/or muscle biopsy. The density of myelinated fibres ranged from 25 to 7880 per mm2 (n = 8470 +/- 706 (SD]. There was a marked inequality in the density of nerve fibres between the fascicles of individual nerves with a mean coefficient of variation of 41 +/- 37 (SD) % versus 7.4 +/- 3.0% in controls. Loss of myelinated fibres, which was greater for fibres larger than 7 microns in diameter, was more severe than that for unmyelinated axons. Regeneration, which was assessed by the number of clustered axons, decreased when the density of myelinated fibres decreased, suggesting that severe nerve ischaemia precludes axonal regeneration. Wallerian degeneration affected on average 58% (range 5-100%) and segmental demyelination, mainly of the secondary type, on average 1.94% (range 1-10%) of teased fibres. It was concluded that (1) myelinated fibres are more vulnerable to ischaemia than unmyelinated axons; (2) large myelinated fibres are affected before the smaller ones; (3) segmental demyelination is uncommon in this context; (4) severe nerve ischaemia precludes axonal regeneration."
-How do endogenous free radical scavengers impact gastric ulcer formation in the experimental rat model?,"The role of endogenous free radical scavengers on tissue recovery in the experimental ulcer model. The role of lipid peroxidation and endogenous oxygen-derived free radical scavengers on ischemia-reperfusion injury and tissue recovery in rat ulcer model corresponding to the gastric histopathology was investigated. Male Wistar rats weighting 200-250 g were heparinized before occlusion of the celiac axis for 1.5 h. Endogenous CuZn-superoxide dismutase (SOD), Mn-SOD, glutathione peroxidase, fumarase, cytochrome c oxidase, and thiobarbituric acid-reactive compounds as lipid peroxidation products were measured in the gastric tissue at 3 h, and 1, 2, 4, and 7 days after release and in the controls (no occlusion). At 3 h after release, erosion of the gastric mucosa was observed, and gastric ulcers beyond the muscularis mucosae were present in the gastric body 2 days later. Seven days after release, gastric ulcers had disappeared. Activity levels for all five enzymes (CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase) were low for days 1-4 after release and did not return to control levels by the seventh day. It was observed that the ulcer formation, as evidenced by the histopathology, was significantly related to the levels of endogenous CuZn-SOD, Mn-SOD, glutathione peroxidase, fumarase, and cytochrome c oxidase activities. Thiobarbituric acid-reactive compounds were also low through the entire course of ulcer formation. The study concludes that decreases in the levels of these oxygen-derived free radical scavengers may result in the formation of gastric ulcers; however, endogenous free-radical scavengers may not correspond with tissue recovery. Lipid peroxidation may not be related to ulcer formation."
-What was the overall hospital mortality rate in the urokinase and heparin groups after 16 days in this study of acute myocardial infarction patients?,"Comparison of intravenous urokinase plus heparin versus heparin alone in acute myocardial infarction. Urochinasi per via Sistemica nell'Infarto Miocardico (USIM) Collaborative Group. In a randomized trial of the effects on in-hospital mortality of intravenous urokinase plus heparin versus heparin alone, 2,531 patients with acute myocardial infarction in 89 coronary care units were enrolled for greater than 30 months. Patients admitted within 4 hours of the onset of pain were randomized to receive either intravenous urokinase (a bolus dose of 1 million U repeated after 60 minutes) plus heparin (a bolus dose of 10,000 U followed by 1,000 IU/hour for 48 hours) or heparin alone (infused at the same rate). Complete data were obtained in 2,201 patients (1,128 taking urokinase and 1,073 taking heparin). At 16 days, overall hospital mortality was 8% in the urokinase and 8.3% in the heparin group (p = not significant). Among patients with anterior infarction, mortality was 10.3% in the urokinase and 13.9% in the heparin group (p = 0.09; relative risk = 0.73). The incidence of major bleeding (urokinase 0.44%, heparin 0.37%) as well as the overall incidence of stroke (urokinase 0.35%, heparin 0.20%) was similar in the 2 groups. The rates of major in-hospital cardiac complications (reinfarction, postinfarction angina) were also similar."
-What language-related difficulties were observed in patients with progressive supranuclear palsy?,"Language functions in progressive supranuclear palsy. Language functions were studied in 6 patients with clinically diagnosed progressive supranuclear palsy who conformed to the characteristic pattern of 'subcortical dementia'. Dysarthria, reading difficulties and disturbances of handwriting were present in all patients. Some patients showed additional deficits including visual dyslexia, constructional dysgraphia and an increased rate of self-corrections and misnamings in object confrontation naming. In most instances, the naming errors referred to an object visually similar to the target object, suggesting that visual misperception is the major cause of the naming disorder. It is concluded that a variety of language impairments may develop secondary to other neurological and neuropsychological changes in progressive supranuclear palsy."
-How does the growth cycle of malaria parasites in erythrocytes contribute to the periodic nature of malaria fever?,"Periodic and chaotic host-parasite interactions in human malaria. It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite."
-How did hypotensive epidural anaesthesia impact the quality of cement-bone interface in total hip arthroplasty?,"Effect of hypotensive epidural anaesthesia on acetabular cement-bone fixation in total hip arthroplasty. We selected 20 matched pairs of patients who had had total hip arthroplasty by the same surgeon using the same cemented technique. Matching was by age, sex, height, weight and diagnosis. One of each pair had received hypotensive epidural anaesthesia, with less than 300 ml blood loss: the other had normotensive general anaesthesia with more than 500 ml of blood loss. Early postoperative radiographs were evaluated independently by three blinded observers, using a scoring criteria which assessed the quality of the cement-bone interface. The results showed that patients who had received epidural anaesthesia had significantly better radiographic scores (p less than 0.02). Our findings suggest that hypotensive anaesthesia facilitates penetration of cement into bone."
-What echocardiographic measurements were found to be risk factors for perioperative death in infants with isolated aortic valve stenosis?,"Echocardiographic estimation of critical left ventricular size in infants with isolated aortic valve stenosis. With the current trend to performing surgical valvotomy for infantile aortic stenosis without cardiac catheterization, there is a need to develop echocardiographic criteria for adequacy of left ventricular size. The echocardiograms and catheterization data of all 25 infants less than 3 months of age undergoing aortic valvotomy for isolated aortic valve stenosis from September 1980 through July 1990 were reviewed. Significant differences (p less than 0.05) between the survivors and nonsurvivors were noted for age at operation (30 +/- 28 vs. 3 +/- 1.5 days), mitral valve diameter (10.1 +/- 1.7 vs. 7.7 +/- 1.5 mm), left ventricular end-diastolic dimension (18.4 +/- 6.4 vs. 11.4 +/- 3 mm), left atrial dimensions (15.3 +/- 3.8 vs. 10 +/- 2.4 mm), left ventricular cross-sectional area on the parasternal long-axis echocardiogram (4 +/- 1.9 vs. 2 +/- 1.9 cm2) and angiographically determined left ventricular end-diastolic volume (43 +/- 23 vs. 11 +/- 5 ml/m2). There was no difference with respect to patient weight, body surface area, aortic root dimension or left ventricular ejection fraction. Left ventricular cross-sectional area less than 2 cm2 as measured on the parasternal long-axis echocardiogram was found in 5 of 7 nonsurvivors and 0 of 12 survivors, making this a risk factor for perioperative death (p less than 0.05). Left ventricular end-diastolic dimension less than 13 mm was found in 5 of 6 nonsurvivors and 2 of 17 survivors, making this another risk factor for early mortality (p less than 0.05)."
-What medical condition did the 27-year-old man with osteogenesis imperfecta develop after sustaining a femoral fracture?,Compartment syndrome of the thigh with osteogenesis imperfecta. A case report. Compartment syndrome of the thigh has been sporadically reported in the orthopedic literature. A 27-year-old man with osteogenesis imperfecta sustained a femoral fracture with relatively minor trauma and subsequently developed compartment syndrome of the thigh. Fat embolism syndrome and hyperplastic callus developed postoperatively.
-What were the acute hemodynamic effects of intravenous nicardipine in patients with a healed myocardial infarction?,"Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure. Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation."
-What is bioelectric impedance analysis and how was it used in this study of cirrhotic patients?,"Bioelectric impedance analysis: experience with male patients with cirrhosis. Bioelectric impedance analysis is a new, convenient and portable method used to estimate total body water and to assess body composition in healthy people. We used the tetrapolar bioelectrical impedance analysis method in 58 cirrhotic patients to assess its clinical applicability. Whole-body resistance, reactance and impedance were measured and compared with those of 30 healthy volunteers matched for age and sex. The resistance and impedance values of ascitic cirrhotic patients (resistance = 461 +/- 80 omega; impedance = 462 +/- 80 omega) and nonascitic cirrhotic patients (resistance = 487 +/- 96 omega; impedance = 489 +/- 97 omega) were comparable with the resistance (488 +/- 44 omega) and impedance (491 +/- 44 omega) of controls. However, a significant (p less than 0.05) reduction in whole body reactance was found in patients with ascites and in those without ascites (34 +/- 9 omega vs. 47 +/- 12 omega) as compared with healthy subjects (56 +/- 7 omega). In 10 ascitic patients total body water was determined both before and after paracentesis; the volume of intraperitoneal fluid removed (7.9 +/- 3.8 L) could not be fully accounted for but only detected as an average volume of 1.9 +/- 1.0 L independently of the initial volume of the ascites. Our data clearly demonstrate that tetrapolar bioelectric impedance analysis is not adequate for measuring variations of ""compartmentalized"" fluid in the abdomen."
-How did the MR receptor imaging with asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide differ in normal liver tissue versus hepatocellular carcinoma (HCC) tissue?,"Experimental hepatocellular carcinoma: MR receptor imaging. Relaxation time measurements and magnetic resonance (MR) imaging were performed in three different animal models of hepatocellular carcinoma (HCC). After intravenous administration of asialoglycoprotein-directed arabinogalactan-stabilized ultrasmall superparamagnetic iron oxide (10 mumol Fe/kg receptor agent), T2 of normal liver decreased from 41.6 msec +/- 1.0 to 19.4 msec +/- 1.7 (P less than .05) in rats. T2 of HCC implanted in normal liver or liver with chronic hepatitis was essentially unchanged. These results were similar to those obtained by administration of a reticuloendothelial cell-directed conventional iron oxide; however, the required dose of receptor agent was lower. MR imaging in a woodchuck model of virally induced HCC confirmed the distribution of the hepatocyte-directed agent to regions of functioning and differentiated hepatocytes but not to malignant tumor tissue. The results suggest that MR receptor imaging may play a role in the differentiation between primary liver tumor and functional liver tissue such as that in normal liver hepatitis or regenerating nodules."
-What were the key findings of the study regarding the effects of dexamethasone in treating bacterial meningitis in infants and children?,"The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. BACKGROUND. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San Jose, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis."
-How does collateral circulation impact left ventricular function in patients with total occlusion of the left anterior descending coronary artery?,"Evolution of myocardial ischemia and left ventricular function in patients with angina pectoris without myocardial infarction and total occlusion of the left anterior descending coronary artery and collaterals from other coronary arteries. Repeated episodes of myocardial ischemia might lead to progressive impairment of left ventricular (LV) function. This radionuclide study assessed myocardial ischemia and LV function several years after documented coronary occlusion without myocardial infarction. Over 5 years, 24 consecutive patients, who underwent cardiac catheterization for angina pectoris without myocardial infarction, had isolated total occlusion of the left anterior descending coronary artery with well-developed collateral vessels. Five patients were successfully treated by coronary bypass grafting and 3 by coronary angioplasty. Among the 16 medically treated patients, 1 was lost to follow-up and 1 died (extracardiac death). The mean (+/- standard deviation) follow-up (14 patients) was 48 +/- 15 months. At follow-up, 8 patients still had clinical chest pain, 11 received antianginal therapy, 4 patients had no stress ischemia and the other 10 had greater than or equal to 1 sign of stress ischemia. All patients had a normal LV ejection fraction at rest (mean 60 +/- 3%; range 55 to 65%). Collateral circulation preserves LV function at the time of occlusion and, in some cases, prevents the development of myocardial ischemia; in patients with persisting myocardial ischemia after well-collateralized coronary occlusion, LV function is not impaired at long-term follow-up."
-What was the median survival time for melanoma patients with metastases to two or more lymph node areas?,"The prognosis of melanoma patients with metastases to two or more lymph node areas. The prognosis of melanoma patients who present with metastatic involvement of two or more noncontiguous lymph node regions before the detection of extranodal metastases has not been previously reported. We identified 21 patients with metastatic melanoma in at least two nodal basins in a review of 175 patients with melanoma undergoing lymphadenectomy at the National Cancer Institute. The median survival time of these patients was 46 months, with 55%, 27%, and 17% of the patients alive 2, 5, and 10 years, respectively, after the second lymphadenectomy. Because the prognosis of melanoma patients with metastases to two or more regional nodal areas appears equivalent to that of patients with metastatic involvement of only one regional node site, lymphadenectomy of the involved groups should be performed with therapeutically curative intent."
-What is the Currarino triad and what are its key characteristics in the described family?,"Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality."
-What was the effect of leuprolide acetate depot treatment on uterine volume in women with leiomyomata uteri?,"Treatment of leiomyomata uteri with leuprolide acetate depot: a double-blind, placebo-controlled, multicenter study. The Leuprolide Study Group. The purpose of this study was to evaluate efficacy and safety parameters in women with leiomyomata uteri treated with the GnRH agonist leuprolide acetate depot, 3.75 mg intramuscularly every 4 weeks for 24 weeks. One hundred twenty-eight patients were enrolled in a randomized, double-blind, placebo-controlled multicenter study involving 13 investigative centers. Mean uterine volume decreased by 36% at 12 weeks and 45% at 24 weeks of leuprolide therapy. Patients treated with placebo had increased in mean uterine volume of 16% at 12 weeks and 5% at 24 weeks. Seventy-seven percent of leuprolide-treated patients had a more than 25% reduction in uterine volume, compared with 9% of placebo-treated controls. Mean uterine volume returned to pre-treatment size 24 weeks after cessation of leuprolide treatment. The majority of patients had resolution or improvement of their fibroid-related symptoms after 24 weeks of leuprolide treatment. Of 38 leuprolide-treated patients presenting with menorrhagia, 37 (97%) had resolution of this symptom at the time of the final visit. Although 95% of women treated with leuprolide acetate experienced some side effects related to hypoestrogenism, only five patients (8%) terminated treatment prematurely. We conclude that leuprolide acetate depot treatment of leiomyomata uteri is safe and causes significant but temporary reductions in uterine size and fibroid-related symptoms."
-How does the presence of bile affect bacterial growth and clearance in Escherichia coli peritonitis?,"Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis. The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis."
-What are the main side effects observed in the low-dose recombinant interferon-gamma study?,"Recombinant interferon-gamma (rIFN-gamma) in dermatology. This paper gives a short review on the function, pharmacokinetics, and therapeutic application of recombinant interferon-gamma (rIFN-gamma) in dermatology. Simultaneously, our own experiences are presented for 57 patients (phase II study) suffering from genital warts (21 patients), psoriatic arthritis (10 patients), psoriasis vulgaris (three patients), malignant melanoma (six patients), bowenoid papulosis (four patients), Behcet's disease (four patients), basal cell carcinoma (six patients), as well as herpes simplex recidivans, epidermodysplasia verruciformis, and mycosis fungoides (one patient each). We conclude that there might be an indication for treatment with rIFN-gamma in genital warts, bowenoid papulosis, Behcet's disease, and microbial infections, such as leprosy and cutaneous leishmaniasis. Even though there are reports of a limited beneficial effect of rIFN-gamma on arthritis and skin lesions in psoriasis, we failed to observe any in 10 patients. The main side effects in our low-dose study (50-100 micrograms/d) were mild fever (78%), fatigue (78%), and myalgia (65%). Laboratory tests revealed an increase in the serum triglyceride level, in particular, in psoriatic patients."
-What is the Currarino triad and what are its key characteristics in the described family?,"Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. A family with autosomal dominant inheritance of sacral agenesis is described. Ten members were affected; four had associated presacral teratomas and anterior sacral meningoceles, giving rise to serious complications in three, including bacterial meningitis, local recurrence of teratoma and perianal sepsis. Three of those with presacral masses presented initially with anorectal anomalies. Other associated abnormalities included tethering of the cord, hydrocephalus, duplex ureter, hydronephrosis, vesicoureteric reflux, neurogenic bladder, bicornuate uterus, rectovaginal fistula and hereditary spherocytosis. Early diagnosis and surgical excision of a presacral mass is advised to prevent future morbidity and mortality."
-What multimodality treatment approach was used for patients with malignant pleural mesothelioma in this study?,"Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma. Malignant pleural mesothelioma has been considered a uniformly fatal disease associated with a median survival of 4 to 18 months. Extrapleural pneumonectomy alone has proved disappointing in the treatment of this disease, as have chemotherapy and radiotherapy. From 1980 to 1990, 31 patients with pleural mesothelioma underwent multimodality therapy that included extrapleural pneumonectomy with resection of the pericardium and diaphragm. The age of the patients was 53.4 +/- 8.6 years; 26 were male. All patients had the pathologic diagnosis reviewed before treatment. At thoracotomy six patients had residual (unresectable) gross disease, and in 23 there was histologic evidence of disease at the resection margin. The perioperative morbidity and mortality rates were 19% and 6%, respectively. The mean length of hospital stay for the 29 patients who survived the operation was 10.9 +/- 3.5 days. Postoperatively 26 patients received cyclophosphamide, doxorubicin, and cis-platinum chemotherapy with or without radiotherapy. The survival rates were 70% at 1 year and 48% at 2 years. Trends toward improved survival in the patients with complete resections approached but did not reach statistical significance. These data suggest that this multimodality protocol can be administered with acceptable morbidity and mortality. Prospective trials are justified to further clarify the role of this approach."
-What are the three distinct cell types observed in the adamantinoid basal cell carcinoma during the ultrastructural study?,"Adamantinoid basal cell carcinoma. An ultrastructural study. We describe an adamantinoid basal cell carcinoma that has developed in the mucocutaneous border of the upper lip. An ultrastructural study disclosed three types of cells that were morphologically distinct in the tumor nest. Cells of the first type were basically the same as those of ordinary basal cell carcinoma. Cells of the second type showed varying degrees of cytoplasmic content loss in a worm-eaten pattern and seemed to consist of degenerating cells. Cells of the third type possessed a well-developed rough endoplasmic reticulum filled with medium electron-dense fine substance, which was also seen in the extracellular space. In relationship with the histochemical findings, and based on the histogenesis of adamantinoid basal cell carcinoma, we propose that subpopulations of tumor cells undergo spontaneous degeneration and that the spaces of such disappearing cells are refilled with products containing glycosaminoglycans secreted by another subpopulation of the tumor cells."
-What imaging techniques were used to diagnose choledochal cyst and biliary atresia in the neonates?,"Choledochal cyst and biliary atresia in the neonate: imaging findings in five cases. The radiologic findings in five neonates with choledochal cyst associated with extra-hepatic biliary atresia are described. All five patients (age range, 13-72 days) presented with jaundice and acholic stools. In all four patients who underwent sonographic examination, a cystic structure separate from the gallbladder representing the choledochal cyst was shown. The diagnosis of atresia of the distal common bile duct was made preoperatively in all cases by hepatobiliary scintigraphy. Diagnosis was confirmed by surgical findings and was demonstrated by intraoperative cholangiography in four cases. All patients were successfully treated with surgical intervention within 1 month from the time of diagnosis. Early detection of this rare disorder, which may be distinct from choledochal cyst found in children and adults, is important to prevent fatal complications of biliary obstruction. The combined use of sonography and hepatobiliary scintigraphy can correctly identify this subset of patients with persistent neonatal jaundice and provide valuable information for prompt surgical management."
-How does the HBx gene of hepatitis B virus contribute to liver cancer development in transgenic mice?,"HBx gene of hepatitis B virus induces liver cancer in transgenic mice. The exact role of hepatitis B virus in the development of liver cancer is not known. The recent identification of a viral regulatory gene HBx suggests a possible direct involvement of the virus whereby the HBx protein, acting as a transcriptional transactivator of viral genes, may alter host gene expression and lead to the development of hepatocellular carcinoma. We have tested this possibility of placing the entire HBx gene under its own regulatory elements directly into the germline of mice. Transgenic animals harbouring this viral gene succumbed to progressive histopathological changes specifically in the liver, beginning with multifocal areas of altered hepatocytes, followed by the appearance of benign adenomas, and proceeding to the development of malignant carcinomas. Male mice developed disease and died much earlier than females. This transgenic animal model appears ideal for defining the molecular events that follow the expression of the viral HBx gene and are responsible for the development of liver cancer."
-What is the significance of bacterial translocation in trauma patients according to the study?,"Bacterial translocation in trauma patients. Sepsis and multiple system organ failure (MSOF) are major causes of morbidity and mortality in trauma patients. Bacterial translocation induced by hypotension, endotoxemia, or burns is a reproducible phenomenon in the laboratory. The incidence of bacterial translocation to mesenteric lymph nodes (MLNs) in 29 critically ill patients was evaluated to determine its relationship to subsequent sepsis and MSOF. Bacterial translocation was documented in 3 of 4 patients who underwent laparotomy for gastrointestinal (GI) disease. No trauma patient (25 patients), even at second exploration 3-5 days after injury, had a positive MLN culture. Five patients died; 4 trauma patients, one with GI disease. Forty percent of the trauma patients had major complications, predominantly pulmonary infections with gram-negative bacteria. However, infectious complications and outcome were not related to MLN culture results. The classical progression of bacteria from the gut to the bloodstream via the MLNs may require time and gut mucosal injury. The data suggest that bacterial translocation to the MLNs is not a common occurrence in acutely injured trauma patients."
-What were the main objectives of the study on optical properties of myocardium?,"Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength. Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation."
-How does the presence or absence of an androgen receptor affect blood pressure in hybrid male rats?,"Androgen receptor and the testes influence hypertension in a hybrid rat model. The objective of this study was to determine if males with a deficient androgen receptor would develop hypertension when crossed with a hypertensive parent. Female King-Holtzman rats (n = 15), heterozygous for the testicular feminization (Tfm) gene, were crossed with male spontaneously hypertensive rats (SHR), and blood pressure was measured weekly from 5-14 weeks in the F1 hybrid males. Approximately 50% of the F1 hybrid males were Tfm males and androgen receptor-deficient, and 50% were normal. Blood pressure in the parent King-Holtzman males, Tfms, and female rats was also followed for the same time period. The F1 normal male hybrids had a significantly higher (p less than 0.05) systolic blood pressure than the Tfm hybrid males after 12 weeks (195 +/- 8 versus 170 +/- 8 mm Hg, respectively). Blood pressure in the male and Tfm Holtzman rats was 120 +/- 5 mm Hg and 110 +/- 6 mm Hg, respectively. Castration lowered blood pressure by 38 mm Hg in the hybrid males and 27 mm Hg in the Tfm hybrids. Female F1 hybrids also showed a pressure rise above that of female Holtzman controls (155 +/- 6 mm Hg versus 110 +/- 6 mm Hg, p less than 0.01) but lower than the F1 males and Tfm hybrids. Ovariectomized females with testosterone implants did not show an elevation in blood pressure. Plasma electrolytes, norepinephrine, and cholesterol were not significantly different between normal and Tfm hybrid males. The results suggest that the presence of an androgen receptor and a testis-derived factor mediate the blood pressure rise in the hybrid males."
-What was the primary aim of the study investigating total parenteral nutrition in patients with head and neck cancers?,"Tumor cytokinetic response to total parenteral nutrition in patients with head and neck cancers. Refeeding of patients with malignant tumors may induce tumor-cell DNA synthesis. The present study was aimed at evaluating whether induction of altered cell-cycle kinetics could be induced by intravenous total parenteral nutrition (TPN) in tumor biopsies from head and neck cancers. Nine malnourished patients with squamous cell carcinoma in the head-and-neck area were investigated before and after 5-7 d of continuous TPN. Tumor biopsies were taken in both fasted and fed states for determination of 1) ornithine decarboxylase (ODC) activity, which is rate limiting for polyamine synthesis; 2) flow-cytometric-DNA-distribution measurements; and 3) the fraction of proliferating cells expressed as immunohistochemical reactivity with the monoclonal antibody Ki-67. The histopathological differentiation, the fraction of aneuploidic cells, ODC activity, and Ki-67 reactivity were not significantly related to each other, although the number of aneuploidic cells in replicative phases correlated with the number of cells expressing the Ki-67 antigen (r = 0.86, P less than 0.01). Tumor cytokinetics showed no evidence of being changed by TPN administration."
-What is the importance of obtaining a comprehensive patient history during preoperative evaluation of a cardiac patient undergoing non-cardiac surgery?,"Preoperative evaluation of the cardiac patient for noncardiac surgery. In summary, obtaining a comprehensive patient history is a critical part of the diagnostic and risk stratification process of the patient with cardiac disease undergoing non-cardiac surgery. Many of the factors associated with perioperative cardiac morbidity are treatable and early and aggressive management appears to have beneficial effects on morbidity and mortality rates."
-What is the rare medical condition described in this case report involving a plasmacytoma and superior vena cava syndrome?,"Superior vena cava syndrome caused by an intrathoracic plasmacytoma. A case of an extramedullary intrathoracic plasmacytoma causing superior vena cava syndrome is described. Review of the literature on intrathoracic plasmacytomas and superior vena cava syndrome revealed that no similar cases have been described to date. The initial presentation, management, and response to treatment are described."
-What is the rare cause of left-sided portal hypertension described in this medical case report?,"Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature."
-How does the accumulation of PrPSc in different brain regions correlate with scrapie infectivity in Syrian hamsters?,"Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases."
-What is the rarity and pattern of association between squamous cell carcinoma of the upper aerodigestive tract and well-differentiated thyroid carcinomas?,"Squamous cell carcinoma of the upper aerodigestive tract associated with well-differentiated carcinoma of the thyroid gland. The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer."
-What are the key endogenous mediators involved in gastroprotection according to the review?,"Mechanisms of gastric mucosal injury and protection. This article emphasizes and reviews the premise that because the pathogenesis of acute gastric mucosal injury is multifactorial, several protective mechanisms should also be considered in analyzing gastric mucosal defense. The first part of the article reviews the pathogenesis of acute gastric mucosal injury by major etiologic factors such as hypoxia and chemical and biological agents, and emphasizes the common endogenous mediators of damage (e.g, endothelins, leukotrienes, thromboxane, platelet-activating factor, monoamines, free radicals, proteases, ammonia, hydrochloric acid, and bile acids--in decreasing potency). The second part of the review is devoted to the gastroprotective mechanisms that are analyzed by anatomical (histologic) location and biochemical processes. The endogenous mediators of acute gastroprotection include prostaglandins, sulfhydryl (SH) compounds, non-SH antioxidants, polyamines, and epidermal growth factor, whereas the protective and mediatory role of glucocorticoids, somatostatin, pentagastrin, histamine, gangliosides, and calcitonin gene-related peptide need further studies. A list of endogenous and exogenous chemicals that exert biphasic, damaging, and protective effects on the gastric mucosa in also included. The final common pathway of acute gastroprotection at the structural and functional level seems to be the preservation of subepithelial microvascular integrity leading to maintenance of mucosal blood flow that allows the energy-dependent rapid restitution (cell migration) from surviving gastric neck cells to repair the superficial epithelial defect. Very new data on the contribution of a histodilutional barrier and release of proteases to gastroprotective processes are also discussed."
-What percentage of patients in the study had at least one preoperative risk factor?,"Comorbidities and perioperative complications among patients with surgically treated benign prostatic hyperplasia. We address the question of whether or not age and comorbidity are related to intra- and postoperative complications after a transurethral resection. The data are derived from a retrospective, population-based study conducted in Hagen, Germany, which included all patients with an initial prostatectomy for benign prostatic hyperplasia (N = 621) during the five-year period 1984-1988. Seventy-seven percent of the patients had at least one of the following preoperative risk factors: heart disease, hypertension, smoking, chronic obstructive lung disease, and diabetes. There was no intraoperative death. The risk of intraoperative circulatory complications was found to be related to age only for patients without a history of heart diseases or hypertension. The incidence of major complications was 3.1 percent and was significantly higher in the oldest age group. Three patients (0.54%) died postoperatively in the hospital. Infections were the most frequent postoperative complications. The relationship of age and overall postoperative complications was not statistically significant either for patients with (p = 0.121) or without any comorbidity (p = 0.651). Based on this study it seems reasonable to conclude that age is not a clinically relevant risk factor for perioperative complications in patients who have a transurethral resection for benign prostatic hyperplasia."
-"What is the purpose of using a free gastric mucosal flap with microvascular transfer in the reconstruction of malignant lesions in the oral cavity, base of tongue, and oropharynx?","Tolerance of gastric mucosal flap to postoperative irradiation. When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered."
-What are the key clinical characteristics of the dominantly inherited mitochondrial myopathy described in this study?,"Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies. We studied a large family with a dominantly inherited mitochondrial myopathy characterized by progressive external ophthalmoplegia, dysphagia, cataract, lactic acidosis, exercise intolerance, and early death. Morphologic studies of muscle biopsies suggested mitochondrial heteroplasmy and revealed ragged-red fibers and decreased histochemical reactions for cytochrome c oxidase and succinate dehydrogenase. Biochemistry showed a partial defect of cytochrome c oxidase and a mild generalized reduction of other mitochondrial enzymes requiring mitochondrial DNA-encoded subunits. Southern blot analysis and PCR amplification showed mitochondrial DNA deletions in muscle of all affected members, but not in lymphocytes or fibroblasts, suggesting a tissue-specific distribution. Deletions were multiple and seemed to increase with time and to correlate with the severity of the disease."
-What correlation was found between periventricular lesions on MRI and the severity of white matter changes in elderly patients?,"Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. Magnetic resonance imaging (MRI) was performed postmortem on the brains of 40 patients aged over 60 yrs who had died from causes other than brain disease. Periventricular lesions of increased signal intensity on T2-weighted images, graded as moderate or severe, were found in 10% of the patients in the age group between 60 and 69 yrs, and in 50% between 80 and 89 yrs. Macroscopic and microscopic whole-brain sections were studied in 19 brain specimens (8 with normal white matter, 4 with moderate lesions and 7 with severe lesions of the white matter on MRI). The presence or absence of periventricular lesions on MRI correlated well with the severity of demyelination and astrocytic gliosis. Demyelination was always associated with an increased ratio between wall thickness and external diameter of arterioles (up to 150 microns). A variable degree of axonal loss in Bodian-stained sections was present in the white matter of all brains with demyelination. Dilated perivascular spaces were found and studied morphometrically in 9 brain specimens; their presence correlated strongly with corrected brain weight, but incompletely with demyelination and arteriolosclerosis. Our findings suggest that arteriolosclerosis is the primary factor in the pathogenesis of diffuse white matter lesions in the elderly. This is soon followed by demyelination and loss of axons, and only later by dilatation of perivascular spaces."
-What are the key considerations in sphincter-sparing surgery for patients with ulcerative colitis or rectal tumors?,"Sphincter-sparing surgery. Since World War II, a variety of technical innovations have been introduced to preserve the anal sphincter in patients with chronic ulcerative colitis or tumors of the rectum. Studies of anorectal physiology have yielded guidelines for preserving continence and minimizing morbidity. For example, preservation of the anal rectal angle is essential; the rectal mucosa can be removed without impairing neural mechanisms; construction of a reservoir increases rectal compliance. Following these guidelines, surgeons have introduced new techniques and applications benefiting a larger and more varied patient population. Some technical problems remain, however, and patient selection criteria for restorative rectal surgery need to be refined."
-What was the mean time from symptom onset to diagnosis for patients with an identifiable syndrome in this study of adrenal tumors?,"Efficient management of adrenal tumors. A retrospective analysis was carried out on 121 patients with primary adrenal tumors operated on at 2 Vancouver hospitals between the years 1970 and 1990. The purpose of the study was to identify discriminating factors between the various diagnoses in order to minimize both the time and the cost of the investigative process. There were 57 cortical adenomas, 35 pheochromocytomas, 15 carcinomas, 8 cases of cortical hyperplasia, and 6 miscellaneous tumors. The mean time from the onset of symptoms to diagnosis of those patients presenting with an identifiable syndrome was 48.3 months. Those with a hypertensive syndrome presented significantly later than those with Cushing's syndrome (57.7 months versus 22.8 months, p less than 0.01). There was a significant delay in diagnosis in those patients with hypertension on the basis of an aldosteronoma as compared with those with hypertension secondary to a pheochromocytoma (75.4 months versus 36.1 months, p = 0.02). Cortical carcinomas were significantly larger than benign cortical tumors (12.7 cm versus 5.5 cm). No malignant neoplasm measured less than 5 cm in diameter. Diagnostic sensitivity for intravenous pyelogram (IVP) was 59%, for ultrasound 71%, for venography 50%, for meta-iodobenzylguanidine (MIGB) (pheochromocytoma only) 80%, and for angiography 70%. However, for those patients with adrenal carcinomas, angiography was positive in 100% of cases. Computed tomography (CT) was the most sensitive localizing investigation with a sensitivity of 98%. While other localizing techniques were less sensitive than CT, they may still play a useful role in selected situations. Factors causing delay in diagnosis and the role of the various imaging modalities are discussed."
-What were the key findings of the Jamaican study regarding nutritional supplementation and growth in stunted children?,"Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study. The benefits of nutritional supplementation, with or without psychosocial stimulation, on the growth of stunted children were evaluated. Children aged 9-24 mo with lengths less than -2 SD of the National Center for Health Statistics references (n = 129) were randomly assigned to four groups: control, nutritional supplementation, stimulation, and both interventions. A fifth group with lengths greater than -1 SD was also enrolled. Length, weight, head and arm circumferences, and triceps and subscapular skinfold thicknesses were measured on enrollment and 6 and 12 mo later. Multiple-regression analysis was used to determine the effects of the interventions in which age, sex, initial status, initial dietary intake, and several socioeconomic variables were controlled for. Stimulation had no effect on growth and there was no interaction between the interventions. After 12 mo supplemented children had significantly increased length, weight, and head circumference (all P less than 0.01). The effects of supplementation were not cumulative but occurred in the first 6 mo."
-How is gastric cancer different during pregnancy compared to other periods of a woman's life?,"Gastric carcinoma presenting as an exacerbation of ulcers during pregnancy. A case report. Gastric cancer is unusual during pregnancy. Also, because of the physiologic changes that occur with pregnancy, it is rare to see a worsening of peptic ulcers during pregnancy. A patient with an exacerbation of peptic ulcers presented with gastric carcinoma during pregnancy."
-What are the key diagnostic and treatment strategies for stress fractures in athletes?,"Stress fractures in athletes. How to spot this underdiagnosed injury. Stress fractures are an increasingly common injury in competitive athletes, especially runners. Amenorrheic athletes are at particularly high risk. A radionuclide bone scan should be considered when the index of suspicion for stress fracture is high. Plain radiographs are of little use in establishing the diagnosis in the early stages of the injury. Early diagnosis and prompt institution of conservative therapy allow for a favorable outcome in most cases. Avoidance of or reduced participation in the inciting activity is important for pain control. Certain stress fractures, such as those involving the femoral neck, should be monitored closely and treated aggressively with internal fixation when conservative measures fail. Runners who have exercise-induced amenorrhea should be advised to decrease their training intensity to a level where menses resume. Cyclic therapy with conjugated estrogens and progesterone should also be considered, as should daily calcium supplementation."
-What were the main causes of death among patients treated with human pituitary growth hormone in this study?,"Mortality, neoplasia, and Creutzfeldt-Jakob disease in patients treated with human pituitary growth hormone in the United Kingdom OBJECTIVE--To determine the cause of death and incidence of neoplasia in patients treated with human pituitary growth hormone. DESIGN--A long term cohort study established to receive details of death certification and tumour registrations through the Office of Population Censuses and Surveys and NHS central register. PATIENTS--All patients (1246 male, 662 female) treated for short stature with pituitary growth hormone under the Medical Research Council working party and health services human growth hormone committee. MAIN OUTCOME MEASURES--Death or development of neoplasia. RESULTS--110 patients died (68 male, 42 female; aged 0.9-57 years) from 1972 to 1990. Fifty three death were from neoplasia responsible for growth hormone deficiency (27 craniopharyngioma, 24 other intracranial tumour, two leukaemia); two from histiocytosis X; and 13 from pituitary insufficiency. Six patients died of Creutzfeldt-Jakob disease, six of other neurological disorders, and eight of acute infection. Other deaths were apparently unrelated to growth hormone deficiency or its treatment. Seventeen tumours (in 16 patients) were identified during or after growth hormone treatment. Four were in patients with previous intracranial neoplasia and two were after cranial irradiation. Thirteen were intracranial, the others being Hodgkin's lymphoma, osteosarcoma, carcinoma of colon, and basal cell carcinoma. CONCLUSIONS--Recurrence or progression of intracranial tumours and potentially avoidable metabolic consequences of hypopituitarism were the main causes of death. Growth hormone treatment probably did not contribute to new tumour development. Creutzfeldt-Jakob disease after pituitary growth hormone treatment continues to occur in the United Kingdom. This cohort must remain under long term review."
-What differences were observed in neutralizing antibody development among patients treated with different interferon-alpha preparations?,"Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. The frequencies of antibody development so far reported in patients treated with different interferons (IFNs) are not readily comparable because of differences in treatment regimens and assay methods. Thus the frequency of neutralizing antibody development was analyzed in a large sample of sera derived from a relatively homogeneous group of patients treated with different IFN-alpha preparations. The frequency of developing neutralizing antibody to IFN varied according to the IFN given. Particularly, the seroconversion frequency was significantly higher in patients treated with recombinant IFN-alpha 2a (20.2%) than in patients treated with either recombinant IFN-alpha 2b (6.9%) or IFN-alpha N1 (1.2%), a lymphoblastoid IFN-alpha. Furthermore, sera obtained from patients treated with either recombinant IFN neutralized both types of recombinant IFNs but failed to neutralize IFN-alpha N1."
-What is the significance of Glial fibrillary acidic protein (GFAP) expression in pleomorphic adenomas and chordomas?,"Glial fibrillary acidic protein expression in pleomorphic adenoma, chordoma, and astrocytoma. A comparison of three antibodies. Glial fibrillary acidic protein (GFAP) is a major constituent of glial cytoplasmic intermediate filaments. Glial fibrillary acidic protein expression has been accepted as a marker of astroglial differentiation or origin. However, GFAP expression has been demonstrated in a variety of normal and neoplastic tissues outside the central nervous system, including pleomorphic adenomas, chordomas, bone, and cartilage. It has been postulated that coexpression of GFAP and vimentin in neoplastic myoepithelial cells in pleomorphic adenomas reflects early chondroid differentiation. Glial fibrillary acidic protein expression in chondromyxoid and chordoid tumors was studied in formaldehyde solution-fixed, paraffin-embedded sections of 20 pleomorphic adenomas and 10 chordomas by the immunoperoxidase method with the use of commercially available monoclonal (n = 2) and polyclonal (n = 1) antibodies. All pleomorphic adenomas and chordomas demonstrated expression of GFAP with the use of the polyclonal antibody (Biomeda Corp [Foster City, Calif]). Variable expression of GFAP was present in 90% (18/20) and 70% (14/20) of pleomorphic adenomas, and in 20% (2/10) and 0% of chordomas, with the use of the two monoclonal preparations (Dakopatts [Glostrup, Denmark] and BioGenex Laboratories [San Ramon, Calif]), respectively. Normal brain tissue and eight astrocytomas were used as ""controls"" to compare staining intensity and quality between the polyclonal and monoclonal anti-GFAP antibodies. Glial fibrillary acidic protein positivity with the polyclonal antibody was more intense than that with either monoclonal antibody despite similar (congruent) distributions of tumor cell types that were stained in control brain and astrocytoma tissues. The GFAP polyclonal antibody was more frequently immunoreactive than the monoclonal antibodies, particularly in cells that exhibited chondroid differentiation. These findings may have practical application in surgical pathology."
-What was the primary purpose of the study on endovascular stents in congenital heart disease?,"Use of endovascular stents in congenital heart disease. BACKGROUND. Balloon expandable intravascular stents have been used to support vessel walls in coronary and peripheral arteries in adults. The purpose of this study was to examine the efficacy and safety of these stents in the treatment of congenital heart disease. METHODS AND RESULTS. Forty-five stents were placed in 30 patients, who were 0.2-30.2 years old (weight, 3.5-76 kg). Patients with areas of stenosis that were difficult to approach surgically were chosen. Stents were mounted over balloons and placed by standard catheterization techniques. Twenty-three patients had branch pulmonary artery stenosis. Thirty-six stents were placed successfully and had reduced pressure gradients from 50.6 +/- 24 to 15.9 +/- 13.4 mm Hg. Five patients had stents placed after atrial surgery: three in obstructed Fontan repairs, one at the superior vena cava-right atrial junction after sinus venous defect repair, and one at the site of a Glenn shunt. Atrial stents reduced pressure gradients from 9.8 +/- 8.2 to 2.0 +/- 2.6 mm Hg. One patient had a stent placed in the descending aorta after coarctation dilation, and the pressure gradient was reduced from 50 to 25 mm Hg. One patient had pulmonary vein dilation with stent placement. Two stents migrated at the time of placement; one required surgical removal, and one was anchored in place by balloon dilation. One patient died within 24 hours of catheterization because of thrombus obstruction of the Fontan repair. Nine patients have undergone recatheterization. All stented vessels have remained at the same caliber as at original stent placement. CONCLUSIONS. We conclude that balloon expandable stents are useful in selected postoperative stenoses in congenital heart disease."
-What potential complication can tissue plasminogen activator (t-PA) cause during treatment of acute myocardial infarction?,"Intracerebral hemorrhage related to cerebral amyloid angiopathy and t-PA treatment. Tissue plasminogen activator (t-PA) has been approved as thrombolytic therapy for the treatment of acute myocardial infarction, but this agent can cause serious bleeding complications including intracerebral hemorrhages. Mechanisms underlying the development of these hemorrhages have not been clarified. We report a patient who developed two intracerebral hemorrhages shortly after receiving t-PA for the treatment of an acute myocardial infarction, and who was found to have cerebral amyloid angiopathy at autopsy. Staining of cortical sections with Congo red and an antibody directed against beta amyloid protein (A4 peptide) disclosed specific involvement of most of the subarachnoid and superficial cortical vessels in the region of the two hemorrhages. Based on the findings in this patient and in 6 additional patients reported recently, it is likely that cerebral amyloid angiopathy plays a pathogenic role in some intracerebral hemorrhages associated with the administration of t-PA. The cautious use of t-PA with heparin in patients who are elderly or demented may be advisable."
-What percentage of patients with clinical stage A1 and A2 prostate cancer were found to have no cancer during radical prostatectomy?,"Radical prostatectomy for stage A adenocarcinoma of the prostate: staging errors and their implications for treatment recommendations and disease outcome. Of 148 patients with clinical stage A1 (32) or A2 (116) disease who had radical prostatectomy only 63% and 62%, respectively, had pathological stage A disease. Although 25% of those with clinical stage A1 and 9% of those with clinical stage A2 disease had no cancer at radical prostatectomy, 12% and 29%, respectively, had pathological stage C disease or higher. Clinical Mayo grade 1 was never associated with extracapsular disease but 60% of those with grade 3 or higher tumor did have extracapsular disease. Over-all survival was comparable to the expected survival. Clinical stage A2 cancer was associated with a significantly higher progression rate (when prostate specific antigen values were considered, p = 0.0011) and cancer death rate (p less than 0.045) than stage A1 disease, whereas pathological stage was not significantly related to disease outcome, possibly because of the use of adjuvant treatment (hormonal or radiation) for some patients with pathological stage C or higher disease. The vagaries of clinical staging associated with stage A disease, as well as the previously documented progression on long-term followup (8 to 10 years) in younger (60 years old or less) patients with stage A1 prostate cancer make radical prostatectomy with its limited morbidity an acceptable treatment choice."
-What is the overall mortality rate for patients with group B streptococcal endocarditis of the tricuspid valve?,"Group B streptococcal endocarditis of tricuspid valve. We report three cases of group B streptococcal endocarditis of the tricuspid valve. Two patients were intravenous drug abusers. In the literature review, and including our cases, ten patients had group B streptococcal endocarditis of the tricuspid valve. Half of the patients were intravenous drug abusers. Four of the other patients had underlying conditions. All patients were treated with a penicillin with or without an aminoglycoside. Three patients underwent tricuspid valve surgery. The overall mortality was 20 percent. Both patients who died received medical therapy only."
-What diagnostic technique ultimately revealed the presence of a myocardial abscess in this case of aortic valve endocarditis?,"Coronary artery narrowing due to extrinsic compression by myocardial abscess. A case of aortic valve endocarditis complicated by perivalvular abscess extending into myocardium is presented. Echocardiography and aortography failed to detect the abscess, but coronary angiography revealed its presence by extrinsic compression of left anterior descending and diagonal arteries. Morphological features of this rare cause for coronary narrowing are described."
-What preoperative evaluations are recommended for diagnosing urethral diverticulum and stress incontinence in female patients?,"Surgical treatment of concomitant urethral diverticulum and stress incontinence. Urinary incontinence is frequently associated with a urethral diverticulum in female patients. Preoperative evaluation including a thorough history and physical examination, voiding cystourethrogram, urethroscopy, and urodynamic studies can diagnose both the urethral diverticulum and any concomitant bladder-urethral dysfunction. Preoperative recognition of stress urinary incontinence or patients at risk for this problem postoperatively permits effective treatment with concomitant transvaginal bladder neck suspension and urethral diverticulectomy."
-What surgical technique was used to treat chronic infected hip arthroplasty wounds in this study?,"Treatment of chronic infected hip arthroplasty wounds by radical debridement and obliteration with pedicled and free muscle flaps. Nine patients with extensive wounds of the hip joint due to chronic infection following total hip arthroplasty or internal fixation of fractures of the femoral head and neck have been treated by serial radical debridements to remove infected bone, contaminated remnants of bone cement, and the surrounding fibrotic soft tissues. The resultant deep cavity extending down to the acetabulum has then been obliterated with either pedicled muscle flaps or free muscle flaps. Subcutaneous or transpelvic transposition of rectus abdominis muscle flaps is preferred for smaller defects, but only the free latissimus dorsi muscle flap provides sufficient volume of tissue to obliterate the more extensive hip defects. Systemic antibiotics have been continued only for a short-term course of 14 days postoperatively. There has been no recurrence of infection, with follow-up ranging between 6 months and 3 1/4 years. One patient has undergone reimplantation of a second custom hip prosthesis into the vascularized bed of a free latissimus dorsi muscle flap."
-What technique was used to treat large bony defects after cystectomy in this study?,A modified technique for obliteration of large bony defects after cystectomy. Thirteen cysts treated by enucleation followed by collapsing an osteoperiosteal flap to eliminate dead space are presented. Four of the cysts were dentigerous and nine were radicular. The bony defects ranged in size from 3 to 7 cm in greatest dimension. Healing by primary intention occurred in all cases. This method has been found to be successful in the obliteration of large bony defects after cystectomy.
-"What were the antibody response levels for pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens in infants aged 3 to 8 months and children aged 24 to 30 months after the fourth vaccine dose?","A comparative trial of the reactogenicity and immunogenicity of Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids. Outcome in 3- to 8-month-old infants, 9- to 23-month-old infants and children, and 24- to 30-month-old children. The reactogenicity and immunogenicity of the Takeda acellular pertussis vaccine combined with tetanus and diphtheria toxoids were compared in 139 infants aged 3 to 8 months, 60 infants and children aged 9 to 23 months, and 99 children aged 24 to 30 months. Good antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), and agglutinogens occurred in all age groups after both the third and fourth doses. After the fourth (booster) dose, the mean antibody values in initially seronegative infants vaccinated at 3 to 8 months of age were as follows: anti-PT, 67.8 enzyme-linked immunosorbent assay units (EU) per milliliter; anti-FHA, 149.5 EU/mL; the agglutinin titer was 125.6. The values in initially seronegative children vaccinated at 24 to 30 months of age were as follows: anti-PT, 92.9 EU/mL; anti-FHA, 251.7 EU/mL; the agglutinin titer was 275.8. Reactions following immunization were minimal. Except for drowsiness after the first dose in infants, there were no clinically significant differences in reactions between infants and older children. The findings in this study coupled with the recent demonstration of efficacy of this vaccine in 2-year-old children supports the recent Japanese recommendation to lower the age of immunization with acellular pertussis vaccine combined with tetanus and diphtheria toxoids to 3 months."
-What is a ganglioglioma and how can it cause hemifacial spasm in an infant?,"Hemifacial spasm in an infant due to fourth ventricular ganglioglioma. Case report. The case of an infant is reported in which hemifacial spasm due to a ganglioglioma of the fourth ventricle was relieved by surgery. Previously described causes of hemifacial spasm are summarized, and the relevance of this case to theories on the pathogenesis of the condition is discussed."
-What was the key finding regarding the relationship between spinal cord ischemia duration and neurologic outcomes in the rabbit study?,"The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. To clarify the cause of delayed-onset paraplegia, the authors evaluated the neurologic outcome after temporary (10 to 30 minutes) spinal cord ischemia in the awake rabbit. Loss of motor function occurred in less than 2 minutes in all animals. Restoration of flow within 16 minutes always resulted in full return of function, whereas with occlusion times of greater than 27 minutes all animals remained paralyzed. After temporary occlusion of 20 to 21 minutes, however, 71% of animals returned to normal neurologic function but developed delayed-onset paraplegia 14 to 48 hours later. This appears to be a reliable method for the creation of a model of delayed-onset paraplegia in the awake animal, and will facilitate more detailed studies of the pathophysiology of ischemia-induced paraplegia."
-What were the long-term surgical outcomes for patients who underwent lateral cranial base surgery between 1970 and 1987?,"Long-term results after lateral cranial base surgery. The surgical management of patients with slow-growing benign temporal bone neoplasms has been criticized because of its significant morbidity and mortality compared with results after radiation therapy, but long-term control by irradiation remains unproved. Long-term surgical results have not been studied previously. One hundred twenty-nine skull base operations were performed in 126 patients at the Otology Group, Nashville, Tenn., from January 1970 through May 1987. Fifty-eight patients responded to questionnaires focusing on recovery from loss of cranial nerves. All patients regained some degree of facial function (class V or better), no alimentary tubes or tracheotomies were in use, and no patients had debilitating aspiration. Long-term compensation from the cranial nerve deficits of lateral skull base surgery can be expected in most patients and should not be used as an argument for irradiation in patients with a long life expectancy at time of diagnosis."
-How does gastric intramucosal pH relate to mortality rates in critically ill patients?,"Gastric mucosal pH as a prognostic index of mortality in critically ill patients. OBJECTIVE: To determine if measurements of gastric intramucosal pH have prognostic implications regarding ICU mortality. DESIGN: Prospective comparison of outcome. SETTING: General adult ICUs in two teaching hospitals. PATIENTS: Eighty consecutive patients age 18 to 84 yrs (mean 63.4), 50 men and 30 women, 55% in the medical and 45% in the surgical services. METHODS: Gastric intramucosal pH was measured on ICU admission and again 12 hrs later. A value of greater than or equal to 7.35 was used to differentiate between normal and low gastric intramucosal pH. MEASUREMENTS AND MAIN RESULTS: Fifty-four patients had a normal gastric intramucosal pH and 26 patients had a low gastric intramucosal pH on ICU admission. The mortality rate was greater in the low gastric intramucosal pH group (65.4% vs. 43.6%; p less than .04). The frequency of sepsis and the presence of multisystem organ failure also were greater in the low gastric intramucosal pH group (p less than .01). Further stratification of patients according to gastric intramucosal pH measured 12 hrs after admission showed a greater mortality rate in patients with persistently low gastric intramucosal pH when compared with patients with normal gastric intramucosal pH during the first 12 hrs (86.7% vs. 26.8%; p less than .001). CONCLUSIONS: Measurements of gastric intramucosal pH on ICU admission, and again 12 hrs later, have a high specificity for predicting patient survival in this ICU patient population (77.8% to 80.6%). Furthermore, given its relative noninvasive nature, tonometrically measured gastric intramucosal pH may be a useful addition to patient monitoring in the ICU."
-What percentage of patients showed allelic loss at the retinoblastoma (RB) locus in their ovarian tumor tissues?,"Allele loss at the retinoblastoma locus in human ovarian cancer. To gain a broad spectrum on allelic loss of specific loci in ovarian tumors, we initially examined DNA from 23 pairs of ovarian tumors and matched peripheral blood lymphocyte samples from the same patients, using 27 polymorphic DNA markers distributed on 13 chromosomes. Significant high frequency of allelic deletion (22%-44%) at chromosome 13 loci (D13S31, D13S32, D13S33, and D13S34) at bands q12-q34 was observed in tumor tissues. These results led us to investigate the loss of heterozygosity at the retinoblastoma (RB) locus in ovarian tumors, because the RB gene is a tumor-suppressor gene located at 13q14. Analysis of the variable number of tandem repeat sequence polymorphism in intron 20 in the RB gene revealed that 6 (30%) of 20 patients with informative samples showed allelic loss at the RB locus in their tumor tissues. This loss, of relatively high frequency, suggests that the RB gene, or a closely linked gene, seems to be involved in the development of ovarian cancer."
-What were the most frequently reported prodromal symptoms in soldiers who experienced exertional sudden death?,"Exertional sudden death in soldiers. To address the problem of a significant rise in the incidence of exertional sudden death worldwide, the medical records and necropsy reports of all deaths that occurred in the Israel Defence Forces (IDF) during 1974-1986 were scrutinized. Twenty male soldiers, aged 18-29 yr, died suddenly and unexpectedly within 24 h of strenuous exercise. Necropsy results, available for 90% of the subjects, included underlying cardiac disease in 50% and noncardiac causes of death in 33.3%; the cause of death was unidentifiable in 16.7% of the subjects. Prodromal symptoms in 70% of the subjects are presented as a main focus of this investigation. The most frequently reported symptom was exertional or nonexertional syncope in 40% of the subjects. Chest pain, acute gastrointestinal symptoms, or febrile disease were reported in 30% of the cases. The findings of this research suggest that syncope is a major antecedent symptom of exertional sudden death. An attack of syncope in young conditioned individuals should be followed by thorough medical surveillance, and strenuous exercise should be avoided until this procedure is completed. Sports and military officials have the obligation to promote awareness that strenuous exercise should not be performed in the presence of acute gastrointestinal symptoms or febrile illness."
-How does early chronic administration of clonidine affect portal pressure and mesenteric-systemic shunts in portal vein-stenosed rats?,"Prevention of portal hypertension and portosystemic shunts by early chronic administration of clonidine in conscious portal vein-stenosed rats. The hemodynamic effects, including mesenteric-systemic shunts of early chronic administration of clonidine, were studied in conscious, unrestrained, portal vein-stenosed rats. In rats receiving early chronic clonidine (600 micrograms.kg-1.day-1 by gavage), begun 3 days before portal vein stenosis and then administered continuously for 10 consecutive days, portal pressure (10.0 +/- 1.5 mm Hg) and degree of mesenteric-systemic shunts (58% +/- 25%) were significantly lower than in the placebo group (15.2 +/- 1.5 mm Hg and 83% +/- 7%, respectively). The effects were observed either 2 to 3 hr or 18 to 24 hr after the last dose of clonidine. In rats receiving clonidine continuously for 5 days, starting 5 days after portal vein stenosis, portal pressure (11.0 +/- 1.3 mm Hg) was significantly lower than in the placebo group, but mesenteric-systemic shunts (82% +/- 8%) were not significantly different. In rats receiving a single oral dose of clonidine (600 micrograms/kg) 10 days after portal vein stenosis, portal pressure (11.8 +/- 2.1 mm Hg), measured 2 to 3 hr after clonidine administration, was significantly lower than in the placebo group. Mesenteric-systemic shunts (83% +/- 8%), however, were not significantly different from the placebo group. In addition, 18 to 24 hr after a single dose of clonidine, hemodynamic values returned to basal conditions. We also demonstrated that chronic clonidine administration begun before portal vein stenosis can reduce the initial increase in portal pressure after this procedure. We concluded that early chronic clonidine administration reduces the severity of portal hypertension and the development of portosystemic shunts in portal vein-stenosed rats."
-What was the primary hypothesis tested in this study regarding atrial natriuretic factor in cerebrospinal fluid?,"Cerebrospinal fluid atrial natriuretic factor in intracranial disease. We tested the hypothesis that the concentration of atrial natriuretic factor in the cerebrospinal fluid is an indicator of brain injury in patients with intracranial disease. Atrial natriuretic factor concentration was measured in 72 samples of cerebrospinal fluid from 28 patients with intraventricular drains and in nine samples from outpatient controls undergoing diagnostic lumbar puncture. Levels were correlated with diagnosis; systemic fluid administration; concentration of atrial natriuretic factor in the plasma; intracranial pressure; sodium, glucose, and protein concentrations, osmolality, and cell count in the cerebrospinal fluid; sodium concentration in the serum; and hemodynamics. Atrial natriuretic factor concentration was highest in cerebrospinal fluid from patients with intracerebral hematoma, followed by those with obstructive hydrocephalus and subarachnoid hemorrhage (19 +/- 2, 13 +/- 3, and 8 +/- 2 pg/ml, respectively); atrial natriuretic factor concentration was less than 4 pg/ml in the controls. Patients treated with fluid restriction had significantly higher atrial natriuretic factor levels than those receiving maintenance or high-volume fluids (16 +/- 3, 8 +/- 2, 10 +/- 1 pg/ml, respectively). The concentration of atrial natriuretic factor in the plasma was significantly elevated in patients with intracerebral hematoma and subarachnoid hemorrhage (155 +/- 38 and 92 +/- 20 pg/ml, respectively) and did not correlate with fluid administration or the concentration of atrial natriuretic factor in the cerebrospinal fluid. Neither cerebrospinal fluid nor plasma concentrations of atrial natriuretic factor correlated with intracranial pressure; cerebrospinal fluid sodium, glucose, or protein concentrations, osmolality, or cell count; serum sodium concentration; or hemodynamics. We conclude that the concentration of atrial natriuretic factor in the cerebrospinal fluid is a nonspecific indicator of brain injury."
-"How did exercise-induced myocardial ischemia affect the peak E and A velocities and E/A velocity ratio in the>>
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-Human question:","Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study Previous studies using Doppler echocardiography to evaluate left ventricular diastolic filling have shown that myocardial ischemia induced by coronary balloon angioplasty or atrial pacing results in a decrease in the left ventricular inflow peak early (E) to peak atrial (A) velocity ratio. To investigate the effects of exercise-induced ischemia on Doppler-derived filling variables, 20 patients with coronary artery disease and exercise-induced electrocardiographic changes and regional wall motion abnormalities determined by two-dimensional echocardiography were evaluated and compared with 20 patients without evidence of exercise-induced ischemia. Doppler echocardiography was performed at rest and immediately after exercise before the resolution of exercise-induced wall motion abnormalities. Peak E and A velocities increased from rest to postexercise in both the ischemic and nonischemic groups, although the ischemic group demonstrated a greater increase in peak E velocity (from 68 +/- 15 cm/s at rest to 88 +/- 22 cm/s after exercise) than the nonischemic group (70 +/- 13 to 77 +/- 18 cm/s) (p less than 0.05 for the difference in response between groups). Accompanying these changes was a slight increase in the peak E/A velocity ratio in the ischemic group (1.04 +/- 0.28 at rest to 1.13 +/- 0.42 after exercise) versus a decrease in the nonischemic group (1.07 +/- 0.30 to 0.90 +/- 0.28) (p less than 0.05 intergroup difference)."
-What are the long-term pathologic consequences of CNS treatment for childhood cancer?,"Long-term consequences of CNS treatment for childhood cancer, Part I: Pathologic consequences and potential for oncogenesis. The pathologic changes associated with the treatment of cancer of the nervous system are reviewed. Computed tomographic, magnetic resonance imaging, and positron emission tomographic findings of these abnormalities are described, followed by discussion of the known histopathologic features. For the most part, pathologic effects are primary vascular and/or demyelinating. We review each of these effects at all levels of the neural axis. This review concludes with a discussion of the risk of developing second malignancies. Although this complication is infrequent, the likelihood that survivors of childhood cancer will develop a second malignancy is 10 times that of age-matched controls. This phenomenon in part relates to genetic predisposition, environmental factors, and host susceptibility. These qualifications not withstanding, most studies implicate central nervous system radiation with and without chemotherapy as the primary etiology for second malignancies."
-"What clinical and laboratory features characterize the ""lymphoma syndrome"" in childhood acute lymphoblastic leukemia?","Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the ""lymphoma syndrome"" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL."
-How effective was the 2-mm choledochoscope in exploring small bile ducts and the pancreatic duct during intraoperative procedures?,"Intraoperative use of a 2-mm choledochoscope for the exploration of small bile ducts and the pancreatic duct. Intraoperative visualization of the biliary and pancreatic ducts can be difficult in a nondilated system. Very small extra- and intrahepatic bile ducts occasionally require visualization but do not admit the traditional 6.5-mm intraoperative flexible choledochoscope. We have prospectively examined the use of a 2-mm choledochoscope for the intraoperative evaluation of the biliary and pancreatic ducts in 36 patients. In 27 patients, the choledochoscope was advanced through the cystic duct stump for examination of the common bile duct following cholangiography. The scope was successfully passed into the cystic duct stump and into the common bile duct in 76 per cent of patients. Inability to pass the scope through the cystic duct was usually due to acute angulation of the cystic duct/common duct junction. In an additional five patients, intraoperative cholangiography revealed a filling defect in a very small duct. A choledochotomy was made and the 2-mm choledochoscope was used to exclude the presence of stones in a small bile duct. In four patients the choledochoscope was used during a Puestow procedure to visualize and help extract stones in the tail and head of the gland. No complications occurred in these patients due to the use of the choledochoscope. We conclude that the 2-mm choledochoscope aids in internal visualization of small intra- and extrahepatic bile ducts and the pancreatic duct. It may be useful as an adjunct to cholangiography in determining the nature of filling defects."
-What is hemifacial spasm and how was it diagnosed in this case report?,AAEM case report #21: hemifacial spasm: preoperative diagnosis and intraoperative management. A 75-year-old man developed progressive involuntary hemifacial spasm. Electrophysiologic evidence of abnormal cross-transmission between neurons of the facial nerve was demonstrated. Electrodiagnostic studies were used to confirm the diagnosis preoperatively and determine the adequacy of vascular decompression of the facial nerve intraoperatively.
-What gene rearrangement and deletion mechanisms are involved in the generation of human IgE-secreting cells?,"Generation and cloning of stable human IgE-secreting cells that have rearranged the C epsilon gene. Although the secretion of Ig isotypes other than IgM is generally accompanied by a DNA rearrangement that deletes C mu (and the other IgCH genes located between VDJ and the expressed CH gene), a system has recently been described that generates a high frequency of IgE-secreting cells that have failed to delete IgCH genes or to rearrange their C epsilon genes. These cells, derived from EBV-transformed human PBMC, secrete IgM and IgD as well as IgE. To determine whether the absence of C epsilon rearrangement and CH gene deletion is a general phenomenon for human IgE-secreting cells, we have characterized IgE-secreting cells that are generated by culturing purified human B cells with EBV plus IL-4 in the presence of irradiated human PBMC. In contrast to the earlier observation, we have not been able to detect any cells that demonstrate cytoplasmic staining for IgE and concurrently stain for a second Ig isotype. Stable IgE-secreting cell lines and clones produced by this method have rearranged one of their C epsilon genes and have deleted both C mu genes. These observations demonstrate that the generation of human IgE-secreting cells can involve the same gene rearrangement and deletional mechanisms that lead to the generation of cells that secrete other isotypes."
-What diagnostic method was used to evaluate lower-extremity vascular grafts in this study?,"Lower-extremity vascular grafts placed for peripheral vascular disease: prospective evaluation with duplex Doppler sonography. Eighty-five men with 92 vascular grafts placed for peripheral vascular disease of the lower extremity underwent a total of 264 examinations with duplex Doppler over a 2.5-year period. In 64 patients who underwent more than one examination, the total follow-up encompassed 740 months. In 220 native femoral arteries (96.0%) the peak systolic velocity (PSV) was higher than that in the graft. Arteriovenous shunting was associated with a normal PSV and a markedly elevated diastolic component at spectral analysis. Focal fluid collections were common initially near the graft and usually disappeared uneventfully. An average PSV of 32 cm/sec or less was always associated with impending occlusion. The sensitivity of an average PSV of 40 cm/sec or less to indicate impending graft occlusion by the next visit was only 33%; the specificity, 94%. At initial examination, stenoses were associated with high PSV focally in the graft or low PSV with absent diastolic flow."
-How do migraine sufferers describe their family environment differently compared to headache-free controls?,"The role of family structure, functioning, and pain modeling in headache. In an initial attempt to examine relationships between family functioning and chronic headache disorders, the present study examined: a) family structure characteristics, b) family functioning, and c) family pain modeling. Subjects completed an assessment battery consisting of several measures of family functioning. Analyses showed that migraine sufferers (N = 42) as compared to headache-free controls (N = 59) were more likely to describe their families as emphasizing clear organization, structure, rules, and overall control, but less likely to encourage emotional expression. No differences were found between tension headache subjects (N = 43) and headache-free controls. While only an initial exploration of the importance of family characteristics in chronic headache, these results suggest that there are important differences in headache subjects' (particularly migraine) reports of family environment and functioning."
-What are the five key managerial challenges identified for ensuring effective delivery of cancer services through strategic alliances?,"Community cancer programs as strategic alliances: challenges and guidelines for action. This paper assesses the utility of strategic alliances as a way of expanding and improving the quality of cancer care provided in communities with limited access to major treatment centres. Alliances provide an organizational model for future community-based cancer programs by accommodating a growing need for interdependence among organizations and providers while permitting substantial independence and autonomy. Five managerial challenges to ensuring effective and efficient delivery of cancer services are identified: to secure mutually reinforcing exchanges between and within all levels of cancer care, to develop protocols and programs relevant to the unique characteristics of patients and providers, to provide treatment and cancer control services, to involve interdisciplinary teams of providers at all levels of care and to achieve quality assurance, improvement and evaluation. In addition, the paper includes a set of guidelines to facilitate the implementation of community cancer programs as strategic alliances: reaffirm the role of community oncologists, primary care physicians and nurses as partners in the program; define the structure and culture necessary for commitment rather than simply compliance; redefine the role of management; establish data-monitoring systems; modify reward systems; and set realistic time frames and expectations."
-What were the most common CT findings in patients after liver transplantation?,"Abdominal CT findings after liver transplantation in 66 patients. CT scanning is used frequently to assess the condition of patients after liver transplantation. The CT records of 174 adult patients who underwent liver transplantation were studied retrospectively to determine the number and timing of CT studies as well as the frequency and significance of the findings. One-hundred seventy CT scans were obtained in 66 (38%) of the 174 patients, with a mean of 2.6 scans/patient. The interval between transplantation and scanning was 1 day to 24 months; in 59 (89%) of 66 patients, the first CT scan was obtained within 30 days. The acute indications for CT scanning were fever or leukocytosis in 54 (92%) of 59 patients and abnormal liver function tests in five (8%) of 59 patients. CT scans obtained more than 30 days after transplantation were repeat scans in all but seven patients. Indications in this latter group were the same as for the acute group, plus evaluation of hepatic neoplasia in three patients. CT findings included periportal low attenuation in 41 (62%) of 66 patients; ascites in 25 (38%); splenomegaly in 19 (29%); loculated intraperitoneal noninfected fluid collections in 13 (20%); intrahepatic, splenic, pancreatic, or perihepatic abscesses in seven (11%); hepatic infarction in six (9%); splenic infarction in three (4%); and hepatic calcification in two (3%). Other major abnormalities included inferior vena caval thrombosis (one patient), pseudoaneurysm of the hepatic artery with rupture (one patient), and recurrent hepatocellular carcinoma (one patient). CT scanning after liver transplantation is used predominantly in the acute setting to evaluate for liver infarction or intraabdominal abscess. In this setting, CT showed these abnormalities, in addition to tumor recurrence or vascular abnormalities, in 15 (23%) of 66 patients."
-What were the key differences in outcomes between patients who received prosthetic valves and those who received human allografts during emergency aortic valve replacement for infective endocarditis?,"Comparison of allografts and prosthetic valves when used for emergency aortic valve replacement for active infective endocarditis. Aortic valve replacement (AVR) using allografts is an established method of treating aortic valve disease. It is uncertain, however, whether the increased technical demands of allograft AVR can be justified in emergency operations. This study reports 15 patients treated between 1987 and 1990 for acute bacterial or fungal endocarditis involving the aortic valve. Patients underwent emergency AVR because of severe congestive failure, overwhelming sepsis or cerebral emboli. Eight patients received prosthetic valves (group I: 4 mechanical, 4 porcine) and 7 received human allografts (group II: 5 aortic and 2 pulmonary). The groups were comparable in age (group I, 55 years; group II, 51 years), intravenous drug abuse (group I, 1; group II, 3), and previous AVR (group I, 3; group II, 2). One group I and 4 group II patients had septal abscesses. Additional procedures in group I included mitral valve replacement (2), tricuspid valve replacement (1) and aortic root replacement (1). Additional procedures in group II were mitral valve repair (1), root replacement (1), atrial septal defect closure (1) and aortocoronary bypass (1). Mean bypass times (group I, 189 minutes; group II, 204 minutes) and cross-clamp times (group I; 108 minutes; group II, 121 minutes) were similar. Operative deaths occurred in 4 of 8 group I and 1 of 7 group II patients. All surviving patients have been successfully followed (group I, 28 months; group II, 18 months). No group I patient has required reoperation. One group II patients required reoperation for recurrent infection affecting the allograft, and another group II patient died 10 months postoperatively from noncardiac causes."
-What did the review of 200 consecutive patient case notes reveal about the necessity of specialist opinion in hearing aid prescription?,Hearing aid prescribing: is the specialist opinion necessary? A restructuring of the service for provision of hearing aids has been proposed by the Royal National Institute for the Deaf. This is based on the assumption that very few patients referred for hearing aids have significant ear disease and it is not necessary for them to see an ENT specialist. The case notes of 200 consecutive patients referred to the Hearing Aid clinic were reviewed. In only half of these would a hearing aid have been prescribed without a specialist opinion. The remainder either did not need a hearing aid or required further investigation and surgical or medical treatment. In addition there was significant evidence of lack of expertise amongst General Practitioners in recognizing ear disorders. It is imperative that any patient requiring a hearing aid be seen by someone experienced in otology rather than be dealt with by the General Practitioner alone.
-How does the expression of P-glycoprotein change in bladder cancer patients before and after chemotherapy treatment?,"Flow cytometric determination of the multidrug resistant phenotype in transitional cell cancer of the bladder: implications and applications. We detail our experience with a monoclonal antibody to detect the cell surface P-glycoprotein product of the multidrug resistance gene (MDR-1) in the human bladder. A total of 32 patients had 44 different specimens analyzed. The samples consisted of 8 normal bladders, 21 transitional cell carcinomas, 1 mucinous adenocarcinoma, 3 P-0 bladder wall specimens and 10 nonmalignant urothelial samples from cystectomies. P-glycoprotein was not detected in the normal adult or pediatric bladder. Bladder specimens from 3 children with a neurogenic bladder revealed enhanced expression (21%, 14% and 4% positivity). Transitional cell carcinoma usually demonstrates low expression at diagnosis (less than 6%), although 3 patients had enhanced initial expression (11%, 12% and 31%). Three patients treated with chemotherapy demonstrated 56%, 76% and 50% expression of MDR-1. Nonmalignant tissue from cystectomy specimens had low expression of MDR-1. The specificity of this system was confirmed with human bladder cell lines. The ability of flow cytometry to detect and quantify the expression of MDR-1 may allow for the early detection of chemotherapy resistance in patients with transitional cell carcinoma treated with systemic and intravesical therapy."
-How does sucralfate potentially enhance healing in the experimental pig ulcer model?,"Administration of sucralfate prolongs survival of animals with experimental peptic ulceration. Ligation of the pig bile duct (BDL) results in 100% incidence of pars esophageal ulceration within 48 hours of the procedure. Usually such ulceration is uniformly fatal unless a highly selective vagotomy is performed simultaneously with the BDL. The administration of sucralfate to pigs with BDL prolonged their survival for up to 7 days, with evidence of healing of the ulcer on macroscopic and histologic observations. An increase in cell proliferation in the squamous epithelium of the ulcerated area was also seen in this sucralfate group. These features were not seen in controls, pigs with BDL only, or pigs with BDL and with magaldrate (Riopone), colloidal bismuth subcitrate (DeNol), or carbenoxolone. Analysis by Sepharose 2B gel filtration showed that there was no significant difference in the amounts of polymeric mucin in any group, with a wide scatter of the data seen especially for pigs in the untreated BDL-only group. This study suggests that sucralfate may enhance healing in this experimental pig ulcer model via a mechanism independent of the stimulation of mucus secretion. We propose that coating the mucosa with sucralfate provides a temporary substitute barrier that creates a microenvironment conducive to wound repair by mucosal proliferation."
-How did the variability among surgeons impact postoperative outcomes and survival rates for patients undergoing colorectal cancer surgery?,"Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival. OBJECTIVE--To assess the differences among surgeons in postoperative complications, postoperative mortality, and survival in patients undergoing surgery for colorectal cancer. DESIGN--Prospective study of patients with colorectal cancer managed by one of 13 consultant surgeons, none of whom had a special interest in colorectal surgery. SETTING--Royal Infirmary, Glasgow. PATIENTS--645 sequential patients with colorectal cancer presenting over the six years from 1974 to 1979. MAIN OUTCOME MEASURES--Postoperative complications, postoperative mortality (within 30 days), and survival (up to 10 years); predictive factors for postoperative mortality and survival; and relative hazard rate ratios for individual surgeons. RESULTS--The proportion of patients undergoing apparently curative resection varied among surgeons from 40% to 76%; overall postoperative mortality varied from 8% to 30%. After curative resection postoperative mortality varied from 0% to 20%, local recurrence from 0% to 21%, and the rate of anastomotic leak from 0% to 25%. Survival at 10 years in patients who underwent curative resection varied from 20% to 63%, two year survival in those who underwent palliative resection varied from 7% to 32%, and median survival in those who underwent palliative diversion varied from one to eight months. The hazard rate ratios among individual surgeons, taking into account the identified risk factors, varied from 0.56 to 2.03, from 0.17 to 1.92, and from 0.57 to 1.50 for curative resection, palliative resection, and palliative diversion, respectively. CONCLUSION--There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery were undertaken by surgeons with a special interest in colorectal surgery or surgical oncology."
-"What rare complication of diagnostic cardiac angiography is discussed in this context, and how was it successfully managed?",Coronary occlusion following diagnostic angiography: salvage by intracoronary stenting. Catheter-induced coronary artery dissection and occlusion is a rare but serious complication of diagnostic cardiac angiography. This report describes the successful management of this complication with an intracoronary stent after prolonged balloon inflations and intracoronary thrombolytic therapy were unsuccessful.
-How do serum aluminum levels change during and after plasmapheresis treatment?,"Trace elements and plasmapheresis. The relationship between serum aluminum (Al), zinc (Zn), copper (Cu), and iron (Fe) and plasmapheresis (PP) treatment was examined. Three patients with rheumatoid arthritis, six with myasthenia gravis, and 6 with multiple sclerosis were studied. Serum Al, Zn, Cu, and Fe were measured before and after PP. Plasma was separated by first filtration; a second filtration separated the plasma components. Three liters of plasma were treated in each PP session. With each PP treatment, total protein (TP) removed was 20 +/- 5% and serum albumin removed was +/- 6%. Serum Al rose significantly (p less than 0.01 from 1.1 +/- 0.2 micrograms/dl pre-PP to 2.8 +/- 0.4 micrograms/dl post-PP. Serum Zn, Cu, and Fe decreased significantly (p less than 0.01) from 86.2 +/- 7.4 micrograms/dl, 126 +/- 18 micrograms/dl, and 108 +/- 14 micrograms/dl pre-PP to 58.4 +/- 10.2 micrograms/dl, 104 +/- 6 micrograms/dl, and 82 +/- 16 micrograms/dl post-PP, respectively. Two days after the end of the six-month PP treatment, serum Al levels rose significantly (p less than 0.01), from 1.1 +/- 0.2 micrograms/dl to 3.6 +/- 0.8 micrograms/dl. However, serum TP, serum albumin, and serum Zn, Cu, and Fe did not change significantly. It thus appears essential in PP treated patients, to remove Al from the blood to protect against aluminum intoxication."
-"What were the key findings comparing surgical and percutaneous placement of Greenfield filters in terms of safety, efficacy, and cost?","Analysis of the transition to percutaneous placement of Greenfield filters. To establish whether a transition from surgical to percutaneous placement of Greenfield filters was justified, a review of the safety, efficacy, and cost-effectiveness of the two approaches was conducted. Between 1984 and 1989, 168 filters were placed in 169 patients, 48 surgically and 120 percutaneously. Placement was successful in 45 (94%) of the 48 surgical patients and 120 (99%) of the 121 percutaneous patients. Filter misplacement occurred in three (6%) surgical patients and no percutaneous patients. Clinically evident femoral vein thrombosis occurred in only four (5%) of the percutaneous patients, while inferior vena cava thrombosis occurred in three (3%) of the percutaneous patients. One pulmonary embolus occurred after percutaneous filter placement and resulted in death. The cost of percutaneous placement was 58% that of surgical placement. A retrospective review of the experience in our patient population indicates that safety, cost, and ease of insertion make the percutaneous approach the procedure of choice for Greenfield filter placement."
-What medical condition did the 32-year-old woman develop 20 years after receiving 198Au synoviorthesis for juvenile rheumatoid arthritis?,"Chronic myeloid leukemia in a woman with Still's disease treated with 198Au synoviorthesis. A 32-year-old woman presented with chronic myeloid leukemia 20 years after 2 198Au synoviortheses to her knees for severe juvenile rheumatoid arthritis. She progressed to blast phase of her disease and died from complications of therapy. The literature on rheumatoid arthritis, its therapy, radioisotopes and leukemia is reviewed."
-What is K-edge energy digital subtraction arthrography (KEDSA) and how does it improve the detection of hip prosthesis loosening?,"K-edge digital subtraction arthrography of the painful hip prosthesis: a feasibility study. K-edge energy subtraction radiography is a method for detecting the presence of iodinated contrast material by subtracting two digital radiographs produced by X-ray beams with energies above and below the iodine K edge. We performed a feasibility study on the application of K-edge energy digital subtraction arthrography (KEDSA) to painful hip prostheses. During arthrography, loosening of the prosthesis is implied if contrast material is seen dissecting around the prosthesis, an often difficult detection task because of adjacent prosthesis metal or cement. In conventional arthrography a preliminary mask image is thus used from which films obtained after injection of iodinated contrast material are subtracted. Movement by the patient during this process may preclude subsequent subtraction. With KEDSA, since multiple image pairs may be obtained after the injection of contrast material, the problem of patient motion is virtually eliminated. A conventional X-ray tube operating between 55 and 65 kVp was alternately filtered by iodine and cerium filters to produce the KEDSA images. The apparatus was capable of producing a subtracted image within 3 sec. The technique was applied to phantoms and to six patients immediately after hip arthrography that had been positive for prosthesis loosening. Although of lower spatial resolution, the KEDSA images were, in all cases, positive for loosening in a pattern consistent with the conventional arthrographic images. KEDSA was shown to be successful in detecting extraarticular contrast material. During a single study, subtraction in various imaging planes as well as postexercise subtraction imaging can be accomplished-techniques not heretofore possible in routine subtraction arthrography."
-What were the key findings regarding the sensitivity of 12-lead electrocardiogram versus limb-lead monitoring in detecting ischemia during percutaneous transluminal coronary angioplasty?,"Twelve-lead electrocardiographic evaluation of ischemia during percutaneous transluminal coronary angioplasty and its correlation with acute reocclusion. The sensitivity of the surface 12-lead electrocardiogram and that of standard (limb-lead) monitoring for the detection of ischemia during percutaneous transluminal coronary angioplasty were compared in 115 patients. The purpose was to identify the electrocardiographic leads that provide the most sensitive indicators of coronary ischemia during percutaneous transaluminal coronary angioplasty and to evaluate the ""ischemic fingerprint"" that is obtained with 12-lead electrocardiogram during balloon inflation as a predictor of abrupt reocclusion after successful percutaneous transaluminal coronary angioplasty procedures. During balloon inflations of 30 seconds, ischemia was detected in 61 of 145 vessels (42%) by limb-lead monitoring alone versus 130 of 145 vessels (90%) by 12-lead electrocardiography (p less than or equal to 0.001). In the nine patients (7.8%) who experienced abrupt reocclusion within 24 hours, the electrocardiogram during chest pain after percutaneous transaluminal coronary angioplasty was identical to that obtained during percutaneous transaluminal coronary angioplasty (""ischemic fingerprint""). None of the six patients who had chest pain after percutaneous transaluminal coronary angioplasty without evidence of abrupt reocclusion reproduced their ischemic fingerprint. The suggested optimal leads for monitoring ischemia are as follows: left anterior descending coronary artery, V2, and V3; circumflex artery, V2, and V3; and right coronary artery, III and aVF."
-What type of adenoma was found in the left lung of the 28-year-old woman during autopsy?,"Adenoma of type 2 pneumocytes with oncocytic features. An adenoma of type 2 pneumocytes in the periphery of the left lung was an incidental finding at the autopsy of a 28-year-old woman. Light microscopy revealed a predominantly papillary growth with oncocytic features. Ultrastructurally, multilaminated bodies and many mitochondria were found in the tumor cells and tubular myelin in the extracellular spaces. Immunohistochemistry revealed surfactant apoprotein in tumor cells and extracellularly."
-What factors can increase the risk of vasovagal syncope during spinal anesthesia?,Vasovagal asystole during spinal anaesthesia. A patient in whom vasovagal asystole was induced by the performance of a spinal anaesthetic in the upright position is described. This illustrates the importance of routine monitoring of the electrocardiograph during regional anaesthesia. The risk of vasovagal syncope may be increased by the use of the sitting position and by the omission of anxiolytic premedication.
-How do motor initiation and execution differ between normal subjects and Parkinson's disease patients?,"Motor initiation versus execution in normal and Parkinson's disease subjects. We studied motor initiation and execution using wrist extension movements to changing target locations in eight normal subjects and nine Parkinson's disease (PD) patients before and after medications. Late changes resulted in double trajectories, indicating commitment to the initial target acquisition program followed by a correcting movement. There was compensation for earlier changes, even after onset of agonist muscle activity, resulting in a single trajectory, implying that the original trajectory had not yet been specified. However, movements were slowed in PD patients implying an abnormality in the content of the target acquisition program but not in the timing of its specification. In PD patients, the timing of the second movement onset correlated best with the timing of target location change and did not depend on initial movement completion. Thus, PD patients were able to program the second movement while the first movement was under way."
-What is sonoelasticity imaging and how does it potentially help in detecting neoplasms?,"Sonoelasticity imaging: results in in vitro tissue specimens. The authors present a method for imaging tissue stiffness (sonoelasticity) that has been developed and tested in a laboratory setting by using in vitro canine and human prostate glands. A low-frequency acoustic source was used to induce vibration in tissue under examination, and a color Doppler ultrasound (US) instrument was modified to detect vibration amplitude. The resulting image is a color ""map"" of tissue vibration superimposed on conventional gray-scale US images. Stiffer tissues vibrated less in response to audible sound, regardless of echogenicity. Normal human and canine prostate glands demonstrated a uniform vibration pattern. Four of four human prostatic adenocarcinomas and two stiff inclusions injected into canine prostate glands demonstrated a lack of vibration in comparison with normal surrounding tissue. The authors conclude that while further study is necessary, sonoelasticity imaging may enhance the detection of neoplasms by enabling their identification solely on the basis of stiffness."
-What were the key prognostic factors significantly associated with disease recurrence in clinical stage I endometrial adenocarcinoma according to the multivariate analysis?,"Prognostic factors associated with recurrence in clinical stage I adenocarcinoma of the endometrium. Two hundred sixty-four consecutive patients with clinical stage I endometrial adenocarcinoma who underwent primary surgical therapy between July 1979 and August 1988 were followed prospectively and evaluated for disease recurrence for 8-112 months (mean 51.5). Thirty-three patients (12.5%) developed recurrence or died of disease. In univariate statistical analysis, prognostic factors significantly associated with disease recurrence were as follows: age (mean 68.6 years with versus 60.3 years without recurrence; P = .0001); histology (adenocarcinoma 8.8%, adenosquamous 35.7%, papillary 25%, clear-cell 57.1%; P less than .0001); tumor grade (grade 1, 7.7%, grade 2, 10.5%, grade 3, 36.1%; P less than .0001); depth of myometrial invasion (none 9.8%, less than one-half 7.4%, one-half or greater 29.6%; P = .0001); lymph node status (negative 8.3%, positive 47.6%; P less than .0001); non-nodal extrauterine disease spread (absent 11.0%, present 50%; P = .0003); peritoneal cytology (negative 9.4%, positive 26.3%; P = .004), and tumor size (2 cm or less 7%, greater than 2 cm 17.3%; P = .05). Cervical extension and uterine size had no significant effect on recurrence. Using multivariate analysis, grade 3 tumor (P = .002), advancing age (P = .004), lymph node metastasis (P = .006), and presence of extrauterine disease spread other than lymph node metastasis (P = .038) were the only variables significantly associated with disease recurrence or death. This study supports the new International Federation of Gynecology and Obstetrics surgical staging system for endometrial cancer."
-What percentage of patients developed aneurysms at the surgical repair site during childhood years after coarctation of the aorta repair?,"Preoperative and postoperative ""aneurysm"" associated with coarctation of the aorta. The reported incidence of aortic aneurysm after surgical repair or balloon angioplasty for aortic coarctation varies widely. To determine the incidence of aneurysm formation after surgery, preoperative and postoperative cineangiograms from 65 patients who underwent operation at age 1.5 +/- 3.4 years were examined. Repair included a prosthetic patch in 14 patients, end to end anastomosis in 28 and subclavian flap in 23. Aneurysm was documented by change in contour or irregularities in contour at the repair site or by abnormal dimensions at the repair site, defined by the ratio of the widest measurement at the repair site to the measurement of the aorta at the diaphragm. An aneurysmal bulge above the ductus diverticulum was identified in 14 (23%) of 60 patients preoperatively; the area showed no change 4.72 +/- 4.07 years after surgery. Significant changes at the repair site were seen in only three patients, all of whom had Dacron patch repair. One patient had a change in contour at the repair site, one had an abnormally high repair site to diaphragmatic aorta ratio and one had a progressive increase in this ratio. Thus, during childhood years, 3 (5%) of 65 patients were diagnosed as having aneurysm at the surgical repair site. In conclusion, 1) comparison with preoperative cineangiograms, especially for aneurysmal bulges above the ductus arteriosus, is essential before an aneurysm can be attributed to coarctation repair by any technique, and 2) aneurysm developed only in patients subjected to Dacron patch repair."
-What is unique about the lymphoma case described in this context?,"Ki-1-positive lymphoma developing 10 years after the diagnosis of hairy cell leukemia. The case is described of a 62-year-old man with a 10-year history of hairy cell leukemia (HCL) who subsequently had a large-cell anaplastic or so-called Ki-1-positive lymphoma. Immunocytochemical staining of the lymphomatous node revealed positivity for Ki-1 (CD30) and epithelial membrane antigen in the tumor cells, and flow cytometric analysis showed simultaneous expression of Leu M5 (CD11c) and Leu 14 (CD22). Although HCL has been reported to coexist with both Hodgkin's disease and non-Hodgkin's lymphoma, the authors believe this is the first case in which a Ki-1-positive lymphoma developed in a patient with HCL. The clinicopathologic and immunologic features of both entities are discussed, as is the association of HCL with other neoplasms."
-What is the weaning index (WI) and how is it calculated in this study?,"Evaluation of a new weaning index based on ventilatory endurance and the efficiency of gas exchange. We hypothesized that the ventilatory capacity needed to wean from mechanical ventilation (mv) depends on two variables: ventilatory endurance and the efficiency of gas exchange. We also hypothesized that these variables could be assessed from data readily available at the bedside, including tidal volume (VT) on mv and during spontaneous breathing (sb), ventilator peak inspiratory pressure (Ppk), and patient negative inspiratory pressure (NIP). Ventilatory endurance was evaluated using a modified pressure-time index: PTI = TI/Ttot x Pbreath/NIP, where Pbreath = Ppk x VTsb/VTmv. Defining VE40 as the minute ventilation needed to bring PaCO2 to 40 mm Hg, the efficiency of gas exchange was evaluated by calculating VE40/VTsb = (VE x PaCO2)mv/VTsb x 40. Because high levels of inspiratory effort might cause patients to reduce VTsb and thereby compromise CO2 elimination, we devised a weaning index (WI) that combines ventilatory endurance and the efficiency of gas exchange: WI = PTI x (VE40/VTsb). The study population comprised 38 patients with chronic obstructive pulmonary disease, adult respiratory distress syndrome, pneumonia, neuromuscular disease, and miscellaneous other conditions. They had been mechanically ventilated more than 3 days and were considered by clinical criteria to be ready for weaning. Of 46 weaning trials, 19 were successful, 2 were partially successful, and 25 failed. PTI and VE40/VTsb were higher in patients who failed (p less than 0.05), but neither variable alone had sufficient sensitivity or specificity to predict the outcome of weaning trials accurately."
-What percentage of postmenopausal women experienced persistent side effects from tamoxifen treatment in this study?,"Symptoms associated with tamoxifen treatment in postmenopausal women. Adjuvant breast cancer therapy with tamoxifen is associated with greater disease-free survival and possibly overall survival. Long-term treatment, possibly of indefinite duration, is being evaluated. Compliance with long-term therapy will depend largely on the nature and severity of tamoxifen's side effects. We evaluated the symptoms associated with tamoxifen therapy in 140 postmenopausal women with axillary node negative breast cancer in remission (mean years since menopause, 9.3) enrolled in a placebo-controlled, randomized toxicity study. Tamoxifen recipients reported moderated or severe vasomotor symptoms up to 17%, and gynecologic symptoms up to 4% more frequently than placebo subjects. Persistent vasomotor, gynecologic, or other major side effects were reported by 48% of tamoxifen recipients, and by 21% of placebo subjects. These carefully collected data suggest significant perceived symptom 'cost' of tamoxifen therapy in postmenopausal women, of a magnitude likely to compromise long-term compliance."
-What was the primary objective of the experimental in vivo model described in the study?,"Nephrotoxic potential of Bence Jones proteins BACKGROUND. The renal manifestations of diseases associated with the production of monoclonal light chains--myeloma (cast) nephropathy, light-chain deposition disease, and amyloidosis AL--result from the deposition of certain Bence Jones proteins as tubular casts, basement-membrane precipitates, or fibrils, respectively. For unknown reasons, the severity of the renal manifestations of these diseases varies greatly from patient to patient. We employed an experimental in vivo model to determine the pathologic importance of various Bence Jones proteins. METHODS. Mice were injected intraperitoneally with 300 mg of Bence Jones protein from 40 patients with multiple myeloma or amyloidosis AL and killed 48 hours later. The mouse kidneys were examined by light and electron microscopy, and light-chain deposits were identified immunohistochemically with highly specific antihuman light-chain antiserum. RESULTS. Of the 40 different human Bence Jones proteins studied, 26 were deposited in the mouse kidneys predominantly as tubular casts, basement-membrane precipitates, or crystals; no light-chain deposits were detected in the kidneys of the mice that received the other 14 Bence Jones proteins. Of the 18 patients for whom renal tissue was available for study, the findings in 14 were comparable to those in the mice. Furthermore, the proteins obtained from 22 of the 27 patients whose serum creatinine concentrations equaled or exceeded 168 mumol per liter (1.9 mg per deciliter) were deposited in the mouse kidneys, whereas protein deposition occurred after the injection of proteins from only 4 of the 13 patients with serum creatinine concentrations below 168 mumol per liter. The repeated injection of Bence Jones proteins from two patients who had amyloidosis AL resulted in deposition of the protein in the mouse kidneys as amyloid. CONCLUSIONS. Particular Bence Jones proteins are primarily responsible for producing the distinctive types of protein deposition in renal tissue and the clinical manifestations that occur in patients with light-chain-associated diseases. This experimental model has potential value for the identification of nephrotoxic or amyloidogenic light chains."
-Does the level of axillary lymph node involvement independently predict survival in clinical stage I and II breast cancer patients?,"Level of axillary involvement by lymph node metastases from breast cancer is not an independent predictor of survival. We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance."
-What is the purpose of the in situ venous valve construction technique described in the context?,"In situ venous valve construction. A technique of in situ deep venous valve construction based on vein wall intussusception is described. The technique has been used to construct a size-matched, autogenous valve in the femoral vein of the dog. Forty-one valves have been constructed. Immediately after construction, all 41 were patent at ascending phlebography and Harvey's test showed them to be competent. Descending phlebography demonstrated competence in 38 valves. Hydrostatic testing was performed on 27 valves in the vertical position at pressure gradients in the range 0.2-250 cmH2O. Of these, 24 valves were fully competent. Six valves were studied at intervals between 1 and 112 days after construction. All six were competent by Harvey's test and five were competent at descending phlebography. There was no evidence of thrombosis in any valve. This technique may be suitable for replacement of deep venous valves in patients with the calf pump failure syndrome caused by deep venous reflux."
-What was the relationship between the degree of coronary stenosis and mortality in patients who survived an anterior wall Q-wave acute myocardial infarction?,"Prognostic importance of collateral flow and residual coronary stenosis of the myocardial infarct artery after anterior wall Q-wave acute myocardial infarction. Residual high-grade coronary stenosis and collateral flow are frequent findings in the chronic phase after a Q-wave acute myocardial infarction (AMI). The prognostic importance of a residual stenosis of the infarct artery and of collateral flow to the infarct area was analyzed in a group of 102 young patients (mean age 35 years, range 22 to 39) who had survived an anterior wall Q-wave AMI. Patients whose only significant lesion (greater than 50% luminal diameter reduction) was in the proximal portion of the left anterior descending artery were enrolled in the study. A 50 to 74% diameter stenosis was present in 33 of 102 patients (32%), 43 (42%) had a 75 to 99% stenosis and 26% had a total occlusion of the infarct vessel. Collateral vessels, which were evaluated by a scoring system, were present in 52 of 102 patients (51%). Four percent had only faint (score 1), 17 of 102 patients (17%) had moderate and 32 patients (31%) had good collateral flow (score greater than 4). The 8-year cumulative mortality was 15.2%--an eightfold increase compared with the age-matched general population. No patient with less than 75% stenosis died during follow-up, whereas the cumulative 8-year mortality was 23 and 17% in patients with a 75 to 99% stenosis or total occlusion, respectively (p less than 0.01). Patients with at least moderate collateral flow had a mortality rate of 21%, versus 8% for patients without or with faint collateral flow (p less than 0.05)."
-How many deaths and new cases of illness are estimated to occur annually in the United States due to occupational diseases?,"The recognition and control of occupational disease. Occupational diseases account each year in the United States for an estimated 50,000 to 70,000 deaths and 350,000 new cases of illness. Often, however, occupational diseases are not correctly diagnosed, because they mimic diseases due to other causes and because most physicians are not well trained in their recognition. Opportunities for prevention and treatment are therefore lost. The occupational history is the most effective means for proper diagnosis of occupational illness. It should routinely be obtained for every patient. A brief but systematic guide for obtaining an occupational history is presented in this report. Also, approaches are summarized for the recognition and diagnosis of such important occupational diseases as occupational cancer, asbestosis and other respiratory disorders, and occupational neuropsychologic disorders. The management and prevention of occupational diseases depend on reduction of hazardous exposures in the workplace and better education of workers, industrial managers, and physicians. This report outlines a program for the control of occupational disease based on (1) preventing exposures in the workplace, (2) premarket toxicity testing of new chemicals and technologies, and (3) astute clinical diagnosis."
-What was the main objective of the North American Symptomatic Carotid Endarterectomy Trial?,"Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators BACKGROUND. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS. Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery."
-How does insulin resistance potentially contribute to increased blood pressure through altered cation transport mechanisms?,"Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What percentage of superficial femoral artery stenoses did not progress after a mean follow-up interval of 37 months?,"The natural history of superficial femoral artery stenoses. Since the natural history of specific superficial femoral artery stenoses is not known, we examined progression rates of superficial femoral artery stenoses in 45 lower extremities found when arteriograms were obtained of 38 patients for symptomatic atherosclerotic disease in the opposite leg or abdomen. These initial superficial femoral artery arteriograms were compared with later arteriograms in 25 limbs, duplex scans in 27 limbs, and both modalities in 7 limbs. After a mean interval of 37 months, most superficial femoral artery stenoses (72%) did not progress. However, 12 superficial femoral artery stenoses progressed (28%; mean follow-up, 37 months, including 7 that occluded (17%). Superficial femoral artery stenoses progressed among patients who complained of symptom progression at a rate faster than that among asymptomatic patients (15.6%/year vs 3%/year; p = 0.006). Superficial femoral artery lesions also progressed more rapidly among patients whose contralateral superficial femoral artery was occluded (10%/year vs 1.6%/year; p = 0.04). By multivariate regression analysis, symptom progression and smoking history were predictive of superficial femoral artery stenosis progression. In the seven patients whose superficial femoral artery stenoses progressed to occlusion, the average rate of stenosis progression was 12%/year (maximum predicted rate, 30% per year by 95% confidence limit). These results indicate that superficial femoral artery stenoses usually progress with synchronous symptomatic deterioration. Other than symptom progression, only cumulative smoking history and contralateral superficial femoral artery occlusion could be associated with superficial femoral artery stenosis progression in this small series."
-What misconceptions about cancer were found among the socioeconomically disadvantaged patients in the study?,"Knowledge and beliefs about cancer in a socioeconomically disadvantaged population. Americans living in poverty experience a higher incidence of and greater mortality from cancer than the nonpoor. At least 50% of the difference in mortality is believed to be due to delay in diagnosis, although risk-promoting lifestyles and behaviors also contribute to decreased survival. A potential exacerbating factor among the poor is inadequate information and knowledge about cancer and its treatment. Interviews were conducted with 128 cancer patients from a socioeconomically disadvantaged population to assess knowledge of cancer and its treatment and to evaluate care-seeking behaviors. Results indicated that although patients relied primarily on their physicians for information about their disease and treatment, a number of misconceptions regarding cancer existed in this population. Notably, nearly 50% of the patients surveyed either denied or did not know that smoking was related to the development of cancer. Additionally, patients frequently reported inappropriate care-seeking behaviors when asked to respond to a series of common disease-related signs or symptoms. These findings suggest that misinformation and misconceptions regarding cancer and its treatment among patients in this sample may contribute to inappropriate care-seeking behaviors."
-What were the key differences in safety and tolerance between amphotericin B lipid complex (ABLC) and amphotericin B desoxycholate (AB) in the study?,"Comparative safety, tolerance, and pharmacokinetics of amphotericin B lipid complex and amphotericin B desoxycholate in healthy male volunteers. Amphotericin B lipid complex (ABLC), a lipid complex formulation of amphotericin B, and amphotericin B desoxycholate (AB) were compared for safety, tolerance, and pharmacokinetics in two groups of eight healthy male volunteers. After a 1-mg test dose, study drug was infused at 0.1, 0.25, and 0.5 mg/kg; the 0.5-mg/kg dose was not given to subjects receiving AB. ABLC caused few acute adverse effects except for mild somnolence (drowsiness) in six volunteers. In addition, three of eight ABLC recipient had asymptomatic, transient serum transaminase elevations that resolved spontaneously. The AB recipients experienced more acute side effects, but only one had a mild shaking chill: three of eight also experienced sleepiness. No significant changes in vital signs, electrocardiogram, oximetry, pulmonary function, or clinical status were observed in either group. Due to its increased estimate volume of distribution and estimated clearance. ABLC yielded decreased amphotericin B levels and area under the serum concentration versus time curve relative to AB."
-How does continuous positive airway pressure (CPAP) affect ventilatory output and pulmonary resistance during different stages of non-rapid-eye-movement (NREM) sleep?,"Effects of sleep-induced increases in upper airway resistance on ventilation. To determine the effects of the sleep-induced increases in upper airway resistance on ventilatory output, we studied five subjects who were habitual snorers but otherwise normal while awake (AW) and during non-rapid-eye-movement (NREM) sleep under the following conditions: 1) stage 2, low-resistance sleep (LRS); 2) stage 3-4, high-resistance sleep (HRS) (snoring); 3) with continuous positive airway pressure (CPAP); 4) CPAP + end-tidal CO2 partial pressure (PETCO2) mode isocapnic to LRS; and 5) CPAP + PETCO2 isocapnic to HRS. We measured ventilatory output via pneumotachograph in the nasal mask, PETCO2, esophageal pressure, inspiratory and expiratory resistance (RL,I and RL,E). Changes in PETCO2 were confirmed with PCO2 measurements in arterialized venous blood in all conditions in one subject. During wakefulness, pulmonary resistance (RL) remained constant throughout inspiration, whereas in stage 2 and especially in stage 3-4 NREM sleep, RL rose markedly throughout inspiration. Expired minute ventilation (VE) decreased by 12% in HRS, and PETCO2 increased in LRS (3.3 Torr) and HRS (4.9 Torr). CPAP decreased RL,I to AW levels and increased end-expiratory lung volume 0.25-0.93 liter. Tidal volume (VT) and mean inspiratory flow rate (VT/TI) increased significantly with CPAP. Inspiratory time (TI) shortened, and PETCO2 decreased 3.6 Torr but remained 1.3 Torr above AW. During CPAP (RL,I equal to AW), with PETCO2 returned to the level of LRS, VT/TI and VE were 83 and 52% higher than during LRS alone. Also on CPAP, with PETCO2 made equal to HRS, VT, VT/TI, and VE were 67, 112, and 67% higher than during HRS alone."
-What was the average functional rating of the hips before and after total hip arthroplasty in patients who had childhood sepsis?,"Total arthroplasty of the hip after childhood sepsis. Total hip arthroplasty was performed in 45 hips of 44 patients who had pyogenic arthritis of the hip during childhood. The average age of the patients was 36.4 years (range 19 to 50). The interval between active infection and arthroplasty ranged from 11 to 40 years, and average follow-up was 65.4 months (range 58 to 80). Specimens of tissue taken before and during operation gave negative cultures in all hips, and no patient had reactivation of infection. The mean functional rating of the hips was 58 points before operation and 90 at the final review. Complications were seen in 11 cases (24%), loosening of components occurred in six (13%) and one hip had to be revised for acetabular component migration. Acetabular allografts were required in 27 hips (60%). All allografts united but there was partial resorption of the graft in the non-weight-bearing area in all."
-What are the key findings suggesting that the postsurgical hemorrhage resulted from venous thrombosis after AVM excision?,"Hemorrhagic venous infarction after excision of an arteriovenous malformation: case report. A case of arteriovenous malformation (AVM) in which postoperative hemorrhagic infarction developed, probably because of occlusion of the former draining veins, is reported. The hemorrhage developed in the temporal lobe 3 days after the initial operation and was located in the immediate vicinity of the site of the AVM. The following findings suggest that the postsurgical hemorrhage probably resulted from a venous thrombosis: 1) no evidence of residual AVM; 2) delayed onset of the hemorrhage, inconsistent with the time course of a hemorrhage developing according to the breakthrough theory or with insufficient hemostasis with a high-pressure afterload; 3) good correlation between the location of the hemorrhage and the occlusion of the draining veins; and 4) multifocal hemorrhage affecting both the gray matter and the subcortical white matter. Postoperative hemorrhagic infarction caused by thrombosis in the draining veins is rare, but it should be considered as a distinct postoperative complication after removal of an AVM."
-How did the use of hyaluronidase affect cell recovery during intestinal perfusion?,"Cell recovery during segmental intestinal perfusion in healthy subjects and patients with Crohn's disease. The recovery of cells arising from small intestinal mucosa alone was studied during continuous perfusion of a closed segment of jejunum. The perfusion technique minimised the contamination of the perfused segment with, for example, proteolytic enzymes from pancreas, allowing recovery of viable cells. The use of hyaluronidase in the perfusion fluid increased the recovery of cells fivefold, the median recovery being 8 x 10(6) cells. The cells were analysed with monoclonal antibodies and flow cytometry. Nearly all cells (98-99%) recovered during perfusion of healthy control subjects and patients with Crohn's disease were epithelial cells. The jejunal cells expressed HLA-DR in similar proportions--around 30%--in patients and control subjects. The ratio between CD4+ and CD8+ lymphocytes was similar (0.2) in control subjects and patients with inactive Crohn's disease but decreased (0.03) in patients with active Crohn's disease in the ileum."
-What is the potential outcome of untreated or late-treated candidal mediastinitis?,"Candidal mediastinitis after surgical repair of esophageal perforation. Candidal mediastinitis, like Boerhaave's syndrome, is uncommon, and both, if treated late or incompletely, frequently result in death. Early recognition and aggressive medical and surgical intervention are the best means to convalescence and cure in both conditions."
-How does the experimental model (open-chest vs. conscious dog) affect the assessment of postischemic myocardial stunning?,"Postischemic myocardial ""stunning"". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog. Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial ""stunning""). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically ""protective"" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What immune system abnormality was observed in the patient with primary sclerosing cholangitis?,"Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study. Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters."
-What is the key characteristic of the chondroblastomalike extraskeletal tumor found in the patient's right thumb?,Chondroblastomalike extraskeletal chondroma. An unusual extraskeletal tumor occurring in the right thumb of a 44-year-old man exhibited histologically a chondroblastomalike appearance. The tumor was characterized by dense proliferation of chondroblastic cells admixed with a few multinucleated giant cells of osteoclast type. The patient had no evidence of local recurrence or metastasis three-and-a-half years after a simple excision.
-How was bile peritonitis managed in this patient without resorting to exploratory laparotomy?,"Novel approach to iatrogenic bile peritonitis. Bile peritonitis after injury to the biliary tree is a serious complication that requires exploratory laparotomy. Our patient had an obstructing ampullary carcinoma, and generalized bile peritonitis developed from attempted percutaneous transhepatic cholangiography. The patient's condition was managed by peritoneal lavage and endoscopic transampullary stenting, with immediate relief of pain and toxicity. Exploratory laparotomy was avoided, and an eventual pylorus-sparing Whipple resection was the definitive treatment. We believe this to be the first report of successful nonoperative treatment of a patient with bile peritonitis with obstructive jaundice."
-What quantitative liver function tests were found to be significant predictors of survival in patients with cirrhosis?,"Prognostic value of galactose elimination capacity, aminopyrine breath test, and ICG clearance in patients with cirrhosis. Comparison with the Pugh score. Seventy-eight patients with cirrhosis were prospectively followed for up to 20 months, on the average. At entry into the study, galactose elimination capacity, aminopyrine breath test, and ICG clearance were measured. At the end of the study, 27 patients had died. Univariate analysis using the Kaplan-Meier method showed that both quantitative liver function tests (galactose elimination capacity: P less than 0.025; aminopyrine breath test: P less than 0.001; ICG clearance: P less than 0.005) and common clinical and biochemical data (encephalopathy: P less than 0.001; ascites: P less than 0.001; serum bilirubin: P less than 0.005; serum albumin: P less than 0.001; prothrombin index: P less than 0.05) were significant predictors of survival. To investigate whether quantitative liver function tests could contribute to a better definition of the prognosis, once Pugh score had already been taken into account, a multiple regression analysis according to the Cox model was performed. Pugh score and galactose elimination capacity resulted in the only independent prognostic covariates. From them a prognostic index was calculated, and the model was validated in an additional sample of 70 patients investigated according to the same protocol. The contribution GEC gave to the assessment of overall prognosis over that obtained using the Pugh score was slight, as estimated by the statistical parameters of the Cox's model, but was significant as assessed by a ROC curve analysis (P = 0.05). These data show that all quantitative liver function tests were predictors of survival in cirrhosis, and that the galactose elimination capacity added some new prognostic information to those already available using the Child-Turcotte-Pugh classification."
-What factors were found to be associated with increased elastic recoil after percutaneous transluminal coronary angioplasty?,"Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study. The immediate result of percutaneous transluminal coronary angioplasty is influenced by both plastic and elastic changes of the vessel wall. To evaluate the amount of elastic recoil after coronary balloon angioplasty, the minimal luminal cross-sectional area of the largest balloon used at highest inflation pressure was compared with the minimal luminal vessel cross-sectional area directly after final balloon deflation in 607 lesions (526 patients). Elastic recoil was defined as the difference between balloon cross-sectional area and minimal luminal cross-sectional area of the dilated coronary segment immediately after balloon withdrawal. A videodensitometric analysis technique was used to avoid geometric assumptions on stenosis morphology directly after angioplasty. Mean balloon cross-sectional area was 5.3 +/- 1.6 mm2 and minimal luminal cross-sectional area after angioplasty was 2.8 +/- 1.4 mm2. Reference areas before and after angioplasty did not differ (6.0 +/- 2.6 and 6.2 +/- 2.6 mm2, respectively). Univariate analysis revealed that asymmetric lesions, lesions located in less angulated parts of the artery and lesions with a low plaque content showed more elastic recoil. Lesions located in distal parts of the coronary tree were also associated with more elastic recoil probably related to relative balloon oversizing in these distal lesions."
-What was the key finding regarding CD34 mRNA expression in the B-precursor acute lymphoblastic leukemia cell subpopulations?,"Differentiation in B-precursor acute lymphoblastic leukemia cell populations with CD34-positive subpopulations. B-precursor acute lymphoblastic leukemia bone marrow specimens that contained subpopulations of cells with immunophenotypes corresponding to early (CD34) and late (CD20) and (CD22) stages of normal B-cell differentiation were studied. Subpopulations of cells were isolated according to immunophenotype and then analyzed by both a clonogenic assay and molecular genetic methods. Clonal equivalence of the early and late immunophenotypic subpopulations was confirmed for each case by the demonstration of identical lg gene rearrangements. The in vitro colony-forming assay consistently showed a growth advantage for the CD34+ subpopulations over the CD34- subpopulations. CD34 mRNA was detected readily in these isolated precursor cells. When two specimens in which virtually all of the leukemia cells were CD34+ and CD34+CD20+ and CD34+CD22+ subpopulations were also present the CD34 mRNA was limited to the cells without the late-stage differentiation antigens on their surface. Furthermore, the c-myb mRNA was found only in the subpopulations that also contained CD34 mRNA. Our results show that a limited program of differentiation reminiscent of normal B-cell development may be present in this leukemia."
-What is the gender distribution observed in the study of global T wave inversion?,"Global T wave inversion. Because global T wave inversion has not been specifically characterized, 100 electrocardiograms (ECGs) with this pattern (frontal plane T vector -100 degrees to -170 degrees with precordial T inversion) were prospectively collected from approximately 30,000 consecutively interpreted ECGs and analyzed blindly. There was a striking female predominance (82 women vs. 18 men; p less than 0.0005) despite an essentially equal number of female and male hospital admissions. There was a single statistically significant ECG correlate: a more vertical QRS axis in women (+14.1 degrees +/- 45.3 degrees vs. -5.6 degrees +/- 31.3 degrees; p = 0.034). The T waves were basically symmetric (68%), the influence of this factor usually altering the characteristically asymmetric T wave inversions of right bundle branch block (4 of 5) and left ventricular hypertrophy (21 of 36). Asymmetry was mainly associated with digoxin therapy (21 of 32 patients taking digoxin; p less than or equal to 0.0005) and a corrected QT (QTc) interval (0.433 +/- 0.095) shorter than with symmetric T wave inversions (0.507 +/- 0.074; p less than or equal to 0.0005) though not reaching the degree of shortening expected for digitalization. Twenty-eight patients admitted for acute myocardial infarction and 23 for a central nervous system disorder accounted for the majority of patients with symmetric T wave inversion. Fifteen of 18 patients who had coronary angiography had some degree of coronary artery disease: 3 had angiographically normal coronary arteries."
-What was the suspected pathophysiologic mechanism causing the referred pain in this patient with a spinal cord tumor?,"Somato-somatic referred pain caused by suprasegmental spinal cord tumor. Tactile stimulation of a coin-sized area in a T-2 dermatome consistently triggered a lancinating pain in the ipsilateral C-8 dermatome in a 38-year-old woman. The SEP and an MRI led to a diagnosis of a tumor at the left cervico-medullary junction, much higher than the clinically suspected level. Surgical exploration revealed an exophytic glioma, and the pain was abolished postoperatively. Ephaptic transmission at the tumor site was suspected as a pathophysiologic mechanism."
-What medical condition developed in a 52-year-old man after an inferior wall myocardial infarction complicated by Dressler's syndrome?,Early constrictive pericarditis and anemia after Dressler's syndrome and inferior wall myocardial infarction. Early constrictive pericarditis and anaemia developed in a 52 year old man after he had an inferior wall myocardial infarction complicated by Dressler's syndrome. Total pericardiectomy at the time of coronary artery bypass surgery resulted in complete resolution of signs and symptoms.
-"How does sinorphan, an enkephalinase inhibitor, affect plasma atrial natriuretic factor (ANF) and sodium urinary excretion in cirrhotic patients with ascites?","Effect of sinorphan, an enkephalinase inhibitor, on plasma atrial natriuretic factor and sodium urinary excretion in cirrhotic patients with ascites. We examined the acute effects of sinorphan, an inhibitor of enkephalinase, on plasma atrial natriuretic factor (ANF) and urinary sodium excretion in cirrhotic patients with ascites. A single oral dose of sinorphan (100 or 30 mg in 11 and 5 patients, respectively) was administered against placebo according to a double blind cross-over protocol. Basal plasma ANF levels varied over a large range between 2.6-79 pmol/L. Sinorphan, at a dose of 100 mg, inhibited 70% of plasma enkephalinase activity 60 min after ingestion and elicited simultaneously an increase in plasma ANF and cGMP levels 1.8 and 1.5 times basal values, respectively. There was a transient increase in sodium urinary output without a change in creatinine clearance over the initial 2-h period following drug administration. An increase in urinary cGMP was also observed on a longer period of 6 h. Plasma aldosterone decreased significantly, but the lowest concentration was reached 1 h later than the peak of plasma ANF. Mean blood pressure and PRA were unmodified. The effects of 30 mg sinorphan on plasma ANF, cGMP, and aldosterone were also significant, but less marked than those of the higher dose. Therefore, enkephalinase inhibition transiently increases sodium urinary excretion in cirrhotic patients with ascites via a mechanism that is likely to imply reduction of ANF catabolism. These results suggest that ANF could play a role in the control of sodium homeostasis in liver cirrhosis with ascites."
-What medical procedure was performed to treat the patient's aneurysm in this case report?,"Aneurysm of the distal anterior inferior cerebellar artery unrelated to the cerebellopontine angle: case report. This is a case report of an unusual aneurysm of the distal anterior inferior cerebellar artery. A 44-year-old woman had a severe frontal headache and vomiting of sudden onset. On the day after admission, the patient began to demonstrate nuchal rigidity and difficulty with upward gaze bilaterally. There were no complaints at this time suggestive of a syndrome of the cerebellopontine angle. A computed tomographic scan revealed an intraventricular hemorrhage of the 3rd and 4th ventricles; however, multiple attempts at four-vessel angiography were required before an aneurysm could be demonstrated. On the 28th hospital day, a suboccipital craniectomy using the retromastoid approach in the lateral position was performed. A saccular aneurysm with a surrounding hematoma in the distal anterior inferior cerebellar artery was found and clipped. The operative findings revealed that the aneurysm was unrelated to the cerebellopontine angle. After surgery, the patient had an uneventful recovery and complete resolution of symptoms."
-What was the standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared to the general population?,"Cancer incidence in Norwegian Seventh-Day Adventists 1961 to 1986. Is the cancer-life-style association overestimated? Standardized incidence ratio for cancer in Norwegian Seventh-Day Adventists compared with the general population was not significantly different from unity (men 91, women 97). Persons converting late in life had a higher incidence than those converting at an earlier age. Respiratory cancers (standardized incidence ratio [SIR] 59, 95% CI = 36 to 91) and cancers with an unspecified site (SIR 53, 95% CI = 25 to 97) were rarer and cancer of the uterine corpus (SIR 164, 95% CI = 109 to 237) was more common in Seventh-Day Adventists before the age of 75 years. Inclusion of all registered Seventh-Day Adventists regardless of religious activity and the relatively low cancer incidence rates in the Norwegian population could contribute to the nonsignificant result with regard to total cancer. Main etiologic factors in cancer development in Norway should be sought in areas where Seventh-Day Adventists do not differ from the general population."
-At what postnatal ages did the rats show the highest incidence of epileptiform EEG activity during hypoxia?,"Epileptogenic effect of hypoxia in the immature rodent brain. The response to cerebral hypoxia/ischemia may be different in the neonate compared to other age groups. An in vivo model was developed in the rat to determine whether there are age-dependent differences in the effects of hypoxia on electroencephalographic (EEG) activity. EEG recordings were obtained from Long Evans hooded rats deprived of oxygen at five ages: postnatal days 5 to 7, 10 to 12, 15 to 17, 25 to 27, and 50 to 60. Oxygen concentration was varied from 0, 2, 3, and 4% between animals. EEGs were recorded in all animals before, during, and at 1 hour after exposure to the hypoxic condition and at 1 to 7 days afterward in a subset of animals. All animals were deprived of oxygen until the onset of apnea and bradycardia to 20 to 40% of baseline heart rate values. Hypoxia resulted in isoelectric EEG significantly more frequently in the animals deprived of oxygen at postnatal days 25 to 27 and 50 to 60 than in the younger age groups. A highly significant effect was that the animals deprived at postnatal days 5 to 17 revealed a high incidence of epileptiform EEG activity during hypoxia. In contrast, the older animals exhibited only rare isolated EEG spikes before reaching an isoelectric EEG. The severity of hypoxia-induced epileptiform EEG changes was highest in the animals subjected to moderately hypoxic conditions (3% and 4% oxygen) at postnatal days 10 to 12. Furthermore, epileptiform changes persisted for hours to days following prolonged episodes of hypoxia in the younger animals. This study demonstrates a unique response of the immature brain to exhibit epileptiform activity during hypoxia."
-What differences were observed in childhood cancer incidence and outcomes between Polynesian and non-Polynesian children in the study?,"Childhood cancer among the Polynesian population. From June 1981 through June 1989, 95 Polynesian children were seen for initial care of malignancy at the Princess Mary Hospital for Children (PMHC). The incidence of malignancy in the Polynesian populations served, the histology of the malignancies, and the outcome of therapy were reviewed and compared with 185 non-Polynesian (non-P) patients seen during the same period. Incidence figures for Polynesians and non-P were similar, but histologic patterns differed, showing an increased occurrence of leukemia, particularly nonlymphoblastic leukemia, an increased occurrence of bone tumors, and a decreased incidence of central nervous system tumors for Polynesians. Survival for Polynesian children with acute lymphoblastic leukemia was worse than for non-P. Survival in all other disease categories was similar."
-What factors were associated with major or minor hemorrhagic events during thrombolytic therapy for acute myocardial infarction?,"Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. OBJECTIVES: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. DESIGN: A multicenter, randomized, controlled trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). INTERVENTIONS: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. MEASUREMENTS: Patients were monitored for hemorrhagic events during hospitalization. MAIN RESULTS: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. CONCLUSIONS: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy."
-How does mifepristone potentially help in treating unresectable meningiomas?,"Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. The possibility that meningioma growth may be related to female sex hormone levels is suggested by several lines of evidence. Meningiomas are twice as common in women as in men, have been observed to wax and wane with pregnancy, and are positively associated with breast cancer. A physiological explanation for these phenomena is provided by the finding of steroid hormone receptors in meningiomas. However, unlike breast cancer, meningiomas are much more commonly positive for progesterone receptors than for estrogen receptors. The authors initiated a study on long-term oral therapy of unresectable meningiomas with the antiprogesterone mifepristone (RU486). Fourteen patients received mifepristone in daily doses of 200 mg for periods ranging from 2 to 31+ months (greater than or equal to 6 months in 12 patients). Five patients have shown signs of objective response (reduced tumor measurement on computerized tomography scan or magnetic resonance image, or improved visual field examination). Three have also experienced subjective improvement (improved extraocular muscle function or relief from headache). The side effects of long-term mifepristone therapy have been mild. Fatigue was noted in 11 of the 14 patients. Other side effects included hot flashes in five patients, gynecomastia in three, partial alopecia in two, and cessation of menses in two. Long-term therapy with mifepristone is a new therapeutic option that may have efficacy in cases of unresectable benign meningioma."
-What is a transscleral leiomyoma and how did it manifest in the 31-year-old woman described in the context?,"Transscleral leiomyoma. A bluish-pink epibulbar lesion, which slowly enlarged over a period of 5 years, developed in a 31-year-old woman. The lesion initially resembled a staphyloma, based on the very thinned overlying sclera, but subsequent evaluation suggested that it was a solid mass. At the time of surgical removal, the mass appeared to have originated in the supraciliary region and to have eroded outward through the sclera. Histopathologically, the mass proved to be a leiomyoma. The authors propose theoretic possibilities to explain the location of this rare type of ocular smooth muscle tumor."
-How effective is electromyographic monitoring in detecting facial nerve injuries caused by carbon dioxide lasers during surgical procedures?,"Detection of intraoperative laser injury to the facial nerve by electromyographic monitoring of facial muscles. Injury to the facial nerve is a significant risk during resection of cerebellopontine angle tumors. To minimize the risk of facial nerve injury, intraoperative electromyographic monitoring of facial musculature is frequently used. However, the reliability of such monitoring systems for detection of thermal nerve injury resulting from the use of carbon dioxide lasers has not been systematically evaluated. We determined the sensitivity of a computerized electromyographic monitor for detection of laser facial nerve injury in an anesthetized rat model. The mandibular and buccal branches of the facial nerve were isolated in 12 rats. A carbon dioxide laser was used to create controlled sites of thermal injury to both nerves over a 3-hour period. When a laser injury was created distal to previous injury sites, electromyographic discharge was noted in 72% to 82% of injuries. Laser injury proximal to previous injury sites was detected with 33% efficiency. These detection rates did not change significantly over a 3-hour period. This preliminary data suggests that electromyographic monitoring of facial musculature allows detection of facial nerve injury caused by carbon dioxide lasers."
-"What were the key differences in acute coronary lesions among patients with unstable angina, sudden coronary death, and acute myocardial infarction?","Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. The frequency and type of acute lesions in the four major (right, left main, left anterior descending, left circumflex) epicardial coronary arteries were examined at necropsy in 14 patients with unstable angina pectoris, 21 patients with sudden coronary death and 32 patients with a fatal first acute myocardial infarction. None of the 67 patients had a grossly visible left ventricular scar (healed myocardial infarct) and only the group with acute myocardial infarction had left ventricular myocardial necrosis. Although the frequency of intraluminal thrombus was similar in patients with unstable angina (29%) and sudden death (29%) and significantly lower than in those with acute infarction (69%) (p = 0.02), the thrombus in the patients with unstable angina and sudden death consisted almost entirely of platelets and was nonocclusive, whereas the thrombus in the group with acute infarction consisted almost entirely of fibrin and was occlusive. The frequency of plaque rupture was insignificantly different in the groups with unstable angina (36%) and sudden death (19%), and was significantly lower than in the group with acute infarction (75%) (p = 0.02). The frequency of plaque hemorrhage was insignificantly different in the groups with unstable angina (64%) and sudden death (38%) and was significantly lower than in the group with acute infarction (90%) (p = 0.04)."
-What imaging features are characteristic of adrenal hemangioma on magnetic resonance imaging?,"Adrenal hemangioma: an unusual adrenal mass delineated with magnetic resonance imaging. Adrenal hemangioma should be included in the differential diagnosis of any large calcified adrenal mass. We report to our knowledge the eighth surgically removed lesion and describe its appearance on magnetic resonance imaging. This imaging includes features seen in hemangiomas elsewhere, in particular a heterogeneous mass with enhancing peripheral high intensity foci on T1 images."
-What modifications were made to the standard aortography technique to improve visualization of lower limb arteries?,"A modified technique of pre-operative aortography to demonstrate the complete arterial tree of the lower limb. One hundred consecutive aortograms were studied to establish the efficacy of conventional arteriography in demonstrating distal vessels and the pedal arch. The standard technique was modified by using a long injection time, a large volume of contrast material (iopamidol 370), prolonged filming and multiple exposures of the feet. On the basis of these examinations each limb was classified as having aorto-iliac disease (18 limbs), superficial femoral disease (103 limbs), combined segment disease (28 limbs) or generalised disease (51 limbs). Calf and ankle arteries were seen in 196 of the 200 limbs (98%). Patency of the pedal arch was established in 184 (92%). Fourteen percent of the group of patients with combined segment disease did not have their pedal arch visualised and this group contained most of the examination failures. This modified method of aortography can demonstrate the entire arterial tree from the aorta to the foot in 92% of limbs with symptomatic chronic atherosclerotic disease. This allows the majority of peripheral vascular reconstructions to be planned and performed without the need for intra-operative arteriography."
-What is the recommended treatment for cerebral air embolism and how effective is it when administered late?,"Hyperbaric treatment of cerebral air embolism sustained during an open-heart surgical procedure A case of cerebral air embolism sustained during replacement of the mitral valve resulted in postoperative coma and seizures. Hyperbaric treatment, begun 30 hours after the occurrence of the air embolism, resulted in good immediate and long-term recovery. Mild deficits of the left hemisphere were present at follow-up 53 days after the embolus was sustained, and lesser, minimal residua were present at 14-month follow-up. Hyperbaric treatment is the definitive therapy for cerebral air embolism. Although it is most effective when administered early, the outcome may be excellent even with late treatment."
-What were the key findings of the study regarding the growth of human basal cell carcinomas transplanted to beige-nude mice?,"Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJ/bgJ nu/nu (beige-nude) mice. The purpose of this study was to measure growth parameters of transplanted basal cell carcinoma (BCC) to beige-nude mice during a 4-month observation time. Forty male beige-nude mice were transplanted with human BCC with our reported subcutaneous implantation technique. Initial volume and wet weight were determined for each tumor. The tumors were measured every 2 weeks by calipers with a final volume determined at 120 days, at which time the tumors were harvested, weighed, and processed for routine histology. Thirty-two tumor sites were positive for persistent tumor at harvest. Tumor volumes declined by an average of 51% and average tumor weight by 33%. There were increased numbers of mast cells surrounding the BCC tumor lobules. These results indicate that BCC can survive for 120 days in the beige-nude mouse."
-Does carbon dioxide laser treatment disperse human papillomavirus deoxyribonucleic acid during genital infection procedures?,"Carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields. The possibility of dispersing viral deoxyribonucleic acid during carbon dioxide laser treatment of human papillomavirus-containing genital infections has been investigated with a commercially available dot blot hybridization technique. The viral ribonucleic acid probes were specific for groups of human papillomavirus types 6/11, 16/18, and 31/33/35. Laser energy was delivered by continuous-wave mode and the plume of smoke was evacuated by a vacuum suction system. Samples were taken with Dacron swabs from lesional tissues of 43 patients as well as from the treated areas and from the 5 cm surrounding normal skin before and after laser vaporization. Human papillomavirus deoxyribonucleic acid was identified in swabs from 34 of 43 (79%) lesional tissues and 7 of 43 (16%) treatment fields. Although a trend for higher human papillomavirus deoxyribonucleic acid positivity in laser margins after therapy (7/43, 16%) than before (4/43, 9%) was observed, the rates were not statistically significant. It is concluded that carbon dioxide laser energy disperses human papillomavirus deoxyribonucleic acid onto treatment fields and the adjacent normal epithelium. Viral contamination of treated areas may be reduced by positioning the fume evacuator within 1 cm of the field of laser vaporization and cleaning the treated areas and surrounding tissue after therapy."
-What is Bouveret's syndrome and how does it typically manifest?,"Bouveret's syndrome: an unusual twist on the classic cause. Bouveret's syndrome is a duodenal obstruction caused by a gallstone, manifested mostly as a gastric outlet obstruction. We have reported an instance of Bouveret's syndrome caused by two separate stones, either of which could independently have caused the obstruction. It is imperative to be sure that the obstruction is relieved before terminating the operative procedure."
-What is the primary medical intervention discussed for managing retroperitoneal hemorrhage from renal angiomyolipoma in a patient with polycystic kidney disease?,"Angiographic management of retroperitoneal hemorrhage from renal angiomyolipoma in polycystic kidney disease. Angiographic management of bilateral angiomyolipomas complicated by hemorrhage in autosomal dominant polycystic kidney disease is presented. The patient had mild stigmata of tuberous sclerosis, and a family history of tuberous sclerosis and autosomal dominant polycystic kidney disease. The radiographic features at diagnosis, and those present during and after embolization are described. Radiological criteria for diagnosis and successful control of bleeding with intra-arterial selective embolization are discussed. Radiographic features before, during and after embolization are exhibited."
-What is the primary purpose of the study on CGS 16949A (fadrozole hydrochloride) in postmenopausal women with metastatic breast cancer?,"Specificity of low dose fadrozole hydrochloride (CGS 16949A) as an aromatase inhibitor. CGS 16949A (fadrozole hydrochloride), a potent cytochrome P450-mediated steroidogenesis inhibitor, blocks aromatase at low doses, but other biosynthetic steps at higher concentrations. Recent studies demonstrated inhibition of C11-hydroxylase, corticosterone methyloxidase-II, and deoxycorticosterone to corticosterone conversion with this agent at some-what higher concentrations than those required for blockade of aromatase. Based upon phase I studies, we postulated that relatively selective inhibition of aromatase might be possible if sufficiently low doses of CGS 16949A were used. A phase II study in 54 postmenopausal women with metastatic breast cancer examined the effects of low dose CGS 16949A on estrogen, mineralocorticoid, and glucocorticoid secretion. Two dose schedules and two dose levels were chosen based upon our prior dose escalation protocol study. Plasma estrone, estradiol, and estrone sulfate as well as urinary estrone and estradiol fell equally with 1.8-4 mg CGS 16949A given either on a twice daily or three times daily dose schedule. Isotopic kinetic studies demonstrated an 84% decrease in the rate of conversion of androstenedione to estrone to 0.40 +/- 0.07% (patients receiving 1.8-4 mg CGS 16949A daily). With these three regimens, basal levels of aldosterone and cortisol did not change significantly over a 12-week period of observation. Clinical examination, plasma electrolytes, and urinary sodium/potassium ratios suggested no biological evidence of mineralo-corticoid deficiency. ACTH-stimulated cortisol concentrations, however, were blunted at each dose level compared to pretreatment values. Nonetheless, peak responses exceeded 550 nmol/L, or a basal to peak difference of 190 nmol/L or greater, in 97% of instances. This probably reflected inhibition of C11-hydroxylase, since basal and ACTH-stimulated levels of 11-deoxycortisol were increased in response to CGS 16949A. Androstenedione and 17 alpha-hydroxyprogesterone also exhibited an upward trend in response to drug treatment. ACTH-stimulated aldosterone levels were blunted to a greater extent than those of cortisol, probably as a reflection of corticosterone methyloxidase type II blockade. Overall, the results suggest that CGS 16949A, at doses of 1.8-2 mg daily, blocks aromatase effectively and does not produce clinically important inhibition of cortisol or aldosterone biosynthesis. Thus, this agent can probably be used safely without glucocorticoid or mineralocorticoid supplementation."
-What are the different histologic patterns of isolated neurofibromas of the conjunctiva observed in the study?,"Isolated neurofibromas of the conjunctiva. We studied four histologically verified cases of isolated neurofibromas of the conjunctiva. The histologic pattern was diffuse in two patients, plexiform in one patient, and solitary in one patient. Simple excision was curative in all cases. We emphasize the importance of distinguishing neuromas (which may be associated with multiple endocrine neoplasia) from neurofibromas."
-What is a double anal canal and how can it develop as a complication of chronic constipation?,"Double anal canal: complication of rectal fecalith. Fecaliths and stercoraceous ulcerations are well-known complications of chronic constipation. The authors present the case of a double anal canal in an elderly man. This anorectal fistula (complex anal fistula) developed as a complication of an impacted rectal fecalith with resultant stercoraceous ulceration. Eventually, a persistent epithelialized canal developed and was demonstrated at double-contrast barium enema examination. The patient remained continent at all times."
-What percentage of patients with closed-head injury were discharged in a vegetative state according to the Traumatic Coma Data Bank Report?,"Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report. To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state."
-What were the key findings regarding the prognosis of B-cell and T-cell diffuse large-cell lymphomas in this Stanford study?,"Similar outcome of treatment of B-cell and T-cell diffuse large-cell lymphomas: the Stanford experience. Although previous studies have suggested a relatively poor prognosis for some patients with peripheral T-cell lymphoma, the clinical significance of immunologic phenotype in diffuse large-cell lymphoma (DLCL) remains controversial. One hundred one patients with a uniform morphologic diagnosis of DLCL treated at Stanford between 1975 and 1986 with cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine, and prednisone (CHOP), methotrexate, bleomycin, Adriamycin, cyclophosphamide, vincristine, and dexamethasone ([M]BACOD), or methotrexate, Adriamycin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) chemotherapy were studied with regard to immunologic phenotype. Immunologic analysis, performed on frozen or paraffin-embedded tissue, identified 77 cases of B-cell origin, 21 cases of T-cell origin, and three cases that lacked B-cell or T-cell markers. Analysis of complete remission (CR) rates (84% v 95%), 5-year actuarial freedom from disease progression (38% v 53%), and 5-year actuarial overall survival (52% v 79%) showed no statistically significant differences in prognosis between B- and T-cell patients, respectively. The 5-year actuarial survival of patients with stage IV T-cell DLCL (56%) also did not differ in a statistically significant way from stage IV B-cell patients (36%). We conclude that treatment selection for DLCL should not be based on immunologic phenotype alone."
-"What type of cancer was successfully treated in this case report, and how long did the patient survive after the surgical intervention?","Long survival after excision of a primary malignant melanoma of the oesophagus. A woman who had a large primary malignant melanoma of the oesophagus, with evidence of submucosal invasion and several local metastases, underwent resection two years after the onset of retrosternal pain and has survived for 12 years with no recurrence."
-What were the main findings of the study regarding the use of beta-adrenergic-antagonist drugs in preventing gastrointestinal bleeding in patients with cirrhosis and esophageal varices?,"Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. BACKGROUND. The value of beta-adrenergic-antagonist drug therapy for the prevention of initial episodes of gastrointestinal bleeding in patients with cirrhosis and esophageal varices is uncertain, both positive and negative study results having been reported. METHODS. In this study, we analyzed data on individual patients from four randomized, controlled trials to assess the efficacy of this treatment. Of the 589 patients studied, 286 received a beta-adrenergic-antagonist drug (propranolol in 203 and nadolol in 83) and 303 received placebo. RESULTS. After two years, the mean (+/- SE) percentage of patients who had had no upper gastrointestinal bleeding was 78 +/- 3 percent in the beta-adrenergic-antagonist treatment group and 65 +/- 3 percent in the control group (P = 0.002). The percentage of patients without fatal bleeding was 90 +/- 2 percent in the treatment group and 82 +/- 3 percent in the control group (P = 0.01). The percentage of patients surviving after two years was 71 +/- 3 percent in the treatment group and 68 +/- 3 percent in the control group (P = 0.34). After age and severity of cirrhosis were taken into account, the survival rate was better in the treatment group (P = 0.09). The percentage of surviving patients who had had no bleeding after two years was 62 +/- 3 percent in the treatment group and 53 +/- 3 percent in the control group (P = 0.04). Both propranolol and nadolol prevented a first episode of bleeding. Severe cirrhosis and especially the presence of ascites were associated with bleeding (P less than 0.001) and death (P less than 0.001) in both groups. The efficacy of beta-adrenergic-antagonist therapy in the prevention of bleeding (P less than 0.001) and of fatal bleeding (P = 0.004) and in the prevention of bleeding or death (P = 0.005) was the same after adjustment for cause and severity of cirrhosis, ascites, and size of varices. CONCLUSIONS. Propranolol and nadolol are effective in preventing first bleeding and reducing the mortality rate associated with gastrointestinal bleeding in patients with cirrhosis, regardless of severity."
-What were the key findings from the renal biopsy in the patient with Donohue syndrome?,"Glomerulopathy in patient with Donohue syndrome (leprechaunism). OBJECTIVE: To evaluate renal structure in a child with Donohue syndrome (leprechaunism), who at 10 yr of age was noted to have hypertension, microalbuminuria, and enlarged kidneys, a renal biopsy was performed. RESEARCH DESIGN AND METHODS: The renal biopsy tissue was evaluated by light and electron microscopy with standard stereological techniques to measure glomerular volume, glomerular basement membrane width, fractional mesangial volume, and peripheral capillary filtering surface density. RESULTS: On renal biopsy, there was a marked increase in glomerular volume, glomerular basement width, and mesangial volume, findings similar to those seen in patients with diabetic nephropathy. CONCLUSIONS: This patient with marked insulin resistance associated with Donohue syndrome demonstrates renal and glomerular enlargement and morphometric glomerular changes similar to those seen in patients with diabetic nephropathy. In unusual syndromes with hyperglycemia and hyperinsulinemia, renal structural and functional changes typical of traditional diabetes mellitus may be seen."
-How does endolymphatic pressure differ between normal and hydropic ears in guinea pigs?,"The measurement and manipulation of intralabyrinthine pressure in experimental endolymphatic hydrops. Three to four months after unilateral surgical ablation of the endolymphatic duct and sac, endolymphatic and perilymphatic pressures were measured in both the normal and hydropic ears of 11 guinea pigs. In normal ears, endolymphatic pressure always approximated perilymphatic pressure. Endolymphatic pressure exceeded perilymphatic pressure in all ears with hydrops, except one in which these pressures were equal. The effect of postural inversion on inner ear pressures were studied in both normal and hydropic inner ears. Normal ears showed endolymphatic and perilymphatic pressure to rise equally during this maneuver. In hydropic ears, the difference between endolymphatic and perilymphatic pressure was notably reduced from measurements obtained in the prone position. This study indicates that an alteration in pressure regulation within the inner ear may be important in the pathogenesis and manifestation of experimental endolymphatic hydrops in the guinea pig. Physiologic mechanisms and clinical implications of these results are described."
-What was the cumulative success rate of custom-made distal femoral prostheses at five and seven years?,"Prosthetic replacement of the distal femur for primary bone tumours. Over a 16-year period, 135 custom-made distal femoral prostheses, based on a fully constrained Stanmore-type knee replacement, were used in the treatment of primary malignant or aggressive benign tumours. Survivorship analysis showed a cumulative success rate of 72% at five years and 64% at seven years. Intact prostheses in 91% of the surviving patients gave good or excellent functional results. Deep infection was the major complication, occurring in 6.8% of cases; clinical aseptic loosening occurred in 6.0%. Revision surgery was carried out for loosening and infection, and the early results are encouraging. We conclude that prosthetic replacement of the distal femur can meet the objectives of limb salvage surgery."
-What are the key neurological features observed in patients with endemic cretinism across different types of the syndrome?,"The neurology of endemic cretinism. A study of two endemias. Endemic cretinism is the most severe manifestation of dietary iodine deficiency. Two forms of the syndrome are traditionally described: neurological and myxoedematous. Although this classification highlights the important neurological sequelae of the disorder it implies that myxoedematous cretins have an alternative mechanism. Further, the nature of the neurological deficit associated with both types of endemic cretinism has received scant attention in recent times considering that it remains a common disorder in many parts of the world. The nature and extent of the neurological deficit found in endemic cretinism was investigated in 104 cretins from a predominantly myxoedematous endemia in western China and in 35 cretins from central Java, Indonesia, a predominantly neurological endemia. We found a similar pattern of neurological involvement in nearly all cretins from both endemias, regardless of type (myxoedematous or neurological), and of current thyroid function. Hallmarks of the neurological features included mental retardation, pyramidal signs in a proximal distribution and extrapyramidal signs. Many patients exhibited a characteristic gait. This probably reflected pyramidal and extrapyramidal dysfunction, although joint laxity and deformity were important contributing factors. Other frequently encountered clinical features were squint, deafness, and primitive reflexes. Cerebral computerized tomography (CT) revealed basal ganglia calcification in 15 of 50 subjects. The presence of basal ganglia calcification was confined to cretins with severe hypothyroidism. Otherwise, cerebral CT scanning demonstrated only minor abnormalities which did not contribute to the localization of the clinical deficits. We conclude that the same neurological disorder is present in both types of endemic cretinism reflecting a diffuse insult to the developing fetal nervous system. These clinical findings support the concept of maternal and fetal hypothyroxinaemia, arising from severe iodine deficiency, as the primary pathophysiological event in endemic cretinism. Differences between the two types of cretinism may be explained by continuing postnatal thyroid hormone deficiency in the myxoedematous type, which results in impaired growth, skeletal retardation and sexual immaturity."
-What rare complication did the patient experience following a middle and lower lobectomy?,"Pulmonary vein thrombosis following bilobectomy. Acute thrombosis of the pulmonary vein following lobectomy or bilobectomy is a rare complication with no standard guideline for diagnosis or management. In this report, we present a case of right upper lobe vein thrombosis following a middle and lower lobectomy. Diagnosis was confirmed by ventilation-perfusion lung scan, pulmonary angiogram, and bronchoscopy. The patient was treated conservatively with no further complications and had a partial recovery of the circulation to the right upper lobe. A review of the literature is also presented along with the experimental data demonstrating the mechanisms of recovery."
-What percentage of women with atypical squamous cells on Papanicolaou smears were found to be positive for HPV DNA in the study?,"Atypical squamous cells. A case-series study of the association between papanicolaou smear results and human papillomavirus DNA genotype. Thirty women with ""atypical"" squamous cells but not cervical intraepithelial neoplasia (CIN) on their Papanicolaou smears were tested for the presence of human papillomavirus (HPV) with the Southern blot hybridization technique. The Papanicolaou smears were reviewed for the presence of atypical squamous cells according to Patten's criteria. Comparison groups consisted of 30 patients with normal, 29 patients with CIN I and 24 patients with CIN II Papanicolaou smears. Ten of the 30 women (33%) with atypical cells on Papanicolaou smears were positive for HPV DNA as compared to 17% with normal and 59% with CIN I or II Papanicolaou smears. HPV 16 was present in 70-80% of the HPV DNA-positive patients in each Papanicolaou smear group. Concurrent CIN was also identified on colposcopically directed biopsies in 27% of the patients with squamous atypia. Patients with atypical squamous cells on Papanicolaou smears had coexisting HPV infection and CIN in about one-third of the cases. Colposcopy and further follow-up are recommended for such patients."
-How does the injury current affect the excitability of normal tissue during acute regional myocardial ischemia?,"Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. During acute regional myocardial ischemia, a ""current of injury"" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the ""ischemic"" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia."
-How does intraoperative facial nerve monitoring with electrical stimulation (IFNMES) help predict facial nerve function during acoustic tumor removal?,"Intraoperative facial nerve monitoring: prognostic aspects during acoustic tumor removal. Intraoperative facial nerve monitoring with electrical stimulation (IFNMES) has become an integral part of acoustic tumor surgery. We reviewed the records of fifty-six patients who underwent translabyrinthine acoustic tumor removal with IFNMES. There was excellent correlation between intraoperative facial nerve activity and immediate postoperative facial nerve function (24 hours after surgery and at hospital discharge). Our data would suggest that patients who exhibit less than 500 microvolts of ongoing EMG activity during surgery, and who yield at least a 500-microvolt contraction when stimulated with 0.05 milliamps at the brainstem after tumor removal, can expect an excellent immediate facial nerve result (grade I or II)."
-What is the typical treatment approach for diskitis in children according to the study?,"Diskitis in children. Thirty-six patients diagnosed with diskitis from 1978 to 1988 and followed for an average of 29.2 months were reviewed. The study included 23 boys and 13 girls with an average age of 5.3 years. The initial symptoms varied, but distinct clinical patterns emerged and were identifiable in different age groups. Both the leukocyte count and sedimentation rate were elevated. Routine roentgenograms were positive for intervertebral disk space narrowing in 82% of cases, technetium bone scans positive in 72%, and magnetic resonance imaging positive in all recent cases. Treatment consisted of bed rest for all patients, plaster casts for 50%, antibiotics for 40%, and traction for 23%. Regardless of the treatment combination, the course of the disease in most children is benign. At the completion of the study, all patients were asymptomatic including three children who had recurrences. In spite of being asymptomatic, 74% had persistent roentgenographic changes. The administration of antibiotics appears to be appropriate when indicated, i.e., failure to respond to immobilization. Disk space aspiration or biopsy should be reserved for those cases that are refractory to immobilization and antibiotics."
-How does external leg counterpressure affect cardiovascular parameters in simulated mild hypovolemia?,"The autotransfusion effect of external leg counterpressure in simulated mild hypovolemia. We examined the cardiovascular response of external leg counterpressure in healthy volunteers at 100 mm Hg compression pressure. To stimulate mild hypovolemia, measurements were made with the subjects in a 60 degrees head-up tilt position. Left ventricular end-diastolic volume (LVEDV) and cardiac output (CO) were calculated from two-dimensional echocardiography. Flow through the inferior vena cava (IVC) below the origin of the hepatic veins was determined by the Doppler ultrasound technique. The application of counterpressure significantly increased LVEDV, CO, and arterial blood pressure over that seen with tilting without the device. These responses were accompanied by a small but significant increase in IVC flow. We therefore concluded that external leg counterpressure transferred blood to the central circulation by compression of the venous capacitance vessels (an autotransfusion effect) in mild hypovolemia, but such an effect may not benefit patients in a hypovolemic shock state because of the small amount of translocated blood."
-How do cardiovascular reflexes differ between Parkinson's disease patients and healthy subjects in this study?,"Cardiovascular reflexes and autonomic dysfunction in Parkinson's disease. Cardiovascular reflexes were analysed in a group of 20 patients suffering from Parkinson's disease and in 12 age-matched healthy subjects, in order to ascertain the incidence and degree of autonomic dysfunction. The following were measured: heart rate variation during normal breathing, postural change (30/15 ratio) and during the Valsalva manoeuvre: blood pressure variation after standing. These measurements were taken at least 12 h after therapy had been withdrawn and were repeated after therapy had been resumed. Significant changes in the different heart rate variation indices were found in the parkinsonian patients which correlated with the duration and severity of the extrapyramidal symptomatology. After standing the patients showed a significant drop in blood pressure, when compared respectively with their base values and with the response in controls. Anticholinergic drugs had no significant effect on the heart rate variation indices, whereas antiparkinsonian therapy seems to have contributed to the drop in blood pressure after standing."
-What are the potential clinical manifestations of dysfibrinogenemia during pregnancy?,"Dysfibrinogenemia associated with thrombosis and third-trimester fetal loss. A case report. Dysfibrinogenemias are rare genetic disorders that are clinically silent, cause a mild bleeding tendency or have thromboembolic manifestations. During pregnancy they often cause hemorrhage and first-trimester abortions. A patient with a severe thrombotic tendency during pregnancy had a third-trimester fetal loss."
-What were the comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction?,"Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study. BACKGROUND. Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study. METHODS AND RESULTS. One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died. CONCLUSIONS. The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications."
-What method was used to assess DNA profiles in the oral exfoliative cytologic study?,"Detection of field change in oral cancer using oral exfoliative cytologic study. Four smears were taken from the normal buccal mucosa of 55 oral cancer patients and 76 cancer-free patients. In each case, two were stained by the Papanicolaou method and two underwent Feulgen hydrolysis. Quantitative assessment of nuclear area (NA) and cytoplasmic area (CA) of the Papanicolaou smears was undertaken using a semiautomatic image analysis system. DNA profiles were assessed from the Feulgen smears using a Vickers M85 microdensitometer (Vickers Instruments, York, England) and were found to be diploid for all patients. Results were then analyzed with respect to those patients who took alcohol, tobacco, combination of alcohol and tobacco, and those who took neither. A significant reduction in CA for the oral cancer group (P equals 0.001) but no change in NA (P equals 0.74) was observed. A detailed analysis of alcohol and tobacco habits could identify no significant role for these two factors, in the reduction in cytoplasmic area. Such field change may prove to be of value in predicting the development of second malignant tumors."
-What percentage of respondents in the Norwegian population study believed penicillin to be effective against viral infections?,"Fever: knowledge, perception and attitudes. Results from a Norwegian population study. To investigate the layman's knowledge, perception and attitudes regarding normal body temperature, fever, infections and the effect of penicillin on virus infections a representative sample of the Norwegian population (619 women and 592 men over the age of 15) was interviewed in 1988 as part of a monthly national opinion poll. One-third thought body temperatures up to 40.5 degrees C to be life-threatening, but the results do not justify the application of the term 'fever phobia' as described in other studies based on non-representative samples. More respondents were afraid of viral infections (48%) than bacterial infections (9%), which may be due to the media focus upon the HIV/AIDS epidemic. Thirty-five per cent believed penicillin to be effective against virus infections. Educational programmes on fever should also include information about virus infections and their treatment."
-How does fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) help in assessing the response to cancer therapy?,"Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography. In order to evaluate the usefulness of 18F-FDG PET in the assessment of therapeutic effects, FDG-PET studies were performed both before and after therapy in 26 patients with miscellaneous malignant tumors. The change in FDG uptake by therapy was compared with the change in tumor size and prognosis. All 26 lesions had a high FDG uptake before therapy. Five of seven lesions which had a relatively low FDG uptake before therapy showed no change or increase in tumor size by therapy. The decreased FDG uptake after therapy was more prominent in the partial response group than in the no change group. FDG uptake before therapy in the non-relapse group was higher than that in the relapse group. However, a decreased FDG uptake did not necessarily indicate a good prognosis. One patient with no change in tumor size and a decreased FDG uptake had no recurrence. This suggests that FDG-PET has a complementary role in the assessment of therapeutic effects."
-What rare medical condition is described in this case report involving the cauda equina?,Subarachnoid hemorrhage from multiple neurofibromas of the cauda equina: case report. The authors report a case of spinal subarachnoid hemorrhage caused by neurofibromas of the cauda equina. An examination of the literature revealing 13 similar cases and an analysis of this case showing three neurofibromas of the cauda equina prompted an hypothesis emphasizing the origin of bleeding and the difficulties associated with a correct diagnosis.
-How does compression-ischaemia nerve block differently affect warm sensation and heat-induced pain in human volunteers?,"Differential effect of compression-ischaemia block on warm sensation and heat-induced pain. The effect of compression-ischaemia nerve block on psychophysical thresholds for warm sensation and heat-induced pain was studied on 19 normal human volunteers. Although those two sensory submodalities should be predicted to block simultaneously, based on the fact that both are served by unmyelinated primary afferents, it was actually found that warm sensation was much more vulnerable to compression-ischaemia than heat-induced pain. This is interpreted as resulting from different summation requirements for each of the two sensory modalities; sensation of warmth depends on spatial summation to a larger extent than heat-induced pain. Such differential vulnerability is in line with recent clinical studies reporting deterioration of warm sensation associated with preservation of heat pain in peripheral nerve disorders caused by diabetes, ageing and other neuropathic processes."
-What challenges are associated with detecting and treating acoustic schwannomas in children?,"Acoustic schwannomas in children. The clinical presentation and treatment of three cases of acoustic schwannoma occurring in children are described. All the tumors were detected late, when they had attained a large size and were extremely vascular. The use of preoperative tumor embolization as an adjunct to surgical excision is discussed."
-What characteristic of Doppler ultrasound helps differentiate between bland thrombus and tumor thrombus in the main portal vein?,Hepatofugal arterial signal in the main portal vein: an indicator of intravascular tumor spread. Five patients with thrombosis of the main portal vein underwent Doppler ultrasound (US). Three of these patients had confirmed hepatocellular carcinoma. Doppler US allowed differentiation between bland thrombus and tumor thrombus in two of the three patients. Tumor thrombus of the main portal vein was characterized at US by an intraportal arterial waveform in a hepatofugal direction.
-How can forensic experts differentiate between hydrocephalic calf and human calvariae?,"Differentiation of hydrocephalic calf and human calvariae. Occasionally, partial calvariae of hydrocephalic calves are found in forensic contexts and mistakenly identified as human. Such specimens can be properly identified through immunological assessment of associated soft tissue, microscopic analysis of associated hair, and morphological comparison with documented museum specimens. Morphological comparison should focus on the form of the occiput, supraorbital grooves, and bulbous vault and presence of coronal processes."
-What are the key risk factors for infusion-related phlebitis in peripheral intravenous catheters?,"Risk factors for infusion-related phlebitis with small peripheral venous catheters. A randomized controlled trial. OBJECTIVE: To identify risk factors for infusion-related phlebitis with peripheral intravenous catheters. DESIGN: A randomized trial of two catheter materials, with consideration of 21 potential risk factors. SETTING: A university hospital. PATIENTS: Hospitalized adults without granulocytopenia who received a peripheral intravenous catheter. INTERVENTIONS: House officers or ward nurses inserted the catheters, and each insertion was randomized to a catheter made of tetrafluoroethylene-hexafluoropropylene (FEP-Teflon) or a novel polyetherurethane without leachable additives (PEU-Vialon). MEASUREMENTS: Research nurses scored insertion sites each day for inflammation and cultured catheters at removal. RESULTS: The Kaplan-Meier risk for phlebitis exceeded 50% by day 4 after catheterization. intravenous antibiotics (relative risk, 2.00), female sex (relative risk, 1.88), prolonged (greater than 48 hours) catheterization (relative risk, 1.79), and catheter material (PEU-Vialon: FEP-Teflon) (relative risk, 0.73) strongly predicted phlebitis in a Cox proportional hazards model (each, P less than 0.003). The best-fit model for severe phlebitis identified the same predictors plus catheter-related infection (relative risk, 6.19), phlebitis with a previous catheter (relative risk, 1.54), and anatomic site (hand: forearm, relative risk, 0.71; wrist:forearm, relative risk, 0.60). The low incidence of local catheter-related infection was comparable with the two catheter materials (5.4% [95% CI, 3.8% to 7.6%] and 6.9% [CI, 4.9% to 9.6%]); none of the 1054 catheters prospectively studied caused bacteremia. CONCLUSIONS: Multiple factors, including the infusate and the duration of cannulation, contribute to the development of infusion-related phlebitis. The use of peripheral intravenous catheters made of PEU-Vialon appears to pose the same risk for catheter-related infection as the use of catheters made of FEP-Teflon, and PEU-Vialon can permit longer cannulation with less risk for phlebitis. The risk for catheter-related bacteremia with FEP-Teflon and PEU-Vialon catheters is sufficiently low that it no longer seems justifiable to recommend the use of small steel needles for most peripheral intravenous therapy."
-What medical condition was the surgical depilation primarily used to treat in this study?,"Surgical depilation for the treatment of pseudofolliculitis or local hirsutism of the face: experience in the first 40 patients. Forty patients underwent surgical depilation for pseudofolliculitis barbae or local hirsutism of the face during a 15-year period. The operative method and its results and pitfalls are discussed. Although it is not the treatment of choice, this operation is very useful when other therapy has not been successful. This seems especially true in male-to-female transsexuals."
-How do the muscle characteristics of Himalayan Sherpas differ from sedentary lowlanders and Caucasian climbers?,"Muscle structure and performance capacity of Himalayan Sherpas. The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg(-1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross-sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density."
-What was the purpose of the study on isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis?,"Test-retest reliability of isokinetic knee extension and flexion torque measurements in persons with spastic hemiparesis. The purpose of this study was to evaluate and compare the test-retest reliability of isokinetic torque measurements in the involved and uninvolved knee musculature of 20 subjects with spastic hemiparesis. An isokinetic dynamometer was used to measure maximal voluntary knee extension and flexion at 60 degrees and 120 degrees/s. Peak torque (PT) and average peak torque (APT) data were collected from five repetitions on two separate occasions. Average peak torque was defined as the mean of the PT values obtained during each of the five repetitions. Spasticity was measured in the involved knee musculature prior to isokinetic testing using the Ashworth Scale. Pearson Product-Moment Correlation Coefficients and intraclass correlation coefficients (ICCs) were high (greater than or equal to .90) for both knees for PT and APT at both angular velocities. No clinically meaningful differences were found between the Pearson correlation coefficients and the ICCs of the involved versus the uninvolved knee for any testing conditions. We concluded that isokinetic evaluation of torque, as measured by PT and APT in subjects with spastic hemiparesis, can yield reliable results in both extremities."
-What is the purpose of the thrombogenic microballoon developed in this research?,"Thrombogenic microballoon for cerebral aneurysms, arteriovenous malformations, and carotid cavernous fistula occlusion. Preliminary technical note. A thrombogenic microballoon was developed to overcome the problems of cerebral aneurysm rupture during microballoon inflation and incomplete aneurysm obliteration by microballoons with subsequent fatal rupture. These complications occur in about 35% of reported series with current microballoon embolization techniques. The wall of the new thrombogenic microballoon allows 80% aneurysm occlusion by inflation, thus avoiding mechanical rupture, and at the same time it produces a blood clot in the space remaining between the microballoon and the aneurysm wall. This clot undergoes fibrosis with firm adherence of the microballoon to the aneurysm wall. Experimental evidence is presented to support these conclusions. This thrombogenic microballoon system is also applicable to carotid-cavernous fistulas and arteriovenous malformations."
-What surgical technique was developed to safely perform resternotomy in patients with valved conduits adherent to the sternum?,"Resternotomy in patients with valved conduits adherent to the sternum. Twenty-two patients with valved conduits adherent to the sternum underwent resternotomy. Mean age was 10 +/- 6 years, and mean conduit age was 4 +/- 4 years. Diagnoses were D-transposition (7), truncus arteriosus (7), univentricular heart (6), Taussig-Bing anomaly (1), and corrected transposition (1). The majority of patients (68%) had reoperation for outgrown or degenerated conduits. In 17 patients, the sternum was opened with a chisel. Two of these patients sustained conduit neointimal collapse from manipulation, and 3 had conduit tear requiring immediate cardiopulmonary bypass through the femoral vessels. In the last 5 patients, the sternum was opened above and below the conduit, and the inner table was chiseled and left attached to the conduit avoiding injury and undue conduit manipulation. Cardiopulmonary bypass and operation were carried out uneventfully. We believe that the recent technique described provides a safe alternative approach to valved conduits adherent to the sternum."
-How did the QRS vector changes correlate with infarct size and left ventricular ejection fraction in patients treated with recombinant tissue-type plasminogen activator (rt-PA)?,"Dynamic QRS-complex and ST-segment monitoring in acute myocardial infarction during recombinant tissue-type plasminogen activator therapy. The TEAHAT Study Group. Changes of the QRS complex are the electrocardiographic expression of irreversible injury of the myocardium. In humans, the process of infarction occurs over several hours. A more rapid development of QRS changes has been reported in patients treated with thrombolytic agents. Patients with strongly suspected acute myocardial infarction (AMI) included in a placebo-controlled trial of 100 mg of recombinant tissue-type plasminogen activator (rt-PA) were monitored for 24 hours with continuous, on-line vectorcardiography. The magnitude of the QRS vector changes correlated with infarct size estimated by the maximal value of lactate dehydrogenase-1 (r = 0.69, p less than 0.001) as well as with left ventricular ejection fraction 30 days after randomization (r = 0.49, p less than 0.001). Treatment with intravenous rt-PA limited total QRS vector change but the QRS vector changes observed occurred more rapidly and reached a plateau 131 minutes earlier in patients treated with rt-PA than in those receiving placebo (p less than 0.01). A certain pattern of highly variable ST vector magnitude was identified and was associated with higher maximal lactate dehydrogenase-1 values (23 +/- 13 vs 14 +/- 10 mu kat/liter, p less than 0.001) and a tendency to higher 1-year mortality (24 vs 9%, p = 0.08) than in patients without this pattern. In patients with this pattern, rt-PA did not affect maximal lactate dehydrogenase-1, time to maximal creatine kinase and final magnitude of QRS vector change."
-How do pulse pressure patterns in hypertensive pregnant women relate to birth weight and gestational age?,"Peripheral pulse pressure patterns in pregnancy hypertension. Maternal heart rate and pulse pressure patterns were examined in 30 hypertensive pregnant women using noninvasive methodology described previously. ""Narrow"" and ""wide"" pulse patterns were identified. Narrow cutaneous pulse pressure patterns, which are thought to be caused by vasoconstriction, were associated with lower birth weight infants (1870 +/- 983 versus 3225 +/- 838 g; P less than .001) and earlier deliveries (34.2 +/- 5.2 versus 37.9 +/- 2.8 weeks; P less than .05). The data suggest that these adjunctive maternal cardiovascular-system evaluation techniques may be useful in identifying patients at risk of adverse perinatal outcome by detecting vasospasm of the peripheral microcirculation."
-What techniques were used to detect right-to-left vascular shunting in patients with stroke or neurologic defects?,"Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound. Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization."
-What was the purpose of the study on intrathecal fibrinolytic therapy in patients with aneurysmal subarachnoid hemorrhage?,"Effect of intrathecal fibrinolytic therapy on clot lysis and vasospasm in patients with aneurysmal subarachnoid hemorrhage. A prospective series of 30 patients with a single, angiographically verified aneurysmal subarachnoid hemorrhage (SAH) was studied for the effect of intrathecal thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) on outcome, angiographic vasospasm, and computerized tomography (CT) findings after surgery. The patients included fulfilled the following criteria: operation was performed by Day 3 after the hemorrhage, CT showed only blood in the basal cisterns, and the patient had a single aneurysm or multiple aneurysms that could be treated surgically at the same operation. The patients were divided into groups of 10, with patients receiving 3, 10, or 13 mg of rt-PA in a single intracisternal injection at the end of the operation. There were no differences between the treatment groups in overall outcome. One patient from the 3-mg rt-PA group developed a postoperative intracerebral hemorrhage, and one patient from the 10-mg rt-PA group had a postoperative epidural hematoma. There was one death in the 13-mg rt-PA group that was caused by inclusion of a segment of pericallosal artery in the clip. In all treatment groups a reduction was observed in the amount of blood seen on the postoperative CT scans compared to the preoperative CT scans. The reduction in SAH grade between the 10-mg and 13-mg rt-PA groups was significant (p less than 0.05). The difference in the severity of angiographic vasospasm between the 3-mg and 13-mg rt-PA groups was also significant (p less than 0.05)."
-What were the 4-year actuarial local control and disease-free survival rates for patients undergoing resection in this study of retroperitoneal soft tissue sarcoma?,"Intraoperative electron beam radiation therapy for retroperitoneal soft tissue sarcoma. From December 1981 to December 1989, 20 patients with primary or recurrent retroperitoneal sarcoma received 4000 to 5000 cGy of external beam radiation therapy (EBRT) in conjunction with surgical resection and intraoperative radiation therapy (IORT). Seventeen of 20 patients underwent complete (14 patients) or partial (3 patients) resection. Three patients had shown evidence of metastases after EBRT by the time of surgery. The 4-year actuarial local control and disease-free survival rates of the 17 patients undergoing resection were 81% and 64%, respectively. Twelve patients received IORT at the time of resection for microscopic disease (10 patients) or gross residual sarcoma (2 patients). Of the ten patients receiving IORT for microscopic tumor, one patient has died of local failure and peritoneal sarcomatosis and two patients have died of distant metastases only. The remaining seven patients are disease-free. One patient treated for gross residual sarcoma has experienced a local failure 1 year after IORT and is without disease 7 years after salvage chemotherapy. The other patient treated for gross residual sarcoma has died of local failure. Five patients did not receive IORT at the time of resection because of the extensive size of the tumor bed. Three of these patients are disease-free with one patient alive with lung metastases and one patient dying of hepatic metastases. Aggressive radiation and surgical procedures appear to provide satisfactory resectability and local control with acceptable tolerance."
-How did the patient develop a meningioma 30 years after receiving a Torkildsen shunt and irradiation treatment?,"Meningioma: the role of a foreign body and irradiation in tumor formation. A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented."
-How did the researchers use PET and radiolabeled microspheres to measure critically ischemic myocardial tissue during acute coronary occlusion?,"Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET. Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography."
-What happened to the patient's auditory evoked potentials after the acoustic neurinoma excision surgery?,"Progressive deterioration of auditory evoked potentials after excision of an acoustic neurinoma: case report. The authors report the case of a 17-year-old girl who underwent excision of bilateral neurinomas of the cerebellopontine angle. Although her auditory evoked potentials were well maintained during the operation, they deteriorated gradually and progressively for the following 2 months. This seemed to reflect degeneration of the cochlear nerve fibers initiated by operative manipulation in the cerebellopontine angle in a patient who had no hearing when she awoke from surgery."
-What is diffuse pulmonary hemorrhage and what are its key clinical manifestations?,"Diffuse pulmonary hemorrhage. Diffuse pulmonary hemorrhage is a syndrome consisting of hemoptysis, anemia, and air-space consolidation. The radiologic appearance is non-specific. Pulmonary hemorrhage may be due to a number of different causes. The differential diagnosis and the diagnostic approach are different in the immunologically intact host as compared with the immunocompromised host. This article reviews the main diagnostic considerations in diffuse pulmonary hemorrhage."
-What are the key characteristics of gonococcal endocarditis during pregnancy based on the case report?,"Gonococcal endocarditis complicating pregnancy: a case report and literature review. The incidence of gonorrhea has decreased substantially in the past decade. Disseminated gonorrhea is more common in women than in men, although gonococcal endocarditis is more common in men. Disseminated gonorrhea is most commonly described in women during menses or pregnancy. Only two cases of gonococcal endocarditis during pregnancy have been reported in the literature since 1942. We report a patient who experienced sudden hemodynamic decompensation at 30 weeks' gestation, resulting in fetal death. Aortic valve replacement was performed, but extensive involvement of the aortic root made complete eradication of infection impossible and eventually resulted in maternal death."
-How do the biomechanical properties of the ankle joint differ between hemiparetic stroke patients and normal subjects?,"Biomechanical changes at the ankle joint after stroke. The resistance of the relaxed ankle to slow displacement over the joint movement range was measured on both sides of a group of hemiparetic stroke patients, in whom spasticity had been established for at least one year and who showed no clinical signs of contractures. The ankle joints of the age-matched normal subjects were flexible over most of the movement range, showing dramatically increasing stiffness only when the foot was dorsiflexed beyond 70 degrees, with a neutral range between 90-100 degrees, and a less dramatic increase in stiffness during plantarflexion. Hemiparetic patients showed identical curves to the normal subjects on the ""healthy"" side, ipsilateral to the causative cerebral lesion, but were significantly stiffer in dorsiflexion on the contralateral side, without change in the minimum stiffness range or during plantarflexion. Therefore significant changes in passive biomechanical properties occur at the affected ankle of hemiparetic subjects, predominantly as the result of a loss of compliance in the Achilles tendon, although an increase in the passive stiffness of the triceps surae may also occur. The contribution of these changes to the locomotor disability of hemiparetic patients is discussed."
-How did the medical team use auditory brainstem responses to help map electrodes in a child with cochlear ossification?,"Multichannel cochlear implant and electrically evoked auditory brainstem responses in a child with labyrinthitis ossificans. Ossification of the cochlea following meningitis presents a surgical challenge. Electrode mapping, especially in the young child, is difficult given the uncertainty of electrode contact with viable neural elements. This paper reviews surgical technique and the use of auditory brainstem responses to map the electrodes. A 4-year-old child deafened by meningitis at age 20 months had bilateral cochlear ossification by computed tomography. At surgery, a canal wall-down mastoidectomy and closure of the ear canal were performed. A trough around the modiolus was drilled, and the electrode array was placed in it. Post-operatively, the patient gave aversive or no responses to electrode stimulation. To assess electrode function, auditory brainstem responses to individual electrode activation were obtained under general anesthesia. Functioning electrodes could thus be selected for mapping. The patient now responds well to sound."
-What is the significance of left ventricular diastolic collapse in the context of regional cardiac tamponade?,"Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade. BACKGROUND. Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade. METHODS AND RESULTS. We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade. CONCLUSIONS. We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients."
-What was the effect of balloon dilation on the diameter of stenotic Blalock-Taussig shunts in patients with cyanotic heart disease?,"Percutaneous transluminal balloon angioplasty of stenotic standard Blalock-Taussig shunts: effect on choice of initial palliation in cyanotic congenital heart disease. To date, attempted balloon dilation of stenotic standard Blalock-Taussig shunts has been largely disappointing. It has been suggested that this may be due to the use of balloons of insufficient diameter. Balloon dilation of stenotic Blalock-Taussig shunts was attempted with use of relatively large balloons in five patients (11 to 67 months old) with cyanotic heart disease who were becoming progressively cyanotic and polycythemic (hemoglobin 17.9 +/- 1.1 g/dl) because of discrete shunt stenosis at the site of pulmonary anastomosis. Balloon diameters selected were equal to or within 1 mm of the unobstructed proximal shunt diameter. Before balloon dilation the diameter at the site of the stenosis was 2.8 +/- 0.8 mm (range 1.7 to 4); after balloon dilation it was 5.7 +/- 1.1 mm (range 4.5 to 7.5). The diameter increased in all patients (range 2.0 to 3.5 mm); the mean increase was 2.8 +/- 0.2 mm (p less than 0.005). Expressed as a percent, the increase in diameter at the stenosis ranged from 80% to 182.4% (mean 108.2 +/- 16.8%). Before balloon dilation the systemic oxygen saturation was 72.8 +/- 9.2% (range 55% to 80%) and after balloon dilation it was 83.6 +/- 2.9% (range 80% to 87%). A satisfactory increase (range 6% to 25%) in blood oxygen saturation was seen in all patients; the mean increase was 10.8 +/- 3.2% (p less than 0.01). At follow-up, the oxygen saturation by pulse oximetry was 85.8 +/- 2.9% (mean 5.8 +/- 1.7 months after balloon dilation) and the hemoglobin was 15.6 +/- 1.9 g/dl (mean 6.6 +/- 1.5 months after balloon dilation)."
-How do limited access to healthcare and cultural barriers impact neurological care for minority populations in the United States?,"Access to neurological care for minorities. Minority groups comprise a major segment of the estimated more than 34 million Americans without insurance coverage and also the underinsured. Neurologic disease and neurologic complications of the major causes of morbidity and mortality affect minorities protracted by limited access to health care. Hypertension, a major cause of stroke in the black population, is just one example of the impact of accessibility to intervention in central nervous system disease. Health statistics note the persisting gap between minority groups and the nation's norms for life expectancy. Aging America and particularly black elderly women, combined with the lagging infant mortality among minority groups, demonstrate limited access issues beyond economics, reflecting inner city mores, cultural barriers, and communication delay limiting contact with the practicing neurologist. Awareness of such access limitations to neurological care for minorities demands the attention of the practicing neurologist and the neurological societies."
-What was the most frequent recognized abnormality in the study of cerebral infarction among young patients?,"Cerebral infarction in young people. A study of 148 patients with early cerebral angiography. The aetiology of strokes was studied in a hospital based series of patients aged up to 40 years with precise clinical and radiological criteria. One hundred and forty five patients (75 males and 73 females) aged five to 40 years with cerebral ischaemia were evaluated. Aetiology was heterogeneous and could be classified into seven groups. Cerebral arteriograms were performed in all cases and indicated the aetiological diagnosis in most patients. Embolism was the most frequent recognised abnormality (38.4%). There were no complications of arteriography. Arterial dissections discovered by arteriography were the cause of the stroke in 10.1% of the patients. Atherosclerosis was diagnosed in 32 cases and was the commonest cause (21.6%). In one fifth of cases no cause was found. Contraceptive drugs were considered as potential cause of ischaemic stroke in 11.5%, cardiac diseases in 12.8% and haematological disorders in 8.1%. Other potential causes included migraine, inflammatory diseases, pregnancy and lacunas. Follow up in 126 cases showed that many patients had good functional recovery."
-What were the predominant indications for knee arthrodesis using an intramedullary nail in this study?,"Arthrodesis of the knee with an intramedullary nail. The cases of twenty patients who had an arthrodesis in which an intramedullary nail was used for stabilization were reviewed at an average follow-up of six years. The predominant indications were infection after total knee arthroplasty and post-traumatic pain and instability. Other indications included aseptic loosening of the components of a total knee arthroplasty, reconstruction after resection of a giant-cell tumor, non-union of a fracture of the distal part of the femur or the proximal part of the tibia, and failed external-compression arthrodesis. Success was achieved in seventeen patients (85 per cent), and functional stability immediately postoperatively was gained in all twenty. Of the three patients in whom the arthrodesis failed, all had sustained an intraoperative fracture, and infection eventually developed. Of the twelve nails that were secured to the greater trochanter with a loop of stainless-steel wire, none showed evidence of proximal migration. Of the eight nails that were not thus secured, two migrated proximally, necessitating removal of the nail. Two drawbacks to this operation are the long duration and the large amount of blood that is lost. The major advantage is that a high percentage of patients have progression to a stable fusion despite serious problems. Furthermore, all but seven patients (including the six who had a tumor or who had sustained an intraoperative fracture) were able to bear full weight by the second postoperative week. Only a few patients needed an external support for walking."
-How do thromboxane A2 and serotonin contribute to platelet-mediated obstruction in coronary artery stenosis?,"Role of thromboxane and serotonin as mediators in the development of spontaneous alterations in coronary blood flow and neointimal proliferation in canine models with chronic coronary artery stenoses and endothelial injury. Platelet-mediated obstruction of stenotic and endothelium-injured coronary arteries may be important in the abrupt progression from chronic stable to unstable coronary heart disease syndromes in patients. Transcardiac accumulation of thromboxane A2 and serotonin has been demonstrated in patients as chronic stable angina is converted to unstable angina. In this study in anesthetized open chest dogs with coronary artery stenosis and endothelial injury, thromboxane A2 and serotonin were shown to be important mediators of intermittent coronary obstruction caused by platelet aggregation and dynamic vasoconstriction. Furthermore, thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists, singly and together, provided substantial protection against repetitive platelet aggregation and dislodgment in canine models with coronary artery stenosis and endothelial injury even when systemic catecholamine concentrations were markedly elevated. These same observations apply in chronically instrumented, awake, unsedated dogs with coronary artery stenosis and endothelial injury in which recurrent platelet attachment and dislodgment cause cyclic flow alterations that may be prevented by thromboxane A2 synthesis inhibitors and receptor antagonists and serotonin receptor antagonists. Chronically instrumented dogs with coronary stenosis and endothelial injury in which recurrent platelet attachment and dislodgment occurred also developed neointimal proliferation of varying severity within 10 days to 3 weeks; the morphologic appearance of the neointimal proliferation was identical to that found in patients who develop restenosis after coronary angioplasty."
-How does a leucine to isoleucine substitution in the retroviral envelope surface glycoprotein affect the lytic properties of the Friend murine leukemia virus?,"Substitution of leucine for isoleucine in a sequence highly conserved among retroviral envelope surface glycoproteins attenuates the lytic effect of the Friend murine leukemia virus. Friend murine leukemia virus is a replication-competent retrovirus that contains no oncogene and that exerts lytic and leukemogenic properties. Thus, newborn mice inoculated with Friend murine leukemia virus develop severe early hemolytic anemia before appearance of erythroleukemia. To identify the retroviral determinants regulating these effects, we used chimeric infectious constructions and site-directed point mutations between a virulent Friend murine leukemia virus strain and a naturally occurring variant attenuated in lytic and leukemogenic effects. We found that severe hemolytic anemia was always associated with higher numbers of blood reticulocytes with budding retroviral particles. Furthermore, a remarkably conservative leucine to isoleucine change in the extracellular SU component of the retroviral envelope was sufficient to attenuate this lytic effect. Also, this leucine at position 348 of the envelope precursor protein was located within the only stretch of five amino acids that is conserved in the extracellular SU component of all murine, feline, and primate type C and type D retroviral envelopes. This observation suggested an important structural function for this yet undescribed conserved sequence of the envelope. Lastly, we observed that lytic and leukemogenic effects were attenuated by a deletion of a second repeat in the transcriptional enhancer region of the viral long terminal repeats of the variant strain."
-What is mesonephric rest hyperplasia and how can it be misdiagnosed?,"Mesonephric rest hyperplasia. A potential diagnostic pitfall. A case of mesonephric rest hyperplasia, an incidental finding in the hysterectomy specimen of a 48-year-old woman, was initially misdiagnosed as a well-differentiated cervical adenocarcinoma. We highlight the histologic, histochemical, and immunohistochemical features of this potential diagnostic pitfall and review the relevant literature."
-What are the potential disadvantages of the subclavian flap aortoplasty procedure in treating coarctation?,"Coarctation: do we need to resect ductal tissue? A review of the literature as well as a retrospective review of 100 neonates undergoing operation for coarctation at Children's Hospital in Boston between 1972 and 1984 has not established clear superiority for either resection and end-to-end anastomosis or subclavian flap aortoplasty with respect to risk of recurrent coarctation. However, there is histological evidence that the juxtaductal coarctation shelf is composed of smooth muscle of ductal origin, which subsequently fibroses. This abnormal tissue may be at risk for late aneurysm development, particularly if balloon dilatation angioplasty is required. The fact that this abnormal tissue is not removed by the subclavian flap procedure is one of the inherent disadvantages of that procedure. Other disadvantages include the need to sacrifice the left subclavian artery and the fact that, unlike resection and end-to-end anastomosis, the subclavian flap procedure does not lend itself to augmentation of the hypoplastic distal aortic arch. Furthermore, occasionally a secondary coarctation membrane is present within the distal aortic arch, and though it is readily detected during the resection procedure, it can be missed with the subclavian flap procedure. Based on these considerations rather than on a demonstrated superiority of either procedure, my colleagues and I currently prefer resection and end-to-end anastomosis over subclavian flap aortoplasty."
-What variations were observed in the classical activation pattern during atrial flutter entrainment in the canine sterile pericarditis model?,"Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo. BACKGROUND. Recently, we used a custom designed ""jacket"" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels. METHODS AND RESULTS. In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a ""classical"" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry. CONCLUSIONS. The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the ""figure-eight"" reentrant circuit."
-What was the primary aim of the study on nasal calcitonin in treating post-traumatic algodystrophy?,"The use of nasal calcitonin in the treatment of post-traumatic algodystrophy. Calcitonin is widely used in the treatment of algodystrophy but a major disadvantage is the need for its parenteral administration. For this reason, we evaluated the effect of 400 iu of nasal calcitonin in the treatment of post-traumatic algodystrophy in a prospective randomized double-blind study. We found no demonstrable effect on the clinical or skeletal progression of the disorder using sensitive methods of measuring the response to treatment. There was, however, a small but significant hypocalcaemic response in the treatment group despite no change in the other indices of bone turnover. Possible reasons for this lack of clinical and skeletal effect are discussed."
-What is the primary diagnostic procedure for identifying blunt traumatic bladder rupture according to this study?,"Blunt traumatic bladder rupture: the role of retrograde cystogram. STUDY OBJECTIVE: We evaluated the importance of microscopic and gross hematuria and the role of retrograde cystography and computed tomography (CT) in the diagnosis of blunt traumatic bladder rupture. DESIGN: All cases at a Level I trauma center between January 1, 1986, and March 31, 1989, were reviewed retrospectively. SETTING: Level I trauma center, university hospital. TYPE OF PARTICIPANTS: All patients with acute blunt abdominal trauma admitted to this Level I trauma center. INTERVENTIONS: The patients' charts were reviewed with emphasis on mode of diagnosis, treatment, and outcome. MEASUREMENTS AND MAIN RESULTS: Twenty-one patients had bladder rupture. All 21 had hematuria with more than 50 RBCs/high-power field, 17 gross and four microscopic. Twenty patients underwent retrograde cystography, which accurately identified bladder rupture, and one was found at laparotomy for other injuries. Seven patients had CT of the abdomen and pelvis, which failed to demonstrate bladder rupture. There were no associated urethral injuries in any of the patients with bladder rupture. CONCLUSION: Significant (more than 50 RBCs/high-power field) hematuria is the principal indication for evaluation for blunt bladder injury, and retrograde cystography is the diagnostic procedure of choice. CT is neither sensitive nor specific enough as primary diagnostic modality."
-What novel mutation was discovered in the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis patients?,"A novel mutation in the invariant AG of the acceptor splice site of intron 4 of the beta-hexosaminidase alpha-subunit gene in two unrelated American black GM2-gangliosidosis (Tay-Sachs disease) patients. Samples of genomic DNA from three unrelated American black infants having both biochemical and clinical features of classical infantile Tay-Sachs disease were sequenced following PCR amplification. A G----T transversion was observed in the AG acceptor splice site preceding exon 5 of the beta-hexosaminidase alpha-subunit gene in the first black family. This transversion changed the acceptor splice site from the consensus sequence, AG, to AT, thereby interfering with splicing at this intron 4/exon 5 junction. The proband was homozygous for this mutation; his mother and a brother are heterozygous. The same mutation was found in a second, apparently unrelated, black GM2-gangliosidosis patient. The second patient was a compound heterozygote, as only one allele carried this mutation. The mother and a brother in this second family are carriers for this mutation, while the father and a noncarrier sister are normal for this region of the gene. The third proband did not have this mutation; nor did the mother of a fourth black proband. Eight other independently ascertained non-black, non-Jewish, GM2-gangliosidosis families did not have this mutation. The observation of the same novel mutation in two unrelated black GM2-gangliosidosis patients indicates that the American black population has segregating within it at least one GM2-gangliosidosis mutation which may be specific to this population and not a result of migration."
-What are the main advantages of bopindolol in treating hypertension?,"Bopindolol: Czechoslovak experience with a new beta blocker in the treatment of hypertension. Bopindolol is a nonselective beta blocker with mild intrinsic sympathomimetic activity. One of the drug's main benefits is its prolonged effect, lasting for 24 hours, which makes it possible to administer bopindolol in a single daily dose, a fact that may improve patient adherence to therapy. A double-blind study was performed in two centers, comparing bopindolol with metoprolol in 86 hypertensive patients. Baseline diastolic blood pressure (BP) was 100 to 120 mm Hg. The effects of bopindolol or metoprolol on BP and heart rate were similar: return to normal values was achieved in 70% of patients with either drug. A 6-month study at another center found that bopindolol did not affect the levels of total cholesterol, low-density and high-density lipoprotein cholesterol or triglycerides. Another 12-month study documented a decrease in total cholesterol, apolipoprotein (apo) A1 and apo B. The apo A/B ratio rose, thus improving the atherosclerotic index. No deterioration of glucose tolerance or immunoreactive insulin response to glucose was seen after 6 months of bopindolol administration. Bopindolol satisfactorily modifies not only resting but also exercise BP during isometric and isotonic load, thus reducing BP fluctuation during physical activities of the hypertensive patient. The drug exerts no effect on renal and liver function, electrolyte balance and hematologic parameters. Bopindolol is a very useful drug of first choice in mild and moderate hypertension. Bopindolol's main advantages include its prolonged action, good tolerance and a beneficial effect on risk factors of atherosclerosis (lipid and carbohydrate metabolism)."
-What were the key findings of the NHLBI PTCA Registry comparing outcomes of percutaneous transluminal coronary angioplasty in patients with stable versus unstable angina pectoris?,"Short and long term outcome of percutaneous transluminal coronary angioplasty in unstable versus stable angina pectoris: a report of the 1985-1986 NHLBI PTCA Registry. In a cohort of 1,720 consecutive patients from the National Heart, Lung, and Blood Institute, Percutaneous Transluminal Coronary Angioplasty (PTCA) Registry (August 1985-May 1986), we compared 768 patients (45%) with stable angina and 952 patients (55%) with unstable angina pectoris. Unstable angina patients exhibited at least one of the following characteristics: new onset angina, rapidly progressing angina, angina at rest, angina refractory to medication, variant angina, acute coronary insufficiency, or angina recurring shortly after an acute myocardial infarct. The distribution of single- and multi-vessel disease was similar among stable and unstable angina patients; multi-vessel disease predominated. Average severity of stenosis and incidence of tubular and diffuse stenosis morphology were higher among patients with unstable angina (both p less than 0.001). Patient success rates were similar in stable and unstable patients. However, on a per lesion basis, overall angiographic success rate and average reduction of severity of stenosis in successfully dilated lesions were significantly higher among patients with unstable angina (both p less than 0.001). Incidence of major patient complications (p less than 0.01) and of emergency coronary bypass surgery (p less than 0.05) were also higher in patients with unstable angina but consistent with their more precarious clinical condition and stenosis morphology. During a two year follow-up, the cumulative distributions of death, myocardial infarct, repeat PTCA, and coronary bypass surgery were not significantly different in patients with stable angina compared to patients with unstable angina. Comparison of the current PTCA Registry cohort with the cases reported in the 1979-1982 Registry revealed a 19% higher success rate for both stable and unstable angina patients. Major complication rates decreased between time periods for stable but not for unstable angina patients. Incidence of emergency bypass surgery decreased more for stable than for unstable angina patients. Coronary angioplasty is indicated in properly selected patients with unstable angina and both single- and multi-vessel coronary disease."
-What was the purpose of comparing laser-assisted thrombolysis (LAT) with enzymatic thrombolysis (ET) in the experimental treatment of thrombotic vascular occlusion?,"Experimental treatment of thrombotic vascular occlusion. The role of laser energy in the treatment of thrombotic vascular occlusion was evaluated in two sets of experiments. First, 10 polytetrafluoroethylene grafts were used to replace segments of the superficial femoral arteries in dogs and were thrombosed by distal ligation. Occlusion was maintained for one hour, or for 7, 14, 21, and 28 days in each of two grafts. Patency was restored in all 10 grafts without perforation or anastomotic disruption using a 2 mm hot tip probe powered by an Argon laser. However, increased organization of thrombus related to the duration of occlusion lead to decreased laser channel diameters, and 75% of the 28 day thrombus remained in the graft after recanalization. The second experiments tested the added benefit of thrombolytic infusion following laser recanalization. Bilateral external iliac artery thrombosis was induced in dogs by operative vessel isolation, de-endothelialization, and thrombin injection. At 7 days the efficacy of laser-assisted thrombolysis (LAT) versus enzymatic thrombolysis (ET) alone was compared. Eight vessels underwent ET by urokinase (4000 I.U./min.); 14 vessels were laser recanalized prior to thrombolytic infusion. LAT was performed from a carotid artery approach in 8 vessels (antegrade) and from a femoral artery in 6 vessels (retrograde). In contrast to studies using the hot tip alone, both ET and LAT accomplished complete thrombus removal. However, LAT lead to significant iliac arterial flow in 9 +/- 8 min. (antegrade) and 25 +/- 8 min. (retrograde) while ET required 109 +/- 47 min (p less than 0.01)."
-What is the Pena-Shokeir phenotype and what are its key pathological characteristics in an infant born to a cocaine-using mother?,"Fetal akinesia deformation sequence (Pena-Shokeir phenotype) associated with acquired intrauterine brain damage. An infant with Pena-Shokeir phenotype was born to a cocaine-using mother. The pathologic findings included polyhydramnios, facial anomalies, arthrogryposis, camptodactyly, pulmonary hypoplasia, and tetralogy of Fallot. The neuropathologic findings were diffuse brainstem and spinal cord neuronal degeneration and focal cerebral infarction, consistent with acquired intrauterine ischemic damage."
-What percentage of patients in the study experienced otolaryngic complications during cancer chemotherapy?,"The infectious and hematologic otolaryngic complications of myelosuppressive cancer chemotherapy. The otolaryngologist-head and neck surgeon is frequently consulted to evaluate patients before the administration of myelosuppressive cancer chemotherapy. Fifty consecutive patients treated at the University of Pennsylvania Oncology Center were studied before and during chemotherapy for adult leukemia or bone marrow transplantation. Otolaryngic history, physical examination, radiographic studies, and hematologic surveys were analyzed for the duration of therapy in an attempt to identify risk factors for infectious and hematologic otolaryngic complications. Two-thirds of the patient studied experienced untoward effects that required the further attention of an otolaryngologist-head and neck surgeon. The various complications and associated correlations with the study parameters before and during chemotherapy are discussed."
-What percentage of patients with stage D2 prostate cancer showed elevated plasma chromogranin-A levels in the study?,"Elevated plasma chromogranin-A concentrations in prostatic carcinoma. Chromogranin-A is considered a sensitive immunohistochemical tissue marker in neuroendocrine prostatic carcinoma. We report that the plasma chromogranin-A level was elevated in 48% of 25 patients with stage D2 prostate cancer, and suggest that this marker can be used to monitor the clinical course of these patients."
-What is the recommended surgical procedure for treating thoracic myelopathy caused by ossification of the ligamentum flavum (OLF)?,"Thoracic myelopathy caused by ossification of the ligamentum flavum. Clinicopathologic study and surgical treatment. The authors reviewed 14 patients with thoracic myelopathy caused by ossification of the ligamentum flavum (OLF). The predominant locality of symptomatic OLF was at the thoracolumbar junction, particularly at T10-11 followed by T11-12. At the level of the thickest OLF in each patient, there were three types of OLF from computed tomography and operative findings: a lateral type in 3 patients, diffuse in 8, and thickened nodular in 3. The diagnosis of OLF-related thoracic spinal canal stenosis was best made by enhanced computed tomography. Histologic study revealed that the developmental mode of OLF was mainly endochondral ossification. Numerous fibrocartilaginous cells were found in the increased and swollen collagen fibers forming the hypertrophic ligamentum flavum (HLF). Ossification extended along the superficial layer of HLF. The size or extension of OLF was relevant to the corresponding diathesis of spinalhyperostosis. Results of laminectomy for OLF were poor because of the high occurrence of complications early on or later deterioration. Therefore, laminoplasty is recommended as a successful procedure for OLF-related thoracic myelopathy, avoiding further local mechanical stress due to tensile force."
-What is the significance of a negative exercise thallium test in patients with critical residual stenosis after thrombolysis for acute myocardial infarction?,"Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction. BACKGROUND. After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia. METHODS AND RESULTS. The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1-16.3). CONCLUSIONS. The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance."
-How does the genetically engineered toxin DAB486IL-2 specifically target and kill leukemic cells?,"Therapeutic effects of genetically engineered toxin (DAB486IL-2) in patient with chronic lymphocytic leukaemia. In DAB486IL-2 the receptor-binding domain of native diphtheria toxin is replaced by human IL-2 sequences. This recombinant fusion protein is selectively cytotoxic for cells bearing high-affinity IL-2 receptors--eg, leukaemic cells. A patient with chronic lymphocytic leukaemia who did not respond to gamma interferon and conventional antileukaemic drugs has responded to DAB486IL-2."
-What was the prevalence of autoantibodies in different pregnancy conditions according to the study?,"The prevalence of autoantibodies during third-trimester pregnancy complicated by hypertension or idiopathic fetal growth retardation. Lupus anticoagulant, anticardiolipin, antinuclear, anti-deoxyribonucleic acid, antithyroglobulin, and antithyroid microsomal antibodies were assayed during third-trimester pregnancy (100 normal, 100 with complications). In spite of a normal activated partial thromboplastin time in all instances, lupus anticoagulant was further investigated by three additional procedures: tissue thromboplastin inhibition time, platelet neutralization procedure, and cephalin neutralization test. The prevalence of autoantibodies in pregnancies with hypertension reaches 16% (four with lupus anticoagulant, two with anticardiolipin, and two with antithyroid microsomal antibodies), which is significantly greater than that for idiopathic fetal growth retardation (2%) (one with lupus anticoagulant antibodies) and normal pregnancies (3%) (two with antithyroglobulin and one with autithyroid microsomal antibodies) (p less than 0.01). Autoantibodies were equally distributed between patients with gestational hypertension and those with preeclampsia. When compared with the 42 patients with hypertension and no autoantibodies, the eight patients with autoantibody had a more frequent history of fetal growth retardation (p less than 0.05), but there was no difference in the severity of hypertension, the frequency of obstetric complications, or the outcome of pregnancy. They did not require any specific treatment."
-What is the proposed relationship between autonomic dysreflexia and atrial fibrillation in patients with high-level spinal cord injury?,"Atrial fibrillation associated with autonomic dysreflexia in patients with tetraplegia. Atrial fibrillation is an arrhythmia characterized by disorganized atrial depolarizations and an irregular ventricular response. Most patients with atrial fibrillation have underlying cardiac pathology. This paper presents the cases of three patients with high-level spinal cord injury and symptoms of autonomic dysreflexia who developed atrial fibrillation without any cardiac or metabolic disease that would predispose them to this. The paper proposes that autonomic dysreflexia might predispose a patient to atrial fibrillation by altering the pattern of repolarization of the atria, making the heart susceptible to a reentrant type of arrhythmia. High-level spinal cord injured patients may be at increased risk for the development of atrial fibrillation, an arrhythmia which, if left untreated, can increase the incidence of an embolic cerebrovascular accident that could further impair the patient's functional status."
-What techniques were used to extend the exposure of the distal internal carotid artery in the anatomic dissection study?,"Selection of the approach to the distal internal carotid artery from the second cervical vertebra to the base of the skull. Although several approaches for exposure of distal internal carotid artery lesions have been reported, the precise anatomic levels for which each of these maneuvers are most appropriate have not been well described. Since these techniques may require preoperative preparation, it is useful to determine in advance how much exposure will be needed and to select the most suitable and effective technique. We used anatomic dissection in 12 human cadaver specimens (24 carotid bifurcations) to define the limits of distal internal carotid artery exposure by several commonly advocated methods. The standard anterior approach along the sternocleidomastoid muscle allowed exposure of the internal carotid artery to the level of the upper one third of the second cervical vertebra. The upper limit of this exposure was extended to the middle of the first cervical vertebra by division of the posterior belly of the digastric muscle. Anterior subluxation of the mandible increased the distal exposure of the internal carotid artery to the superior border of the first cervical vertebra. Styloidectomy in combination with the preceding maneuvers extended the exposure an additional 0.5 cm cephalad. Lateral mandibulotomy did not significantly extend exposure beyond that obtained with mandibular subluxation and styloidectomy. Exposure of the internal carotid artery in the 1 cm immediately below the base of the skull required a posterior approach with mastoidectomy."
-How does cardioversion with multiple shocks potentially impact the diagnosis of myocardial infarction?,"Time course of creatine kinase release after termination of sustained ventricular dysrhythmias. Differentiation between primary and secondary (caused by acute myocardial infarction) ventricular fibrillation has important therapeutic and prognostic implications. The diagnosis of myocardial infarction is based on clinical, ECG, and creatine kinase MB isoenzyme (MBCK) activity. Enzymatic criteria might not be able to confirm the diagnosis of myocardial infarction after recent cardioversion. The routine use of electrophysiologic studies involving the induction and termination of ventricular dysrhythmias provides a setting in which enzyme release as a result of cardioversion alone can be examined. Therefore a systematic investigation of the magnitude and time course of creatine kinase (CK) and MBCK release was performed after termination of ventricular dysrhythmias in 57 patients undergoing electrophysiologic studies. Of patients requiring external cardioversion, only 50% had an elevation in CK and MBCK activity. Elevation when present corrected with the number of shocks and cumulative energy delivered. The magnitude of MBCK release exceeded 10% of the total CK activity in 9% of observations. Pace-termination of ventricular tachycardia did not result in enzyme release. Arrhythmia characteristics, coronary artery disease, and left ventricular function did not affect the magnitude of the time course of enzyme release. These data suggest that cardioversion with multiple shocks may result in a component of MBCK release, and thus a false positive diagnosis of primary acute myocardial infarction may be made by relying exclusively on the enzyme release pattern."
-What is the significance of the mitral valvuloplasty performed 5 years after the repair of a sinus venosus atrial septal defect?,"Percutaneous mitral valvuloplasty following surgical repair of sinus venosus atrial septal defect. Mitral valvuloplasty performed 5 y after repair of a sinus venosus ASD was difficult because of a thickened septum, but resulted in improved mitral valve opening and did not lead to ASD. Thus, prior repair of a sinus venosus ASD may not be an absolute contraindication to mitral valvuloplasty."
-What was the attitude of Danish anaesthetic departments towards using lumbar regional anaesthesia in patients receiving prophylactic anticoagulant therapy?,"Lumbar regional anaesthesia and prophylactic anticoagulant therapy. Is the combination safe? A survey has been carried out in all Danish anaesthetic departments (n = 80) regarding the attitude towards the use of epidural/spinal lumbar analgesia in patients who were receiving prophylactic anticoagulant therapy for the prevention of thromboembolism. About 60% of the departments used the techniques in patients receiving low-dose heparin and no side effects had been experienced. Spinal and epidural anaesthesia were in general regarded as being contraindicated in patients fully anticoagulated with vitamin K antagonists. In the world literature, the attitude towards the combination is conflicting. No randomised trial has been performed and complications are almost entirely confined to patients fully anticoagulated with vitamin K antagonists. Only one case of an epidural haematoma has been recorded when subcutaneous low-dose heparin was used as thromboprophylaxis."
-What adverse reactions did patients experience when receiving subcutaneous methadone for cancer-related pain?,"Local toxicity with subcutaneous methadone. Experience of two centers. We report on 8 patients treated with subcutaneous methadone for cancer-related pain at 2 institutions. The success of other subcutaneous agents for pain control has been well demonstrated. It was felt that methadone would be useful due to its low cost. Unfortunately, 7 of the 8 patients experienced adverse reactions at the subcutaneous sites requiring cessation of subcutaneous methadone."
-How does calcification affect the mechanical response of rabbit arteries during balloon dilation?,"Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation. BACKGROUND. Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term ""hardening of the arteries."" METHODS AND RESULTS. To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients. CONCLUSIONS. It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial ""hardening"" associated with atherosclerosis."
-Does the timing of aneurysm surgery after subarachnoid hemorrhage affect the development of delayed cerebral ischemia?,"Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia. A consecutive series of 145 patients with acute aneurysmal subarachnoid hemorrhage (SAH) were operated on within 7 days of SAH and were prospectively evaluated over a 4-year period to determine if the timing of aneurysm surgery influenced the development of delayed cerebral ischemia. All patients were managed with a standardized policy of urgent surgical clipping and treatment with aggressive prophylactic postoperative volume expansion. Patients with delayed ischemic symptoms were additionally treated with induced hypertension. Forty-nine patients underwent surgery on Day 0 or 1 (Group 1) post-SAH, 60 patients on Day 2 or 3 (Group 2), and 36 patients on Days 4 through 7 (Group 3). Postoperative delayed cerebral ischemia developed in 16% of (Group 1) patients, in 22% of Group 2 patients, and in 28% of Group 3 patients. Cerebral infarction resulting from delayed cerebral ischemia developed in only 4% of Group 1 patients, 10% of Group 2 patients, and 11% of Group 3 patients. A bad clinical outcome as a result of delayed cerebral ischemia occurred in one Group 1 patient (2%), two Group 2 patients (3%), and one Group 3 patient (3%). Preoperative grade was not significantly correlated with the incidence or severity of delayed cerebral ischemia at any time interval except that patients in modified Hunt and Hess Grade I or II who underwent surgery on Day 0 or 1 after SAH had no strokes or bad outcomes from delayed cerebral ischemia. This study demonstrates that there is no rationale for delaying aneurysm surgery based on the time interval between SAH and patient evaluation."
-What is the potential benefit of L-carnitine treatment for patients with ornithine transcarbamylase deficiency?,"Carnitine deficiency associated with ornithine transcarbamylase deficiency. An infant with X-linked recessive ornithine transcarbamylase deficiency is described who also had severe deficiency of plasma and liver carnitine during normoammonemic periods. Treatment with L-carnitine (100 mg/kg/day) for 12 months decreased the frequency of hospitalizations for hyperammonemia, although it did not alter his neurologic status. This report demonstrates that persistent carnitine deficiency may be present in patients with ornithine transcarbamylase deficiency even when plasma ammonia is normal. Carnitine evaluation and supplementation may be important in the treatment of patients with this metabolic disorder."
-How do primary dysfunctions in neural control of arterial pressure potentially contribute to the development of hypertension?,"Do primary dysfunctions in neural control of arterial pressure contribute to hypertension? This article is a summary of the physiological and clinical evidence that links the cause of essential hypertension to the brain. We stress the potential importance of a biochemical disturbance in the central role of angiotensin II in the regulation of arterial pressure. While the evidence is compelling, we acknowledge the need for further complete studies on this timely subject."
-"What is the relationship between oral contraceptive use, liver cell adenoma, and the potential progression to hepatocellular carcinoma?","Oral contraceptive-associated liver cell adenoma and hepatocellular carcinoma. Cytomorphology and mechanism of malignant transformation. From January 1976 to May 1990, 1673 patients with a liver mass or masses detected by imaging techniques underwent percutaneous fine-needle aspiration biopsy of the liver. Of these, 99 were diagnosed cytologically as ""hepatocellular carcinoma"" and 9 as ""consistent with liver cell adenoma."" The cytologic diagnoses were confirmed in the follow-up of all cases. Among the 99 patients with hepatocellular carcinoma, 3 had taken oral contraceptives for a period of 10, 11, and 12 years, respectively. The nine patients with liver cell adenoma were all users of oral contraceptives over a period ranging from 5 to 10 years. Of these, two who had taken oral contraceptives for a period of 8 and 10 years, respectively, had foci or areas of liver cell dysplasia within the adenomas. The cytologic criteria for the diagnosis of liver cell dysplasia included cytoplasmic and nuclear enlargement, nuclear pleomorphism together with prominent nucleoli, hyperchromasia and multinucleation. The cytologic features of liver cell dysplasia strikingly mimic hepatocellular carcinoma. From this study, the foci or areas of liver cell dysplasia arising within the liver cell adenomas appear to be the missing link responsible for the transformation of liver cell adenoma to carcinoma. It is believed that liver cell adenomas are not premalignant and may undergo reversible change after withdrawal of causative agents, whereas liver cell dysplasia is an irreversible, premalignant change and will eventually progress to hepatocellular carcinoma."
-What were the ovarian ablation failure rates for breast cancer patients above 40 years old in the two different radiation dose schedules?,Ovarian ablation failures by radiation: a comparison of two dose schedules. Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.
-"What similarities were found in olfactory dysfunction among Alzheimer's disease, Parkinson's disease, and the parkinsonism-dementia complex of Guam?","Olfactory dysfunction in three neurodegenerative diseases. Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate."
-What is the predominant method for evaluating nonpalpable breast lesions detected by mammography?,"Mammographic guidewire localization of nonpalpable breast lesions. Guidewire-directed biopsy is the predominant method of evaluating nonpalpable breast lesions detected by mammography. It is an accurate and safe procedure for obtaining a histologic evaluation of abnormal tissue, leading to early diagnosis and improved survival rates. This report reviews 526 needle localizations and biopsies of nonpalpable breast lesions performed in two community hospitals over a 39-month period and compares early results with those achieved in the last 13 months of the study. This review indicates that as experience in using this modality increased, the cancer detection rate increased and the percentage of invasive cancers decreased. The percentage of cancers detected in the final 13 months of the study (19%, Group II) was higher than in the first 26 months of the study (13%, Group I). Although microcalcifications were found in 24 per cent of the mammograms leading to a diagnosis of cancer, they did not prove to be a reliable indicator of malignancy in this study."
-"What was the mean incidence rate of Parkinson's disease per year in the Local Health Service of Ferrara, Italy, between 1967 and 1987?","Parkinson's disease in Ferrara, Italy, 1967 through 1987. Epidemiological surveys on Parkinson's disease that have been carried out in different parts of the world have suggested that the disease is uniformly distributed in white populations. The position with regard to the Mediterranean peoples is still controversial, because of the large variation of the frequencies observed in the different areas that have been investigated. We therefore studied the frequency of Parkinson's disease in the Local Health Service of Ferrara, northeastern Italy (mean population, 187,000). Based on 394 patients, the mean incidence per year for the period from 1967 through 1987 was 10.01/100,000. The incidence rate of Parkinson's disease among cases with early onset was found to be statistically higher in rural areas as compared with urban ones (6.32/100,000 vs 3.11/100,000). Moreover, the study revealed a significantly higher incidence rate among agricultural workers (20.6/100,000). These results would seem to give further support to the hypothesis of a possible causal role of environmental factors that are mainly linked to agriculture, most likely due to the continual exposure to toxic agents in this area. However, further studies, which are not exclusively epidemiological, are necessary before any conclusions may be drawn, because many confounding variables may account for the results from surveys of this type."
-What was the outcome of transhepatic electrohydraulic lithotripsy in the 50 patients studied?,"Common bile duct and intrahepatic stones: results of transhepatic electrohydraulic lithotripsy in 50 patients. Percutaneous, transhepatic, intracorporeal, electrohydraulic shock wave lithotripsy was performed in 50 patients after failure of endoscopic treatment (n = 43) or directly in patients with a strictured hepaticojejunostomy (n = 7). Twenty-seven patients had common bile duct stones; 23, intrahepatic stones. Three steps were used: A transhepatic bilicutaneous fistula was created, a wide communication between the bile duct and the gut was established, and contact shock wave lithotripsy was performed under endoscopic guidance. Afterward, 46 patients were free of stones. In four patients with diffuse intrahepatic lithiasis, only 75% of stones could be cleared. Severe complications, seen in 11 patients (hemobilia necessitating transfusion [n = 6], bile duct perforation resulting in cholangitis [n = 3], acute pulmonary edema [n = 1], and hemothorax [n = 1]), were fatal in four patients; all occurred early in the study. The authors modified their technique by dilating the biliary tract in two sessions 3 days apart, waiting 6 days for the tract to mature, and then introducing the cholangioscope directly through the skin, significantly reducing complications and mortality (P less than .005)."
-How does mucociliary clearance change in asthmatic patients during and after an acute exacerbation?,"Changes in mucociliary clearance during acute exacerbations of asthma. Previous studies have suggested that mucociliary clearance (MC) is impaired in asthmatic subjects. If so, impaired clearance may be an important factor in acute exacerbation. We proposed that if MC plays a significant role in acute illness, MC should be impaired during the exacerbation but improve after recovery. To test this hypothesis, five asthmatic patients with attacks requiring hospitalization underwent measurement of MC using radiolabeled aerosol and a gamma camera. They were studied on the second or third day after admission with repeat measurements after discharge. Spirometry was performed before all studies. After an equilibrium xenon scan (133Xe), which defined lung borders and measured regional volume, radiolabeled saline particles containing technetium-labeled (99mTC) sulfur colloid were deposited and used to label airway mucus. Deposition patterns were matched by regulating particle distribution and breathing pattern. MC was then measured as percentage retention of radioactivity at 10-min intervals for 2 h. When hospitalized, 96.0 +/- 2.06% (SEM) of the initial radioactivity was retained in the lung after 2 h, indicating little clearance of mucus from the lung. In fact, no significant changes were detected when activity at 120 min was compared with measurements at 10 min (99.2 +/- 0.22%, NS). After discharge clearance was markedly enhanced. That is, retention of lung activity was significantly lower at all time intervals from 10 min onward, with only 70.9 +/- 3.86% retained at 120 min (p = 0.008). During an asthmatic attack warranting hospital admission, MC is significantly impaired, with marked improvement following recovery."
-How do changes in circulating pancreatic enzymes and protease inhibitors relate to the development of ERCP-induced pancreatitis?,"The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors. The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis."
-How does hypoxia affect glucose transport in skeletal muscle?,"Stimulation of glucose transport in skeletal muscle by hypoxia. Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia."
-What is tegmental dehiscence and what are its potential clinical manifestations?,"Tegmental dehiscence and brain herniation into the middle ear cleft. The tegmen tympani may occasionally be breached by herniation of the temporal lobe with or without dural cover. The clinical presentation may be obvious with CSF otorrhoea but less so with apparent middle ear effusion, CSF rhinnorrhoea, conductive hearing loss, recurrent meningitis or intracranial sepsis. Diagnosis requires suspicion of the condition, which may be aided by radiological imaging. Surgical repair is to be recommended: various techniques are available but bone enveloped by fascia placed by subtemporal approach is preferred. The features of this problem are highlighted by four cases."
-What are the key clinical and biochemical characteristics of the 32-year-old patient with chronic GM1 gangliosidosis?,"A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies. Clinical and biochemical studies are reported on a 32-year-old man with GM1 gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM1 ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM1 ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM1 ganglioside beta-galactosidase activity was only 10% of normal. These findings suggest that impaired GM1 ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM1 gangliosidosis."
-What treatment was used to manage the patient's intractable axial dystonia after spinal instrumentation for scoliosis?,"Intrathecal baclofen for intractable axial dystonia. Following spinal instrumentation for scoliosis, a patient developed intractable axial dystonia refractory to conservative medical management. We describe the successful treatment of this dystonia with a continuous infusion of intrathecal baclofen and the subsequent long-term management."
-What is the primary goal of treatment for metastatic breast cancer?,"The treatment of metastatic breast cancer. While metastatic breast cancer is not curable, it is treatable. Its treatment is associated with a relatively high rate of success, and patients are able to maintain a good quality of life for periods ranging from a few months to several years. This knowledge should encourage both the patient and the oncologist to maintain treatment as long as potentially effective therapeutic methods are available. Progress is ongoing both in the development of new forms of treatment and in new ways of using and combining already existing therapeutic modalities. There is still no established ""best"" or ""only"" first treatment of metastatic breast cancer. When secondary and later treatment is to be undertaken, the task of selecting the most appropriate treatment becomes even more complex. It is only through controlled clinical trials that useful therapeutic guidelines will develop. Treatment is a joint endeavor involving both the physician and the patient. Communication must remain open. In the final stages of the illness, treatment should be directed toward the relief of distressing symptoms and anxiety."
-What unusual presentation of cryptococcal infection was observed in the HIV-positive patient described in this case report?,Cryptococcal pleural effusion preceding cryptococcal meningitis in AIDS. The authors report a case in which a small cryptococcal pleural effusion preceded the development of severe cryptococcal meningitis in an HIV-positive patient. The appearance of an isolated transient pleural effusion is a very unusual presentation for AIDS-related complications. The authors suggest that cryptococcal infection be considered in this setting.
-What is the estimated number of premature deaths in the United States in 1985 attributed to smoking-related diseases?,"Smoking-attributable mortality and years of potential life lost--United States, 1988. Smoking is a leading cause of diseases associated with premature mortality in the United States; in 1985, these diseases accounted for an estimated 390,000 premature deaths. In this report, mortality data and estimates of smoking prevalence for 1988 are used to calculate smoking-attributable mortality (SAM), years of potential life lost (YPLL), and age-adjusted SAM and YPLL rates for the United States. Calculations were performed using Smoking-Attributable Mortality, Morbidity, and Economic Cost (SAMMEC II) software, which includes relative risk estimates for 22 adult (i.e., greater than or equal to 35 years of age) smoking-related diseases and relative risk estimates for four perinatal (i.e., less than 1 year of age) conditions. Age-, sex-, and race-specific mortality data for 1988 were obtained from CDC's National Center for Health Statistics. Data on burn deaths caused by cigarettes were obtained from the Federal Emergency Management Agency. The estimated number of deaths among nonsmokers from lung cancer attributable to passive smoking was obtained from a report of the National Academy of Sciences. Age-, sex-, and race-specific current and former smoking prevalence rates in 1988 for adults aged greater than or equal to 35 years and for women aged 18-44 years were estimated by linear extrapolation using National Health Interview Survey data for 1974-1987."
-What are the questionable cancer treatment practices found in Tijuana and other Mexican border clinics?,"Questionable cancer practices in Tijuana and other Mexican border clinics. Tijuana, Mexico, has become a refuge for cancer patients who have been convinced that they may be cured of their terminal illness by unconventional, unproved, and disproved methods offered in the border clinics. About a dozen United States promoters have joined with Mexican colleagues to offer a variety of treatments. Some patients are diagnosed using standard methods prior to arrival at the clinics, but many healthy individuals are misdiagnosed as having cancer or ""precancer"" and are then treated there. Others are told they have been cured or are improving even though they still have active disease. The modalities and regimens used are often referred to as ""metabolic therapy"" and, for the most part, are either not based on sound scientific principles or have been shown in controlled clinical trials to be useless or even dangerous. A basic metabolic regimen consists of three phases: detoxification with fasting and bowel cleansing, strengthening the immune system with numerous ""supplements,"" and attacking cancer with ""natural and non-toxic"" chemicals. Popular treatments include injections of hydrogen peroxide, large quantities of pressed liver and carrot juice, coffee enemas, infusions of Laetrile mixed with massive doses of vitamins and dimethylsulfoxide (DMSO), special diets, and a host of other pseudoscientific regimens. Unfortunately, no evidence exists that any of these modalities is more effective than no treatment at all. Patients traveling to the Mexican border clinics for metabolic therapy are subjecting themselves to costly and hazardous regimens, especially if they forgo responsible medical care in the process. The American Cancer Society, therefore, strongly urges individuals with cancer not to seek treatment with metabolic therapies in the Mexican border clinics."
-What did the study reveal about Ki-67 reactivity and proliferative activity in different histological subtypes of breast carcinoma?,"Ki-67 staining in histological subtypes of breast carcinoma and fine needle aspiration smears. Thirty four cases of invasive breast carcinoma were analysed for heterogeneity of Ki-67 reactivity in a tumour, and proliferative activity in various histological subtypes was compared. The growth factions determined in areas of central and peripheral tumour were the same. Mucinous and lobular carcinoma showed lower Ki-67 activity than ductal carcinomas. When ductal carcinomas were subdivided according to their dominant growth pattern, the carcinomas with a solid or comedo growth pattern showed the highest proliferative activity. These results largely confirm data from previous cell kinetic studies on the incorporation of radioactively labelled thymidine. A correlation between the growth fraction determined by Ki-67 in fine needle aspiration smears and cryostat sections of corresponding tumours was shown, implying that the immunostaining of cytological smears gives a reliable impression of the growth fraction of a tumour and may therefore be used in prospective studies."
-What was the healing rate of transmetatarsal amputations in different patient groups based on revascularization?,"Transmetatarsal amputation: the role of adjunctive revascularization. Over a 12-year period, 160 transmetatarsal amputations were performed in patients with peripheral vascular occlusive disease. The following groups were defined: group 1 - nonreconstructable disease (n = 40); group 2 - transmetatarsal amputation in conjunction with distal revascularization (n = 99); group 3 - reconstructable disease but transmetatarsal amputation performed without simultaneous revascularization (n = 21). There were nine early deaths in the entire series, for an operative mortality rate of 5.6%. The lowest rate of transmetatarsal amputation healing (24%) occurred in group 1. An 86% healing rate was achieved in group 3, but in seven cases (33%) some type of revascularization was required within 3 months of the amputation. In group 2 the healing rate was 62% but reached 83% where the bypass remained patent for at least 3 months after the amputation. Long-term patency rates also affected healing. Healing was not influenced by the number of local procedures (single vs multiple). The presence of severe infection or extensive necrosis necessitated open transmetatarsal amputation in 89 cases; the remaining 71 amputations involved primary closure. Since many patients were treated at a time when diagnostic modalities as well as the operative indications and techniques differed somewhat from the current practice, much of the information regarding group I patients in particular should be considered as a negative historical control and any conclusion from our data should be adjusted accordingly. Healing after amputation at the transmetatarsal level can be expected in the majority of instances in which revascularization can be performed with predictable patency, even when the standard criteria for performing such amputations are liberalized."
-What medical specialties are involved in investigating the relationship between esophageal motility disorders and unexplained chest pain?,"The relationship between esophageal motility disorders and microvascular angina. Patients with unexplained chest pain have caused investigators in cardiology, gastroenterology, and psychiatry to find abnormalities with overlap among the three specialties. This article reviews the data concerning the potential interrelation of chest pain of cardiac or esophageal origin."
-What are the key challenges and uncertainties associated with using deep brain stimulation for pain control in humans?,"Deep brain stimulation: a review of basic research and clinical studies. Deep brain stimulation for pain control in humans was first used almost 30 years ago and has continued to receive considerable attention. Despite the large number of clinical reports describing pain relief, numerous studies have indicated that the results of these procedures vary considerably. In addition, many neurosurgeons find the procedures unpredictable, and considerable disagreement still exists regarding important issues related to the technique itself. This review gives an historical overview of the relevant basic and clinical literature and provides a critical examination of the clinical efficacy, choice of stimulation sites, parameters of stimulation, and effects on experimental pain. Finally, we give suggestions for future research that could more definitively determine the usefulness of deep brain stimulation for pain control."
-How did A-LAK cells demonstrate their ability to establish contact with metastatic melanoma cells in this murine model?,"Establishment of cell-to-cell contact by adoptively transferred adherent lymphokine-activated killer cells with metastatic murine melanoma cells. A murine model of pulmonary B16 melanoma was used to study the infiltration into metastases of lymphokine-activated killer (LAK) cells and adherent lymphokine-activated killer (A-LAK) cells and, specifically, to study whether A-LAK cells are able to leave the tumor microcirculation and establish cell-to-cell contact with malignant cells. Fluorescence microscopy demonstrated that A-LAK cells accumulated in metastases twice as efficiently as LAK cells during interleukin-2 stimulation. Electron microscopy of pulmonary metastases 16 hours after administration of 2.5 x 10(7) A-LAK cells revealed A-LAK cells, identified by the presence of typical two-compartment granules, in direct contact with melanoma cells. This finding was confirmed by using A-LAK cells prelabeled with polycationized ferritin. In conclusion, our observations demonstrate unambiguously the ability of adoptively transferred A-LAK cells to establish contact with extravascular metastatic melanoma cells."
-How did the cardiovascular responses of hypertensive and nonhypertensive patients differ during social interactions in the coronary care unit?,"A comparison of hypertensive and nonhypertensive coronary care patients' cardiovascular responses to visitors. Patients with and without hypertension in a coronary care unit (n = 24) were compared with respect to cardiovascular responses to both a family visit and an interview by an investigator. Variables for each of the four cardiovascular indicators (systolic blood pressure, diastolic blood pressure, heart rate, and premature ventricular contractions) included the value before, the highest value during, the lowest value during, and the value after each social interaction condition. The highest group means for systolic blood pressure and heart rate were significantly higher for patients with hypertension than for patients without hypertension under both the interview and visit conditions. Differences in cardiovascular responses were not significantly greater for family visits than for interviews for patients with hypertension compared with those without hypertension. Thus, although hypertensive patients had greater cardiovascular reactivity to both social interaction conditions than nonhypertensive patients in the coronary care unit, family visits were no more physiologically stressful than a comparative interaction condition."
-What was the primary objective of the study involving surgical manipulation of primate cerebral arteries in established vasospasm?,"Surgical manipulation of primate cerebral arteries in established vasospasm. It is generally believed that surgery in the face of angiographic vasospasm is dangerous due to an increased incidence of postoperative cerebral ischemia. One theory is that arterial narrowing is exacerbated by surgical manipulation of vasospastic vessels during aneurysm dissection and clipping. This theory was tested in a primate model of cerebral vasospasm and the results reported. Six monkeys underwent baseline cerebral angiography, followed by induction of subarachnoid hemorrhage (SAH) on both sides of the circle of Willis. An equal amount of fresh autologous blood clot was placed around each internal carotid, anterior cerebral, and middle cerebral artery. Six days later, angiography was repeated and the right craniectomy was reopened for clot evacuation and surgical manipulation of the right cerebral arteries, including placement of a temporary aneurysm clip on the right middle cerebral artery. The left cerebral arteries were not exposed or manipulated, and served as controls. Twenty-four hours later angiography was repeated, then the animals were killed. Equal and significant vasospasm (greater than 40% reduction in vessel caliber compared to baseline, p less than 0.05) was seen in the middle cerebral arteries on both sides of the circle of Willis in all animals 6 and 7 days after SAH. There was no significant change in the severity of vasospasm on Day 7 compared with Day 6 in the right cerebral arteries. Increased risk of postoperative cerebral ischemia for surgery in the peak vasospasm period may be due to mechanisms other than increased arterial narrowing precipitated by surgical manipulation."
-"What was the frequency of pulmonary embolism at autopsy during the 1980s in the surgical department of Malmo, Sweden?","Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. A retrospective analysis was undertaken of all surgical patients in Malmo, Sweden, during the period from 1951 to 1988 in whom pulmonary emboli were found at autopsy. The analysis included a comparison with the earlier analysed and reported time period from 1951 to 1980. A continued high frequency of pulmonary embolism at autopsy was seen during the 1980s (20.3 per cent of deaths, 31.7 per cent of autopsies). Of the 391 autopsy-verified pulmonary emboli found between 1981 and 1988, 113 (28.9 per cent) were considered fatal, 104 (26.6 per cent) contributed to death and 174 (44.5 per cent) were incidental. Few patients had symptomatic deep vein thrombosis or pulmonary embolism before death. The overall frequency of major pulmonary embolism in surgical patients remained unchanged (0.3 per cent). The frequency of major postoperative pulmonary embolism showed an increase during the 1950s and 1960s (maximum 0.4 per cent) but a decrease in the last 5-year period of the 1970s (0.3 per cent), which has earlier been reported upon. This decrease continued during the 1980s (0.2 per cent) (P less than 0.05). An increase was found in the number of patients operated on who had autopsy-proven pulmonary embolism and who received thromboprophylaxis. Pulmonary embolism continues to be a major cause of death in surgical patients; however, postoperative major pulmonary embolism has shown a reduction in the last 15-year period."
-How does acetylcysteine improve hemodynamics and oxygen transport in patients with fulminant hepatic failure?,"Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. BACKGROUND. When administered early after an overdose of acetaminophen, intravenous acetylcysteine prevents hepatic necrosis by replenishing reduced stores of glutathione. How acetylcysteine improves the survival of patients with established liver damage induced by acetaminophen, however, is unknown. This study was undertaken to determine whether the beneficial effect of acetylcysteine under such circumstances could be due to enhancement of oxygen delivery and consumption. METHODS. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure and 8 patients with acute liver failure from other causes. The acetylcysteine was given in a dose of 150 mg per kilogram of body weight in 250 ml of 5 percent dextrose over a period of 15 minutes and then in a dose of 50 mg per kilogram in 500 ml of 5 percent dextrose over a period of 4 hours; measurements were made before treatment began and after 30 minutes of the regimen. RESULTS. In the patients with acetaminophen-induced liver failure, the infusion of acetylcysteine resulted in an increase in mean oxygen delivery from 856 to 975 ml per minute per square meter of body-surface area (P = 0.0036), due to an increase in the cardiac index from 5.6 to 6.7 liters per minute per square meter (P = 0.0021). Mean arterial pressure rose from 88 to 95 mm Hg (P = 0.0054) despite a decrease in systemic vascular resistance from 1296 to 1113 dyn.sec.cm-5 per square meter (P = 0.027). There was an increase in oxygen consumption from 127 to 184 ml per minute per square meter (P = 0.0007) associated with an increase in the oxygen-extraction ratio from 16 to 21 percent (P = 0.022). The effects in the patients with acute liver failure from other causes were similar. CONCLUSIONS. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen."
-"What are the two major pathological alterations observed in the mutant rats zitter, tremor, and spontaneously epileptic rat (SER)?","CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER. The pathological alterations in the central nervous system (CNS) were examined in three kinds of mutant rat; the zitter (zi/zi; Zi), the tremor rat (tm/tm; Tm) and the spontaneously epileptic rat (SER) which is a double mutant carrying both zitter and tremor genes. Two major alterations demonstrated in these mutants were hypomyelination and vacuolation or spongy degeneration. Hypomyelination was observed predominantly in SER and to a lesser extent in Zi, and was accompanied by a redundant or aberrant myelin sheath formation in addition to a decreased number of myelinated fibres. This appeared to be related to the occurrence of tremor. There was no abnormality in the structure of the myelin lamellae and oligodendrocytes or any destruction of myelin sheaths by phagocytic cells. The number of radial components in CNS myelin was increased almost equally in Zi, Tm and SER. Vacuolation was prominent in SER and Tm, especially in the brainstem and thalamus. Zi also developed mild vacuolation with advancing age. Vacuolation seemed to be related to the epileptic phenomena in SER and Tm. Vacuoles consisted mainly of swollen astrocytic processes and enlargement of the extracellular space, as well as occasional enlargement of periaxonal spaces. Thus both pathological findings--the hypomyelination derived from the zitter mutation with tremor, and the vacuolation from the tremor mutation with epileptic symptoms--were mutually exaggerated in SER. It is postulated that the two different genetic loci with zi and tm mutations interact and synergistically reinforce each other both clinically and pathologically in SER."
-What were the most prevalent pathogens identified in the pneumonia cases among Filipino children in this study?,"Etiology of infection and morphologic changes in the lungs of Filipino children who die of pneumonia. Histopathologic studies and isolation of virus and bacteria in culture were carried out for 71 children less than 5 years of age with fatal pneumonia. A potential microbial etiology was identified for 61 children (86%): bacteria for 19 (27%), virus for 16 (23%), and virus plus bacteria for 26 (37%). Staphylococcus was the most prevalent pathogen, alone or in combination with other organisms, followed by Pseudomonas aeruginosa. Viral infection may predispose to bacterial infection in some children. A correlation of clinical course, results of cultures, and morphologic changes revealed cofactors that may have contributed to a fatal outcome. Lung abscess, pericarditis, myocarditis, endocarditis, and meningitis were associated with bacterial infection. Many patients in this study had severe bronchopneumonia, with a high prevalence of complications such as abscess (62%), atelectasis (40%), pericarditis (28%), and empyema (7%). Such complications added to multiple infections, measles, and malnutrition contributed to the fatal outcome in these children."
-How sensitive is magnetic resonance imaging in detecting dysplastic lesions in temporal lobe epilepsy?,"Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations. Cortical dysplasia has been documented in histological specimens surgically removed for treatment of refractory temporal lobe epilepsy. We studied 10 patients with cortical dysplasia and complex partial seizures who underwent temporal lobectomy. Magnetic resonance imaging revealed abnormalities in 5 of the patients who had microscopically detectable major abnormalities. Magnetic resonance imaging revealed an abnormal cortical-white matter architectonic pattern in 2 patients with moderate cortical dysplasia. In the remaining 3 patients, magnetic resonance imaging findings were unremarkable. These observations suggest that magnetic resonance imaging is sensitive in the detection of certain dysplastic lesions in temporal lobe epilepsy. Preoperative identification of these abnormalities by magnetic resonance imaging may permit early and optimal surgical treatment in patients with refractory epilepsy."
-What were the five-year patency rates for femoro-femoral and ilio-femoral grafts in this study?,"Femoro-femoral or ilio-femoral bypass for unilateral inflow reconstruction? Femoro-femoral and ilio-femoral bypass are two popular options for unilateral inflow reconstruction. In order to evaluate these alternative approaches, the records of 70 consecutive patients who underwent either femoro-femoral (n = 50) or ilio-femoral (n = 22) grafts were retrospectively reviewed. There were 46 men and 24 women, ranging in age from 27 to 84 years (mean: 66 years). Operative mortality was 10% for all femoro-femoral procedures, including 50% for emergent, 14% for synchronous, and 0% for solitary procedures; mortality was 9% for all ilio-femoral grafts including 20% for synchronous and 6% for solitary procedures. Among the elective solitary procedures, there was no significant difference with respect to operative time, blood loss, fluid requirement, time until resuming an oral diet, or duration of postoperative course for the two procedures. Five-year patency was 93% for all ilio-femoral and 57% for all femoro-femoral grafts. Although femoro-femoral bypass has been the more popular option for unilateral inflow reconstruction in this and other institutions, these findings justify the more widespread use of ilio-femoral bypass."
-What is the function of the vasoactive intestinal peptide (VIP) receptor identified in this study?,"Cloning and expression of the human vasoactive intestinal peptide receptor. Vasoactive intestinal peptide (VIP) is a neuroendocrine mediator found in the central and peripheral nervous system. Distinct subsets of neural, respiratory, gastrointestinal, and immune cells bear specific high-affinity receptors for VIP, which are associated with a guanine nucleotide-binding (G) protein capable of activating adenylate cyclase. A cDNA clone (GPRN1) encoding the human VIP receptor was identified in libraries prepared from the Nalm 6 line of leukemic pre-B lymphoblasts and the HT-29 line of colon carcinoma cells. The deduced 362-amino acid polypeptide sequence encoded by GPRN1 shares a seven-transmembrane-segment hydropathicity profile with other G protein-coupled receptors. Northern blot analyses identified a 2.7-kilobase transcript of the VIP receptor in Nalm 6 and HT-29 cells as well as in tissues from rat brain, colon, heart, lung, kidney, spleen, and small intestine. COS-6 cells transfected with GPRN1 bound 125I-labeled VIP specifically with a dissociation constant (Kd) of 2.5 nM. VIP--and less effectively secretin, peptide histidine isoleucine (PHI), and glucagon competitively displaced bound 125I-VIP from transfected COS-6 cells, with potencies in the order VIP greater than secretin = PHI much greater than glucagon. VIP stimulated adenylate cyclase activity in stably transfected Chinese hamster ovary K1 cells, inducing a 3-fold increase in the intracellular level of cAMP. When the antisense orientation of the VIP receptor clone was introduced into HT-29 cells, there was a 50% suppression of the specific binding of 125I-VIP and of the VIP-induced increase in cAMP level, relative to untransfected cells. The VIP receptor cloned exhibits less than or equal to 24% homology with other receptors in the same superfamily and thus represents a subset of G protein-coupled receptors for peptide ligands."
-What is the rare cause of left-sided portal hypertension described in this medical case report?,"Acinar cell carcinoma of the pancreas: a rare cause of left-sided portal hypertension. Isolated splenic vein obstruction with left-sided portal hypertension is a rare clinical condition. Owing to the close relationship of the splenic vein and the pancreas, this rare phenomenon is usually secondary to pancreatic inflammation or neoplasm. Acinar cell carcinoma has long been recognized as a distinctive, rare type of pancreatic carcinoma. A case of isolated splenic vein obstruction with left-sided portal hypertension secondary to acinar cell carcinoma of the pancreas, which we are reporting here, is thought to the first documented in the literature."
-What were the age-adjusted incidence rates for squamous cell carcinoma and basal cell carcinoma in men and women in New Hampshire and Vermont?,"Incidence of nonmelanoma skin cancer in New Hampshire and Vermont. A survey of skin cancer occurrence between June 1979 and May 1980 among residents of New Hampshire and Vermont identified 277 cases of squamous cell carcinoma and 1761 cases of basal cell carcinoma. The age-adjusted incidence rates for squamous cell carcinoma (32 per 100,000 in men, 8 per 100,000 in women) and for basal cell carcinoma (159 per 100,000 in men, 87 per 100,000 in women) were similar to those reported in other populations in the northern United States. Skin cancer incidence was particularly high among men more than 70 years of age and a large proportion (greater than 30%) of patients 55 years or older had a history of at least one previous skin cancer."
-What are the key clinical features associated with T-cell ALL cases having the t(11;14) translocation?,"Clinical and biologic features of childhood T-cell leukemia with the t(11;14). Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations."
-"How does the affinity of thyroxine-binding globulin differ between hepatocellular carcinoma patients, cirrhotic patients, and normal subjects?","Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease. To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma."
-What is the key difference between parenchymal and reticuloendothelial iron overload in the liver as revealed by MR imaging?,"Parenchymal versus reticuloendothelial iron overload in the liver: distinction with MR imaging Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial (RE) cells after blood transfusions or rhabdomyolysis. Magnetic resonance images of patients with decreased liver signal intensity on T2-weighted images at 1.5 T were blindly compared in an effort to distinguish these conditions. In each of five patients with hemochromatosis, the pancreas had low signal intensity, but splenic signal intensity was decreased in only one. In contrast, only three of the 16 patients with RE iron overload had low pancreatic signal intensity, while all of these patients either had low splenic signal intensity (n = 14) or previously underwent splenectomy (n = 2). Distinction among these causes of iron deposition is clinically important because parenchymal iron overload from hemochromatosis may produce significant tissue damage, while the RE iron of transfusions and rhabdomyolysis is of little clinical consequence."
-What was the 5-year survival rate for elderly patients with locoregional breast cancer treated with tamoxifen alone?,"Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. One hundred and thirteen women aged 70 years or more with locoregional breast cancer were treated with tamoxifen alone as primary treatment. They were followed for a minimum of 5 years. Complete response occurred in 38 women, partial response in 17, no change in 34 and progressive disease in 24. Where progressive disease occurred, or where patients relapsed after an initial response, the most suitable conventional therapy was given. The actuarial 5-year survival rate was 49.4 per cent for all patients and was much higher (92 per cent) in those showing an initial complete response. Seventy patients (61.9 per cent) were not controlled by tamoxifen alone to death or most recent follow-up. Tamoxifen provides an alternative treatment for operable breast cancer in older women in the short term and may be particularly suitable for those with concurrent disease or who are unwilling to undergo surgery. The low morbidity rate from tamoxifen must be balanced against the need to maintain close follow-up. In the medium to long term, sole primary treatment by tamoxifen delays more definitive therapy."
-What did the study reveal about blood pressure responses in black and white children during a stressful video game?,"Stability of ethnic differences in children's pressor responses during three annual examinations. In this study, 395 healthy children had blood pressure and heart rate measured both at rest and during a stressful video game. Identical measurement procedures were used for three annual examinations. Consistently, black children demonstrated significantly greater pressor responses than white children. In view of the greater prevalence of hypertension among black adults than white adults, these data suggest that blacks exhibit hemodynamic irregularities well before the onset or diagnosis of hypertension."
-How does baseline skin microcirculation differ between patients with primary Raynaud's phenomenon and control subjects?,"Adrenoceptors on blood cells from patients with primary Raynaud's phenomenon. 1. alpha 2-Adrenoceptors on platelet membranes and beta 2-adrenoceptors on lymphocytes were studied in 24 patients with primary Raynaud's phenomenon and in 24 age- and sex-matched control subjects. In two subgroups, a standardized mental arithmetic test and a finger-cooling test were performed. 2. Baseline blood pressure, heart rate and forearm blood flow did not differ between the two groups. 3. Baseline skin microcirculation (laser Doppler flux) was decreased in primary Raynaud's phenomenon (19 +/- 15 arbitrary units) compared with control subjects (33 +/- 14 arbitrary units) (P less than 0.01). 4. Baseline plasma noradrenaline concentration (2.00 +/- 1.44 versus 1.16 +/- 0.36 nmol/l) and alpha 2-adrenoceptor density (301 +/- 119 versus 210 +/- 82 fmol/mg) were increased in patients with primary Raynaud's phenomenon in comparison with the control subjects. The alpha 2-adrenoceptor density/beta 2-adrenoceptor density ratio in patients with primary Raynaud's phenomenon was, with a value of 0.37 +/- 0.04, higher than in the control subjects, where a value of 0.25 +/- 0.02 was measured (P less than 0.001). Plasma adrenaline concentration, beta 2-adrenoceptor density and the antagonist affinity to both receptor subtypes did not differ between both groups under baseline conditions. 5. Whereas during the finger-cooling test no differences were seen in the responses of the parameters measured, the mental arithmetic test induced an increase in laser Doppler flux in patients with primary Raynaud's phenomenon and a decrease in the control group."
-What were the different management approaches used for various types of choledochal cysts in this study?,"Variation in management based on type of choledochal cyst. The management of 23 patients treated for choledochal cysts at the Oregon Health Sciences University between 1969 and 1990 is reviewed. The median age was 27 years, with a range from 1 month to 90 years. Seventy-eight percent of patients presented with abdominal pain, and 35% were jaundiced. Three patients presented with cholangitis, two with cyst rupture, and one with recurrent pancreatitis. Nine patients had had previous biliary surgery. The diagnosis was made in all patients with ultrasound and/or cholangiography. Fifteen patients (65%) had type I cysts, 2 had a type II cyst, 5 (22%) had type III cysts, and 1 had a type IV cyst. Stones were present in four (17%) cysts, and all excised cysts were benign. Seventeen patients with type I and II choledochal cysts had complete cyst excision and choledochoenterostomy. Four of five patients with type III cysts had endoscopic cyst incision and drainage, while the fifth patient had transduodenal cyst excision and sphincteroplasty. The patient with a type IV cyst had extrahepatic cyst excision and choledochojejunostomy. There were no operative deaths. Two postoperative complications occurred: cholangitis and a prolonged ileus. All patients had resolution of their pain and jaundice. Two patients had late cholangitis. Cyst excision and choledochojejunostomy are the treatment of choice for types I and II choledochal cysts. Extrahepatic cyst excision and choledochojejunostomy may be adequate treatment for type IV cysts. Endoscopic incision and drainage is appropriate for selected patients with type III cysts."
-How does the combination of tetracycline and corticosteroid affect the development of crystalline stromal opacities in rabbit corneas infected with Streptococcus mitis?,"Characterization of infectious crystalline keratitis caused by a human isolate of Streptococcus mitis. Streptococcus mitis isolated from a human with infectious crystalline keratitis was injected intrastromally into corneas of adult New Zealand white rabbits that were treated with tetracycline hydrochloride, methylprednisolone acetate, or a combination of tetracycline and methylprednisolone. Animals were followed up for up to 44 days; untreated corneas and those treated with tetracycline developed no disease or ""fluffy"" stromal infiltrates with overlying epithelial defects representing an abscess. Corneas treated with the combination of tetracycline and corticosteroid usually developed crystalline stromal opacities that on histopathologic examination were shown to be intrastromal aggregates of cocci. Transmission electron microscopy of crystalline lesions within 10 days of infection revealed typical cocci intermixed with a fibrillar material having periodicity characteristic of fibrinogen or fibrin, and immunoperoxidase staining for fibrinogen was positive. By 1 month, electron microscopy revealed aggregates of degenerated bacteria that were surrounded by cellular processes of activated keratocytes. Our studies demonstrate a model for crystalline keratitis in which organisms are seen to reside within the stroma for up to 44 days without an inflammatory response. Periocular corticosteroids appear to be necessary to create this model. It is possible that the organisms are isolated from the host response by fibrin or by keratocytes."
-What advantages does intraoperative transesophageal echocardiography (TEE) offer in assessing surgical repair of congenital heart defects in children?,"Application of intraoperative transesophageal echocardiography in infants and small children. Intraoperative echocardiography is gaining increasing acceptance in the assessment of the surgical repair of congenital heart defects. Because of its ideal imaging location, intraoperative transesophageal echocardiography (TEE) has been especially helpful in evaluating pulmonary venous return and the integrity of the left atrioventricular valve following mitral valvuloplasty, complete atrioventricular valve repair and correction of complex congenital heart disease. It has not been routinely used in infants and small children because of a prohibitively large probe size. We report the successful use of a recently developed ""pediatric"" TEE probe capable of Doppler and color flow imaging in two patients less than 7 years of age. No complications were encountered. Recommendations regarding optimal probe imaging positions in infants are provided."
-What are the key steps in treating patients who survive out-of-hospital cardiac arrest?,"Current treatment of patients surviving out-of-hospital cardiac arrest. Most out-of-hospital cardiac arrests result from the sudden onset of a sustained ventricular arrhythmia in the absence of a new myocardial infarction. Individuals who survive cardiac arrest are at high risk for recurrent arrhythmias and sudden unexpected death. To prevent recurrent cardiac arrest, effective treatment must be provided during hospitalization after the initial episode. Caring for the survivor of cardiac arrest requires a detailed clinical investigation to define the underlying cardiac anatomy and left ventricular function and to elucidate the mechanism and characteristics of the patient's arrhythmia. Appropriate antiarrhythmic therapy, such as drugs or a nonpharmacological intervention (eg, implantable cardioverter-defibrillator), is then selected based on these considerations. In addition, ischemia is treated aggressively with beta-adrenergic blocking agents and, when appropriate, with surgical coronary artery revascularization."
-What is the significance of Tissue Polypeptide Antigen (TPpA) in detecting central nervous system metastases in breast cancer patients?,"Tissue polypeptide antigen activity in cerebrospinal fluid: a marker of central nervous system metastases of breast cancer. Tissue polypeptide antigen (TPpA) in the cerebrospinal fluid (CSF) was measured in 59 consecutive breast cancer patients with suspected central nervous system (CNS) metastases. Subsequently, we determined that 13 patients had parenchymal brain metastases, 10 had leptomeningeal carcinomatosis, and 36 had no CNS involvement. The concentration of TPpA, which is a nonspecific marker for cell proliferation, was significantly higher in patients with CNS metastases than in those without it (P less than .0001; Mann-Whitney test). A tentative cutoff value for CNS metastases was set at 95 U/L TPpA; the upper limit of values indicating absence of CNS metastases was 89 U/L. Given these cutoff points, the sensitivity of TPpA as a marker for CNS metastases was 74% and the specificity was 100%; the predictive values of positive and negative tests were 100% and 86%, respectively. In 16 patients with CNS metastases, no correlation was found between TPpA activity in corresponding CSF and blood samples (correlation coefficient, Spearman's rho = .4; P greater than .1). In three patients treated for leptomeningeal carcinomatosis, the measurements of CSF TPpA showed correlation between the presence of tumor cells in the CSF and neurological clinical function. TPpA concentrations decreased in parallel with the clinical response and increased prior to CNS disease progression. As a marker for CNS metastases, the level of TPpA in the CSF in breast cancer patients appears to be superior to the level of protein, lactate dehydrogenase, or glucose, which showed very low sensitivity (41%, 47%, and 8%, respectively). For quantitative evaluation of treatment for leptomeningeal carcinomatosis, the TPpA level appears to be valuable and superior to CSF cytology, because tumor cells are not always present in CSF samples from patients with this condition."
-How did the researchers investigate the roles of thrombin inhibition and platelet membrane glycoprotein IIb/IIIa in platelet deposition after balloon angioplasty?,"Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model. BACKGROUND. Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. METHODS AND RESULTS. In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. CONCLUSIONS. At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters."
-What was the cause of subarachnoid hemorrhage in the seventy-one-year-old Japanese man?,"Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery."
-How does interleukin-4 (IL-4) affect the growth of Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) cells?,"Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. We investigated the effect of recombinant human interleukin-4 (rhIL-4) on the in vitro growth of human leukemia cells in liquid culture and 3H-thymidine incorporation and found inhibitory effects on the growth of leukemic cells from patients with Ph1-positive acute lymphoblastic leukemia (Ph1 ALL) and three Ph1 ALL cell lines. However, no inhibitory effects were seen in Ph1-positive leukemic cell lines derived from patients with chronic myelogenous leukemia in blast crisis and various types of Ph1-negative leukemia cells, including B-lineage leukemia cells. In a flow cytometry assay of IL-4 receptor (IL-4R), all three Ph1-positive ALL cell lines showed the presence of IL-4R on their cell surfaces, and the IL-4-dependent inhibition on the growth of Ph1-positive ALL cells was abrogated by the addition of either monoclonal or polyclonal antibodies against rhIL-4. Other cytokines, including IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, and IL-6, showed no inhibitory effects on the growth of Ph1-ALL cells, but tumor necrosis factor-alpha (TNF-alpha) and interferon (IFN)-alpha, -beta, and -gamma displayed slight inhibitory effects in a high concentration. The growth inhibition induced by rhIL-4 in the Ph1-positive ALL cells was not abrogated by the addition of antibodies against either IFN-gamma or TNF-alpha. Furthermore, these cells showed no significant production of IFN-alpha, -beta, or -gamma or TNF-alpha after exposure to rhIL-4, thus indicating that the growth inhibition of Ph1-positive ALL cells by rhIL-4 is not associated with IL-4-stimulating production of these factors. rhIL-4 caused significant inhibition of the tyrosine kinase activity in these Ph1-positive ALL cells, similar to Herbimycin A, an inhibitor of tyrosine kinase that inhibited the tyrosine kinase activity in these cells. Our finding suggests that the clinical evaluation of rhIL-4 may offer promising therapeutic possibilities for patients with Ph1-positive ALL."
-How did aztreonam and cefotaxime compare in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients?,"Aztreonam vs. cefotaxime in the treatment of gram-negative spontaneous peritonitis in cirrhotic patients. Aztreonam and cefotaxime were compared in 44 cirrhotic patients who had 52 episodes of gram-negative spontaneous peritonitis. Patients were randomized into two therapeutic groups of similar characteristics. Group A (28 episodes) received 0.5 gm of aztreonam every 8 hr, and group B (24 episodes) received 1 gm of cefotaxime every 6 hr, for a planned 14-day period. Peak and trough serum and ascitic fluid levels of both antibiotics were several times higher than the minimum inhibitory concentrations of causative microorganisms. Eleven patients (21%) died within the first 48 hr after beginning therapy, which included seven in the aztreonam group and four in the cefotaxime group. In the remaining patients, signs and symptoms of infection were promptly controlled, and ascitic fluid cultures became negative after 48 hr in all cases, except in one patient from the aztreonam group, who was a clinical failure. Two patients from the aztreonam group and one from the cefotaxime group relapsed after treatment. The overall mortality rate was 50%, which was lower than classically reported: 12 patients (43%) died in the aztreonam group, and 14 (58%) died in the cefotaxime group (p = 0.265, NS). Hepatorenal syndrome and digestive tract hemorrhage were the most frequent causes of death occurring after the first 48 hr of treatment. Streptococcal superinfections developed in three patients (14.2%) in the aztreonam group. We conclude that both antibiotics at the low doses used in this study are similarly well tolerated and effective in controlling this infection. Because the use of aztreonam as the initial empirical treatment requires a concomitant antibiotic against gram-positive infections and the possibility of streptococcal superinfections, cefotaxime seems to be a more advantageous therapeutic alternative for this patient population."
-"How do passive upright tilting, Valsalva maneuver, and respiration affect the atrial flutter cycle length?","Effects of posture, Valsalva maneuver and respiration on atrial flutter rate: an effect mediated through cardiac volume. The effects of passive upright tilting from 0 degrees to +60 degrees (n = 27), Valsalva maneuver (n = 16) and respiration (n = 10) on the rate of atrial flutter were studied in 27 patients. After tilting to +60 degrees, the atrial flutter cycle length shortened in all patients from 247.5 +/- 7 to 236.7 +/- 6.9 ms (range of shortening 1 to 21 ms, p less than 0.001). The Valsalva maneuver (strain of 40 mm Hg) shortened the flutter cycle length during the strain (phase 2) from 242.2 +/- 4.6 to 230.5 +/- 5 ms (range of shortening 2 to 19 ms, p less than 0.001). In 10 patients whose respiration was monitored, the flutter cycle length consistently prolonged during inspiration and shortened during expiration. Combined beta-adrenergic and muscarinic receptor blockade in six patients did not significantly alter the flutter cycle length at rest or the effects of the various maneuvers on the changes in flutter cycle length. This study revealed that the atrial flutter cycle length can be shortened by passive upright tilting, the strain phase of the Valsalva maneuver and expiration. Changes in flutter cycle length were independent of autonomic tone, implying that by decreasing cardiac volume, these maneuvers affect characteristics of the atrial flutter circuit, thereby producing dynamic changes in the rate of atrial flutter."
-What is neoplastic angioendotheliomatosis (NAE) and how did it manifest in the two described cases?,"Two cases of neoplastic angioendotheliomatosis presenting with myelopathy. We describe two patients with autopsy-proven neoplastic angioendotheliomatosis (NAE) presenting only as a transverse myelopathy for 10 to 12 months, followed by disseminated intracranial manifestations. Postmortem examination disclosed a vasculocentric distribution of neoplastic cells in various organs that stained positively with B-lymphocyte-specific monoclonal antibody. These cases were unusual because they manifested as an isolated myelopathy for many months."
-How do DNA ploidy and cell proliferation index relate to survival rates in Stage B2 and C colorectal adenocarcinoma?,"DNA ploidy and cell kinetic measurements as predictors of recurrence and survival in stages B2 and C colorectal adenocarcinoma. DNA content and cell proliferation were measured by flow cytometry on paraffin-embedded Stage B2 or C colorectal adenocarcinomas from 694 patients enrolled in adjuvant trials conducted by the North Central Cancer Treatment Group. Patients with diploid tumors had a higher survival rate than those with nondiploid tumors (P less than 0.001). The proliferation index (the sum of the percent of cells in S-phase plus those in G2M phase) was also a strong prognostic factor (P less than 0.001). The ploidy and proliferation data were combined, and the patients in the favorable group (diploid and low proliferative index) had a 5-year survival of 74% compared with 54% for the unfavorable group (high proliferative index or nondiploid, P less than 0.001). This grouping was prognostic for survival in B2 (P less than 0.001), C (P = 0.013), colon (P less than 0.001), and rectal (P = 0.026) patient subsets. This study indicates that cell kinetic parameters are important and independent prognostic factors for Stages B2 and C colorectal cancer."
-What is poststenotic dilatation and how does it develop in arteries?,"Poststenotic dilatation. Partial narrowing of arteries produces poststenotic dilatation. This appears as a dilation of the vessel wall 1 to 3 centimeters distal to the area of a partial stenosis. When a stenotic band is placed in dogs, poststenotic dilatation develops rapidly, often within eight to ten days. Moderate stenoses that produce a bruit and thrill are effective in eliciting poststenotic dilatation, whereas very tight and very mild stenoses usually are ineffective. Thus, development of poststenotic dilatation requires the presence of flow disturbances sufficient to produce an audible bruit and a palpable thrill. Although the exact flow disturbance is uncertain, statis, increased lateral pressure, cavitation, abnormal shear stresses and turbulence all have been postulated to be the cause of poststenotic dilatation. Of these, experimental studies support abnormal shear stresses and turbulence as the most likely causes. Whatever the flow disturbance, it must make the wall vibrate to produce poststenotic dilatation. Vibrations are thought to produce alterations in wall elastin and possibly in vascular smooth muscle tone. This leads to dilatation of the vessel. If the dilatation is slight, removal of the stenosis may cause reversal of poststenotic dilatation with recovery beginning within hours of correction of the stenosis. If the dilated area is enlarged to twice normal diameter, it may exhibit permanent aneurysmal changes and, therefore, requires resections with reanastomosis. Arteries that are dilated to as little as one-third more than normal size may contain areas of ulceration with overlying thrombus. These vessels also may require resection with reanastomosis."
-How do running shoes and spikes affect pronation and torsion angles compared to running barefoot?,"The effects of shoes on the torsion and rearfoot motion in running. Excessive pronation is accepted as a good indicator for various running injuries. The least amount of pronation takes place when running barefoot. The latest investigations show that this is connected to a large torsional movement between forefoot and rearfoot which can be influenced by the shoe sole construction. The shoes which are in use among runners in track and field are basically of two types, running shoes (in general torsionally stiff) and spikes (torsionally flexible). The possibly varying effect of these shoes on the shoe/foot motion in running is not known. The purpose of this investigation was therefore to show whether the pronation angle and the torsion angle differ when running barefoot, with spikes, and with running shoes (forefoot touchdown, N = 9 left and right). A film analysis provided the angular movements of the lower leg, rearfoot, and forefoot as well as pronation and torsion in the frontal plane. The results show that at touchdown the torsional movements with both shoe types are quite different from those of running barefoot. With shoes, the torsion angle is reduced back to zero--with running shoes more than with spikes--and the pronation angle is increased beyond the barefoot values (P less than 0.01). In order to reduce the risk of injury, both shoe types should be improved--the running shoes with respect to torsion and the spikes with respect to pronation."
-What was the significance of blood group antigen immunoreactivity in the study of superficial esophageal carcinomas?,"Immunohistochemical studies of blood group-related antigens in human superficial esophageal carcinomas. A total of 63 surgically resected esophageal carcinomas (including 49 superficial esophageal carcinomas) and histologically normal tissue adjacent to the superficial carcinoma (nontumorous epithelium) were examined immunohistochemically for the blood group antigens (BGA) A, B, H, Lewisa, Lewisb, Lewisx, and Lewisy. Deletion of an expected A, B or H antigen occurred in 12 (24.5%) of the 49 superficial carcinomas and three (21.4%) of the 14 advanced carcinomas. Incompatible expression of an unexpected A or B antigens occurred in only one case (1.6%) in the carcinoma. In the clinicopathologic study, there was a significant correlation between immunoreactivity of Lewisa and depth of cancer invasion (chi-square test, P less than 0.05). In the superficial carcinoma, there were significant correlations between immunoreactivity of Lewisx and lymph node status (chi-square test, P less than 0.05), immunoreactivity of Lewisy and prognosis (Z test, P less than 0.05), and incompatible expression of Lewisb for tumor against nontumorous epithelium and histologic variation (chi-square test, P less than 0.01). The functional significance of alternations in BGA expression that may be associated with oncogenesis is not clear. However, immunohistochemical determination of BGA may be a more advantageous marker to predict the patient's clinical course in superficial esophageal carcinoma."
-What percentage of patients with extraadrenal retroperitoneal paragangliomas had hypertension in this study?,"Extraadrenal retroperitoneal paraganglioma: clinical, pathologic, and CT findings. Paragangliomas of the retroperitoneum arise from specialized neural crest cells distributed along the aorta in association with the sympathetic chain. In order to ascertain characteristic CT features of extraadrenal retroperitoneal paragangliomas to differentiate them from other retroperitoneal tumors, 31 discrete tumors and two cases of paragangliomatosis in 28 patients were reviewed retrospectively, and the CT features were correlated with clinical and pathologic findings. There were 16 men and 12 women. Average age was 37 years (range, 11-70 years). Twenty-four patients (86%) had hypertension. Of these, catecholamine levels were elevated in all 18 patients who had biochemical studies. Four patients (14%) had malignant paragangliomas. The discrete tumors were classified by location as suprarenal (26%), renal hilar (32%), or infrarenal (42%). Suprarenal paragangliomas could not be distinguished from the ipsilateral adrenal gland on CT. The average size of functional tumors was smaller (7.0 cm) than that of nonfunctional tumors (12.0 cm), but the sizes of the two groups overlapped. Smaller tumors were more likely to be homogeneous and have well-defined margins than were larger tumors. Our findings indicate that extraadrenal retroperitoneal paragangliomas are functionally active more often than previously reported and that they are readily detected by CT as soft-tissue masses closely associated with the entire length of the abdominal aorta. However, no CT feature was found that was unique for paraganglioma."
-What unique pattern of nystagmus was observed in a patient with posterior medullary haemorrhage?,"Upbeat and downbeat nystagmus occurring successively in a patient with posterior medullary haemorrhage. In a patient with posterior medullary haemorrhage, first upbeat and later downbeat nystagmus occurred in the primary position. The lesion was limited to the posterior and medial part of the medulla. Clinical and electro-oculographic examination first showed upbeat nystagmus in the primary position and upgaze, with downbeat nystagmus in downgaze. Two and a half months later, there was downbeat nystagmus in the primary position and downgaze and upbeat nystagmus in upgaze."
-How does gadolinium contrast enhance the detection and delineation of choroidal melanoma in magnetic resonance imaging?,"Magnetic resonance imaging of choroidal melanoma with and without gadolinium contrast enhancement. Choroidal melanoma is the most common intraocular tumor and is uniquely suited for evaluation by magnetic resonance imaging (MRI) because of the paramagnetic effect of the melanin molecule. The authors performed T1-, T2-, and proton-density-weighted MRI on 34 patients with choroidal melanoma. Nineteen patients received gadolinium contrast, T1-weighted images were superior in both detecting and delineating tumors, showing increased contrast-to-noise ratios over other images. Gadolinium contrast further increased this ratio. These images are presented as evidence that gadolinium-enhanced MRI is valuable in the evaluation of choroidal melanoma."
-"What were the main findings comparing standard external CPR, open-chest CPR, and cardiopulmonary bypass in this canine myocardial infarct model?","Comparison of standard external CPR, open-chest CPR, and cardiopulmonary bypass in a canine myocardial infarct model. STUDY OBJECTIVES: After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model. TYPE OF PARTICIPANTS: Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight). DESIGN AND INTERVENTIONS: All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas. MEASUREMENTS: Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group. MAIN RESULTS: Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02). CONCLUSION: OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB."
-What was the purpose of the study on creatine kinase MB (CK-MB) time-activity curve in patients with acute myocardial infarction?,"Indices of reperfusion in patients with acute myocardial infarction using characteristics of the CK-MB time-activity curve. The purpose of this study was to identify indices of coronary artery reperfusion in patients treated with thrombolytic therapy for acute myocardial infarction (AMI) by means of characteristics from the serum creatine kinase (CK) isoenzyme MB time-activity curve. Frequent blood sampling as performed in three groups with a first AMI: 29 patients treated with intravenous thrombolytic therapy who had a patent infarct-related artery with normal flow (TIMI-3) at acute catheterization (reperfusion group); four patients with a persistently closed infarct-related artery (no reperfusion group); and 44 patients who did not receive any therapy aimed at coronary reperfusion (no thrombolytic therapy group). In the latter group we prospectively estimated that 25% would have spontaneous reperfusion. A physiologically based computer-calculated multi-compartment method was used to determine the characteristics of the serum CK-MB time-activity curve. In addition to demonstrating an earlier increase, a shorter time to peak of serum CK-MB and a lower estimated infarct size in the reperfusion group (p = 0.025 to 0.00001), the appearance rate constant (k1) and time from estimated initial increase to peak of CK-MB in the blood stream (tRP) were significantly different from those values in the no thrombolytic therapy group (p less than 00001). A cutoff level indicating reperfusion if k1 was greater than 0.185 or tRP was less than 16.5 hours demonstrated overlapping values between these two groups in only four patients (k1), two patients (tRP), and six patients with a combination."
-What makes interstitial ectopic pregnancies more dangerous compared to other tubal pregnancies?,Ruptured interstitial pregnancy presenting as an intrauterine pregnancy by ultrasound. Interstitial pregnancy is an uncommon subset of ectopic pregnancy in which the conceptum implants in the intrauterine portion of the fallopian tube. These pregnancies tend to progress further before rupture than do other tubal pregnancies and subsequently have greater propensity for massive intra-abdominal bleeding and maternal demise. Abdominal ultrasound can be deceptive in evaluating interstitial ectopic pregnancies. Transvaginal ultrasonography is more sensitive in the diagnosis of early ectopic pregnancy. Knowledge of the application and limitations of both transabdominal and transvaginal ultrasound will assist the emergency physician in the timely evaluation of this potentially lethal condition.
-How accurate is transrectal sonography in detecting neurovascular bundle invasion in prostate cancer patients?,"Carcinoma of the prostate: value of transrectal sonography in detecting extension into the neurovascular bundle. Detection of involvement of the neurovascular bundles (NVB) by tumor is important in deciding whether sexual function can be preserved in patients undergoing radical prostatectomy for prostatic cancer. The nerve branches innervating the corpora cavernosa have a rather constant association with the capsular arteries and veins of the prostate, forming the periprostatic neurovascular bundle, which can be identified intraoperatively and spared during radical surgery, thus preserving potency. We examined 160 patients with biopsy-proved clinical stage A or B adenocarcinoma with transrectal sonography before radical prostatectomy to determine how useful the procedure is for predicting tumor extension into the NVB. Correlation with pathologic serial sections was obtained in each patient. The sonograms depicted the NVB on both sides in 77 patients (50%), on the right side only in 13 (8%), and on the left side only in 36 patients (23%). In 29 patients (19%) neither neurovascular bundle could be identified on the sonograms. Ninety-one tumors in this series showed evidence of extraglandular spread pathologically, which was posterolateral or into the NVB in 70 tumors involving 82 hemispheres. Using transrectal sonography, we correctly identified invasion of the NVB in 54 cases and missed it in 28 cases. NVB invasion was predicted incorrectly with transrectal sonography in 51 cases; absence of involvement of the NVB was correctly predicted in 177 hemispheres. The sensitivity of sonography for predicting invasion of the NVB was 66%, with a specificity of 78% and an accuracy of 75%. Positive predictive values and negative predictive values were 51% and 86%, respectively. We conclude that transrectal sonography currently suffers from lack of sufficient spatial resolution to detect accurately invasion of the NVB."
-How does C4b-binding protein (C4bBP) affect the host response to Escherichia coli infection?,"C4b-binding protein exacerbates the host response to Escherichia coli. Activated protein C is a plasma anticoagulant. For activated protein C to function as an anticoagulant, it must form a complex with protein S. Protein S anticoagulant activity is neutralized by formation of a reversible complex with C4b binding protein (C4bBP). C4bBP is an acute-phase plasma protein. When C4bBP levels increase, mass action forces the level of free protein S to decrease, giving rise to an acquired functional protein S deficiency. It has been proposed that these elevated C4bBP levels and the resultant acquired deficiency of protein S that occurs in inflammation could contribute to a hypercoagulable state. An experimental model to test this hypothesis was suggested by our previous studies that demonstrated that inhibition of protein C activation rendered baboons hypercoagulable in response to sublethal Escherichia coli infusion (J Clin Invest 79:918, 1987). We have extended these studies to examine the effect of inhibition of protein S activity with C4bBP in the host (baboon) response to infusion of sublethal concentrations of E coli organisms. Five sets of animals were studied: (1) those challenged with sublethal concentrations of E coli alone (0.4 x 10(10)/kg); (2) those supplemented only with C4bBP (20 mg/kg); (3) those challenged with the same level of E coli but supplemented with C4bBP (20 mg/kg); (4) those challenged with sublethal E coli and supplemented with C4bBP (20 mg/kg) and sufficient protein S (2.3 mg/kg) to fill the protein S binding sites on C4bBP; and (5) those challenged with lethal concentrations of E coli. Sublethal E coli infusion (group 1 animals) caused only an acute-phase response with no consumption of fibrinogen, detectable organ damage, or detectable tumor necrosis factor (TNF) in the plasma. C4bBP infusion (group 2 animals) resulted in no significant physiologic changes, no detectable plasma TNF, and little change in fibrinogen level. The group 3 animals, receiving both sublethal E coli and C4bBP, exhibited rapid consumption of fibrinogen, systemic organ damage, and detectable circulating TNF ultimately leading to death. The overall response of this group was very similar to the response of the group 5 animals receiving an LD100 dose of E coli. The group 4 animals, which were treated exactly as above except that C4bBP was supplemented with a slight excess of protein S, responded essentially like those that received sublethal E coli alone. These studies suggest that the elevation of C4bBP during an inflammatory response can contribute to fibrinogen consumption and vascular damage. This vascular damage may be associated with enhanced elaboration of cytokines like TNF.(ABSTRACT TRUNCATED AT 400 WORDS)."
-What factors were found to be associated with better functional recovery after traumatic transtentorial herniation?,"Functional recovery after traumatic transtentorial herniation. To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation."
-What is the association between L-tryptophan ingestion and eosinophilic fasciitis (EF) according to the study?,"Idiopathic and L-tryptophan-associated eosinophilic fasciitis before and after L-tryptophan contamination. Recently, a causative association has been made between the ingestion of levotryptophan (L-tryptophan) and the eosinophilia-myalgia syndrome (EMS), a new entity manifested by peripheral blood eosinophilia, myalgias, constitutional symptoms, and cutaneous edema with fibrosis. Contaminated levotryptophan preparations produced at a single manufacturing company between October 1988 and June 1989 have been implicated in all EMS cases. In this study, we analyzed retrospectively 49 patients with cutaneous fibrosis for a history of levotryptophan use. Levotryptophan ingestion prior to the onset of their disease was reported by 11 (65%) of 17 patients with eosinophilic fascilitis (EF), two (20%) of 10 patients with localized scleroderma, and none of 22 patients with systemic sclerosis. The onset of levotryptophan-associated cutaneous disease preceded the availability of contaminated levotryptophan preparations in seven (54%) of 13 patients. One patient with levotryptophan-associated generalized morphea also had lichen sclerosus et atrophicus and acanthosis nigricans, findings not previously reported in patients with EMS. In addition, we compared the clinical and laboratory features of levotryptophan-associated EF and idiopathic EF. Myalgias, muscle weakness, paresthesias, morpheaform plaques, cutaneous ulcers, and livedo reticularis were more common in patients with levotryptophan-associated EF. We conclude that levotryptophan-associated EF and localized scleroderma were present before the presumed date of contaminated levotryptophan availability. The clinical spectrum of cutaneous fibrosis associated with the ingestion of levotryptophan includes generalized morphea and EF, which are similar though not identical to their idiopathic counterparts."
-What percentage of subjects in the study had adenomas detected during screening colonoscopy?,"Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men. Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated."
-What was the average number of bypasses per patient in this direct coronary surgery without extracorporeal circulation?,"Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients Between May 1978 and March 1990, 700 patients were operated on with direct coronary surgery without extracorporeal circulation (ECC): 529 (76 percent) were male and 171 (24 percent) were female. The average age was 64 years (range, 35 to 86 years), 454 (65 percent) had unstable angina, 163 (23 percent) had stable angina, 51 (7 percent) had postmyocardial infarction angina, and 32 (5 percent) had acute myocardial infarction at the moment of the operation. In this series of patients, all branches of the coronary arteries were bypassed; the mammary artery was used in 40 percent of the cases, the average bypass per patient was 2.2 (range, 1 to 5), and 26 percent had associated disease of high risk to undergo ECC. The morbidity was 4 percent and the mortality for this series of patients was 1 percent; the probability of survival at seven years was 90 percent. This experience shows us that this surgery is an alternative in the treatment of coronary disease, especially for aged patients with associated disease, in some cases of acute transmural infarction, and also for patients who need coronary angioplasty. Also, it can improve the relation cost/benefit in coronary surgery."
-What was the main finding of the study regarding the use of diazepam in emergency treatment of seizures in children?,"Diazepam and intubation in emergency treatment of seizures in children. STUDY OBJECTIVES: This study was undertaken to determine the incidence of endotracheal intubation after the use of diazepam compared with phenobarbital or phenytoin in emergency treatment of seizures in children. DESIGN: The records of all children (98) were reviewed in a case-control fashion. A logistic regression model was used to determine whether there was an association between diazepam administration and intubation, adjusting for all other covariates (age, weight, convulsion time before first anticonvulsant was given, response latency, diagnosis, and therapy). SETTING: All children were treated in an emergency department and then transported to a tertiary pediatric center by a pediatric transport team. TYPE OF PARTICIPANTS: All patients were children, with a median age of 2.7 years (range 0.17 to 15.3 years). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only the use of diazepam was found to be significantly associated with intubation after adjusting for all other covariates (adjusted odds ratio, 49.4; P less than .001). In the comparison of diazepam versus phenobarbital or phenytoin used as the first anticonvulsant, median response latency did not differ (27.0 vs 32.5 minutes, P greater than .83). CONCLUSION: A significant association was found between diazepam use and intubation. Response latency was not shorter when diazepam was used as the initial anticonvulsant compared with phenobarbital or phenytoin."
-What is the significance of a 'sentinel bleed' after pancreatoduodenectomy?,"Arterial hemorrhage after pancreatoduodenectomy. The 'sentinel bleed'. Experienced centers report reduced operative mortality after pancreatoduodenectomy for cancer, but significant complications continue to occur in as many as 25% of patients. Anastomotic disruption leads to sepsis in the pancreatic bed where major vascular structures have been exposed by regional lymphadenectomy, creating a setting for arterial erosion or ligature slough and massive hemorrhage. Dehiscence of the pancreatojejunostomy is a particular risk. We treated five patients with arterial hemorrhage after pancreatoduodenectomy, all of whom had had ""sentinel"" bleeding from the abdominal drains or gastrointestinal tract. Results of endoscopy were misleading in two patients. Three of five patients were saved by prompt recognition, early operation, and, in one instance, angiographic embolization. Sentinel bleeding after pancreatoduodenectomy indicates local sepsis and probable anastomotic dehiscence. Recognition of its significance and prompt response may prevent exsanguination."
-What was the purpose of the study on neurophysical signs assessment among patients with head injuries?,"Observer variation in assessing neurophysical signs among patients with head injuries. As an early phase in the development of a valid and reliable measure of the neurophysical sequelae after head injury, we carried out assessments of interrater agreement on representative items. The purpose of this study was to determine the degree of agreement among expert raters who independently measured neurophysical signs on patients undergoing physical rehabilitation after brain injury. Agreement was described using the index of crude agreement, expected agreement and Kappa. Therapists showed a high degree of agreement on those items forming part of a routine neurological assessment: prehension, coordination, voluntary movements and tendon reflexes. Crude agreement ranged from 77.8-100%. There was considerable discordance in assessing muscle tonus, equilibrium and protective reactions, spinal reflexes, tremor and dysmetria (crude agreement ranged from 49.7-97.9%). Although, the number of subjects was small, the information generated from this study will be useful in refining our instrument for the assessment of neurophysical signs."
-What are the potential complications of untreated abdominal aortic thrombosis?,"Nontraumatic abdominal aortic thrombosis presenting with anterior spinal artery syndrome and pulmonary edema. A 51-year-old woman with a history of breast cancer developed pulmonary edema and lower extremity paraplegia with preservation of proprioception as the initial manifestation of abdominal aortic thrombosis. Back pain was present in the lumbar region radiating to buttocks and legs in a bilateral radicular pattern. Femoral pulses were initially palpable. Aortic angiography revealed complete abdominal aortic occlusion at L3 as well as total occlusion of the bilateral superficial femoral arteries and bilateral common iliac arteries. Transient occlusion of the anterior spinal artery due to aortic thrombosis may cause paraplegia and may also progress to renal failure, bowel infarction, and limb loss if left untreated. Abdominal aortic thrombosis needs to be considered in a patient who presents with an anterior spinal artery syndrome, which, if present, must be treated as rapidly as possible to preserve motor and sensory function."
-What method was used to screen four large families for potential genetic linkages related to hypertension?,"Use of the robust sib-pair method to screen for single-locus, multiple-locus, and pleiotropic effects: application to traits related to hypertension. Robust sib-pair linkage analysis can be used as a screening tool in the search for the potential involvement of single-loci, multiple-loci, and pleiotropic effects of single loci underlying phenotypic variation. Four large families were each ascertained through one adult white male with essential hypertension. The robust sib-pair method was used to screen these families for evidence of linkage between 39 quantitative traits related to hypertension and 25 genetic marker loci. All traits were analyzed on the untransformed, square-root and log-transformed scales. Among other findings, there is a suggestion of linkage between the 6-phosphogluconate dehydrogenase locus on chromosome 1p36 and mean fifth-phase diastolic blood pressure. There may also be linkage between the following markers and traits: the adenylate kinase-1 marker and/or the Lewis blood group marker and the traits height, weight, and biacromial breadth; the glyoxylase I marker and the traits upper-arm circumference and suprailiac skinfold thickness; the ABO blood group and adenylate kinase-1 markers on chromosome 9q34 and the third component of complement marker on chromosome 19p13 and dopamine-beta-hydroxylase; and the P1 blood group and the traits weight and 1-h postload serum glucose level."
-What was the method used to manage neuropathic cancer pain in patients who did not respond to conventional analgesics?,"Subcutaneous lidocaine for treatment of neuropathic cancer pain. Three patients with terminal malignancy reporting ineffective analgesia using systemic and subsequently spinal opiates were treated with subcutaneous infusion of 10% lidocaine hydrochloride. During the infusion, reasonably stable blood concentrations were achieved and maintained using a subcutaneous infusion at varying dose rates over days to months with improvement of the pain complaints which continued to be refractory to conventional analgesics. Blood lidocaine levels obtained at regular intervals revealed effective concentrations between 2 and 5 micrograms/ml for each patient."
-What are the key differences in breast cancer characteristics based on age and mammographic presentation?,"Not all nonpalpable breast cancers are alike. Clinical and mammographic data of 1009 consecutive patients were correlated with histopathologic data of 1144 biopsy specimens of nonpalpable breast lesions to better define the presentation and biologic behavior of early breast cancer. Patients with malignant neoplasms (269 [24%] of 1144 specimens) were older (mean age, 62.1 years) than patients with benign lesions (mean age, 54.9 years). Furthermore, patients with invasive disease were older (mean age, 63.3 years) than patients with noninvasive disease (mean age, 58.5 years) with an overall increased risk of invasive cancer per year of 1.035. A 58% incidence of invasive cancer was detected for lesions characterized by calcifications, while the incidence of invasive cancer was 84% for isolated mass lesions (relative risk, 4.31 for masses). Isolated mammographic calcifications associated with cancer appeared in a younger population and were significantly associated with noninvasive ductal cancer. Breast cancer presenting as a mammographic mass appeared in an older group and was highly associated with the presence of invasive disease."
-What were the effects of different lipid emulsions on hepatic lipid content and liver histology in rats receiving total parenteral nutrition?,"Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats. The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups."
-What are the two N-methyl-D-aspartate (NMDA) antagonists tested in this study for their anticonvulsant properties?,"Anticonvulsant activity of two orally active competitive N-methyl-D-aspartate antagonists, CGP 37849 and CGP 39551, against sound-induced seizures in DBA/2 mice and photically induced myoclonus in Papio papio. Two novel N-methyl-D-aspartate (NMDA) antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid CPG 37849 and the corresponding 1-ethyl ester CGP 39551, were tested as anticonvulsants in DBA/2 mice and photosensitive Senegalese baboons, Papio papio. In DBA/2 mice, CGP 37849 is more potent than CGP 39551 when administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p.) (ED50 for suppression of clonic seizures at 60 min: i.c.v. 0.038 and 0.21 nmol; i.p. 3.40 and 19.1 mumol/kg, respectively). When administered orally in mice, the two compounds are approximately equipotent (ED50 CGP 37849, 35.2 mumol/kg; ED50 CGP 39551, 28.1 mumol/kg). The time course of action of CGP 39551 is exceptionally prolonged: 42 mumol/kg i.p. protects against clonic seizures for 48 h. Protection provided by other NMDA antagonists in mice is of much shorter duration: 2-amino-5-phosphono-pentanoic acid (AP5) 1 h, 2-amino-7-phosphono-heptanoic acid (AP7) 4 h, 2-amino-7-phosphono-heptanoic acid 1-ethyl ester 3 h, 4-(3-phosphonopropyl)-2-piperazine carboxylic acid (CPP) 2 h, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) 4 h, and CGP 37849 4 h. After oral administration of the drugs, the therapeutic index (TI = ratio of the ED50 values for rotorod performance and anticonvulsant protection) remains relatively constant at 5.9-7.2 for 3 h (CGP 37849) and 4.0-6.1 for 24 h (CGP 39551). After i.p. administration, the TI values are CGP 37849 at 1 h 2.4, and at 3 h 20.0, CGP 39551 at 1 h 2.3, at 3 h 7.1, and at 24 h 3.6. In baboons, acute administration of CGP 37849 at doses of 48-191 mumol/kg intravenously (i.v.) suppresses photically induced myoclonus for at least 285 min, with severe side effects at the highest dose tested. CGP 39551 at doses of 169-675 mumol/kg i.v. shows weak anticonvulsant activity only at the highest dose tested (accompanied by severe side effects). CGP 37849 at 48-96 mumol/kg orally (p.o.) fails to protect against photically induced myoclonus up to 4 h after administration, but 191 mumol/kg (40 mg/kg) p.o. produces complete suppression of seizures after 24 h. On the other hand, CGP 39551 at 169 mumol/kg (40 mg/kg) p.o. produces total suppression of seizure activity at 4 h with a longer duration of anticonvulsant action (2-3 days).(ABSTRACT TRUNCATED AT 400 WORDS)."
-What was the primary aim of the geriatric-anesthesiologic intervention program for elderly patients with femoral neck fractures?,"A geriatric-anesthesiologic program to reduce acute confusional states in elderly patients treated for femoral neck fractures. The aim of this study was to evaluate the effect of a geriatric-anesthesiologic intervention program for the prevention and treatment of acute confusional states (ACS) in elderly patients treated for femoral neck fractures. The intervention program was based on the results of previous prospective studies in similar patient populations. The outcome of the intervention, comprising 103 patients, was compared with that of an earlier study comprising 111 patients. The intervention program consisted of pre- and post-operative geriatric assessments, oxygen therapy, early surgery, prevention and treatment of peri-operative blood pressure falls and treatment of post-operative complications. The incidence of ACS was lower, 47.6%, in the intervention study compared with 61.3% (P less than 0.05) in the control study. Furthermore, the ACS that occurred in the intervention study was less severe and of shorter duration than that in the control study. The incidence of post-operative decubital ulcers, severe falls, and urinary retention was also lower. The mean duration of orthopedic ward stay was 17.4 days in the control study and 11.6 days in the intervention study (P less than 0.001). It can be concluded that the intervention program reduced the incidence, severity, and duration of ACS which resulted in a shortened orthopedic ward stay."
-What are the limitations of routine testicular scanning in diagnosing acute scrotal conditions?,"Testicular scanning: evaluating the acute scrotum in the clinical setting. In a retrospective study of patients with acute scrotal pain presenting to the hospitals of Southern Illinois University School of Medicine from January 1982 until September 1987, determination was made of the appropriate use of testicular scan for definitive diagnosis. Though the testicular scan is a highly sensitive and specific examination in the identification of testicular torsion, we believe its routine use in clinical practice is limited. Appropriate utilization of the examination requires its use in high-risk groups with equivocal physical findings or in patients with unusual presentations of age, anatomy, or neurologic deficit. The scan if used for routine screening of the acute scrotum would result in needless delays and unjustifiable expense when it is mandatory that the treatment be immediate surgical exploration."
-"What distinguishes the ossifying jaw fibromas in this syndrome from the ""brown tumors"" of hyperparathyroidism?","Hereditary hyperparathyroidism and multiple ossifying jaw fibromas: a clinically and genetically distinct syndrome. A large previously reported family with hyperparathyroidism has been reinvestigated recently because of the occurrence of multiple ossifying jaw fibromas in two affected members of the third generation similar to the jaw tumors of four of five affected members of the first generation. These maxillary and mandibular tumors can be differentiated from the ""brown tumors"" of hyperparathyroidism because they can appear and enlarge even though the hypercalcemia is surgically corrected. These tumors are histologically distinct fibroosseous lesions without the giant cells seen in ""brown tumors."" The parathyroid enlargement was mostly uniglandular, with multiple tumors found occasionally. Studies in DNA linkage were performed within this large family and a similar family in Houston to determine if the gene for this syndrome, termed HRPT2, is linked to DNA markers on chromosome 11, to which the gene for multiple endocrine neoplasia (MEN) type 1 has been linked. (This linkage is supported by our findings in one family with MEN 1 reported here.) Linkage studies were also performed with markers on chromosome 10, to which the genes for MEN 2A and MEN 2B have been linked. Evidence against close linkage with chromosome 10 and chromosome 11 markers suggests that this clinically distinct syndrome is also genetically distinct."
-"What medical condition did the 83-year-old woman have, and what was the suspected origin of her tumor?",Carcinoma erysipeloides. We report an 83-year-old woman with carcinoma erysipeloides due to an occult carcinoma. Immunohistochemical study of skin biopsies showed reactivity to S-100 protein and human milk fat globule antigen indicating that the tumour originated in the breast.
-What was the purpose of performing intraoperative transesophageal echocardiography in patients with atrioventricular septal defect?,"Intraoperative transesophageal echocardiography of atrioventricular septal defect. To determine the accuracy and utility of single-plane transesophageal echocardiography in analyzing atrioventricular (AV) septal defect, intraoperative transesophageal echocardiography was performed before and after institution of cardiopulmonary bypass in 16 patients (age 24 days to 14 years, weight 3 to 47 kg). Prebypass transesophageal echocardiography (including two-dimensional echocardiography, Doppler color flow mapping and pulsed wave Doppler ultrasound) correctly diagnosed divided AV valve, common AV valve and unbalanced AV valve, as well as atrial or ventricular septal defect, or both, in all cases. It correctly analyzed AV valve regurgitation in all 10 patients with right and all 14 with left AV valve regurgitation and correctly analyzed 30 of 33 additional cardiac anomalies. Transesophageal echocardiography was able to detect the absence of normal pulmonary venous connections but failed to demonstrate all of the complex anomalous pulmonary venous connections in three patients with atrial isomerism. Postbypass transesophageal echocardiography documented the absence of a significant residual shunt in 11 of 11 patients undergoing corrective surgery and verified residual AV valve regurgitation in 7 of 9 patients with tricuspid regurgitation and 11 of 13 with mitral regurgitation. Transesophageal echocardiographic information that altered or refined the surgical treatment was obtained in 5 (31%) of 16 patients. Epicardial and transesophageal echocardiography results were concordant in all 13 patients in whom both were performed. Transesophageal echocardiography provides useful and accurate imaging of the important two-dimensional, pulsed wave Doppler ultrasound and Doppler color flow mapping features in AV septal defect."
-What is the significance of the patient's survival in this case of primary angiosarcoma of the brain?,Primary angiosarcoma of the brain. We have described a 32-year-old black woman who had a primary angiosarcoma of the right occipital lobe. All three previously reported cases have been fatal within 1 year. Our patient is doing well more than 3 1/2 years after surgery.
-How might abnormal liver enzyme metabolism potentially contribute to the development of Parkinson's disease?,"Abnormal liver enzyme-mediated metabolism in Parkinson's disease: a second look. If toxicant exposure contributes to the cause of Parkinson's disease, poor function of detoxifying enzymes could increase vulnerability for Parkinson's disease. Although no hepatic enzyme system has been shown universally to be dysfunctional in Parkinson's disease patients, several have been suggested to be dysfunctional in subgroups, such as those with young age at disease onset. Specific enzymes implicated include several P450 enzymes, most notably P450 IID6, and cysteine dioxygenase. If hepatic enzyme abnormalities contribute to the development of Parkinson's disease, molecular genetic techniques may allow the development of screening tests to identify at-risk subjects in order to intervene with protective therapies."
-What is the potential serious late complication of aortic bifurcation surgery discussed in this medical report?,"Bilateral ureteral obstruction following aortobifemoral bypass graft. In this report we present a case of bilateral ureteral obstruction, a potentially serious late complication of aortic bifurcation surgery. The incidence, aetiology, clinical presentation and treatment are discussed."
-What was the main finding of the study regarding bacterial colonization in necrotizing enterocolitis?,"Does patient age or intestinal pathology influence the bacteria found in cases of necrotizing enterocolitis? To evaluate the relationship between bacterial colonization in neonatal peritonitis and patient age or intestinal pathology, we retrospectively reviewed peritoneal culture results from 96 infants having surgery for necrotizing enterocolitis. Microorganisms recovered mirrored those usually found as fecal flora within the neonatal intensive care unit. These reflect, in turn, the abnormal colonization intrinsic to care in the intensive care nursery. Analysis revealed no significant correlation between the disease and either age of the infant or intestinal site of disease."
-What were the clinical findings in patients with obstruction of the infrarenal portion of the abdominal aorta?,"Obstruction of the infrarenal portion of the abdominal aorta: results of treatment with balloon angioplasty. Our experience in the treatment of stenoses of the infrarenal portion of the abdominal aorta with balloon angioplasty in 27 patients is reported. Clinical findings were lower limb claudication (all patients), impotence (eight patients), and blue-toe syndrome (two patients). The underlying disease was atherosclerosis in 24 patients and nonspecific aortoarteritis in three patients. Dilatation was successful in all patients. Embolic occlusions of the left common iliac artery (one patient) and left superficial femoral artery (one patient) were the only major complications. Claudication in the affected limb continued in the first patient; the second died when diagnostic angiography, performed 3 months after angioplasty, caused a severe atheroembolus. Of the other 25 patients, nine of the 10 followed up for 13-48 months and all seven followed up for 3-8 months were free of symptoms. Six of eight patients with sexual dysfunction had normal function after angioplasty. Seven patients still awaited follow-up and one was lost to follow-up. Our experience suggests that balloon angioplasty is an effective treatment of stenoses of the infrarenal portion of the abdominal aorta."
-What imaging technique was used to diagnose the pulmonary artery aneurysm in this case report?,Magnetic resonance imaging of pulmonary artery aneurysm. Pulmonary artery aneurysm is a rare condition. We have presented what we believe to be the first case in the English literature to be diagnosed by magnetic resonance imaging.
-Which two monoclonal anti-idiotope antibodies (Ab2) were able to induce specific anti-TAA-specific (Ab1') responses in rabbits?,"Analysis of anti-tumor antibodies in mice and rabbits induced by monoclonal anti-idiotope antibodies. Eight different mouse monoclonal anti-idiotope antibodies (mAb2) generated against a mouse monoclonal anti-human melanoma proteoglycan Ag (MPG) antibody (mAb1), MEM136, were tested for their ability to induce anti-MPG responses in mice and rabbits. All Ab2 were idiotypically cross-reactive and combining site-specific as demonstrated by competitive cross-inhibition studies and their ability to inhibit the binding of MEM136 to the melanoma cells, Colo38. However, only two Ab2, IM32 and IM06, were able to induce specific anti-TAA-specific (Ab1') responses in rabbits. When IM32 and IM06 were tested in allogeneic stains of mice for the induction of anti-MPG responses, only IM32 produced an Ab1' response. In mice, the Ab3 response induced by IM32 is idiotypically cross-reactive with its Ab1. Furthermore, the IM32-induced murine Ab3 and MEM136 recognized a similar MPG epitope on the melanoma cells because the Ab3 inhibited the binding of MEM136 to melanoma cells. The Ab3 induced by IM32 and IM06 in rabbits also recognized a similar epitope as the Ab1. In rabbits, the Ab3 response induced by IM32 and IM06 were idiotypically cross-reactive with each other. However, additional studies indicated that the majority of Ab3 induced by IM32 were IM32 Id-specific and lacked IM06 idiotopes. Further experimentation indicated that IM32-induced rabbit Ab3 were biologically active as demonstrated by the ability of the Ab3 to inhibit melanoma cell invasion in a Matrigel assay."
-What correlation was observed between large amplitude sensory action potentials and myelopathy in the study?,"Large amplitude sensory action potentials in myelopathy: an observation. Subjects with at least one sensory action potential (SAP) amplitude greater than 2 SD above the age-matched mean during standard nerve conduction tests were evaluated for evidence of spinal cord disease. From a total of 153 subjects, 16 had at least one large amplitude SAP and 12 of 16 (75%) had a documented myelopathy. While a mechanism has yet to be determined, this observation suggests that SAP amplitudes greater than 2 SD above normal may be correlated with clinical evidence of injury to the central nervous system."
-What was the primary symptom experienced by the patient with recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue?,"Recurrent adnexal torsion and cystadenoma of aberrant ovarian tissue. Torsion of the adnexa is rare, and diagnosis is difficult because of the sparse clinical findings. I describe a patient with recurrent torsion of the right adnexa, involving a cystadenoma of aberrant ovarian tissue. Her only symptom was recurrent right-sided pelvic pain."
-What is the effectiveness of optic nerve sheath decompression in treating patients with acute and chronic papilledema?,"Treatment of pseudotumor cerebri by primary and secondary optic nerve sheath decompression. We performed optic nerve sheath decompression in 53 patients (101 eyes) with pseudotumor cerebri and visual loss. Sixty-nine eyes (85 patients) with acute papilledema uniformly had improved visual function after optic nerve sheath decompression. Of 32 eyes with chronic papilledema (18 patients), only ten had improved visual function after optic nerve sheath decompression. This difference was significant (P = .0001). Thirteen eyes required secondary or tertiary optic nerve sheath decompression after an initial successful result. Eleven of 13 eyes had improved visual function after repeat optic nerve sheath decompression. We believe that patients with acute papilledema and visual loss should be offered optic nerve sheath decompression, and if symptoms recur, repeat optic nerve sheath decompression is a safe and effective treatment option."
-What was the main finding of the randomized trial comparing ticarcillin and clavulanate with gentamicin and clindamycin in patients with complicated appendicitis?,"A randomized trial of ticarcillin and clavulanate versus gentamicin and clindamycin in patients with complicated appendicitis. Secondary bacterial peritonitis is usually a polymicrobial infection of facultative gram-negative aerobic and anaerobic organisms. Treatment consists of operation and broad-spectrum antibiotic administration. The antibiotic treatment of choice in these infections has been the combination of gentamicin and clindamycin. However, this combination can have toxic side effects and necessitates frequent monitoring of serum levels. Beta-lactam antibiotics provide broad-spectrum coverage and low toxicity, but can be inactivated by species of bacteria producing beta-lactamase enzymes. Clavulanic acid is a potent inhibitor of beta-lactamases and has been shown to extend the efficacy of ticarcillin to bacteria producing these enzymes. This combination was compared with gentamicin and clindamycin in 99 consecutive patients with complicated appendicitis. Eradication of identified pathogens was greater in the ticarcillin and clavulanate group (98 per cent) than in the gentamicin and clindamycin group (92 per cent), even for the subgroup of organisms producing beta-lactamases (97 versus 90 per cent eradication). Complications and clinical response were not significantly different between the two treatment groups. Ticarcillin and clavulanic acid is a safe and effective alternative to gentamicin and clindamycin in the treatment of secondary bacterial peritonitis and offers advantages in dosing simplicity and freedom from ototoxic and nephrotoxic effects."
-What was the accuracy of fine needle aspiration cytologic procedures in diagnosing malignant mammary masses in this study?,"The accuracy of malignant diagnoses established by fine needle aspiration cytologic procedures of mammary masses. Fine needle aspiration cytologic studies are being used with increasing frequency to diagnose carcinoma of the breast. To determine whether or not a diagnosis of carcinoma established by cytologic examination is sufficiently accurate to proceed to treatment without tissue confirmation, we have examined our results in a series of 109 patients who had 111 aspiration cytologic procedures followed by open biopsy between January 1985 and June 1987. From this group, 39 specimens were read as malignant and 19 were read as suspicious. Thirty-eight of 39 specimens with positive readings were from lesions that proved to be malignant on subsequent open biopsy. Seventeen of 19 suspicious specimens were also from malignant lesions. Three of 17 specimens that were inadequate and nine of 36 negative specimens were from lesions that were later shown to be malignant. Our single false-positive result occurred on cells that had been air dried during preparation in the early months of experience with this technique at our institution. Re-evaluated later in our series, the same specimen was called suspicious rather than malignant. We conclude that a positive reading on fine needle aspiration is highly accurate. The positive predictive value should be 100 per cent, once experience is gained in preparing and interpreting the material. Open biopsy is necessary for inadequate, negative or suspicious specimens to exclude a malignant lesion if the clinical or mammographic findings are consistent with carcinoma."
-What is neurocutaneous melanosis and what are its key characteristics?,"Neurocutaneous melanosis: definition and review of the literature. Neurocutaneous melanosis is a rare congenital syndrome characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigment cell tumors of the leptomeninges. The syndrome is thought to represent an error in the morphogenesis of the embryonal neuroectoderm. We review 39 reported cases of neurocutaneous melanosis and propose revised criteria for diagnosis. Most patients with neurocutaneous melanosis presented in the first 2 years of life with neurologic manifestations of increased intracranial pressure, mass lesions, or spinal cord compression. Leptomeningeal melanoma was present in 62% of the cases, but even in the absence of melanoma, symptomatic neurocutaneous melanosis had an extremely poor prognosis. Useful diagnostic procedures include cerebrospinal fluid cytology and magnetic resonance imaging with gadolinium contrast. Patients may be aided by palliative measures such as shunt placement to reduce intracranial pressure. Dermatologists in their follow-up of patients with large or multiple congenital melanocytic nevi should be aware of this condition, to aid in prompt diagnosis and because the treatment of cutaneous lesions may be altered in the presence of symptomatic neurocutaneous melanosis."
-What is the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in treating pancreatic duct stones in patients with chronic calcifying pancreatitis?,"Extracorporeal shock wave lithotripsy of pancreatic duct stones. Chronic calcifying pancreatitis presents a major clinical problem, often requiring extensive surgery. Extracorporeal shock wave lithotripsy (ESWL) offers a new therapeutic option. We applied ESWL after endoscopic sphincterotomy of the pancreatic orifice in eight patients with impacted pancreatic duct stones. An electromagnetic lithotriptor (Siemens Lithostar, Erlangen, FRG) was used. Patients were treated in prone position under fluoroscopic control. A mean of 6,813 shock waves (range 1,500-10,000) was delivered in one or two sessions. Disintegration of stones was achieved in 6/8 patients, initial relief of pain in 7/8 patients, and total clearance of the pancreatic duct in 3/8 patients. One patient had an exacerbation of her pancreatitis one day after ESWL, which resolved rapidly with medical treatment. No other complications were observed. Four of five patients with fragmented stones had no abdominal complaints at follow-up (mean 17 months, range 3-27). Three patients in whom ESWL was not completely successful (two without and one with partial fragmentation) underwent an operation according to Puestow. Two of them still have abdominal complaints after surgery. From these data, we conclude that ESWL of pancreatic duct stones is a promising new alternative for surgery, when endoscopic stone extraction fails."
-What are the key characteristics of Superparamagnetic iron oxide (SPIO) particles in MR imaging of the liver and spleen?,"Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years. Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins."
-How does the polymerase chain reaction (PCR) method compare to viral isolation in detecting herpes simplex virus (HSV) in genital lesions?,"Extended duration of herpes simplex virus DNA in genital lesions detected by the polymerase chain reaction. To evaluate the utility of the polymerase chain reaction (PCR) for documenting herpes simplex virus (HSV) in persons with reactivated genital lesions viral isolation was compared with a recently developed PCR method. Three women experiencing four episodes of recurrent genital herpes were followed for 10 days per episode with daily examination and duplicate swabs of the lesions, one for HSV culture and one for PCR. HSV type 2 was cultured from three of four episodes and the mean duration of viral isolation from recurrent genital lesions was 2.6 days. PCR detected HSV DNA from lesion swabs during all four episodes, and HSV DNA was positive for an average of 6.8 days. HSV DNA was demonstrated in ulcerative lesions on 15 of 17 days versus 3 of 17 days by viral isolation (P less than .01). HSV PCR became negative when the lesions reepithelialized. These data suggest that PCR is a more sensitive measure of HSV infection than routine viral culture and that PCR detects the presence of HSV at times when culture is negative."
-"What combination of immunosuppressive drugs did the authors use to treat serpiginous choroiditis, and how effective was the treatment?","Triple agent immunosuppression in serpiginous choroiditis. Serpiginous choroidopathy is a progressive choroidal inflammatory disorder that typically has a variable saltatory course. Response to steroids is uncertain. By using azathioprine, cyclosporine, and prednisone in combination, the authors have observed rapid remission of active disease in five patients. Remissions have been maintained for periods up to 18 months. Because of the synergistic effects of this combination, doses could rapidly be reduced to maintenance levels without reactivation. Disease in two patients recurred immediately after discontinuation of low-dose therapy but was arrested when therapy resumed. Triple agent immunosuppressive therapy is well tolerated and appears to be effective."
-How does hypertension affect the expression of platelet-derived growth factor (PDGF) receptors in rat aorta and heart?,"Hypertension-induced changes of platelet-derived growth factor receptor expression in rat aorta and heart. Hypertension-associated growth of vascular smooth muscle cells might be mediated in vivo by platelet-derived growth factor (PDGF). Our previous investigations in hypertensive rats failed to demonstrate changes in aortic steady-state mRNA levels of PDGF A or B chains. The current studies were performed to determine whether hypertension might affect the expression of PDGF receptors. We studied PDGF alpha- and beta-receptor gene expression by Northern analysis using human and rat cDNA probes. Studies of tissue distribution revealed that PDGF beta-receptor mRNA was most abundant in total aorta and aortic media, whereas the PDGF alpha-receptor mRNA was most abundant in the lung and was expressed at low levels in aortic tissue. Deoxycorticosterone acetate (DOCA)-salt hypertension induced a threefold increase in aortic steady-state PDGF beta-receptor mRNA levels. Aortic PDGF beta-receptor expression also was higher in spontaneously hypertensive rats (SHRs) when compared with age-matched normotensive Wistar-Kyoto (WKY) controls. Aortic PDGF alpha-receptor steady-state mRNA levels were unchanged in DOCA-salt hypertension and were expressed at similar levels in WKY rats and SHRs. Unlike the findings with aorta, cardiac PDGF beta- and alpha-receptor and PDGF B-chain expressions were unchanged in the DOCA-salt model and were decreased in SHRs. These findings indicate that hypertension can increase aortic steady-state mRNA levels for PDGF beta-receptor. They also indicate that tissue-specific expression of the genes of the PDGF ligand/receptor system are differentially regulated in hypertension."
-What is the purpose of subglottic laryngeal closure in patients with severe neurological disease?,"Subglottic laryngeal closure for aspiration. Aspiration may be life threatening, particularly in those patients with severe central neurological disease. From such a group of patients, several were identified who had severe laryngeal dysfunction and aspiration. The majority of patients in this subgroup existed in a neurologically vegetative state. In an attempt to reduce the degree of aspiration they experienced, the procedure of subglottic laryngeal closure was performed. Essentially, the operation is designed to isolate the tracheal airway from the incompetent larynx. The aim is to protect the lower airway from pharyngeal contamination. In all 5 patients there was a marked improvement in general and pulmonary health."
-What is the most effective and safest form of anesthesia for newborn circumcision according to the context?,"Pain in neonatal circumcision. Because newborn circumcision is a quick and safe surgical procedure, any method to relieve pain must be almost risk-free in order to be acceptable. General anesthesia and narcotic analgesia are not appropriate. Dorsal penile nerve block (DPNB) with lidocaine hydrochloride is probably the most effective and safest form of anesthesia for newborn circumcision currently available, but it can cause significant local and systemic reactions. Only a limited number of cases of DPNB have been reported and we feel that this procedure should be used cautiously until there is more published evidence of its safety. Alternative methods of pain relief including oral acetaminophen and topical anesthesia should also be studied. Of special interest is recent evidence that a sucrose-flavored pacifier is an effective analgesic during newborn circumcision."
-What are the key differences between pre-T and thymic acute lymphoblastic leukaemia (ALL) in terms of immunological features and clinical characteristics?,"Heterogeneity of T cell lymphoblastic leukaemias. Twenty eight out of 170 consecutive cases of acute lymphoblastic leukaemia (ALL) were examined. They were of T cell origin, with the following distribution: seven (28%) cases had pre-T or prothymic features; nine (36%) cases showed early thymocytic features, six (24%) had cortical features; and three (12%) had a ""mature"" phenotype. The remaining three cases could not be sub-classified. A striking finding was that pre-T ALL differed from intrathymic ALL not only in the absence of both E rosettes and intrathymic differentiation antigens, but also in the expression of two non-lineage specific antigens HLA-DR and CD10. Both antigens appear in the bone marrow from the very first stages of lymphoid differentiation, implying that the origin for pre-T ALL is bone marrow. A comparison of the clinical features of pre-T and thymic ALL showed that pre-T ALL disease showed a pattern more similar to non-T ALL disease: a lower incidence of mediastinal mass, absence of extrahaematopoietic disease, lower white cell counts and haemoglobin concentrations, and a higher incidence of bone pain. No obvious difference in response to treatment was apparent. The results show that T-ALL is not only a heterogeneous immunological group but also suggest that it may have different origins: bone marrow for pre-T ALL and the thymus for thymic ALL."
-What is the new provocative test described for chronic mesenteric ischemia?,"A new provocative test for chronic mesenteric ischemia. A new provocative test for chronic mesenteric ischemia is described, based upon the demonstration of a fall in the intramural pH of the small bowel after introduction of a test meal into the stomach. Intramural pH (pHI) is determined indirectly by tonometry, utilizing a tonometer passed per os. Postoperative assessment of revascularization procedures is also possible by the same technique. Application of the test in an 84-yr-old woman showed good correlation between a preoperative fall in jejunal intramural pH and abdominal pain, and the absence of a fall postoperatively after successful revascularization."
-How does the expression of the human HLA-B27 transgene affect susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination in different mouse haplotypes?,"Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination. Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse."
-What is the significance of ventricular arrhythmias in children with a structurally normal heart?,"Ventricular arrhythmias in children with an apparently normal heart. Ventricular ectopy occurs frequently in normal children. In the presence of a normal heart, these arrhythmias, including asymptomatic, nonsustained ventricular tachycardia, carry a benign prognosis and are not associated with sudden, unexpected death. However, complex ventricular arrhythmias frequently indicate the presence of underlying cardiac disease; patients with such arrhythmias must undergo an appropriately thorough evaluation before decisions regarding prognosis and the need for therapy can be made."
-What is the significance of detecting fetal seizure activity during ultrasound?,Does fetal seizure activity mean a poor outcome? A case report. Fetal seizure activity is very rare: only three cases have been reported. A case of fetal seizure activity was detected with ultrasound. Such activity can be associated with a poor outcome.
-How does the carbon-14-urea breath test help in quantifying Helicobacter pylori infection and assessing gastritis severity?,"Quantification of Helicobacter pylori infection in gastritis and ulcer disease using a simple and rapid carbon-14-urea breath test. Gastric urease was studied isotopically in 230 patients with biopsy-proven normal mucosa or chronic gastritis, including 59 patients with ulcer disease. Carbon-14-urea was given in 25 ml of water without substrate carrier or nutrient-dense meal, and breath samples were collected over a 60-min period. The amount of 14CO2 excreted at 10 min was independent of the rate of gastric emptying and was not quantitatively influenced by the buccal urease activity. The 10-min 14CO2 values discriminated well between Helicobacter pylori positive and negative patients (94% sensitivity, 89% specificity) and correlated with the number of organisms assessed by histology. The test was a good predictor of chronic gastritis (95% sensitivity and 96% specificity), and a quantitative relationship was observed between 14CO2 values and the severity and activity of the gastritis. In H. pylori positive patients, breath 14CO2 was found to be similar in patients with and without ulcer disease, suggesting that the number of bacteria is not a determining factor for the onset of ulceration."
-"How does the presence of HCV RNA in serum relate to the progression of non-A, non-B hepatitis?","A long-term study of hepatitis C virus replication in non-A, non-B hepatitis. BACKGROUND. Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis. METHODS. We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 10 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a ""nested"" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome. RESULTS. HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease. CONCLUSIONS. During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease."
-What are the key symptoms and characteristics of acute narrow-angle glaucoma as described in this case report?,"Narrow-angle glaucoma presenting as acute, painless visual impairment. A 42-year-old woman presented with the acute onset of bilateral blurred vision that occurred immediately after bending over. She denied pain or any other associated symptoms. Markedly increased intraocular pressure readings were found. Treatment for acute narrow-angle glaucoma was initiated, and normal vision returned. This case represents an atypical presentation of acute narrow-angle glaucoma, a true ophthalmological emergency. The pathophysiology and treatment options of this disease process are summarized."
-What is the sensitivity of thallium-201 single-photon emission computed tomography during adenosine-induced coronary hyperemia for diagnosing coronary artery disease?,"Assessment of coronary artery disease using single-photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia. Thallium-201 myocardial imaging during dipyridamole-induced coronary hyperemia has been an accepted method for diagnosing coronary artery disease (CAD) and risk stratification. Adenosine is a powerful short-acting coronary vasodilator. Initial results of thallium imaging during adenosine infusion have been encouraging. In 132 patients with CAD and in 16 patients with normal coronary angiograms, adenosine was given intravenously at a dose of 0.14 mg/kg/min for 6 minutes and thallium-201 was injected at 3 minutes. The thallium images using single-photon emission computed tomography were abnormal in 47 of the 54 patients (87%) with 1-vessel, in 34 of 37 patients (92%) with 2-vessel and in 40 of 41 patients (98%) with 3-vessel CAD. The sensitivity was 92% in the 132 patients with CAD (95% confidence intervals, 86 to 96%). In patients with normal coronary angiograms, 14 of 16 patients had normal thallium images (specificity, 88%; 95% confidence intervals, 59 to 100%). The results were very similar when subgroups of patients were analyzed: those without prior myocardial infarction, elderly patients and women. The nature of the perfusion defects (fixed or reversible) was assessed in relation to whether the 4-hour delayed images were obtained with or without the reinjection technique. In patients who underwent conventional delayed imaging, there were more fixed perfusion defects than in patients with reinjection delayed imaging (16 vs 0%, p less than 0.0001). The adverse effects were mild, transient and well tolerated. Thus, adenosine thallium tomographic imaging provides a high degree of accuracy in the diagnosis of CAD. The use of the reinjection technique enhances the ability to detect reversible defects."
-What is the significance of the malignant schwannoma found in this xeroderma pigmentosum patient?,"Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D. A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum."
-How does adenosine affect pulmonary vascular resistance in patients with primary pulmonary hypertension?,"Adenosine as a vasodilator in primary pulmonary hypertension BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension."
-How did the study assess the reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses between two different echocardiography centers?,"Reproducibility of Doppler echocardiographic quantification of aortic and mitral valve stenoses: comparison between two echocardiography centers. Doppler echocardiography has been widely used as a noninvasive method to quantify valvular heart diseases. This study assessed the variability between 2 echocardiography centers concerning 2-dimensional and Doppler echocardiographic results in the quantification of mitral and aortic valve stenoses. Forty-two patients were studied by 2 different echocardiography centers in a blinded, independent fashion. In patients with aortic and mitral valve stenosis, mean and maximal flow velocities were measured. The aortic valve orifice area was calculated according to the continuity equation. Mitral valve orifice area was determined by direct planimetry and by pressure half-time. In patients with an aortic valve stenosis, a close relation between the 2 centers was found for the maximal and mean flow velocities (coefficient of correlation, r = 0.72 to 0.92; coefficient of variation, 3.7 to 7.7%). A close correlation and a small observer variability was found for the flow velocity ratio determined by flow velocities measured in the left ventricular outflow tract and over the stenotic valve (r = 0.88; coefficient of variation, 0.01 +/- 0.009). In contrast, there was a poor correlation between the diameter of the left ventricular outflow tract and the aortic orifice area (r = 0.36 and 0.59, respectively). In patients with a mitral valve stenosis, mean and maximal velocities were closely correlated (r = 0.85 and 0.77, respectively). Velocities were not found to be significantly different between the 2 centers. Variability between the 2 centers for the mitral valve orifice area was 9.8% (2-dimensional echocardiography) and 5.7% (pressure half-time)."
-How do the hypercarbic ventilatory responses (HCVR) of heart-lung transplant recipients compare to those of normal control subjects?,"Hypercarbic ventilatory responses of human heart-lung transplant recipients. To evaluate the effects of chronic pulmonary denervation on ventilatory control, we compared the hypercarbic ventilatory responses (HCVR) of 12 human heart-lung transplant recipients (HL) and 24 normal control subjects (C). The six male HL were subsequently compared with eight male heart transplant recipients (H), as well as the 12 male C. All subjects had normal spirometry, but lung volumes of both transplant groups were somewhat less than those of C. The HCVR of HL and C were indistinguishable (2.68 +/- 0.28 versus 2.71 +/- 0.22 L/min/mm Hg, respectively). The increment of mouth occlusion pressure (delta Pm0.1/delta CO2), however, was markedly greater in HL (P much less than 0.01). The three male groups also had equivalent HCVR, and again, the HL had an increased delta Pm0.1/delta CO2. HL men exhibited larger increments of VT and decreased frequency responses during CO2 rebreathing than did male C and H, although these differences were statistically significant only in the comparison between the transplant groups. We conclude that HL with normal spirometry have appropriate HCVR, despite pulmonary denervation. Pm0.1 responses of these subjects are increased, however, reflecting either a compensatory response to greater respiratory impedances or an occult alteration of ventilatory mechanics. Moreover, compared with subjects with similar pulmonary function, e.g., heart transplant recipients, the breathing pattern of HL during progressive hypercarbia is consistent with the absence of vagal-mediated inflation inhibition."
-What was the initial presentation of the 10-year-old boy that led to the discovery of his obstructive sleep apnea syndrome?,"Antral choanal polyp presenting as obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome (OSAS) in children is commonly caused by adenotonsillar hypertrophy. The diagnostic criteria of OSAS in children are not so well delineated as in adults. We report the first case of antral choanal polyp presenting as OSAS in a 10-year-old boy that initially presented to the child psychiatry service for behavior disturbance, enuresis, and daytime somnolence. Overnight electroencephalogram sleep study revealed events consistent with OSAS. Multiple inhalant allergies, chronic maxillary sinusitis, and obstructive adenoid hypertrophy were diagnosed by the allergy and otolaryngology services. The child was scheduled for adenoidectomy when his sleep apnea symptoms persisted following antimicrobial therapy. Examination under anesthesia revealed a normal adenoid bed and a large left antral choanal polyp. Polypectomy was performed as dictated by parental consent. Postoperatively treatment with an intranasal steroid was begun. However, polypoid nasal mucosa recurred in 2 months and a Caldwell-Luc procedure was performed. Subjective reports following surgery indicated improvement in daytime irritability, attention, and mood. A follow-up overnight electroencephalogram sleep study confirmed resolution of OSAS."
-What percentage of leukemic children in the study were persistently positive for anti-HCV antibodies?,"Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Antibody to the recently identified hepatitis C virus (HCV) was investigated in sera of 50 leukemic children who had chronic liver disease (CLD), observed for 1 to 12.6 years after therapy withdrawal. All patients were tested for anti-HCV at regular intervals: Ortho-enzyme-linked immunosorbent assay (ELISA) test was performed in all cases. Reactive sera were also tested by recombinant immunoblotting assay to define the specificity of the results obtained by ELISA. Twelve cases (24%) were persistently positive (group A), 11 (22%) were transiently anti-HCV+ positive (group B), and 27 (54%) were negative. Mean SGPT peak during follow-up was significantly higher in group A (P = .014, A v B and P less than .00001, A v C). SGPT normalized off-therapy in 1 of 12 cases (group A), 10 of 11 (group B), and 19 of 27 (group C) (P = .0004, A v B and P = .012, A v C). Accordingly, liver histology, available in 37 patients, showed signs of chronic hepatitis in all patients in group A while most patients in group B and C had less severe liver lesions. These results indicate that HCV plays a significant role in the etiology of chronic hepatitis in leukemic patients and that persistent anti-HCV activity correlates with a more severe CLD, which could jeopardize the final prognosis of children cured of leukemia."
-What is the significance of fatty infiltration in the liver for diagnosing medium chain acyl CoA dehydrogenase deficiency?,Fatty infiltration in the liver in medium chain acyl CoA dehydrogenase deficiency. Fatty infiltration of the liver at postmortem examination has been recommended as a criterion for selection of infants who have died suddenly and unexpectedly for further biochemical investigation for disorders of fatty acid oxidation. We describe a boy with medium chain acyl CoA dehydrogenase deficiency who died four months after diagnosis and in whom only minimal hepatic fatty infiltration was found.
-How does the DNA ploidy pattern relate to tumor cell aggregation and metastasis in poorly differentiated stomach adenocarcinoma?,"Nuclear DNA content, tumor cell aggregation, and metastatic events in patients with poorly differentiated adenocarcinoma of the stomach. Data on 100 patients who had undergone resection for poorly differentiated adenocarcinoma of the stomach with serosal invasion were examined to assess the prognostic significance of the DNA distribution pattern in relation to the histologic tumor cell aggregation pattern. DNA distribution patterns were classified into low and high ploidies and tumor cell aggregation patterns were classified into free-cell, small nest, and large nest types. The rates of high ploidy in the free-cell, small nest, and large nest types were 23.1%, 48.0%, and 66.7%, respectively, with a significant increase according to the degree of aggregation. The high ploidy group and large nest type had a higher incidence of lymphogenous and hematogenous metastasis than the low ploidy group and free-cell type, respectively. DNA ploidy had no prognostic value for the free-cell type of tumor, but differences in prognosis and the incidence of metastasis between the DNA ploidies were evident in the nest-forming type. Aneuploid tumors consisting of a poorly differentiated adenocarcinoma were those with nest formation, from the standpoint of histologic structure and metastatic behavior. The DNA analysis of poorly differentiated adenocarcinomas was of prognostic value, especially in the nest-forming type."
-What was the peak level of interferon-gamma detected in urine samples after intravesical BCG therapy?,"Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy Our previous studies suggested that interferon-gamma (IFN gamma) was produced in the local immune response to intravesical BCG. To confirm this we modified a commercially available radio-immunoassay for detection of this lymphokine in urine. The urinary levels of IFN gamma were compared in serial urine samples taken from six patients undergoing treatment with Evans strain BCG and seven patients receiving intravesical mitomycin C/epirubicin. IFN gamma was detected consistently in response to BCG with levels reaching a peak (mean 67.1 U/ml., range 7.9 to 155.9 U/ml.) four to six hours post-instillation whereas after other intravesical agents no IFN gamma was detectable after seven of 13 instillations. After the remaining six instillations lower levels were detected (mean 7.4 U/ml., range 0.6 to 22.4 U/ml.). The difference in peak levels between the two groups was statistically significant (p less than 0.001 Mann Whitney U test). These results are further evidence of specific cellular immune activity in response to intravesical BCG therapy and suggest anti-tumour mechanisms similar to allograft rejection and autoimmunity."
-What is asymptomatic bacterascites and how does it differ from spontaneous bacterial peritonitis?,"Asymptomatic bacterascites: is it spontaneous bacterial peritonitis? Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required."
-What was the main objective of the study conducted by the National Heart Foundation of Australia Coronary Thrombolysis Group?,"A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group. BACKGROUND. This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS. A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS. We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function."
-What is the potential primary treatment for patients with detrusor sphincter dyssynergia and failed sphincterotomy according to the study?,"Permanent urethral stents for detrusor sphincter dyssynergia. A series of 22 patients, most of whom had spinal injuries with detrusor sphincter dyssynergia, have had Medinvent Wallstents placed across the distal mechanism. All but 8 patients had undergone outflow surgery and 11 had had repeated unsuccessful sphincterotomies. The proximal end of the stent was placed over the verumontanum unless fertility was contemplated, when it was placed immediately below the verumontanum. Fifteen patients achieved complete voiding after placement of the first stent; 3 developed bladder neck obstruction after stenting, but in 1 of these cases resolution occurred after bladder neck incision. The 3 patients with artificial urinary sphincters failed to improve after stenting. Use of the urethral stent for patients with detrusor sphincter dyssynergia and failed sphincterotomy is a major advance. It should probably be the primary treatment in selected cases. Its effect on fertility is currently under assessment."
-How does the Tax protein of HTLV-I contribute to cellular transformation through transcription factor pathways?,"Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway. The Tax oncoprotein of the type I human T cell leukemia virus (HTLV-I) activates transcription of cellular and viral genes through at least two different transcription factor pathways. Tax activates transcription of the c-fos proto-oncogene by a mechanism that appears to involve members of the cAMP response element binding protein (CREB) and activating transcription factor (ATF) family of DNA-binding proteins. Tax also induces the nuclear expression of the NF-kappa B family of rel oncogene-related enhancer-binding proteins. We have investigated the potential role of these CREB/ATF and NF-kappa B/Rel transcription factors in Tax-mediated transformation by analyzing the oncogenic potential of Tax mutants that functionally segregate these two pathways of transactivation. Rat fibroblasts (Rat2) stably expressing either the wild-type Tax protein or a Tax mutant selectively deficient in the ability to induce NF-kappa B/Rel demonstrated marked changes in morphology and growth characteristics including the ability to form tumors in athymic mice. In contrast, Rat2 cells stably expressing a Tax mutant selectively deficient in the ability to activate transcription through CREB/ATF demonstrated no detectable changes in morphology or growth characteristics. These results suggest that transcriptional activation through the CREB/ATF pathway may play an important role in Tax-mediated cellular transformation."
-What unusual complication occurred during the sinography of a pancreatic pseudocyst in the described case?,"Drainage of a pancreatic pseudocyst: an unusual complication. A 34-year-old white woman had external drainage of a pancreatic pseudocyst. During sinography, contrast medium filled perigastric varices, causing septic shock. From this experience, we believe that although sinograms are helpful, they should be preceded by prophylactic administration of antibiotics and that contrast material should be sterile. The drainage catheter should be removed as soon as possible."
-What was the most commonly affected test of lung function in patients with advanced liver disease?,"Pulmonary dysfunction in advanced liver disease: frequent occurrence of an abnormal diffusing capacity. PURPOSE: Abnormalities in pulmonary function have been reported in association with chronic liver disease of varied etiology. The aim of this study was to better define the frequency and nature of these abnormalities in patients who were being evaluated for liver transplantation. PATIENTS AND METHODS: We performed a battery of pulmonary function tests and chest radiographs in 116 consecutive patients (50 men, 66 women; aged 19 to 70 years, mean 44.6 years) with severe advanced liver disease who were hospitalized specifically for evaluation for possible orthotopic liver transplantation and were able to perform technically satisfactory tests. In 17 patients, quantitative whole-body technetium-99m macroaggregated albumin perfusion scanning was also performed for assessment of possible right-to-left shunting through intrapulmonary vascular dilatations. RESULTS: The most commonly affected test of lung function was the single-breath diffusing capacity for carbon monoxide (DLCO), which was abnormal in 48%, 45%, and 71% of patients who never smoked, former smokers, and current smokers, respectively. Ventilatory restriction was noted in 25% of all patients, airflow obstruction (reduced ratio of forced expiratory volume in 1 second to forced vital expiratory volume in 1 second to forced vital capacity) in only 3%, and a widened alveolar-arterial oxygen gradient in 45%. Diffusion impairment was accompanied by a restrictive defect in only 35% of the patients and by an abnormally widened alveolar-arterial oxygen gradient in 60%. When diffusion impairment was accompanied by an oxygenation defect, it was also associated with a significantly increased right-to-left shunt fraction (mean 24.9%) assessed from quantitative whole-body perfusion imaging. On the other hand, isolated diffusion impairment unaccompanied by significant hypoxemia (noted in approximately a third of the patients with a reduced DLCO) was not associated with evidence of significant intrapulmonary shunting (mean right-to-left shunt fraction 6.7%). CONCLUSIONS: Most patients with advanced liver disease have one or more types of abnormality in lung function, a reduced DLCO being the single most common functional defect. Mechanisms accounting for the abnormality in gas transfer may include intrapulmonary vascular dilatations, diffuse interstitial lung disease, pulmonary vaso-occlusive disease, and/or ventilation-perfusion imbalance."
-What were the key findings comparing hand-sewn and stapled anastomosis techniques in oesophageal surgeries?,"Comparison of a single layer continuous hand-sewn method and circular stapling in 580 oesophageal anastomoses. A total of 611 patients with carcinoma of the oesophagus or gastric cardia were operated on between July 1982 and December 1989. Resection was performed in 491 patients (one-stage, 483; two-stage, eight), bypass operation in 97, and 23 had exploration alone. The anastomoses of 580 patients with one-stage resection and bypass operations were evaluated. Hand-sewn anastomosis using a single layer of continuous absorbable monofilament suture was performed in 304 patients (221 resections and 83 bypasses). A stapled anastomosis was performed on 276 patients (262 resections and 14 bypasses). Following resection, there were 11 (5 per cent) anastomotic leaks in the hand-sewn group and ten (3.8 per cent) in the stapled anastomosis group (P = 0.69). Excluding anastomotic leaks, hospital mortality and anastomotic recurrence, stricture occurred in 18 of 172 hand-sewn anastomoses (10.5 per cent) and in 57 of 195 stapled anastomoses (29.2 per cent) (P less than 0.001). In patients who had bypass operations there were 12 anastomotic leaks, ten in the hand-sewn group (12.0 per cent) and two in the stapled anastomosis group (14.3 per cent). Only two of the discharged patients with bypass developed anastomotic strictures, a low incidence probably because of short survival. In addition, there were 245 subsidiary anastomoses made in the abdomen by the hand-sewn method as part of the reconstructive procedure, and there was one leak. The results of this non-randomized study suggest that hand-sewn anastomosis using a single layer continuous technique for the oesophagus is as safe as the use of circular staplers; hand-sewn anastomosis is less likely to become stenotic."
-What makes it important to distinguish between general fatigue and depression-related fatigue in cancer patients?,"Depression and chronic fatigue in cancer patients. Fatigue is a very common symptom among cancer patients. It is crucial to diagnose those patients for whom the fatigue is a symptom of depression, and to treat them appropriately. The key to providing complete and satisfying care is to identify and address the psychologic, social, and medical vulnerabilities of each cancer patient. No one is in a better position to accomplish that than the primary physician."
-What are the potential hepatic vascular lesions associated with azathioprine-induced liver disease?,"Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis. Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present."
-What was the purpose of the study on intradermal hepatitis B vaccine administration?,"The immunogenicity and safety of intradermal hepatitis B vaccine. BACKGROUND. One of the chief barriers to a greater use of hepatitis B vaccine is the high cost of the vaccine itself. A number of small research trials have shown that an adequate immune response can be induced at a much lower cost by administering one tenth of the vaccine using an intradermal technique. The purpose of this study was to ascertain whether these results could be replicated in a larger clinical trial. METHODS. Vaccine recipients included health care providers, police officers, and firefighters. Recipients were given 0.1 mL of plasma-derived hepatitis B vaccine intradermally on days 1, 30, and 180. Antibody response was measured on day 210, with seroconversion defined as a sample-to-negative (S/N) ratio of greater than or equal to 10. Any local and systemic side effects were documented. RESULTS. Six hundred sixteen individuals completed the vaccination series, and seroconversion occurred in 534 (86.7%). The rate of seroconversion in those younger than 40 years was 91.2% and in those 40 years and older was 75.1%. The mean S/N ratio was 154.9 (range 0 to 620) and decreased with increasing age (r = -.25, P = .0001). Side effects were largely limited to local reactions. CONCLUSIONS. The results support the use of the intradermal technique as a cost-effective alternative to the intramuscular route in individuals younger than 40 years. The intradermal technique may be used in older individuals if titers are obtained to assure seroconversion. Because of the restricted availability of the plasma-derived vaccine used in this study, similar trials with recombinant vaccine should be undertaken."
-What trends were observed in the occurrence of hemorrhoids in the United States and England based on the study's analysis?,"Temporal changes in the occurrence of hemorrhoids in the United States and England. Although numerous etiologic risk factors have been proposed, the pathogenesis of hemorrhoids remains unknown. The present investigation assesses the temporal distribution of hemorrhoids as depicted by physician visits, hospital discharges, and surgical procedures to provide further insight into potential etiologic risk factors. The analysis was based on five data sources: from the United States, the National Disease and Therapeutic Index (NDTI), the National Hospital Discharge Survey (NHDS), and the Commission on Professional Hospital Activities (CPHA); from England and Wales, the Morbidity Statistics from General Practice (MSGP) and the Hospital In-patient Enquiry (HIPE). Results demonstrated a consistent decline in all data sources from the United States. The decrease occurred in males and females similarly and was most striking in those aged 45-64 years. Physician visits and hospital discharges for hemorrhoids in England and Wales likewise declined although the decrease was not as dramatic. The consistency of the temporal distributions among the two countries, as well as among the different sources, suggests that the observed decline may, in fact, reflect an overall decrease in the occurrence of hemorrhoidal disease."
-What was the main finding of this study regarding kidney protection during aortoiliac surgery in renal transplant patients?,"Aortoiliac surgery in renal transplant patients. Fifteen patients who had undergone renal transplantation 3 months to 25 years earlier were operated on for treatment of complicated aortoiliac atherosclerosis; eight had aneurysms and seven had stenotic or obstructive lesions. Except for the first patient, operated on in 1973, in whom the kidney was protected by general hypothermia, no special measure was used to protect the kidneys. A transient increase in creatinemia occurred in 11 patients during the postoperative period, whereas creatinine values remained unchanged in the other four. All patients had regained renal function identical to the + preoperative state in less than 10 days; three of them had significant improvement as a result of correction of a lesion that was impairing renal blood flow. Results obtained in this series show that protection of the transplant during aortic surgery is not necessary, provided an adequate surgical technique is used. This technique avoids the complex methods employed in the majority of previously reported cases and appears to be a safe procedure."
-Why are baboons considered advantageous for experimental studies of vascular disease and thrombosis?,"Experimental arterial thrombosis in nonhuman primates. The baboon offers many advantages as an experimental animal to study vascular disease, thrombus formation and dissolution, effects of mediating variables, and the relative efficacy of therapeutic interventions. Each specific application for testing therapeutic agents may require testing in somewhat different model systems. For example, although the arteriovenous vascular graft model is efficient, cost effective, and well adapted to study of interventions for acute arterial thrombosis, surgical endarterectomy extends the evaluation to include interactions with the injured vascular wall. As the antithrombotic products of genetic engineering and molecular biology emerge, it will be increasingly important to have relevant, reproducible, and quantitative approaches to evaluate their effects in vivo."
-What was the purpose of screening the expression cDNA library from the human melanoma cell line A375 with sera from melanoma patients?,"Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. The purpose of this study was to identify human melanoma-associated Ag (MAA) that are immunogenic in patients, because these molecules may be useful immunogens to implement active specific immunotherapy. To this end, an expression cDNA library constructed from the human melanoma cell line A375 was screened with sera from patients with melanoma. A 1029-bp cDNA (designated D-1) was isolated. Its nucleotide sequence showed no significant homology with viral and mammalian sequences stored in GE-NETYX. cDNA D-1 hybridized to a 2.0-kb mRNA species from human melanoma, neuroblastoma, erythroleukemia, B lymphoid, and T lymphoid cell lines but not from a renal carcinoma cell line, PBL, and cultured skin fibroblasts. The D-1 clone produced a fusion protein that displayed a significantly higher reactivity with sera from patients with melanoma than from healthy controls. Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells. The structural properties of D-1 MAA are different from those of previously described MAA. These results suggest that the approach we have applied may be useful to identify novel MAA expressed by melanoma cells. Furthermore, the immunogenicity of recombinant D-1 protein suggests that it may be a valuable immunogen to implement active specific immunotherapy in patients with melanoma, if additional experiments show that it has the appropriate tissue distribution."
-What were the key differences between the standard approach and the integrated approach in treating chronic pelvic pain in this clinical trial?,"A randomized clinical trial to compare two different approaches in women with chronic pelvic pain. One hundred six patients with chronic pelvic pain were randomly allocated to one of two treatment groups. In the standard-approach group, organic causes of pelvic pain were excluded first and diagnostic laparoscopy was routinely performed. If no somatic cause could be found, attention was given to other causes such as psychological disturbances. In the second group an integrated approach was chosen. From the beginning equal attention was devoted to somatic, psychological, dietary, environmental, and physiotherapeutic factors. In this group, laparoscopy was not routinely performed. Both groups were similar with respect to clinical characteristics of the patients and the severity of their pain as assessed by various pain parameters. Postcoital pain was reported by 27% of the patients. Twenty percent of the patients had had negative sexual experiences such as childhood sexual abuse or rape. Evaluation of the pain 1 year after the institution of treatment revealed that the integrated approach improved pelvic pain significantly more often than the standard approach for three out of four pain parameters (P less than .01). Laparoscopy played no important role in the treatment of pelvic pain. It is concluded that equal attention to both organic and other causative factors from the beginning of therapy is more likely to result in a reduction of pelvic pain than is a standard approach."
-What is the definition of multivessel disease in the context of this study?,"Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Results of recent studies have suggested that routine cardiac catheterization may be unnecessary after reperfusion therapy for acute myocardial infarction. Therefore to better define the short-term prognostic value of early coronary angiography, and specifically the prognostic significance of multivessel coronary artery disease, the angiographic findings of 855 patients consecutively enrolled in five phases of the TAMI study were correlated with their in-hospital outcome. All patients received intravenous thrombolytic therapy (tissue plasminogen activator, urokinase, or both agents) and underwent cardiac catheterization within 90 minutes of the initiation of therapy. Multivessel disease, defined as the presence of greater than or equal to 75% luminal diameter stenosis in two or more major epicardial arteries, was documented in 236 patients. When compared with the group of patients without multivessel disease, this group had a higher prevalence of coronary risk factors and more frequently had a history of antecedent ischemic chest pain. Although the severity of the infarct zone dysfunction was similar in the two groups (-2.77 +/- 1.00 vs -2.50 +/- 1.09 SD/chord, p = NS), global left ventricular ejection fraction was lower in the group with multivessel disease (48.6 +/- 12.4% vs 51.8 +/- 10.6%, p less than 0.01). This was associated with a significant difference in the function of the noninfarct zone. Whereas this region was hyperkinetic in the group with minimal or single-vessel disease, it was hypocontractile or dyskinetic in those with multivessel disease (+0.66 +/- 1.53 vs -0.52 +/- 1.73 SD/chord, p = 0.0001)."
-How does magnetic resonance imaging (MRI) help in managing diabetic foot infections?,"Impact of magnetic resonance imaging on the management of diabetic foot infections. This combined retrospective/prospective study evaluated the value of magnetic resonance imaging (MRI) in 18 diabetic patients with apparent foot infections. The goal was to define the impact of MRI on directing the expedient and accurate surgical intervention so important in achieving optimal preservation of limb tissue and function. We found that MRI provides a rapid and reliable means of ""viewing"" the diabetic foot. Unsuspected or poorly localized abscess cavities can be pinpointed for thorough drainage with minimal exploration. An abscess can be differentiated from cellulitis or osteomyelitis. Moreover, persistent fever following drainage of a foot abscess can be reliably evaluated via MRI, obviating the need for empiric surgical reexploration. This exciting noninvasive imaging technique leads to the most accurate surgical drainage of foot abscesses and, at the same time, can prevent unnecessary surgical exploration of the tenuous diabetic foot."
-How do posttranscriptional mechanisms contribute to protein increase during renal compensatory growth?,"Regulation of gene expression in renal compensatory growth. Compensatory renal hypertrophy is characterized by an increase in cell protein content. There are a number of different cellular mechanisms by which such an increase could be mediated. The relative contributions of transcriptional and posttranscriptional regulation of gene expression to the increase in constitutively expressed cellular proteins were examined in mouse kidneys undergoing compensatory growth following unilateral nephrectomy (UNI-NX). Over the 14-day study period, total protein per kidney increased by up to 37%. Northern blot analysis of the expression of the mRNAs for a number of genes associated with cell growth indicated that there was no significant increase in steady-state levels of these selected genes in nephrectomized compared with sham-operated animals. In vitro assays to measure transcriptional regulation of the same set of genes in compensatory growth showed no increase in the rate of transcription. However, transcription of the 18S ribosomal RNA gene was increased 24 hours after nephrectomy. Immunoblots of two representative proteins showed that the concentration of these proteins in total kidney protein remained constant in the different experimental groups. Since total protein increased, the concentration of these proteins in the hypertrophied kidney must have increased. Taken together, these data suggest that posttranscriptional mechanisms may account for the increase in at least some constitutively expressed proteins in cells undergoing compensatory growth."
-How does hydralazine prevent nitroglycerin-induced hemodynamic tolerance in experimental heart failure?,"Concurrent hydralazine administration prevents nitroglycerin-induced hemodynamic tolerance in experimental heart failure. BACKGROUND. Organic nitrates such as nitroglycerin and isosorbide dinitrate are useful in the treatment of congestive heart failure (CHF), but tolerance develops rapidly during continuous administration. Because combination therapy of nitrate and hydralazine has been shown to provide both short- and long-term benefit but nitrate alone produces hemodynamic tolerance, we questioned whether hydralazine can preserve the favorable preload effects of nitroglycerin. METHODS AND RESULTS. Using an in vivo model of nitroglycerin tolerance in the CHF rat, we examined the effects of hydralazine bolus dosing during continuous nitroglycerin infusion. Continuous infusion of nitroglycerin alone (10 micrograms/min) produced initial reductions in left ventricular end-diastolic pressure of 40-50%, which returned to baseline by 8 hours (tolerance development). Coadministration of hydralazine (2 x 0.1 mg) maintained the effects of nitroglycerin infusion on left ventricular end-diastolic pressure (45% reduction at 10 hours). This hydralazine dose alone reduced left ventricular peak systolic pressure by approximately 12 +/- 3% but had no effect on left ventricular end-diastolic pressure. Hydralazine dosing did not affect steady-state plasma concentrations of nitroglycerin or metabolites, and hydralazine was unable to prevent nitroglycerin tolerance induced in vitro. CONCLUSIONS. The beneficial interaction of hydralazine on the preload effects of nitroglycerin may explain the long-term clinical efficacy of hydralazine/nitrate combination in CHF. Our results also suggest that the mechanism of in vivo nitrate tolerance in CHF may be systemic rather than vascular in origin."
-How does clonidine affect vesical and somatic reflexes in patients with suprasacral spinal cord lesions?,"Clonidine inhibits vesico-sphincter reflexes in patients with chronic spinal lesions. When administered systemically to spinalized animals, clonidine, the prototypic alpha 2 adrenergic receptor agonist, purportedly acts at spinal sites to suppress motor responses related to painful peripheral and vesical stimulation and spasticity, and to improve vesicourethral coordination. Hence, the action of clonidine (400 micrograms in three divided doses in a 16-hour span) on spinal vesical and somatic reflexes was examined in five patients with suprasacral spinal cord lesions by assessing volume-induced micturition reflexes and limb motor discharges that occurred spontaneously or were elicited by noxious and nonnoxious cutaneous stimulation. Clonidine caused a significant reduction in (1) blood pressure, (2) amplitude of detrusor contraction, and (3) vesical external urethral sphincter dyssynergia. Limb motor electromyography discharges were not markedly attenuated, although spatiotemporal changes (eg, irradiation, after-discharges) were observed in some of the patients. The results are ascribed to binding to spinal cord alpha 2 adrenergic receptors located on segmental and intersegmental (propriospinal) interneurons, released from descending inhibition, with greater motor system specificity on striated sphincter innervation. Clonidine may be clinically effective in the treatment of hyperactive micturition reflexes in patients with chronic spinal lesions."
-How does caffeine affect postprandial blood pressure in elderly subjects?,"The effect of caffeine on postprandial hypotension in the elderly In a double-blind, randomized trial the effects of caffeinated and decaffeinated drinks on postprandial hemodynamic and neurohumoral changes were studied in seven fit, elderly subjects after a standard 2.4MJ meal. There was a significant difference in supine postprandial systolic blood pressure between the placebo and caffeine phases (P less than 0.01); at 60 minutes, supine systolic blood pressure had fallen 14 mmHg [95% confidence interval (CI)-7 to-21 mmHg, p less than 0.01) after placebo, but was unchanged after caffeine (+9 mmHg, CI 0 to 18 mmHg, NS]. Similar differences between placebo and caffeine were seen in erect systolic and diastolic blood pressure (P less than 0.01), although orthostatic tolerance was maintained throughout each study period. Postprandial plasma noradrenaline levels were higher (P less than 0.02) and the increase greater (P less than 0.02) after caffeine than after placebo. Caffeine administered at the end of a standard test meal prevents the postprandial fall in blood pressure in fit, elderly subjects. The clinical relevance of this finding has yet to be determined, but it may offer a simple remedy for patients with symptomatic postprandial hypotension."
-What challenges do urinary tract infections (UTIs) pose for young women and the healthcare community?,"Advances in the understanding and treatment of urinary tract infections in young women. Despite relative ease of management, the high rate of urinary tract infections (UTI) among young women presents substantial problems for the health care community. Although the majority of UTIs in young women are simple and uncomplicated, the rate of recurrence is substantial. Each treatment of UTI recurrence brings greater antibiotic resistance, requiring the use of broader spectrum and more expensive antibiotic therapy. Moreover, infection in patients with underlying urinary tract or systemic diseases can lead to serious medical and financial consequences. A better understanding of antibiotic resistance, particularly in regard to beta-lactamase-producing pathogens, has allowed us to develop more appropriate criteria for selecting antibiotics as well as the duration of therapy. The overall cost for treating UTIs in young women is a substantial health care expenditure, and requires an ongoing examination of new information concerning pathogenesis and available antibiotic therapies."
-What was the survival rate for infants undergoing staged repair of interrupted aortic arch and ventricular septal defect between 1979 and 1990?,"Staged repair of interrupted aortic arch and ventricular septal defect in infancy. Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants."
-How do CEA levels in peripheral and draining venous blood correlate with the risk of hematogenous metastasis in colorectal cancer patients?,"Colorectal cancer patients with high risk of hematogenous metastasis: correlation with CEA levels in peripheral and draining venous blood during the period of operation. Correlations between carcinoembryonic antigen (CEA) levels of peripheral (p) and draining (d) venous blood during the period of operation, and pre- and post-operatively detected hematogenous metastases were examined in 78 patients with colorectal cancer. The metastases were found in 28 patients (HM group), but not found in the other 50 patients (non-HM group). The mean values (43 and 198 ng/ml) and positive rates (61 and 96%) greater than 5 ng/ml of p- and d-CEA levels in the HM group were significantly higher than those (6 and 14 ng/ml, and 22 and 48%, respectively) in the non-HM group. The differences (mean 184 ng/ml and positive rate 49%) of d-CEA levels between both groups were more significant than those (39 ng/ml and 30%) of p-CEA levels. The mean value (155 ng/ml) and positive rate (82%) greater than 5 ng/ml of the gradient between d- and p-CEA levels (d-p CEA gradient) in the HM group were significantly higher than those (8 ng/ml and 34%) in the non-HM group. These results suggest that patients with a high risk of hematogenous metastases are more effectively checked by the determination of d-CEA levels and d-p CEA gradient than of p-CEA levels, and that they are patients with positive d-CEA and d-p CEA gradient levels."
-What are the key characteristics and management strategies for neurofibromatosis-2?,"Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described."
-How did endoscopic variceal sclerotherapy affect portal venous pressure gradient in cirrhotic patients?,"The effects of chronic endoscopic variceal sclerotherapy on portal pressure in cirrhotics. The effect of obliterating esophageal varices by endoscopic sclerotherapy on portal pressure was prospectively studied in 11 cirrhotic patients with variceal hemorrhage. Portal venous pressure gradient, determined as the difference between transhepatic portal and hepatic vein pressure, increased by a mean of 31.1% +/- 14.5% in 8 (73%) and decreased by a mean of 30.1% +/- 11.7% in 3 (27%) patients, with no statistically significant change overall (P = 0.1). These changes in portal venous pressure gradient occurred despite an improvement in the laboratory and clinical parameters of hepatic function. Deep abdominal sonography with color flow imaging at variceal obliteration showed patent paraumbilical veins in 6 (55%) patients, 3 of whom had decreases in portal venous pressure gradient (29%, 19%, 42.5%) at variceal obliteration. In 5 (45%) patients without patent paraumbilical veins, a statistically significant increase in portal venous pressure gradient between initial endoscopic variceal sclerotherapy and variceal obliteration was noted (P = 0.008). Rebleeding (single episode in all 4 patients, before obliteration in 3 patients) occurred in those with an increase in portal venous pressure gradient; all patients with portal venous pressure gradient decreases were nonbleeders. No correlation between changes in portal venous pressure gradient and time to variceal obliteration, number of sclerotherapy treatments, or rebleeding episodes was observed. Thus, an increase in portal venous pressure gradient was noted in the majority of patients at variceal obliteration. Although the portal venous pressure gradient decrease may be explained by a patent paraumbilical vein, the mechanism of portal venous pressure gradient increase is not clear. It is speculated that this portal venous pressure gradient increase may be caused by an increase in collateral resistance or flow or a combination of both, resulting from obliteration of esophageal varices by endoscopic sclerotherapy."
-What improvements are suggested for emergency medical services in the United States to enhance patient care and response times?,"Role of emergency medical services. For thrombolytic therapy to be effective in the treatment of acute myocardial infarction, the patient must enter the health care center delivery system in an efficient manner. Some entry delays are due to patient decisions and interactions with others. In the United States, prehospital care is delivered by a variety of different systems, varying from public service types such as fire-department based to private types of service. These personnel vary in level of training from paramedics with a high level of training to Emergency Medical Technicians-Ambulance with basic training (first aid), even less in some areas. The training should be upgraded so that training as an emergency medical technician with the ability to defibrillate would be the minimum level for emergency ambulance personnel; wherever economically and logistically feasible, ambulance personnel should be paramedics. Although the 911 emergency telephone system exists in some areas, there is no centralized, universal system for access, causing confusion and delays in obtaining care in critical situations such as cardiac arrest. There is a need for a national emergency number--911--with the ability to identify the calling number and address. Since dispatchers have little medical dispatch training, needed instructions are not given to the caller, which can reduce the patient's chance of survival. Trained dispatchers are needed to dispatch resources efficiently and to offer assistance until trained rescuers arrive. Ambulances are inefficiently located in some areas of the United States, slowing response to the patient."
-What is effort thrombosis of the axillosubclavian vein and how is it typically treated?,"Effort thrombosis of the axillosubclavian vein: a disabling vascular disorder. In the natural history of this disorder, resumption of normal activity after a period of recuperation (following an episode of thrombosis) frequently leads to symptoms of upper extremity venous hypertension exacerbated by using the arms in the overhead position. This position can be demonstrated venographically to further occlude collateral vessels in thoracic outlet. A number of patients develop more extensive symptoms of neurogenic thoracic outlet syndrome. Anticoagulation may protect the collateral vessels and interrupt the period of active clot propagation resulting in a better functional result than would be expected from the natural history of the thrombotic event. In our experience, local Urokinase was the most effective means for reestablishing venous patency. With clot dissolution the underlying compression of the vein at the thoracic outlet can be demonstrated. Balloon angioplasty should not be undertaken in the acute setting nor prior to relieving the tendinous compression. The acute phlebitic process should resolve under the protection of Coumadin for three months. At that time it can be determined more effectively which patients require additional therapy. Removal of the first rib will decompress the axillosubclavian vein and the thoracic outlet collaterals permitting the vein to regain its normal configuration particularly in younger patients with more acute onset of compression. In those patients with more chronic compression the vein becomes stenotic. Improvement of the luminal configuration has been accomplished with transvenous balloon angioplasty without the necessity for venous reconstructive procedures in this series. Patients with Paget-Schroetter syndrome have a symptom complex which often reflects more extensive neurovascular compression at the thoracic outlet than that which might result from venous hypertension alone. Although thrombolytic therapy can restore patency of the axillosubclavian vein, first rib resection is necessary to relieve the external compression. This procedure was very effective in patients who had restoration of subclavian vein patency, and to a lesser degree in those with residual occlusion."
-Who was Paul Broca and what significant medical procedure did he perform in 1871?,"Paul Broca and the first craniotomy based on cerebral localization. Paul Broca (1824-1880) was a well-known French surgeon-anthropologist-neurologist. Best known for his work on cerebral cortical localization and speech mechanisms, Broca also carefully worked out skull and scalp localization for underlying cortical regions. In 1871, Broca treated a man who had sustained a scalp laceration from a blow to the head without loss of consciousness or skull fracture. The patient exhibited a nonfluent aphasia about 1 month after injury and became progressively obtunded and eventually comatose. Suspecting an intracranial abscess, Broca trephined at the region of the left third frontal convolution and drained an epidural abscess. The patient improved transiently but died a few days later. Autopsy showed a left-sided, predominantly frontal purulent meningoencephalitis. Broca's other neurosurgical contributions included various surgical cases, methods for scalp localization of the cerebral convolutions, extensive studies of skull and brain abnormalities, thermoencephalography, and the stimulation of younger surgical colleagues and neurologists to make practical use of cerebral localization."
-How was HLA class I antigen expression evaluated in patients with chronic hepatitis B?,"HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy."
-What method did researchers use to detect regional disparities in ventricular recovery in patients with long QT syndrome?,"Dispersion of ventricular repolarization in the long QT syndrome. To identify markers of dispersion of the ventricular repolarization in the idiopathic long QT syndrome, body surface potential maps were analyzed in 40 such patients (mean age +/- standard deviation 21 +/- 11 years) and in 30 healthy control subjects (mean age 24 +/- 7 years). In each subject, 117 chest leads were recorded and maps of the integral values of the QRST interval were calculated. A multipolar distribution of the values, a marker of gross electrical inequalities of repolarization, was found only in 4 patients. To detect minor regional disparities of ventricular recovery, all the ST-T waveforms were analyzed in each subject. The ST-T waves were represented by a discrete series of potential values. The ""similarity index"" was computed by applying a principal component analysis, which represents (in percent) to what extent 1 fundamental pattern of ST-T reproduces all the recorded waveforms. The mean value of the similarity index was significantly lower in patients with long QT syndrome than in control subjects (49 +/- 10 vs 77 +/- 8%, p less than 0.0001). A value less than 61% (corresponding to 2 standard deviations below the mean value for controls) was found in 35 of 40 patients and in only 1 control subject (sensitivity 87%, specificity 96%). Thus, the similarity index is a more sensitive marker than the multipolar distribution of QRST integral maps in revealing electrical disparities of the ventricular recovery times."
-What is spatial misregistration in MR imaging of the CNS and how does it occur?,"Spatial misregistration of vascular flow during MR imaging of the CNS: cause and clinical significance. Spatial misregistration of signal recovered from flowing spins within vascular structures is a common phenomenon seen in MR imaging of the CNS. The condition is displayed as a bright line or dot offset from the true anatomic location of the lumen of the imaged vessel. Its origin is the time delay between application of the phase- and frequency-encoding gradients used to locate spins within the plane of section. The principal condition necessary for the production of spatial misregistration is flow oblique to the axis of the phase-encoding gradient. Flow-related enhancement (entry slice phenomenon), even-echo rephasing, and gradient-moment nulling contribute to the production of the bright signal of spatial misregistration. Familiarity with the typical appearance of flow-dependent spatial misregistration permits confirmation of a vessel's patency; identification of the direction of flow; estimation of the velocity of flow; and differentiation of this flow artifact from atheromas, dissection, intraluminal clot, and artifacts such as chemical shift."
-How did the surgical management of invasive squamous cell carcinoma of the vulva change at Indiana University between 1974 and 1988?,"Trends in the operative management of invasive squamous carcinoma of the vulva at Indiana University, 1974 to 1988. From January 1974 to March 1988, 150 patients with primary invasive squamous cell carcinoma of the vulva underwent surgery at Indiana University. There has been a trend toward more conservative surgical management of this disease. To determine the impact of this trend on clinical outcome, cases were divided into three groups according to date of operation: group I, 1974 to 1978; group II, 1979 to 1983; and group III, 1984 to 1988. Overall, 80 patients had en bloc radical vulvectomy and groin dissection, 20 had modified radical vulvectomy and bilateral groin dissection through three separate incisions, and 36 had modified radical vulvectomy and unilateral superficial groin dissection. Fourteen patients had other operations. Forty-two patients (27.3%) had radiotherapy in addition to surgery. Among the three groups, there were no differences when mean age, International Federation of Gynecology and Obstetrics stage distribution (1988 system), mean lesion size, mean depth of invasion, or grade distribution were compared. A significant trend toward more conservative surgical therapy was observed. En bloc radical vulvectomy was performed in 77.4% of group I patients, 71.1% of group II patients, and 35.8% of group III patients (p less than 0.001). Mean days of hospitalization were also reduced significantly. Group I had a mean stay of 30 days, group II had a mean stay of 23 days, and group III had a mean stay of 11 days (p less than 0.001). Mean operative blood loss (group I, 754.8 ml; group II, 620.0 ml; group III, 393.6 ml; p = 0.03), mean units of blood transfused (group I, 1.4 units; group II, 1.3 units; group III, 0.4 units; p less than 0.01), and mean hours of operating time (group I, 3.7 hours; group II, 3.7 hours; group III, 3.2 hours; p = 0.02) were also reduced."
-What are the potential advantages and challenges of using a detubularised bowel segment in cystoplasty?,"Detubularisation in cystoplasty: clinical review. Cystoplasty using a detubularised bowel segment is preferable to using a tubularised length of intestine. This has been shown experimentally to result in a reduction in the contractility of the neobladder, although contractions are not completely abolished. Incontinence, especially nocturnal, may still be a problem. Assessment of renal function has shown a marked incidence of upper tract dysfunction despite detubularisation. All patients remain at risk of upper tract obstruction following cystoplasty. Because bowel contraction waves are brought on by distension, it may be possible either to postpone or to prevent the onset of contractions by avoiding an excessive build-up of bladder volume. Clean intermittent self-catheterisation is an efficient means of emptying the bladder, although sphincter rebalancing may also be required."
-How did extracorporeal shock-wave cholecystolithotripsy (ESWL) affect gallbladder contractility in the studied patients?,"Altered gallbladder contractility after extracorporeal shock-wave cholecystolithotripsy. Change in gallbladder contractility after biliary extracorporeal shock-wave lithotripsy (ESWL) may significantly influence the clearance of fragments after successful gallstone fragmentation. We assessed changes in gallbladder contractility in response to an oral fatty meal in 50 patients 1 month after biliary ESWL (all fragments were smaller than 3 mm) and also in a separate group of 10 patients 3 months after complete clearance of fragments. The prevalence of persistent lumen-obliterating contraction of the gallbladder after biliary ESWL also was analyzed in 325 patients. Gallbladder contractility remained unchanged in 30, increased in nine, and decreased in 11 of the 50 patients. The average reduction in the fasting gallbladder volume after lithotripsy was 28% (p less than .001). Gallbladder contractility remained unchanged 3 months after complete clearance of fragments in six of 10 patients studied separately. A decrease (n = 2) or increase (n = 2) in contractility was seen in the remaining patients. No significant difference occurred in the average ejection fraction of the gallbladder before lithotripsy and after complete clearance of the fragments. Thirty-four of the 325 patients who have so far undergone biliary ESWL had a completely contracted gallbladder with no lumen visible on sonography. The gallbladder returned to a relaxed state in half of these patients within 1-9 months. Thus, biliary ESWL did not significantly alter gallbladder contractility in 60% of patients. A significant reduction in the volume of the fasting gallbladder occurred after lithotripsy. Successful clearance of fragments did not improve the contractility of stonebearing gallbladders in the majority of patients."
-What modifications were made to the transcochlear approach to improve surgical exposure in the cerebellopontine angle region?,"The modified transcochlear approach to the cerebellopontine angle. We have modified the transcochlear approach to improve exposure of the anterior petrous apex, clivus, anterior cerebellopontine angle, and the prepontine region. These changes include resection of the external auditory canal, middle ear, glenoid fossa, and posterior zygomatic arch. This approach provides improved exposure of the petrous carotid artery, jugular bulb, and clivus. It offers the largest and most lateral access to the anterior cerebellopontine and prepontine region. The results of this approach in 11 patients are discussed."
-What were the key differences observed between radiofrequency and direct current catheter ablation in the experimental study on dogs?,"Comparison of catheter ablation using radiofrequency versus direct current energy: biophysical, electrophysiologic and pathologic observations. The effects of catheter ablation with radiofrequency versus direct current energy were compared in 18 dogs assigned to two groups (of 9 dogs each). Each dog underwent a single ablation at two sites in the left ventricle at energy levels of 100, 200 or 300 J delivered in unipolar configuration to six dogs each. A transient decrease in left ventricular systolic pressure (from 121.3 +/- 24.5 to 94.2 +/- 18.7 mm Hg, p less than 0.01) and wall motion abnormality were noted in dogs with direct current shock. The left ventricular ejection fraction decreased (from 50 +/- 2% to 34 +/- 3%, p less than 0.001) shortly after direct current ablation but improved 4 weeks later to 43 +/- 3%. There were no significant changes in left ventricular pressure, wall motion or ejection fraction in dogs in the radiofrequency ablation group. Sustained ventricular tachycardia (greater than or equal to 30 s) was seen immediately after direct current shock in all dogs, and one dog died of intractable ventricular fibrillation. A 24-h ambulatory electrocardiographic (ECG) monitor obtained immediately after the procedure showed multiple runs of ventricular tachycardia in all dogs exposed to direct current ablation but in only three dogs that underwent radiofrequency ablation. No differences were found in peak creatine kinase, complete blood count with smear and B-beta 15-42 fibrinopeptide levels. Pathologically, direct current-induced lesions were larger (mean length x width x depth 10.9 x 7.5 x 5.2 vs. 4.8 x 4.6 x 4.3 mm) and were poorly circumscribed with inhomogeneous margins of necrosis."
-What was the most significant factor affecting recurrence rate in patients with colorectal liver metastases according to the study?,"The influence of intraoperative hypotension and perioperative blood transfusion on disease-free survival in patients with complete resection of colorectal liver metastases. An increased interest in surgical treatment of liver metastases from colorectal origin has evolved recently. However not all patients benefit from this approach, with early recurrence and death still being encountered. To evaluate clinical as well as perioperative factors that might significantly affect the outcome of patients with completely resected colorectal liver metastases, we examined 116 patients who underwent resection between September 1987 and August 1989. Median follow-up time was 13.2 months (0.6 to 31.4 months). The overall survival rate was 91% at 1 year and 75% at 2 years. Median survival was not reached. Median disease-free survival time was 11.5 months, with 49.4% and 21.2% of the patients being free of disease at 1 and 2 years, respectively. By univariate analysis, site of primary colorectal cancer, preoperative carcinoembryonic antigen (CEA) level, size of metastases, number of metastases, length of operation time, percentage mean arterial pressure, number of hypotensive episodes, duration of hypotensive episodes, and whole blood transfusion significantly affected recurrence rate following resection. However only site of primary tumor, CEA, number of metastases, and number of hypotensive episodes remained significant in the multivariate analysis. The most significant single factor that affected recurrence rate was the number of hypotensive episodes during the operative procedure. It is concluded that hypotensive episodes, even when well controlled, should be avoided during operation to maximize the chances of cure and prolong disease-free survival of patients with colorectal liver metastases."
-Why is acetaminophen hepatotoxicity often missed in chronic alcoholic patients?,"Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics. We encountered six alcoholic patients with severe acetaminophen hepatotoxicity during a 2-year period. All patients had marked elevations of aminotransferases and sometimes remarkably high prothrombin times at, or shortly after, presentation. In five of six cases the diagnosis was missed by the physicians initially caring for the patient. The apparent reasons for the missed diagnosis were insufficient history regarding the use of acetaminophen, an inappropriate reliance on blood acetaminophen levels, and lack of knowledge regarding typical aminotransferase elevations in alcoholic hepatitis vs acetaminophen toxicity. The initial clinical presentation of acetaminophen hepatotoxicity in chronic alcoholics is easily recognized clinically and is distinct from acetaminophen hepatotoxicity in suicide ingestions and from alcoholic hepatitis. Internists and other physicians should be aware of this entity and rely on the clinical picture and the history of acetaminophen use to confirm the diagnosis."
-What alternative explanation is proposed for the genesis of closed-lock symptoms in temporomandibular internal derangement?,"An alternative explanation for the genesis of closed-lock symptoms in the internal derangement process. Clinical and surgical data on 194 operated joints (135 patients) were used to substantiate a new concept challenging the presumed natural history of temporomandibular internal derangement (ID). A number of findings were incompatible with the traditional depiction of a progressive process based on gradual changes in disc position and shape. These findings were a lack or correlation between increasing age and the stages of the process; the percentage of patients in the third stage (closed lock) with limited opening (less than 25 mm) too severe to be caused solely by a nonreducible, displaced disc; the unexpectedly high incidence (greater than 50%) of normally shaped discs in the third stage of the process. A specific condition of severe and stubborn limited maximal mouth opening caused by total cessation of gliding, liable to occur at any age and unrelated to disc shape or position, which responds successfully to simple treatment by lavage and lysis, pressured injection, or arthrocentesis, was discerned. Lack of gliding was attributed to adherence of the disc to the fossa by a reversible effect such as a vacuum and/or decreased volume of synovial fluid of high viscosity. This condition was deemed worthy of an independent identity, dissociated from disc displacement, as a causative factor in the second and third stages of ID, and particularly as an aid to accurate diagnosis and treatment."
-What percentage of acoustic neurinomas in this study were confined to the intracanalicular area?,"Intracanalicular acoustic neurinomas. The cases of 16 patients with acoustic neurinomas confined to the intracanalicular area are presented. These represent 2.7% of the 600 patients with acoustic neurinomas consecutively operated upon at the Neurosurgical Clinic at Nordstadt Hospital during the last 8 years. The comparatively earlier onset of vestibular symptoms and signs was characteristic of this group and precipitated diagnosis. The diagnostic reliability of magnetic resonance imaging was at least equivalent to that of air computed tomographic cisternography. Complete tumor removal was accomplished via the suboccipital approach in all patients, with 100% preservation of facial nerve and facial function; the cochlear nerve was preserved anatomically in 100% of the patients and functionally in 57%. No recurrence has occurred during follow-up periods of up to 8 years in all 16 patients. A broad spectrum of the current literature is considered, and purely intracanalicular acoustic neurinomas are discussed with regard to clinical characteristics, diagnostic steps-including neuroradiological and neurophysiological approaches-and surgical treatment and results."
-What makes gall bladder perforation a challenging medical condition to diagnose early?,Acute gall bladder perforation--a dilemma in early diagnosis. Gall bladder perforation is a rare complication of cholecystitis. A definitive diagnosis is uncommon before surgery and the morbidity and mortality associated with this condition are high. We report six patients with gall bladder perforation to show the difficulty of making an early diagnosis. The history and the clinical findings of these patients are reviewed to highlight diagnostic pitfalls.
-What percentage of men were found to have a genital human papillomavirus infection among the sexual partners of women treated for genital condylomata acuminata?,"Genital human papillomavirus infection in men. Diagnosis and treatment with a laser and 5-fluorouracil. One hundred twenty-eight consecutive men, sexual partners (for more than six months) of women treated for genital condylomata acuminata, were evaluated with colposcopy to assess the percentage of infected men among the couples. Ninety-three (73%) of the men were found to have a genital human papillomavirus infection on colposcopically directed biopsies. All but one patient were treated with outpatient colposcopically guided laser vaporization under local anesthesia (one patient with extensive condylomata required general anesthesia). Two weeks after laser surgery, 5% 5-fluorouracil cream, used in the genital area, was initiated on a weekly basis for two months and every other week for two more months. Patients were followed in the clinic with colposcopy performed every eight weeks for six months to evaluate the regimen's results. Thirty-seven (40%) of the 93 men had ""clinically"" apparent genital HPV infection, and 56 (60%) of the 93 had ""subclinical"" disease (as determined with colposcopy). The majority of the patients (87 of 93, or 94%) responded to one laser treatment followed by 5-fluorouracil cream and had no visible lesions at six months. Colposcopic evaluation of the male partners of infected women and laser surgery followed by topical 5-fluorouracil therapy appear to be safe and effective in controlling genital HPV infection."
-How does 3DFT MR angiography compare to digital subtraction angiography in assessing carotid artery stenosis?,"3DFT MR angiography of the carotid bifurcation: potential and limitations as a screening examination. The authors compared the three-dimensional Fourier transform (3DFT) time-of-flight magnetic resonance (MR) angiograms in 38 patients initially studied with selective intraarterial digital subtraction angiography (DSA) for suspected arteriosclerotic disease of the carotid bifurcation. MR angiograms were successfully obtained in 65 of the 75 carotid arteries (87%) visualized with DSA. DSA and MR angiographic studies were assessed for percentage area stenosis by two independent observers on two occasions. Statistical tests indicated consistency in interpretation for each observer as well as between observers. No significant difference was found between the two modalities in ability to depict changes in percentage area stenosis. For the 32 right carotid arteries in the comparison, the median for the difference between MR angiography and intraarterial DSA was 1.83% (range, -22.38% to 55.60%); for the 33 visualized left carotid arteries, it was 0.00% (range, -20.55% to 49.95%). Receiver operating characteristic analysis indicated that technically adequate MR angiography may be a sensitive screening examination for stenoses."
-How did transoesophageal echocardiography help in diagnosing and managing patients with pericardial haemorrhage after cardiac surgery?,"Pericardial haemorrhage causing right atrial compression after cardiac surgery: role of transoesophageal echocardiography. After cardiac surgery transoesophageal echocardiography showed a large thrombus compressing the right atrium in three hypotensive patients. No satisfactory images were obtained by transthoracic imaging, which is often difficult in ventilated patients after cardiac surgery. Transoesophageal echocardiography, however, provided rapid diagnostic information and permitted prompt surgical intervention."
-What therapeutic intervention led to dramatic and rapid clinical improvement in the case of a 40-year-old woman with eosinophilia-myalgia syndrome and ascending polyneuropathy?,Plasmapheresis in a case of eosinophilia-myalgia syndrome with ascending polyneuropathy. Eosinophilia-myalgia syndrome complicated by ascending polyneuropathy in a 40-year-old woman is described. High-dose intravenous steroids had no beneficial effect on the clinical course. Dramatic and rapid clinical improvement occurred with the use of plasmapheresis. The use of this therapeutic modality should be considered in patients with a similar clinical presentation.
-What were the key findings regarding prosodic features in patients with Parkinson's disease in this study?,"The interpretation of dysprosody in patients with Parkinson's disease. Prosodic features in the speech production of 21 patients with idiopathic Parkinson's disease were tested. The appreciation of vocal and facial expression was also examined in the same patients. Significant intergroup differences were found in the prosody production tasks but, in contrast to previous results, not in the receptive tasks on the recognition and appreciation of prosody and of facial expression. The discrepancy between the production and recognition of prosodic features does not support the suggestion that dysprosody in Parkinson's disease is necessarily a disorder of processing emotional information that could be misinterpreted as a dysarthria."
-What was the purpose of the phase I/II trial involving recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following allogeneic bone marrow transplantation?,"Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical ""good risk"" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients."
-What were the presumed etiologies of rhabdomyolysis/myoglobinuria in the pediatric patients studied?,"Rhabdomyolysis in children: a 3-year retrospective study. The case reports of 4 pediatric patients illustrate the complex clinical scenarios in which childhood rhabdomyolysis/myoglobinuria occurs. Children ranged in age from 8-18 years. Presumed etiologies of rhabdomyolysis/myoglobinuria included Neisseria sepsis, exertion-related episodes, dialysis disequilibrium, and diabetic ketoacidosis. No child developed respiratory or renal failure. all children were discharged with normal muscle power, indicating the benign nature of this disease and the importance of aggressive management."
-What was the outcome of the Strecker stent treatment for renal artery stenosis in the study?,"Renal artery stenosis: preliminary results of treatment with the Strecker stent. Use of the Strecker flexible balloon-expandable tantalum stent for treatment of renal artery stenosis after failed angioplasty or transaortic thromboendarterectomy was evaluated in 10 patients (nine hypertensive, one normotensive). Left (n = 3) and right (n = 5) renal arteries were involved; renal artery stenosis in two patients had developed after kidney transplantation. Indications for stent placement were inadequate immediate postangioplasty response (n = 7), development of considerable restenosis after angioplasty (n = 1), and obstructing intimal flaps following transaortic endarterectomy (n = 2). Stent placement was technically successful (less than 20% residual stenosis) and patency was preserved in eight patients. Of the seven hypertensive patients with successful implantation, two were cured, three had improvement, and two had no change at latest follow-up evaluation (mean, 10.6 months; range, 6-12 months). The Strecker stent may be helpful in treating restenosis after failed revascularization procedures, although the precise indication, true safety, and long-term efficacy of stent placement in renal arteries will not be known until trials with more subjects and longer follow-up periods are completed."
-How can rest-injected thallium-201 imaging help assess the viability of severely asynergic myocardial regions?,"Rest-injected thallium-201 imaging for assessing viability of severe asynergic regions. To evaluate the utility of rest-injected 201Tl initial and delayed images for assessing the viability of severe asynergic regions, we studied 17 patients with apparently prior infarcted myocardium in combination with 99mTc ventriculography before and after revascularization. In 51 regions with severe asynergy, the percent 201Tl uptake was calculated as the ratio of counts on the segment with asynergy to the maximum counts on the normal segment. Eleven of 14 regions with resting 201Tl redistribution (Group 1) had improved wall motion after revascularization. However, 14 of 37 regions without redistribution also improved (Group 2). Twenty-three regions without redistribution or improved wall motion after revascularization (Group 3) had lower regional 201Tl uptake on their delayed images than those in Groups 1 and 2. Moreover, the initial regional uptake of Group 2 was higher than that of Group 3. These results suggest that redistribution on rest-injected 201Tl scans indicates reversibility of severely asynergic myocardium and that high 201Tl uptake in regions without redistribution may predict improvement in wall motion after revascularization. We conclude that 201Tl uptake may be useful as a marker of viability of severe asynergic regions before revascularization."
-What was the outcome of administering ursodeoxycholic acid to a patient with benign recurrent intrahepatic cholestasis?,"Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism. Ursodeoxycholic acid was administered to a patient with benign recurrent intrahepatic cholestasis to prevent cholestatic episodes. A detailed study of bile acid metabolism in this patient was carried out in the anicteric and icteric phases before and after ursodeoxycholic acid (750 mg/day) administration. Urinary, biliary and serum bile acids were measured by gas chromatography-mass spectrometry and by high-performance liquid chromatography techniques. During the anicteric phase the daily urinary excretion and serum concentrations of bile acids were within normal ranges, indicating normal hepatic uptake and secretion of bile acids during the cholestasis-free period. Only slight qualitative differences from normal individuals were observed; the relative proportions of deoxycholic acid in the bile and serum were higher, and 12-oxo-lithocholic acid was the predominant urinary bile acid. During the icteric phase a marked increase in the urinary excretion of primary bile acids and C-1, C-2, C-4 and C-6 hydroxylated metabolites was found. Serum bile acid concentrations increased before the rise in bilirubin, suggesting an acute disturbance in bile acid transport at the onset of the cholestatic attack. After ursodeoxycholic acid administration in the anicteric phase, bile became enriched with the exogenous bile acid, but little qualitative change was found in the other metabolites present in the urine, serum or bile during the anicteric or icteric phases. Prolonged administration of ursodeoxycholic acid failed to prevent recurrence of a cholestatic episode, suggesting that in benign recurrent intrahepatic cholestasis, oral ursodeoxycholic acid may be of little benefit in the treatment or prevention of cholestasis despite marked enrichment of the bile acid pool with this hydrophilic bile acid."
-"How do perceptions of physical and emotional distress during infertility treatment differ among patients, nurses, and physicians?","Physical and emotional stress associated with components of the infertility investigation: perspectives of professionals and patients. OBJECTIVE: The present study examined patients', nurses', and physicians' perceptions of the physical and emotional difficulty of infertility treatment. DESIGN: A mail survey method was used. PATIENTS, PARTICIPANTS: Participants included 26 patients, 76 nurses, and 71 physicians from infertility clinics in the United States and Canada. MAIN OUTCOME MEASURES: A rating scale measured the physical and emotional difficulty level of 36 components from the infertility investigation. RESULTS: Nurses rated the emotional and physical distress of patients higher than did patients and physicians, whereas patients rated their distress higher than did physicians. Older nurses and physicians inferred lower levels of physical and emotional distress than did their younger counterparts. A greater breadth of experience with infertility treatments was associated with higher ratings of emotional distress by nurses and lower ratings by physicians. CONCLUSIONS: Patients, nurses, and physicians perceive infertility treatment from unique vantage points creating differences in perceptions that have implications for patient care. Factors including era of professional training, stage of life, and changes resulting from advancing technology are viewed as influencing health care professionals' perceptions of infertility distress."
-How do renal hemodynamics and renin-angiotensin-aldosterone system characteristics differ in normotensive subjects with different parental hypertension backgrounds?,"Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents. BACKGROUND AND METHODS. The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS. The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS. Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension."
-What is the prevalence of acute pulmonary embolism among pediatric patients awaiting heart transplantation in this study?,"Acute pulmonary embolism in pediatric patients awaiting heart transplantation. Acute pulmonary embolism with infarction can delay urgently needed heart transplantation and increase the postoperative pulmonary complications. Few data are available concerning pulmonary embolization in the pediatric patient with end-stage congestive heart failure. Sixty-two consecutive pediatric patients awaiting heart transplantation were monitored for evidence of acute pulmonary embolism. Acute pulmonary infarction was documented by ventilation-perfusion scan, pulmonary angiography or pathologic examination in six patients. The prevalence differed by diagnosis; 5 of 36 patients with dilated cardiomyopathy and 1 of 20 patients with congenital heart disease developed acute pulmonary embolism with infarction. No significant difference in age at the time of transplantation evaluation, duration of congestive heart failure, presence of cardiac arrhythmias or degree of cardiac dysfunction was seen between patients with and without pulmonary embolism. Two-dimensional echocardiography failed to detect the presence of an intracardiac thrombus in four of the six patients. Two patients who developed acute pulmonary infarction are alive after successful heart transplantation. The remaining four patients died within 6 weeks of initiation of anticoagulant therapy before transplantation could safely be performed. In summary, pediatric patients with end-stage congestive heart failure are at risk for acute pulmonary embolism. No specific clinical factor identified those patients who developed acute pulmonary infarction. Anticoagulant therapy is strongly recommended in the pediatric patient with poor ventricular function awaiting heart transplantation."
-What is the relationship between chronic viral hepatitis and hepatocellular carcinoma in the United States according to the study?,"The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Although hepatocellular carcinoma is a relatively uncommon tumor in the United States, it is quite common in sub-Saharan Africa and the Far East, where most cases are associated with infection with the hepatitis B virus. We have studied 99 American patients with hepatocellular carcinoma for evidence of hepatitis B or hepatitis C viral infection and compared these findings to those in a group of matched controls with other cancers. The two groups differed in proportion, with hepatitis B surface antigen in serum being significantly higher in patients with hepatocellular carcinoma (7% vs. 0%, p = 0.009). Antibody to hepatitis C virus was also found more frequently in patients with hepatocellular carcinoma (13% vs. 2%, p = 0.002). The relative risk for hepatocellular carcinoma in hepatitis B surface antigen-positive patients was calculated to be 17.3 and for antibody to hepatitis C virus to be 7.3. The attributable fraction of cases related to the hepatitis B surface antigen carrier state was 6.7% and for patients infected with the hepatitis C virus was 11.4%. Approximately three quarters of cases of hepatocellular carcinoma did not have evidence of either hepatitis C or hepatitis B virus infection. These findings provide strong evidence that hepatitis C virus infection is associated with the development of hepatocellular carcinoma, and in the United States may even play a more important role than the hepatitis B virus."
-What is compartment syndrome and how can it be caused by prolonged use of the lithotomy position during surgery?,"Compartment syndrome complicating prolonged use of the lithotomy position. Two patients with three postoperative calf compartment syndromes, which followed prolonged lithotomy positioning, will be presented. Potential physiologic mechanisms are described, and a review of current cases in literature are summated."
-What percentage of patients received a correct initial diagnosis from the general practitioners in the study?,"Chest pain: an evaluation of the initial diagnosis made by 25 Flemish general practitioners. Twenty-five general practitioners collected information on 318 contacts of patients with a new episode of chest pain, discomfort or tightness. A list of complaints, signs and symptoms were checked, together with the initial diagnosis, made by the GP immediately after the physical examination. The initial diagnosis was compared to a follow-up diagnosis. The gain in certainty was also compared. The GP made a correct initial diagnosis in 82% of patients. In 8% there was a clinically important difference, and seven of 17 episodes of oesophageal disease were missed. For their initial diagnosis, the GP scored 74% certain, 20% uncertain and no diagnosis in 6%. For the final diagnosis, these figures were 88%, 8% and 4%."
-What were the key differences in complications between nonionic (iopamidol) and ionic (diatrizoate) contrast media during percutaneous transluminal coronary angioplasty (PTCA) procedures?,"Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty. To evaluate the effect of contrast agents on percutaneous transluminal coronary angioplasty (PTCA) complications, 913 patients undergoing 1,058 separate PTCA procedures were prospectively randomized to receive either nonionic iopamidol (Isovue-370) [n = 507 PTCA procedures] or ionic contrast media, meglumine sodium diatrizoate (Renografin-76) [n = 551 PTCA procedures]. Angioplasty operators, technicians, nurses and patients were blinded to the agent used. All patients were pretreated with 0.6 mg of atropine sulfate intravenously before any contrast injections. Hypotension (mean arterial pressure less than 65 mm Hg associated with contrast injections) occurred during 8.5% of PTCA procedures in which the patients were receiving iopamidol and during 9.5% of the procedures in which the patients were given diatrizoate (difference not significant). Bradycardia (heart rate of less than 40 beats/min associated with contrast injections) developed during 5.7% of procedures when patients were given iopamidol and during 5.1% of procedures when patients were given diatrizoate (difference not significant). The need for additional atropine or temporary pacing during the procedure was similar for patients given iopamidol and diatrizoate. The overall incidence of ventricular tachycardia or fibrillation, or both, during the procedure occurred less frequently when iopamidol was used compared with diatrizoate (1 vs 2.5%, p = 0.045). These serious ventricular arrhythmias were attributable to contrast injections in 0.6% of the PTCA procedures when iopamidol was given and in 2.0% of the cases in which diatrizoate was the contrast agent (p = 0.09). Only 1 patient had an allergic reaction to the contrast agent, and this was in a patient who received iopamidol."
-How does monocrotaline treatment affect the vascular structure in rat lungs?,"Monocrotaline-induced angiogenesis. Differences in the bronchial and pulmonary vasculature. Vascular corrosion casting was used to search for angiogenesis in the blood vessels of the lungs of rats given monocrotaline. Animals treated with monocrotaline had new well-differentiated arteries and veins on their pleural surfaces. Animals not treated had no large vessel on their pleural surfaces. Animals receiving monocrotaline had capillaries around major arteries that were more dense, widened, and less tubular than normal. These capillaries occasionally occurred in sheets and had blind endings. The control animals had delicate, uniform, tubular capillaries. Alveolar capillaries in both groups showed no evidence of increase in size or number or change in shape. Light microscopy confirmed the finding of new vessels found with the casts. The finding of angiogenesis on the pleural surface and in the bronchovascular bundle, but not in the alveolar capillaries, suggests a basic difference in how these capillary beds respond to angiogenic stimuli. If alveolar capillaries are unable to undergo angiogenesis, concepts of lung development and tumor growth may be significantly altered. The lung may be a unique organ to study angiogenesis because of the different angiogenic potential of its two circulations. Study of these differences may lead to better understanding of inhibition of angiogenesis."
-What medical condition did the patient have that required pulmonary resection and distal pancreatectomy-splenectomy?,Pancreaticobronchial fistula causing lung abscess: case report and brief discussion of the literature. A case report of a patient with an abscess of the lung caused by a pancreaticobronchial fistula is presented. The patient was treated by pulmonary resection and distal pancreatectomy-splenectomy.
-What potential side effect did the study observe in patients treated with valproate?,"Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate."
-What is the kissing balloon technique in coronary angioplasty?,The kissing balloon technique with two over-the-wire balloon catheters through a single 8-French guiding catheter. Some of the newer over-the-wire coronary angioplasty catheters have shaft sizes of 3.0 French (F) or less. The inner diameter of modern 8-F guiding catheters is large enough to accommodate two of such balloon catheters. We report a kissing balloon procedure with two over-the-wire catheters through a single 8-F guiding catheter.
-What is the purpose of autotransplantation of dispersed pancreatic islet tissue in patients with chronic pancreatitis?,"Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis. Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain."
-What was the main finding of the study comparing recombinant tissue-type plasminogen activator (rt-PA) plus heparin with heparin alone in patients with refractory unstable angina?,"Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris. Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina."
-What was the resectability rate and pathologic complete response rate in this Phase I trial of preoperative pelvic radiation therapy and combined leucovorin/5-fluorouracil for unresectable rectal cancer?,"Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer. Twenty patients with primary or recurrent unresectable rectal cancer limited to the pelvis were entered on a Phase I trial of preoperative pelvic radiation therapy (RT) (5040 cGy) and two cycles of combined high-dose leucovorin (LV) and 5-fluorouracil (5-FU), followed by surgery and ten cycles of postoperative LV/5-FU (sequential). Maximum tolerated doses (MTD) were determined for preoperative combined LV/5-FU and RT and for postoperative sequential LV/5-FU. 5-FU was escalated 50 mg/m2 while the LV remained constant at 200 mg/m2. The initial doses of 5-FU were combined LV/5-FU and RT (200 mg/m2) and sequential LV/5-FU (325 mg/m2). The median follow-up time was 14 months. The resectability rate was 89%, and the pathologic complete response rate was 21%. The MTD for combined LV/5-FU and RT was 300 mg/m2; therefore, the recommended dose of 5-FU is 250 mg/m2. The recommended dose of 5-FU for sequential LV/5-FU is 375 mg/m2. The dose-limiting toxicities in this trial were diarrhea, tenesmus, increased bowel movements, dysuria, and myelosuppression. For the six patients who received 5-FU at the recommended dose level, the median low counts were leukocyte count, 3.7/microliters (range, 2.4 to 4.9/microliters); hemoglobin, 9.0 g/dl (range, 8.2 to 11.9 g/dl); and platelet count (X1000), 146/microliters (range, 89 to 182/microliters). The incidence rate of any Grade 3 toxicity was 17% (diarrhea and frequent bowel movements). The recommended doses of 5-FU used in this protocol were well tolerated. Because there was a long delay before optimal doses of 5-FU could be delivered, the authors do not recommend that high-dose LV be used in conjunction with combined 5-FU and RT with the treatment regimen as currently designed. However, because the resectability and complete response rates were higher than those previously reported for preoperative RT alone, the authors are encouraged by the combined technique approach. New trials are currently being undertaken to determine if the use of a low-dose LV regimen is more tolerable."
-What is the Siriraj stroke score and how does it help differentiate between supratentorial intracerebral haemorrhage and infarction?,"Siriraj stroke score and validation study to distinguish supratentorial intracerebral haemorrhage from infarction. OBJECTIVES--To develop a simple, reliable, and safe diagnostic tool for acute stroke syndromes in a setting where computerised brain scanning was not readily available and to validate its accuracy with regard to pathological types of stroke. DESIGN--13 clinical variables that potentially might differentiate supratentorial cerebral haemorrhage from infarction were recorded and tested by multivariate analysis in a prospective study of 174 patients with acute stroke. In developing the Siriraj stroke score stepwise discriminant analysis of the variables was followed by a linear discriminant equation to differentiate between supratentorial haemorrhage and infarction. The score obtained was validated against scores in 206 other patients with stroke, computerised brain scans being used for definitive diagnosis. SETTING--Siriraj Hospital Medical School, Mahidol University, Bangkok. SUBJECTS--Prospective study: 174 consecutive patients with acute supratentorial stroke syndrome (not subarachnoid haemorrhage) admitted to Siriraj Hospital during 1984-5; validation study: 206 patients admitted to Siriraj Hospital or another hospital for supratentorial intracerebral haemorrhage or infarction. RESULTS--The Siriraj stroke score was developed and calculated as (2.5 x level of consciousness) + (2 x vomiting) + (2 x headache) + (0.1 x diastolic blood pressure) - (3 x atheroma markers) - 12. A score above 1 indicates supratentorial intracerebral haemorrhage, while a score below -1 indicates infarction. The score between 1 and -1 represents an equivocal result needing a computerised brain scan or probability curve to verify the diagnosis. In the validation study of the Siriraj stroke score the diagnostic sensitivities of the score for cerebral haemorrhage and cerebral infarction were 89.3% and 93.2% respectively, with an overall predictive accuracy of 90.3%. CONCLUSION--The Siriraj stroke score is widely accepted and applied in hospitals throughout Thailand as a simple and reliable bedside method for diagnosing acute stroke."
-How do WSP and WSR mice differ in their response to glucocorticoids during ethanol withdrawal?,"Differential modulation by the stress axis of ethanol withdrawal seizure expression in WSP and WSR mice. Withdrawal from both acute and chronic ethanol (EtOH) exposure is associated with increased neural excitability and increased activity of the hypothalamic-pituitary-adrenal axis. There is some evidence that glucocorticoids are necessary for EtOH withdrawal seizure expression. Lines of mice that were selected for severe (WSP) and minimal (WSR) EtOH withdrawal (as estimated from handling-induced convulsion scores) have been shown to differ in their stress response following an acute dose of EtOH. In this study we provide evidence that these lines of mice also differ in their sensitivity to the excitatory effects of glucocorticoids. EtOH withdrawal seizures of WSP mice were significantly increased by chronic and acute corticosterone treatment, whereas those of the WSR mice were unaffected. Neural excitability was decreased in the WSP mice when aminoglutethimide, a glucocorticoid synthesis blocker, was administered. Thus, it appears that genetic differences in EtOH withdrawal seizure severity may be due, in part, to differences in sensitivity to the excitatory effects of glucocorticoids."
-"What was the success rate of percutaneous cholecystostomy in treating patients with persistent, unexplained sepsis?","Treatment of critically ill patients with sepsis of unknown cause: value of percutaneous cholecystostomy. Because of the difficulty in diagnosing acute cholecystitis in critically ill patients with severe intercurrent illness by clinical and imaging methods or percutaneous aspiration of the gallbladder, a trial of percutaneous cholecystostomy was performed in 24 patients in the intensive-care unit with persistent, unexplained sepsis after a complete clinical, laboratory, and radiologic search showed no alternative source of infection. Persistent high fevers, despite antibiotic therapy, were present in all patients, with elevated WBC count in 18 patients, vague abdominal tenderness in 11, and septic shock requiring vasopressors in 15. Sonographically, all patients had distended, spherical gallbladders, six had gallstones, eight had wall thickening, three had pericholecystic fluid, and four had Murphy's sign. All patients were seen by a senior abdominal surgeon, who agreed to a trial of percutaneous cholecystostomy. Fourteen patients (58%) responded to percutaneous cholecystostomy, as evidenced by a decrease in WBC count, defervescence, and the ability to be weaned off vasopressors. Bile cultures were positive in four patients. Ten patients (42%) did not respond to percutaneous cholecystostomy; five eventually died of unrelated causes. A respiratory source of infection was eventually found in three of these 10 patients, with no proved source of infection in the remainder. No complications related to catheter insertion occurred in this group of patients. Bile leaks occurred in two patients when the percutaneous cholecystostomy catheter was removed, but without serious consequence. Our experience suggests that a lower threshold for performing percutaneous cholecystostomy in this difficult clinical subset of patients is worthwhile."
-What is the potential cause of hypoglycemia in patients with mesenchymal tumor-associated nonislet cell tumors?,"Impaired formation of the ternary insulin-like growth factor-binding protein complex in patients with hypoglycemia due to nonislet cell tumors. In some subjects with hypoglycemia associated with tumors of mesenchymal origin, high insulin-like growth factor-II (IGF-II) levels have been described in serum and in the tumors. Tumor IGF-II of 10-15 kDa circulates in a 60-kDa complex, in contrast to the ternary 150-kDa complex in which serum IGFs normally circulate together with the IGF-binding subunit (IGFBP-3) and the acid-labile subunit (alpha-subunit). This study examines the molecular distribution and complex-forming activity of the components of the ternary complex in the serum of subjects with mesenchymal tumor hypoglycemia. Total serum IGFBP-3 levels were 60% of normal in tumor patients and appeared at 60 kDa on gel chromatography, shifting after tumor removal to 150 kDa. Total alpha-subunit levels were 40% of normal in patients with tumors, increasing after tumor removal to 70% of normal and changing in elution profile from a peak typical of uncomplexed alpha-subunit to the normal broad peak representing both complexed and uncomplexed alpha-subunit. Although low by RIA, alpha-subunit activity in a ternary complex formation assay was normal, indicating that the ability of free alpha-subunit in the patients' circulation to combine with exogenous IGFBP-3 plus IGF-I was not impaired. In contrast, in an assay that tested the ability of IGF-IGFBP complexes in the patients' circulation to combine with pure alpha-subunit, complex formation activity was 75-85% below normal in preoperative sera, despite low normal IGFBP-3 levels. Therefore, the cause of hypoglycemia in these patients may be the inability of complexes between the abnormal tumor IGF-II and IGFBP-3 to be sequestered in the biologically inactive ternary complex."
-What is the incidence of portal vein thrombosis after distal splenorenal shunt in this study?,"The significance of portal vein thrombosis after distal splenorenal shunt. The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long-term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival."
-What is an iatrogenic epidermoid cyst and how can it occur in the parotid region following ear surgery?,Iatrogenic epidermoid cyst of the parotid region following ear surgery. Iatrogenic implantation of squamous epithelium may result in formation of an epidermoid cyst. These cysts have been described in various sites around the head and neck following otological procedures. A case of iatrogenic epidermal cyst in the parotid region following repeated myringoplasty is reported. The clinical features and differential diagnosis are discussed.
-What are the potential major complications associated with endoscopic sinus surgery?,"Fatal and other major complications of endoscopic sinus surgery. Endoscopic sinus surgery has become an acceptable technique for the treatment of chronic sinus disease. This report analyzes five complications which came to my attention. Two cases were orbital:1 bilateral blindness due to damage of the optic nerves, and 1 damage of medial rectus muscle. The other 3 cases were intracranial:two cribriform plate damage with frontal lobe injury and hematoma, and 1 damage of the anterior cerebral artery, resulting in death. This rather novel technique, especially when used by less-experienced surgeons, has major complications similar to what has been reported with the traditional intranasal sphenoethmoidectomy. Knowledge of anatomy, good training, and meticulous surgical technique are very important. Endoscopic sinus surgery in patients with extensive pathology should be used with caution, especially if general anesthesia is selected or if excessive bleeding occurs. It would be beneficial to otolaryngologists to have previous experience in the traditional technique before adopting endoscopic sinus surgery to their armamentarium. Even then, major complications may occur in the hands of very experienced surgeons. Early recognition and proper management of these complications are of utmost importance in order to minimize disability or prevent death."
-What percentage of brachial plexus blocks were incomplete in this study?,"Brachial plexus anesthesia for outpatient surgical procedures on an upper extremity We retrospectively reviewed 543 brachial plexus blocks performed on 526 outpatients. Most (98%) of the blocks were performed by means of the axillary approach. Various techniques were used, including paresthesia, transarterial fixation, nerve stimulation, or a combination of techniques; a high success rate was achieved with each of them. Only 7% of the blocks were incomplete and thus necessitated either general anesthesia or block supplementation with thiopental sodium and nitrous oxide. No persistent neurologic deficit was ascribed to the anesthetic technique. This review indicates that brachial plexus block, especially with use of the axillary approach, is a safe and effective option for outpatient surgical procedures on an upper extremity."
-What potential side effect did the study observe in patients treated with valproate?,"Valproate-induced coma with ketosis and carnitine insufficiency. We observed two patients who developed coma following administration of valproate in dosages of 32 to 40 mg/kg per day. Valproate levels were within the therapeutic range, and results of liver function studies were normal. Both patients had ketosis and adipic aciduria. Plasma free carnitine levels were decreased during coma and after recovery. One patient excreted ethylmalonic acid, butyrylcarnitine, and glutarylcarnitine during and after resolution of coma, suggesting a multiple acyl coenzyme A dehydrogenation defect. Low serum carnitine levels may predispose patients to development of altered consciousness when treated with valproate."
-What was the effect of increasing doses of flecainide acetate on the occurrence of tachycardia in patients with paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation?,"Flecainide acetate treatment of paroxysmal supraventricular tachycardia and paroxysmal atrial fibrillation: dose-response studies. The Flecainide Supraventricular Tachycardia Study Group. The dose-response relations for efficacy and tolerance of the antiarrhythmic drug flecainide acetate were studied in 28 patients with paroxysmal supraventricular tachycardia (Group 1) and 45 patients with paroxysmal atrial fibrillation or flutter (Group 2). Recurrent symptomatic tachycardia was documented with use of transtelephonic electrocardiographic recording. Patients received flecainide in doses of 25, 50, 100 and 150 mg twice daily and placebo for 1 month treatment periods. Among 14 patients in Group 1 who qualified for efficacy analysis, 4 (29%) had no tachycardia while taking placebo. The number with no tachycardia increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 12 (86%) of 14 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Among 28 patients in Group 2, 2 (7%) had no tachycardia while taking placebo. The number with no tachycardia also increased with progressively larger flecainide doses; with the 150 mg twice daily dose, 17 (61%) of 28 patients had no tachycardia (p less than 0.01 for overall differences among all treatments). Noncardiac adverse experiences were the leading cause of premature study discontinuation during flecainide treatment periods (five patients in Group 1 and six patients in Group 2)."
-How did hydroxyzine affect histamine release and clinical symptoms in patients with chronic urticaria compared to terfenadine and placebo?,"Effects of H1-antihistamine drug regimen on histamine release by nonlesional skin mast cells of patients with chronic urticaria. Profiles of compound 48/80-induced histamine release (HR) from mast cells of uninvolved skin from patients with chronic urticaria (CU) and from a normal control (NC) group were compared, and the effects of anti-H1 medications were assessed versus placebo. Then, patients with CU (15) and NC subjects (10) were randomly assigned to take either hydroxyzine (100 mg/day), terfenadine (120 mg/day), or placebo for 28 days. The effects of such treatment on the clinical response and on the profile of compound 48/80-induced HR during a 4-hour period were analyzed. Treatment with hydroxyzine in patients with CU improved the clinical symptoms and modified the profile of HR; more histamine was recovered at 1 hour (p less than 0.05) and 2 hours (p less than 0.05), as compared with baseline. Terfenadine and placebo had no effect on the clinical response or on the profiles of HR. In the NC group, the amounts of histamine recovered at 1 hour after challenge with compound 48/80 were lower than amounts of the pretherapy values (p less than 0.01). It could be concluded that (1) the profile of HR in patients with CU is reproducible during a period of 28 days, (2) only hydroxyzine modifies both the clinical response and the profile of HR, and (3) anti-H1 compounds decrease the HR in the NC group."
-What treatment was used to resolve the intraventricular hematoma in this case report?,"Lysis of intraventricular hematoma with tissue plasminogen activator. Case report. A 42-year-old woman suffered a severe intracerebral and intraventricular hemorrhage from a ruptured anterior cerebral artery aneurysm. Evacuation of the frontal hematoma and clipping of the aneurysm was performed but the intraventricular blood clot persisted, causing ventricular dilatation and high intracranial pressure (ICP) 24 hours after surgery despite external ventricular drainage. Over this period of time the patient's clinical condition improved from Grade V to Grade IVb (World Federation of Neurological Surgeons classification). The intraventricular hematoma was lysed with a total of 8 mg recombinant tissue plasminogen activator injected directly into the ventricles on the 1st and 2nd postoperative days, resulting in rapid normalization of ventricular size and ICP. The patient has since made a substantial recovery and has been able to return home."
-How does botulinum toxin treatment affect the neurophysiological characteristics of patients with dystonic blepharospasm?,"Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. Botulinum toxin treatment improves dystonic blepharospasm by inducing transient paresis of the orbicularis oculi muscle. It is not known if it also reduces the enhanced brainstem neuronal excitability found in this disorder. We have performed conventional electromyography (EMG) and blink reflex excitability studies on fifteen patients with blepharospasm before and after botulinum toxin treatment. Denervation signs were found with needle EMG in all treated muscles. Amplitude of the facial compound muscle action potential (CMAP) and R1 response was reduced after botulinum toxin injections. In blink reflex excitability studies, the recovery of R2 response was enhanced after treatment even when patients were tested at the time of maximal benefit from botulinum toxin injections. The results suggest that there is little influence of botulinum toxin treatment upon the enhanced excitability of brainstem interneurons in patients with blepharospasm."
-What are the key diagnostic criteria for quadrilateral space syndrome according to the context?,"Quadrilateral space syndrome: diagnosis and operative decompression technique. We present a series of five patients with quadrilateral space syndrome. All patients had the diagnosis made on the basis of (1) tenderness over the quadrilateral space, (2) paresthesia over the lateral shoulder and upper posterior arm, and (3) deltoid weakness associated with decreased shoulder abduction. A history of trauma was present in each patient. The operative technique described utilizes a cosmetically acceptable incision and is without the need to divide the deltoid from its origin on the scapular spine. The technique minimizes postoperative bleeding and facilities rehabilitation. Arteriography of the posterior circumflex humeral artery was not found necessary to make the diagnosis of axillary nerve entrapment in the quadrilateral space."
-What were the observed effects of the TRH analogue (RX77368) on patients with motor neuron disease?,"Comparative efficacy and safety of intravenous and oral administration of a TRH analogue (RX77368) in motor neuron disease. Ten consecutive patients with motor neuron disease (MND) who had bulbar symptoms received one or two intravenous doses followed by increasing oral doses of a TRH analogue (RX77368). Similar improvements in speech, swallowing and in tongue and jaw movements were seen after iv and oral administration in nine, five and eight patients respectively. The initial time course of improvement correlated with increasing plasma levels of the drug, but most clinical effects persisted when the levels decreased and became undetectable after 24 hours. The oral solution was tasteless and had no, or minimal, side effects."
-What is the purpose of the clinical trial involving Cronassial in patients with Chagas' disease?,"Chagas' cardioneuropathy: effect of ganglioside treatment in chronic dysautonomic patients--a randomized, double-blind, parallel, placebo-controlled study. To date, there is no effective pharmacologic treatment for Chagas' cardioneuropathy, one of the most common causes of congestive heart failure and sudden death in the world. Fifty-eight adults with positive serology for Chagas' disease and abnormal autonomic nervous system tests participated in this placebo-controlled clinical trial with Cronassial (mixed gangliosides), 40 mg daily intramuscular injection for 4 or 8 weeks. We measured postural response (heart rate, systolic and diastolic arterial blood pressure changes in response to standing); heart rate changes induced by cough and hyperventilation reflex tests; dizziness on standing; number of stress-induced arrhythmias; and periodic acid-Schiff (PAS)-positive T-lymphocyte percentage in blood samples. Cronassial is safe and significantly improves systolic blood pressure (p = 0.050) and double product responses to postural stress (p = 0.028), hyperventilation heart rate response (p = 0.007), frequency of dizziness episodes (p less than 0.001), number of arrhythmias (p = 0.033), and percentage of PAS-positive T-lymphocyte counts (p less than 0.001) compared with placebo."
-What were the two methods compared in this study for preventing bone reunion after midline craniectomy for sagittal suture synostosis?,"Midline craniectomy for sagittal suture synostosis: comparative efficacy of two barriers to calvarial reclosure. This report quantitatively compares long-term head remolding achieved by two methods for retarding bone reunion after midline craniectomy for sagittal suture synostosis. In one group of six children the adjacent bone edges were overlayed with 1.0-cm-wide U-channel silicone strips, and in the other group, composed of seven patients, a considerably larger extent of the adjacent cranium was covered with silicone sheets. Mean percent change in the cephalic indices of the former group 18 months postoperatively was 9.1% +/- S.D. = 6.7, and of the latter group 23.7% +/- S.D. = 6.0 (p congruent to 0.01). These results indicate that the use of large silicone sheets lead to a significantly greater normalization of cranial proportions."
-What are the potential consequences of prolonged hiccups that may require medical intervention?,"Hiccups (singultus): review and approach to management. Hiccups are a common, and fortunately usually transient, benign malady. Occasionally, however, hiccups fail to resolve spontaneously, resulting in patient fatigue and incapacitation and the need for the affected individual to seek medical care for resolution of the problem. The approach to the management of these patients consists of the identification and treatment of serious underlying causes of the episode as well as therapeutic interventions to achieve hiccup resolution."
-Where was corticotropin-releasing hormone (CRH) immunoreactivity found in the human placenta and fetal membranes during gestation?,"The localization and distribution of corticotropin-releasing hormone in the human placenta and fetal membranes throughout gestation. Using immunohistochemical techniques, we have determined the localization and distribution of CRH immunoreactivity (CRH-IR) in the human placenta, fetal membranes, decidua, and umbilical cord. Tissues were obtained at 6-8 weeks of pregnancy, at term, in association with premature birth, and from patients with pregnancy-induced hypertension or diabetes mellitus. A polyclonal antibody to the epithelial cell marker cytokeratin was used to identify trophoblast cells. CRH-IR was not detected in placenta or decidua at 6-8 weeks gestation. In tissues obtained after idiopathic premature delivery after 21 weeks gestation, positive CRH staining was found in placenta in syncytiotrophoblast and intermediate trophoblast, but not cytotrophoblast. CRH-IR was present in intermediate trophoblast cells that had invaded maternal blood vessels in decidua basalis. In the fetal membranes, CRH-IR was localized in the epithelium and subepithelial cells of amnion, in the trophoblast layer, in some cells of the reticular and cellular layers of chorion, and in some stromal cells and invasive trophoblast cells of decidua. CRH-IR was found in the amniotic epithelium of the umbilical cord and in the musculature of the umbilical vessels. This pattern of distribution of CRH-IR was found in tissues from 21 weeks gestation to term and postterm, and was similar in tissues examined from patients with pregnancy-induced hypertension and diabetes mellitus. These results show clearly that in placenta and membranes, CRH is localized primarily to syncytiotrophoblast and intermediate trophoblast, but not to cytotrophoblast cells. We suggest that the localization of CRH-IR is consistent with CRH affecting paracrine/autocrine interactions within the placenta, fetal membranes, and decidua that may be involved in the maturation of the fetal hypothalamic-pituitary-adrenal axis and in the stimulus and maintainance of labor."
-How does brain temperature affect the cerebral metabolic rate of oxygen consumption (CMRO2) in dogs during hypothermia?,"The relationship among canine brain temperature, metabolism, and function during hypothermia. Cerebral protection by hypothermia is commonly attributed to cerebral metabolic suppression. However, at temperatures below 28 degrees C, the relationship of temperature to cerebral metabolic rate of oxygen consumption (CMRO2) has not been well characterized. Accordingly, the relationship between brain temperature and CMRO2 was determined in eight dogs during cooling from 37 to 14 degrees C while the EEG was continuously monitored. Cardiopulmonary bypass was initiated and control measurements were made at 37 degrees C during anesthesia with nitrous oxide 50-60% inspired and morphine sulfate 2 mg.kg-1 intravenously (iv). Upon cooling to 27 degrees C, the nitrous oxide was discontinued and the morphine was antagonized with naloxone 2 mg iv. Measurements were repeated at 27, 22, 18, and 14 degrees C and in four dogs again at 37 degrees C after nitrous oxide 50-60% had been reestablished at 27 degrees C along with administration of morphine sulfate 2 mg.kg-1. For each temperature interval, the temperature coefficient (Q10) for CMRO2 was calculated (Q10 = CMRO2 at x degrees C divided by CMRO2 at [x - 10] degrees C). Between 37 and 27 degrees C the Q10 was 2.23, but between 27 and 14 degrees C the mean Q10 was doubled to 4.53. With rewarming to 37 degrees C, CBF and CMRO2 returned to control levels, and brain biopsies revealed a normal brain energy state. During cooling, the EEG developed burst suppression at or below 22 degrees C. With further cooling, the periods of suppression increased; however, burst activity continued in seven of eight dogs even at 14 degrees C."
-What was the most significant prognostic factor for local recurrence in breast cancer patients treated with conservative surgery and radiation therapy?,"Prognostic factors for local recurrence in the conservatively treated breast cancer patient: a cautious interpretation of the data. Between 1962 and 1984, a total of 433 patients were treated at Yale-New Haven Hospital with conservative surgery and radiation therapy (CS + RT) to the intact breast. As of January 1990, with a minimum assessable follow-up of 5 years and a median follow-up of 8.21 years, there have been a total of 50 breast recurrences resulting in a 5-year actuarial breast recurrence rate of 8%. Of all clinical factors tested, young age was the most significant prognostic factor for local recurrence (P less than .03). In addition, patients with pathologically involved lymph nodes were noted to have a lower local recurrence rate than patients with pathologically negative axillae (P less than .05). These findings were especially notable given the fact that the node-positive group had a higher percentage of T2 tumors and a higher percentage of patients in the young age group. These paradoxical findings, however, may be explained by the fact that 88% of the node-positive patients underwent adjuvant systemic therapy in the form of either systemic chemotherapy or hormonal therapy, while only 8% of node-negative patients underwent any adjuvant systemic therapy. When analyzed as a function of adjuvant therapy, those patients receiving adjuvant therapy had a lower local recurrence rate than those patients not receiving adjuvant therapy (P less than .08). We conclude that adjuvant systemic therapy impacts on the ipsilateral breast recurrence rate in patients treated with CS + RT. The implications of this study in light of the widespread use of adjuvant systemic therapy are discussed."
-What are the primary pathophysiologic mechanisms believed to cause sciatica?,"Pathophysiology of sciatica. The exact pathophysiologic mechanisms behind sciatica are incompletely known; however, compression of spinal nerve roots is known to be correlated to both pain and neural dysfunction in a segmental distribution of that specific nerve root. Compression per se may impair the transport of nutrients to the nerve tissue in such a way that affects the nerve root function. There also might be a local affect on nerve roots or root sleeves by substances leaking from the degenerated intervertebral discs."
-What were the main indications for surgical management of extracranial vertebral artery occlusive disease in this study?,"Surgical management of extracranial vertebral artery occlusive disease. Thirty-seven consecutive patients underwent vertebral artery (VA) reconstruction over a 6 years period (1983-1989). Detailed neurologic, medical, and angiographic information was obtained for all patients. Indications for surgery were as follows: (1) stenosis of VA with symptoms of vertebrobasilar insufficiency; (2) very tight stenosis (greater than 75%) of the dominant VA with stenosis or occlusion of the contralateral VA; (3) very tight stenosis of VA with bilateral occlusion of the internal carotid artery (ICA); (4) very tight stenosis of VA with homolateral ICA lesion eligible for simultaneous repair; (5) very tight stenosis of VA and very tight stenosis of the homo or contralateral carotid siphon. There were 15 isolated vertebral lesions (group I), and 22 were VA lesions associated with lesions of the supraaortic trunks which were simultaneously treated (group II). The reconstructions of the first portion of the VA were 30 (12 of group I and 18 of group II) and reimplantation of the VA into the common carotid artery was the procedure of choice. There were 7 revascularizations of the third portion of the VA at C1-C2 level (3 of group I and 4 of group II): carotid-vertebral bypass, using an autogenous vein graft, was the procedure of choice. Three patients in group II died in the immediate postoperative period from myocardial infarction but no patient presented immediate postoperative neurologic deficits. All symptomatic patients but one were relieved of their symptoms in a median follow-up of 31 months. No postoperative complications were observed. Long-term results were satisfactory in all the 28 patients at their last follow-up visit."
-What did the study reveal about transesophageal echocardiography's sensitivity in detecting mitral regurgitation in St. Jude Medical mitral valve prostheses?,"Transesophageal color Doppler echocardiography of the normal St. Jude Medical mitral valve prosthesis. Transesophageal color flow Doppler findings are reported in 36 patients with a St. Jude Medical mechanical mitral valve prosthesis who had no auscultatory evidence for prosthetic valve dysfunction. Multiple jets consistent with mitral regurgitation originating from the central and lateral portion of the prosthesis were found in all patients. Maximum jet length ranged from 11 to 51 mm (mean 21 +/- 9 mm). Maximum jet area ranged from 0.2 to 4.1 cm3 (mean 1.2 +/- 0.9 cm2). The color M-mode Doppler interrogation showed two distinct components of the regurgitant jet: brief early systolic flow consistent with valve closure followed by holosystolic regurgitant flow consistent with transvalvular leakage. Four patients (11%) had a maximum regurgitant jet length exceeding 30 mm and absence of early systolic closure regurgitant flow by M-mode color imaging, suggesting clinically silent paravalvular leakage. Two pin-sized paravalvular suture line defects were confirmed in one patient at cardiac transplantation. We conclude that transesophageal echocardiography is a highly sensitive method for detection of mitral regurgitation in the St. Jude Medical mitral prosthesis. Clinically silent paravalvular leakage should be suspected if the maximum jet length exceeds 30 mm and color M-mode interrogation fails to demonstrate an early systolic closure regurgitant flow component."
-What factors have contributed to the recent reductions in liver cirrhosis deaths in Western countries?,"Factors in recent reductions in liver cirrhosis deaths. Since the mid-1970s, there have been substantial declines in liver cirrhosis deaths in many Western countries following a long period of increases. There is variability in the pattern of changes observed: in a sample of 29 countries between 1974 and 1982-83, seven countries showed a significant linear decline, three revealed a curvilinear pattern, increases were observed in six and the rest (13) showed no notable changes. Although reductions in per capita consumption of alcohol may be a contributing factor, these reductions do not seem to account for all of the decreases in cirrhosis deaths that have been observed. Among other factors that might contribute, changes or increases in treatment for alcohol abuse and AA membership have been most strongly linked to these declines; changes in patterns of consumption, dietary habits, prevention efforts and reduced exposure to predisposing factors may also be involved. In view of the importance of these declines for the understanding and prevention of alcohol problems, further research on this issue, perhaps involving international collaborative studies, is needed."
-"What are the key ultrastructural differences observed between adenomyotic glandular epithelium, proliferative endometrium, and well-differentiated endometrial cancer?",Ultrastructural study of glandular epithelium in adenomyosis in comparison with those of proliferative endometrium and well-differentiated endometrial cancer. Adenomyotic glandular tissue from five patients underwent electron microscopic investigation to observe its ultrastructural characteristics. The adenomyotic epithelium was compared with that of proliferative normal epithelium (two patients) and well-differentiated endometrial adenocarcinoma (two patients). The results revealed that morphologically the adenomyotic glandular epithelium is somewhat less differentiated than proliferative endometrium and that its cytoplasmic organelles have some similarities with those of endometrial cancer. Whether these similarities predispose the adenomyotic glandular tissue to malignant degeneration remains to be elucidated.
-What advantages did the 48 by 48 element biplane transesophageal probe offer compared to single-plane probes?,"Initial clinical experience with a 48 by 48 element biplane transesophageal probe. Recent technologic advances in ultrasound have resulted in the capability of transesophageal echocardiographic imaging in both transverse and longitudinal planes. Previous biplane probes suffered from inferior images because of reduced scan elements. We evaluated the utility of a prototype 48 X 48 element biplane transesophageal probe in 23 consecutive patients. Examinations were well tolerated with no side effects. In comparison to the single transverse plane, imaging with the longitudinal plane gave superior information on prosthetic valve pathology, atrial septal abnormalities, and pathoanatomy of the ascending aorta and mitral valve. Complementary information was provided by the longitudinal plane in patients with endocarditis and vegetations and in mitral protheses. Images obtained with this 48 X 48 element biplane probe along with color and spectral Doppler information were not perceptibly inferior to those obtained by single-plane probes. In conclusion, biplane transesophageal echocardiography with a 48 X 48 element probe indicates a great potential for enhanced three-dimensional understanding of cardiac pathology and diagnostic yield in specific pathologies."
-What is Klippel-Trenaunay syndrome (KTS) and what are its primary clinical characteristics?,"Klippel-Trenaunay syndrome: the risks and benefits of vascular interventions. Our experience with Klippel-Trenaunay syndrome (KTS), a rare congenital malformation, has increased considerably in recent years and now includes 144 patients (65 male and 79 female patients). Hemangioma was present in 137 patients (95.1%), varicosity in 110 (76.4%), and hypertrophy of the soft tissues or bones in 134 (93.1%). In most patients (71.5%) the disease involved one lower extremity. Diagnostic workup included roentgenogram to document limb length discrepancy, noninvasive arterial and venous evaluation, contrast venography, and nuclear magnetic resonance imaging. Most patients did well without treatment or with elastic compression only. Surgical treatment for the vascular malformation in KTS is rarely needed and it continues to be controversial. To evaluate the risks and benefits of vascular interventions, we examined in detail the clinical histories of nine patients who in the last decade underwent operation for a vascular malformation of the lower extremity. In seven patients we removed varicose veins or resected hemangioma of the lower extremity. Although none was cured, all five who underwent resection of varicose veins and one of the two patients who underwent resection of a hemangioma improved. Two additional patients, however, who underwent resection of varicose veins in another institution had worsening of the symptoms. In one patient we performed deep venous reconstruction for atresia of the superficial femoral vein, using the contralateral saphenous vein. Such operation in KTS has not been reported previously. The patient has a patent graft with a competent valve and clinical improvement 6 months after the operation. Although patients with severe chronic venous insufficiency, disturbing cosmetic appearance, or complications of hemangioma may benefit from surgical treatment, detailed preoperative imaging of the extremity and pelvis with magnetic resonance imaging and contrast venography is needed to decrease complications. Rarely, reconstruction for atresia or hypoplasia of the deep veins may be needed."
-How does platelet function change in patients with symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage?,"Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage. To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage."
-What technique was used to minimize postoperative hypotony in Molteno glaucoma implant procedures?,"The use of releasable sutures in Molteno glaucoma implant procedures to reduce postoperative hypotony. We used releasable sutures to minimize immediate postoperative hypotony and flat anterior chamber in 19 cases of refractory glaucoma requiring insertion of a single-plate Molteno implant in a one-stage procedure. A slip knot using 7-0 nylon suture was fashioned around the Molteno tube under a lamellar scleral flap. In 18 of the 19 eyes, anterior chamber depth was normal immediately after surgery."
-What was the purpose of using tissue-type plasminogen activator (tPA) in this study on subarachnoid hemorrhage patients?,"Prevention of vasospasm by clot removal and intrathecal bolus injection of tissue-type plasminogen activator: preliminary report. In this study, we evaluated the efficacy of postoperative intrathecal injections of tissue-type plasminogen activator (tPA) in preventing cerebral vasospasm in cases with a diffuse severe subarachnoid hemorrhage. All 10 cases were graded Group 3 according to the classification of Fisher and associates, and the CT number (Hounsfield number) of the subarachnoid clot was over 75. After clipping the aneurysm and removing the clot, three cisternal drainage catheters were inserted into both sylvian cisterns and the prepontine cistern, and continuous ventricular drainage was performed routinely. Postoperatively, tPA (0.5 mg/2.5 ml) was infused as a bolus into both basal cisterns and the lateral ventricle twice daily for about 6 days. Angiography and cerebral blood flow studies using single photon emission computed tomography were performed on Day 4 or 5 and between Days 7 and 10 after onset of the hemorrhage. To date, there have been no cases that have shown angiographic vasospasm or delayed ischemic neurological deficits. This preliminary study indicates that the intrathecal bolus injection of tPA produces a marked effect on vasospasm."
-What were the two most important independent prognostic factors for survival in this study of vulvar carcinoma?,"Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study). Analysis of 588 patients with vulvar carcinoma delineated four risk groups by the proportional hazards model. Groin node status (laterality and number positive) and lesion diameter were the only two important independent prognostic factors. The 5-year relative survival rates were 98%, 87%, 75%, and 29% for the risk group categories of minimal (negative groin nodes and lesion diameter less than or equal to 2 cm), low (one positive groin node and lesion diameter less than or equal to 2 cm or negative groin nodes and fewer than two lesions less than or equal to 8 cm diameter), intermediate (negative groin nodes and lesion diameter greater than 8 cm diameter, one positive groin node and lesion diameter greater than 2 cm, or two unilaterally positive groin nodes and lesion diameter less than or equal to 8 cm), and high (three or more positive groin nodes or two bilaterally positive groin nodes), respectively. Applying the International Federation of Gynecology and Obstetrics staging (1988) to these data discriminated risk of death (caused by recurrent vulvar cancer); the 5-year rates were 98%, 85%, 74%, and 31% for stages I, II, III, and IV, respectively. However, within International Federation of Gynecology and Obstetrics stage III there were 47 low-, 95 intermediate-, and 28 high-risk patients with relative survivals of 95%, 74%, and 34%, respectively. Overall, this assessment validates current International Federation of Gynecology and Obstetrics vulvar carcinoma staging, but further refinements are warranted in stage III."
-What diagnostic technique was used to study regional cerebral blood flow in a patient with alternating hemiplegia?,"Ictal 99mTc-HMPAO SPECT in alternating hemiplegia. 99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) was performed in a patient with alternating hemiplegia during 2 episodes of the disease. The regional cerebral blood flow patterns correlated with the clinical manifestations during both episodes. Hyperperfusion of the contralateral hemisphere was suggested by asymmetric 99mTc-HMPAO uptake, whereas symmetric 123I-N-isopropyl-p-iodoamphetamine uptake was detected during the interictal period. The results suggested that alternating hemiplegia in infants represents an atypical manifestation of epilepsy, despite the lack of paroxysmal electroencephalographic abnormalities during the episodes. 99mTc-HMPAO SPECT appears to be a useful method for detecting transient regional cerebral blood flow alterations during paroxysmal events because the tracer is rapidly available for emergencies and retains a fixed distribution for 5-8 hours, sufficient time to allow for SPECT acquisition."
-What are the distinctive clinical characteristics of native valve endocarditis caused by Staphylococcus epidermidis compared to endocarditis caused by other organisms?,"Native valve Staphylococcus epidermidis endocarditis: report of seven cases and review of the literature. This report describes seven patients from three university hospitals whose native valve infective endocarditis was caused by Staphylococcus epidermidis. The literature on endocarditis caused by S. epidermidis is also reviewed and the clinical features of patients with native valve endocarditis due to this organism are compared with those of patients from a general series of infective endocarditis cases. Compared with infective endocarditis caused by other organisms, S. epidermidis endocarditis tends to occur more frequently in male patients. Patients with S. epidermidis endocarditis exhibit fewer embolic complications and skin manifestations. The frequency of congestive heart failure is lower in this group. The relative indolent course and apparent rarity of native valve S. epidermidis endocarditis necessitate a high index of suspicion for early diagnosis."
-What was the maximum hypothermic preservation time for skeletal muscle in rat hindlimbs using Euro-Collins solution?,"Preservation of skeletal muscle in tissue transfers using rat hindlimbs. Replantation of major extremities after long periods of ischemia can lead to viable replants in many cases, but functional restoration is often poor owing to fibrosis of the muscle. In this study, maximum hypothermic time in tissue transfers containing skeletal muscle using hindlimbs of Lewis rats preserved in 4 degrees C Euro-Collins solution was investigated. After preserving midthigh amputated legs in this solution for 6, 9, and 12 hours, the legs were transplanted to other inbred rats using microsurgical technique, and 1 week later, gastrocnemii were obtained to analyze ATP, ADP, and AMP using high-performance liquid chromatography. The values were compared with those for healthy legs, nonischemic operated control legs, and legs preserved in the same manner for 6, 9, and 12 hours. Histologic and serologic examinations were conducted. ATP values of the 9-hour preservation group resumed those of the nonischemic operated control group, with the values of the 12-hour preservation group remaining at 61 percent. Histologically, focal necrosis, hyaline degeneration, and regeneration processes were the most characteristic manifestations in the muscles transplanted after cold ischemia of 12 hours. It was concluded that skeletal muscle could be preserved for 9 hours in 4 degrees C Euro-Collins solution."
-What is Henoch-Schonlein purpura and how does it affect children according to the surgical evaluation in this study?,"Surgical evaluation of Henoch-Schonlein purpura. Experience with 110 children. Henoch-Schonlein purpura is a disorder of unknown origin that is probably related to an autoimmune phenomenon. This report concerns 110 children (mean age, 6.2 years; range, 6 months to 14 years) with Henoch-Schonlein purpura. Seventy-two (65%) had abdominal pain associated with nausea and vomiting, bloody stool, and upper gastrointestinal bleeding. Sixty patients with abdominal pain were evaluated and treated conservatively. However, 12 patients underwent laparotomy. Six underwent unnecessary appendectomy for wrongly diagnosed appendicitis. Bowel resection was performed in one patient for an obstructive ileal lesion. Six additional patients had intussusception; surgery was required in three, while barium enema reduction was successfully accomplished in three others. Massive gastric hemorrhage required ligation, vagotomy, and pyloroplasty in two instances. One child with severe scrotal pain, hemorrhage, and swelling underwent unnecessary scrotal exploration. Four additional patients with similar symptoms avoided operation after a testicular scintiscan demonstrated good blood flow. A high index of suspicion and early diagnosis of Henoch-Schonlein purpura based on clinical, roentgenographic, and laboratory findings may avoid unnecessary operations in most cases. However, life-threatening complications (hemorrhage, obstruction, and intussusception) may occur and require operative intervention. All of the patients survived."
-How did chronic hypoxia affect the cardiovascular parameters of spontaneously hypertensive rats in the study?,"Effects of atrial natriuretic factor in chronic hypoxic spontaneously hypertensive rats. The present study was designed first to investigate the pulmonary hypertensive effects of chronic hypoxia in spontaneously hypertensive rats and second to compare the cardiovascular effects of atrial natriuretic factor on rats exposed to hypoxia and on control rats kept at sea level. Catheters were placed in the femoral and pulmonary arteries for measurement of mean systemic arterial pressure and mean pulmonary arterial pressure. The cardiac output was measured by thermodilution method. It was found that 4 weeks of simulated 18,000-foot hypoxia led to polycythemia, right ventricular hypertrophy, and pulmonary hypertension, which resulted from an increased pulmonary vascular resistance. However, systemic arterial pressure was not significantly different between the two groups of rats. Atrial natriuretic factor administration decreased systemic arterial pressure and pulmonary arterial pressure to a lesser extent in the hypoxic group compared with the sea level control group. It is concluded that these animals showed an impaired response to atrial natriuretic factor after long-term exposure to hypoxia."
-How did the second cerebrovascular accident affect the patient's long-standing hyperpathia in the right upper extremity?,"Disappearance of thalamic pain after parietal subcortical stroke. A hypertensive man had a long standing history of contumacious hyperpathia in the right upper extremity, resistant to medical therapy, secondary to a lacunar infarct in the left thalamus. A second cerebrovascular accident caused a small lesion in the left corona radiata, interrupting the thalamoparietal interconnections, and terminated the pain instantly. Interruption of the subcortical parietal white matter may more effectively control pain than cortical lesions. A few surgeons have successfully treated rebellious chronic pain with stereotaxic operations in the corona radiata, resulting in lesions very similar to our patient's. This overlooked and nearly forgotten technique may still have value in treating selected cases."
-What percentage of unselected blood donors were found to have antibodies to hepatitis C virus in the United Kingdom study?,"Hepatitis C virus antibodies in subjects with and without liver disease in the United Kingdom. The prevalence of antibody to hepatitis C virus, evidence of previous or current infection with this agent of parenterally transmitted non-A, non-B hepatitis, was determined in 340 subjects residing in the United Kingdom. The antibody was detected in 3 per cent of unselected blood donors and in 60 per cent of patients with chronic post-transfusion non-A, non-B hepatitis. Evidence for infection was also found in 30 per cent of intravenous drug abusers, and in 75 per cent of haemophiliacs receiving commercial factor VIII concentrate. The infection is uncommon in renal units and amongst sexually promiscuous groups attending sexually-transmitted disease clinics. Although the seropositivity rate in primary biliary cirrhosis and chronic B and delta hepatitis was very low (0-2 per cent), in patients with autoimmune and alcoholic liver disease it was 14-16 per cent which, although lower than that quoted in studies from Spain and Italy, is considerably higher than would be expected by chance. The reason for the high incidence of non-A, non-B hepatitis in this latter group of patients is unclear."
-What medical interventions were used to control blood pressure in the patient with severe hypertension after renal artery injury?,"Severe hypertension with segmental renal infarction following surgical removal of a retroperitoneal malignant hemangiopericytoma: a case report. Severe hypertension developed in a fifty-five year-old woman after surgical removal of a retroperitoneal tumor, when the renal artery was injured. Renal arteriography after the surgery demonstrated a segmental infarction of the right kidney. A close relationship between activation of the renin-angiotensin system and the development of severe hypertension was observed. Satisfactory control of blood pressure concomitant with reduction of plasma renin activity was achieved by a combination of an angiotensin-converting anzyme inhibitor, beta-blocking agent, and calcium-entry blocker. The mechanism of activation of the renin-angiotensin system in renal infarction is discussed."
-What were the predialysis atrial natriuretic peptide (ANP) levels in the three patient groups studied?,"Atrial natriuretic peptide in dialysis patients under various conditions of volume homeostasis. Atrial natriuretic peptide (ANP) and plasma renin activity (PRA) were studied in 19 patients with end-stage renal disease (ESRD) under haemodialysis (HD). On the basis of clinical findings, patients were divided into three groups: group A, 6 patients, of mean age 41 +/- 15 years, without heart failure and in need of ultrafiltration (658 +/- 282 ml h-1); group B, 6 patients, of mean age 54 +/- 15 years, without heart failure under isovolaemic HD; group C, 7 patients, of mean age 60 +/- 3 years, with heart failure (NYHA III-IV) and in need of ultrafiltration (607 +/- 120 ml h-1). The highest predialysis ANP levels were found in group C (1534 +/- 471 pg ml-1) followed by group A (476 +/- 168 pg ml-1) and group B (236 +/- 138 pg ml-1) (normal range 62 +/- 27 pg ml-1). Systolic and diastolic blood pressure and heart rate did not correlate with ANP levels in either of the groups. However, iso-osmotic reduction of the body weight by ultrafiltration was correlated with decreasing ANP levels during HD (for groups A and C, r = 0.88 and 0.98, respectively). Isovolaemic HD did not alter ANP concentrations (group B). All patients received a volume bolus at the end of HD, and they responded with an instant increase in ANP concentration, which was most pronounced in patients with concomitant heart failure. PRA was not significantly correlated with ANP levels during HD. In conclusion, the results of this study indicate that there is a sensitive response of ANP levels to changes in body fluid status in ESRD."
-What were the key findings of the Early Treatment Diabetic Retinopathy Study (ETDRS) regarding aspirin treatment for diabetic retinopathy?,"Effects of aspirin treatment on diabetic retinopathy. ETDRS report number 8. Early Treatment Diabetic Retinopathy Study Research Group. Aspirin treatment did not alter the course of diabetic retinopathy in patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). In this randomized clinical trial supported by the National Eye Institute, 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy were assigned randomly to either aspirin (650 mg per day) or placebo. Aspirin did not prevent the development of high-risk proliferative retinopathy and did not reduce the risk of visual loss, nor did it increase the risk of vitreous hemorrhage. This was true both for eyes assigned randomly to deferral of photocoagulation and for eyes assigned randomly to early argon laser photocoagulation. The ETDRS results indicate that for patients with mild-to-severe non-proliferative or early proliferative diabetic retinopathy, it is likely that aspirin has no clinically important beneficial effects on the progression of retinopathy. The data also show that aspirin 650 mg per day had no clinically important harmful effects for diabetic patients with retinopathy. These findings suggest there are no ocular contraindications to aspirin when required for cardiovascular disease or other medical indications."
-What were the key findings of the Medical Research Council European trial comparing chorion villus sampling and amniocentesis for prenatal diagnosis?,"Medical Research Council European trial of chorion villus sampling. MRC working party on the evaluation of chorion villus sampling. First-trimester chorion villus sampling has the advantage over second-trimester amniocentesis of allowing earlier prenatal diagnosis of various genetic and cytogenetic disorders in the fetus (and therefore earlier termination in affected pregnancies) but the relative safety and diagnostic accuracy remain unclear. Between 1985 and 1989, 3248 women seeking prenatal diagnosis, principally because of their age, were recruited to an international, multicentre, randomised comparison of the safety and diagnostic accuracy of the two techniques--5% of women allocated chorion villus sampling and 8% of those allocated amniocentesis were not tested, usually because of spontaneous miscarriage. 6% and 2% were retested, in most because of sampling failure. The endpoint of a liveborn infant who survived was achieved by 86% of women allocated chorion villus sampling and 91% of those allocated amniocentesis; statistical analysis, after appropriate weighting for a centre's contribution, showed that the typical difference between the groups was 4.6% (95% confidence interval 1.6-7.5%; p less than 0.01). This difference reflected more spontaneous fetal deaths before 28 weeks' gestation (2.9% [0.6-5.3%]); more terminations of pregnancy for chromosomal anomalies (1.0% [0.0-2.1%]); and more neonatal deaths (0.3% [-0.1 to 0.7%]). The difference in neonatal deaths was due to a preponderance of very immature liveborn infants in the chorion villus sampling group, and this factor also explained that group's longer mean stay in hospital. More abnormal diagnoses followed chorion villus than amniotic fluid analyses (5.6% vs 3.9%). This difference was largely due to diagnoses of trisomy 18 and of (usually mosaic) abnormalities known to be confined to the placenta. 3 terminated pregnancies were false positives, 1 tested by chorion villus sampling and 2 by amniocentesis, and 2 other mosaic cases diagnosed by chorion villus sampling may have been false positives. There was 1 false-negative result in the chorion villus sampling group. The possibility of earlier exclusion or diagnosis of some fetal disorders afforded by first-trimester chorion villus sampling must be set against its clinical risks."
-What were the key findings of the Ontario Child Health Study regarding the psychosocial characteristics of parents with children who have chronic health problems?,"Children with chronic illness: family and parent demographic characteristics and psychosocial adjustment. This paper presents the results of an epidemiologic study that compares and contrasts psychosocial characteristics of parents and family units of children with chronic illness or physical disability (chronic health problems) with those of healthy children. Data were derived from the Ontario Child Health Study of 1869 randomly selected families, with 3294 children aged 4 to 16 years. In the absence of significant differences between parents and families of children with chronic illness alone and those with physical disability, these groups were combined for analysis, for which odds ratios (OR) or t tests were used. Significant positive findings included increased rates of parental treatment for ""nerves"" (mothers' OR = 2.1, fathers' OR = 1.9) and increased maternal negative affect scores (Bradburn Affect Balance Scale) (P less than .001) among parents of children with chronic health problems. Important negative findings (95% confidence interval of the OR included 1) included no increase in single-parent families (OR = 1.2), social isolation (OR = 1.0), or alcohol problems (OR = 1.2) among parents of children with chronic health problems. Categorically defined family dysfunction did not differ between the two groups (OR = 1.1). These data contrast with several clinic-based studies and suggest that, in a widely generalizable population survey, families of children with chronic health problems including physical disability do not suffer a marked excess of dysfunction, although some indicators of individual parent psychosocial problems were modestly elevated."
-What was the key finding regarding IL-4 and IL-2 mRNA levels in mice infected with Schistosoma mansoni?,"In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4 mRNA, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymph nodes, and spleens of infected mice. Using Northern Blot analysis, the endogenous levels of IL-4 and IL-2 mRNA in the spleens, mesenteric lymph nodes, and granulomatous livers of male CBA/J mice in the acute phase of infection with Schistosoma mansoni have been quantified. High levels of IL-4 mRNA were detected in all three tissues from infected mice, whereas none was detected in tissues from normal, uninfected, age-matched mice. Isolation of the granulomas from the livers of infected mice and subsequent extraction of total RNA from these lesions resulted in a 70-fold enrichment of IL-4 message compared with the whole, unseparated granulomatous liver tissue. Hence, the predominant source of the IL-4 mRNA detected in livers from infected mice appears to be the schistosome egg-induced granulomas within these livers. In contrast, IL-2 mRNA was never detected in any of these tissues from either infected or normal mice. Control experiments were performed that ruled out the possibility that this inability to detect IL-2 mRNA was due to a difference in the efficacy of the IL-4 and IL-2 probes or due to a selective lability of IL-2 message. These data imply that IL-4-producing, Th2 lymphocytes are active in and possibly integral to the granulomatous, delayed-type hypersensitivity response characteristic of this infection, and directly challenges the current hypothesis that delayed-type hypersensitivity responses are exclusively mediated by Th1 lymphocytes."
-What cardiac disturbances were observed in patients receiving taxol during clinical trials?,"Cardiac disturbances during the administration of taxol. The clinical development of taxol, a new antimicrotubule agent with a unique mechanism of cytotoxic action, has proceeded slowly due to serious hypersensitivity reactions (HSRs) and shortages in its supply. Nevertheless, large-scale phase II trials have been initiated as taxol has recently demonstrated impressive activity in advanced and cisplatin-refractory ovarian carcinoma. Furthermore, the incidence of HSRs has been reduced substantially with premedications and modifications in the administration schedule. However, various manifestations of potential cardiotoxicity have been observed in several patients who participated in four phase I and II studies of taxol. Asymptomatic bradycardia has occurred in a high proportion of patients, including 29% of ovarian cancer patients who were treated with maximally tolerated doses of taxol in a phase II study. More profound cardiac disturbances, including a range of atrioventricular conduction blocks, left bundle branch block, ventricular tachycardia (VT), and manifestations of cardiac ischemia, have been observed in seven of 140 patients (5%) who received taxol. Descriptions of these events are presented in this report to alert investigators to the potential for these adverse effects. Although these disturbances did not result in serious sequelae in most patients, investigators should continue to maintain a high degree of caution until precise risk factors, frequency, and clinical significance of these adverse cardiac effects are determined."
-What was the cause of subarachnoid hemorrhage in the seventy-one-year-old Japanese man?,"Mycotic (Aspergillus) arteritis resulting in fatal subarachnoid hemorrhage: a case report. A seventy-one year-old Japanese man suffering from carcinoma of the common bile duct died from subarachnoid hemorrhage secondary in intracranial mycotic arteritis (MA). Repeated cultures of the discharge from the draining tubes, the tip of intravenous hyperalimentation catheters, blood, sputum, and urine failed to grow any fungus. Autopsy disclosed MA due to Aspergillus at the terminal portion of the right internal carotid artery close to the posterior communicating artery."
-What was the overall 5-year actuarial disease-free survival rate after salvage surgery for patients with carcinoma of the buccal mucosa?,"Evaluation of salvage surgery in heavily irradiated cancer of the buccal mucosa. This report describes the authors' experience with salvage surgery in 78 patients with carcinoma of the buccal mucosa who failed after high-dose radical radiation therapy at Regional Cancer Centre, Trivandrum, India. Forty-four patients (56%) required a hemimandibulectomy for adequate tumor clearance. Fifty-four patients (69%) required a primary reconstructive procedure for wound closure. Follow-up periods ranged from 28 months to 63 months (median follow-up, 41 months). Thirteen patients (17%) developed nonfatal postoperative complications. Thirty-one patients recurred after surgery, five of whom were again salvaged by further surgery. Overall, the recurrence rate was 36%. Most of the recurrences (26/31) were at the primary site. The overall 5-year actuarial disease-free survival after salvage surgery was 59.7%. T stage of the recurrent tumor and its skin infiltration emerged as factors which significantly influenced disease-free survival (P less than 0.05)."
-What percentage of patients achieved complete thrombolysis based on the duration of their limb ischaemia symptoms?,"Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia. A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected."
-What were the key findings of the study comparing different ventilation methods during single-operator cardiopulmonary resuscitation in an ambulance?,"Single operator cardiopulmonary resuscitation in ambulances. Which ventilation device? Cardiopulmonary resuscitation en route to hospital is performed by a single-handed operator in many British ambulances. In this study, three emergency ventilation devices, and mouth-to-mouth breathing, were compared for effectiveness in unintubated patients. Seventeen paramedics used each method on a Laerdal manikin in a randomised order, under identical conditions. Three experienced cardiopulmonary resuscitation instructors repeated the tests in a moving ambulance. There were significant differences in minute volume (p less than 0.01) and number of effective chest compressions (p less than 0.05); mouth-to-mouth breathing produced the best overall results and the simplest device was a close second. The value of automatic ventilators for single-operator cardiopulmonary resuscitation in unintubated patients is questioned."
-What is the significance of the first reported case of HTLV-1 associated T cell lymphoma in South East Asia?,"HTLV-1 associated T cell lymphoma in South East Asia: case report and family study. Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives."
-What is the key finding in this case study regarding neutrophil function and protein abnormalities?,"An inherited defect of neutrophil motility and microfilamentous cytoskeleton associated with abnormalities in 47-Kd and 89-Kd proteins. A 2-month-old male Tongan infant presented with fever, severe skin and mucosal infections, hepatosplenomegaly, thrombocytopenia, and normal neutrophil counts. While polymorphonuclear neutrophil (PMN) morphology was normal, several neutrophil motile functions were found to be altered in the patient. Furthermore, two siblings had died in infancy with a similar clinical picture, raising the possibility of an inherited neutrophil defect. Random migration and chemotaxis, assessed by the under agarose method, were profoundly impaired. Actin polymerization, as measured by flow cytometry of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)phallacidin (NBD-phallacidin)-stained PMNs, showed lower basal F-actin and a 1.75-fold increase in response to 10(-7) mol/L formyl-methionyl-leucyl-phenylalanine (FMLP) compared with a 4.51-fold increase in control. Microscopic examination of NBD-phallacidin-stained PMN spread on glass showed decreased area of spreading and F-actin-rich filamentous projections distinct from control. The early phase of FMLP-induced right angle light scattering was absent, similar to the effect caused by cytochalasin-B (CB), an inhibitor of actin polymerization. Accordingly, FMLP induced secretion of elastase without the addition of CB. Staphylococcus aureus killing was 50% of control whereas superoxide production response to FMLP and surface expression of CD11b were greater than twice normal. Partial defects in actin polymerization and scatter were seen in the parents and release of elastase, in the absence of CB, was also increased in both parents. Sodium dodecyl sulfate-polyacrylamide electrophoresis of whole cell proteins from the patient showed a marked decrease in an 89-Kd protein (8% of control) and a marked increase in a 47-Kd protein (4.2-fold). Both mother and father had decreased 89-Kd (77% and 42% of control) and increased 47-Kd proteins (2- and 3.4-fold), although neither had recurrent infections or chemotactic defects. These studies describe a new inherited actin dysfunction syndrome associated with severe propensity to fungal infection and draw attention to the proteins of apparent molecular weights of 89 Kd and 47 Kd, which may be of great importance in the regulation of actin polymerization in human PMNs."
-What was the purpose of studying programmed ventricular stimulation at different time points after acute myocardial infarction?,"Usefulness of early versus late programmed ventricular stimulation in acute myocardial infarction. To determine the influence of timing on the prognostic value of programmed ventricular stimulation after acute myocardial infarction (AMI), 32 patients were studied on day 19 (early study) and again on day 36 (late study) after AMI using up to 3 extrastimuli. At the early study, sustained monomorphic ventricular tachycardia (VT) was induced in 12 patients (38%), sustained polymorphic VT in 8 (25%), nonsustained monomorphic VT in 1 (3%), nonsustained polymorphic VT in 1 (3%) and no inducible arrhythmia in 10 (31%). At the late study, sustained monomorphic VT, nonsustained monomorphic VT and nonsustained polymorphic VT were induced in 8 patients (25%) each, and no inducible arrhythmia in 8 (25%). Of the 12 patients who had inducible sustained monomorphic VT at the early study, 7 had noninducibility of sustained monomorphic VT at the late study. Of the 20 patients who had noninducibility of sustained monomorphic VT at the early study, 3 had inducible sustained monomorphic VT at the late study. During the follow-up period (mean +/- standard deviation 21 +/- 8 months), there were 2 sudden cardiac deaths and 3 occurrences of sustained VT. Univariate analysis revealed both inducibilities of sustained monomorphic VT at the early study (p = 0.045) and at the late study (p less than 0.001) to be predictive of sudden cardiac death or clinical occurrence of sustained VT. However, inducibility of sustained monomorphic VT at the late study had a higher sensitivity (100%), specificity (89%), positive predictive value (63%) and negative predictive value (100%) than at the early study (80, 70, 33 and 95%, respectively)."
-What is the difference between allochiria and allesthesia according to the original descriptions by Obersteiner and Stewart?,"Allochiria vs allesthesia. Is there a misperception? Allochiria is the mislocation of sensory stimuli to the corresponding opposite half of the body or space. Obersteiner (1882) introduced the term allochiria (Greek allos = other + chiria = hand), and more than 20 authors employed it in this context over the next 25 years. Stewart (1894) described a related phenomenon in which stimuli are displaced to a different point on the same extremity. He noted that the displacements were different than allochiria and coined the term allachaesthesia (ie, allesthesia) (Greek allache = elsewhere + aisthesis = perception). Despite this historical background, Jones (1907) redefined both terms in an attempt to increase diagnostic specificity and attributed allochiria to hysteria. Jones' reinterpretation does not appear to be justified historically, etymologically, or scientifically and has resulted in contradictory definitions of allochiria and allesthesia in present-day medical dictionaries and neurologic textbooks. We advocate a return to usage consistent with the original descriptions and word derivations."
-What was the purpose of the study on autologous fat injection in the canine larynx?,"Autologous fat injection for vocal cord medialization in the canine larynx. This study examined the use of autologous fat as an alternative to Teflon and collagen as the implantable material in vocal cord medialization. Five animals underwent left recurrent laryngeal nerve sections with subsequent fat harvest and implantation into the left true vocal cords. Three animals were killed after 48 hours and 2 after 3 weeks; their larynges were examined with light microscopy. The results of the 48-hour samples show mode-rate acute inflammation and few areas of focal necrosis. The 3-week samples show no necrotic foci, minimal foreign-body reaction, and maintenance of structure and volume of the injected fat. Autologous fat may prove to be a valuable alternative to nonautologous injectable material in vocal cord augmentation."
-What percentage of age-matched elderly subjects made omissions on at least one visuo-spatial neglect test?,"Performance of age-matched controls on a battery of visuo-spatial neglect tests. Examination of 47 independent elderly subjects, matched with a population of patients with acute stroke, found that 55% made at least one omission on a battery of neglect tests. Up to 43% made omissions on any one test. Increasing age and other evidence of cognitive impairment were associated with impaired performance on the battery. Omissions were attributed to an age-related decline in visuo-spatial function. Cut-off points are provided to distinguish between such age-related impairment and visuospatial neglect. The importance of age-matched control studies in developing tests of cognitive impairment in stroke research is highlighted."
-What unique characteristics were observed in the hepatoid adenocarcinoma of the renal pelvis in this case study?,"Hepatoid adenocarcinoma of the renal pelvis producing alpha-fetoprotein of hepatic type and bile pigment. A right renal pelvic mass in a 72-year-old man was resected. The histologic appearance of the tumor was a mixture of tubular adenocarcinoma cells and hepatoid neoplastic cells, and there was a resemblance to hepatoid adenocarcinoma. The intraoperative level of serum alpha-fetoprotein (AFP) was calculated to be 2246 ng/ml, and the postoperative level ranges from 183.6 to 285.6 ng/ml. Lectin binding assays showed that the serum AFP was the hepatic carcinoma type. In a hepatoid portion, an iron-negative, brown to green pigment was positive for bile. Alpha-fetoprotein was immunohistochemically evident in the neoplastic cells. In addition to the hepatic differentiation, the tumor had differentiated into intestinal absorptive or pancreatobiliary tract cells, as deduced from the frequent presence of spicular bodies, a unique light microscopic feature equivalent to microvilli with an actin core. The hepatoid adenocarcinoma is a distinct type of AFP-producing carcinoma present in the organs with epithelium of endodermal origin. Hepatoid adenocarcinoma in the renal pelvis may arise from a metaplasia of neoplastic mesonephric cells into endodermal cells."
-How did the study evaluate the effects of oral magnesium on premenstrual syndrome symptoms?,"Oral magnesium successfully relieves premenstrual mood changes. Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster ""pain"" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster ""negative affect."" In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes."
-What were the key findings regarding the long-term quality of life for childhood and adolescent CNS tumor survivors in this study?,"Quality of life in long-term survivors of CNS tumors of childhood and adolescence. Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or their proxies) who had CNS tumors diagnosed before the age of 20 between 1945 and 1974, survived at least 5 years, and reached 21 years of age. Survivors were 32 years old on average at follow-up. When compared with 479 matched siblings as controls. CNS tumor survivors were more likely to have died or to have become mentally incompetent sometime during the follow-up period. They were more likely to be at risk for such adverse outcomes as unemployment (odds ratio [OR], 10.8; 95% confidence interval [CI], 4.6 to 25.7], to have a health condition that affected their ability to work (OR, 5.9; CI, 3.7 to 9.4), to be unable to drive (OR, 28.8; CI, 6.9 to 119.9), or to describe their current health as poor (OR, 7.8; CI, 1.7 to 35.7). Unfavorable outcomes were more frequent in male survivors than in females, in those with supratentorial tumors compared with infratentorial ones, and in those who received radiation therapy. As clinicians consider improving therapies, they should anticipate late effects, such as those we observed, and attempt to target subgroups for interventions that may improve subsequent quality of life."
-What was the gender distribution of children who were victims of dog bites in the study?,"Dog bites in urban children. As a result of a perceived increase in pit bull injuries, all children who presented to The Children's Hospital of Philadelphia during 1989 for evaluation of dog bite injuries were prospectively studied. Epidemiologic information was collected from parents, either at the time of visit or by phone on the following day. A total of 168 children were enrolled; the mean age was 8 years. Males outnumbered females 1.5:1. Most (61%) injuries occurred in or around the home and involved dogs known to the patient (77%). Types of injuries included abrasions (33%), punctures (29%), and lacerations (38%). Thirteen bites had associated complications; nine developed infection. Twelve (7%) children required admission to the hospital. More than 12 different purebreeds or cross-breeds were identified as perpetrators, including German shepherds (n = 35), pit bulls (n = 33), rottweilers (n = 9), and Dobermans (n = 7). Most (54%) animals were contained (ie, leashed, fenced, in-house) at the time of injury. Fewer (46%) were provoked prior to biting. Significantly more pit bull injuries (94% vs 43%, P less than .001) were the consequence of unprovoked attacks and involved freely roaming animals (67% vs 41%, P less than .01). Children aged 5 or younger were more likely to provoke animals prior to injury than were older children (69% vs 36%, P less than .001). It is recommended that families with young children be the target of pet safety education and that measures be sought that would lead to early identification of a potentially dangerous dog and restrict ownership."
-What medical condition did the 29-year-old man develop that led to the management of megaduodenum through duodenoplasty and feeding jejunostomy?,"Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy. A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo-obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum."
-How did the fentanyl consumption differ between the epidural and intravenous groups in this postoperative pain management study?,"Patient-controlled on-demand epidural fentanyl. A comparison of patient-controlled on-demand fentanyl delivered epidurally or intravenously. A prospective, open, clinical trial is described in which 20 patients having upper abdominal surgery were randomly allocated to receive fentanyl for postoperative analgesia by patient-controlled demand analgesic computer by either the epidural or intravenous route. Hourly pain, sedation and nausea scores were very similar in the two groups during the first 24 hours after surgery. What few differences there were favoured the epidural group. There was a highly significant difference in fentanyl consumption between the two groups, with the intravenous group demanding consistently more than twice as much as the epidural group."
-What were the most common viral and bacterial pathogens causing lower respiratory infections in children in this tropical southern Indian study?,"Etiology of acute respiratory infections in children in tropical southern India. Nasopharyngeal secretions and throat-swab specimens from 809 children less than 6 years old with acute respiratory infection were examined by culture and indirect immunofluorescence for the presence of virus or viral antigen. Blood was cultured for the presence of bacteria in selected cases of lower respiratory infection (LRI); pleural fluid also was cultured in cases of empyema. Viruses were detected in 163 (49%) of 331 children with LRI. Respiratory syncytial virus (RSV) was the commonest agent isolated (106 children). Other viruses isolated included parainfluenza viruses (36 children), adenoviruses (12), and influenza viruses (five). Outbreaks of infection due to RSV occurred during August through October. Pneumonia was the commonest LRI encountered (178 children). Among children with pneumonia, viruses were detected in 65 (37%) of 178 children, and bacteria were isolated from 27 (18%) of the 147 children for whom blood cultures were done. Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus were the common bacterial pathogens isolated. In cases of empyema and pyopneumothorax, S. aureus was the commonest organism isolated. There were 116 children with bronchiolitis, 83 (72%) of whom had viral infections; the majority of these children (81%) had RSV infection. Croup was uncommon (eight cases) and was caused mainly by parainfluenza viruses."
-What were the two treatment methods compared in this study for managing refractory ascites in patients with cirrhosis?,"Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites. BACKGROUND. There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits. METHODS. We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction. RESULTS. During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups. CONCLUSIONS. The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved."
-How does a fish oil-enriched diet affect the microcirculatory manifestations of ischemia-reperfusion injury in hamsters?,"Dietary fish oil blocks the microcirculatory manifestations of ischemia-reperfusion injury in striated muscle in hamsters. Epidemiologic observations and experimental studies have demonstrated a protective effect of dietary fish oil on the clinical manifestations of ischemia-reperfusion injury. To investigate the underlying mechanisms, we used the dorsal skinfold chamber model for intravital fluorescence microscopy of the microcirculation in striated muscle of awake hamsters. In control hamsters (n = 7), reperfusion after a 4-hr pressure-induced ischemia to the muscle tissue elicited the adhesion of fluorescently stained leukocytes to the endothelium of postcapillary venules, capillary obstruction, and the break-down of endothelial integrity. These microvascular manifestations of ischemia-reperfusion injury were significantly attenuated in animals (n = 7) when fed with a fish oil-enriched diet for 4 weeks prior to the experiments. In leukocyte total lipids, the fish oil diet resulted in a substantial displacement of arachidonic acid, the precursor of the potent adhesion-promoting leukotriene (LT) B4, by fish oil-derived eicosapentaenoic acid, the precursor of biologically less potent LTB5, emphasizing the mediator role of LTB4 in ischemia-reperfusion injury. These results suggest that the preservation of microvascular perfusion by dietary fish oil contributes to its protective effects on the clinical manifestations of ischemia-reperfusion injury."
-How does the external anal sphincter function differ between spinal cord injury patients and healthy volunteers?,"External anal sphincter function in spinal patients. Electromyographic and manometric study. Six patients with complete transection of the spinal cord and six healthy volunteers were examined by using anorectal manometry together with electromyographic (EMG) recording of the external anal sphincter composed of striated muscle. Anal pressure and EMG activity of the external anal sphincter were continuously recorded at rest and during gradual rectal distention (10, 20, 30, 40, and 50 ml) by means of an air-filled balloon eliciting a rectoanal inhibitory reflex (RAIR) at the upper part, and an inflation reflex (IR) at the lower part of the anal canal. All patients and controls had a RAIR for each rectal distention volume. A relationship between the duration of the RAIR and the rectal distention volume was present in controls only. In controls the IR was present for each rectal distention volume, whereas it was present in only one patient for a 40-ml volume. During the resting period, all controls showed continuous tonic EMG activity of the external anal sphincter, but after 30 minutes all the patients showed a decrease and ultimately in five cases a disappearance of the tonic EMG activity of the external anal sphincter. In spinal patients, the presence or absence of EMG activity of the external anal sphincter did not modify the anal canal pressure. These results indicate that: 1) the tonic EMG activity of the external anal sphincter seems to be under the control of supraspinal structures, because in spinal patients it disappears in the absence of sensitive inputs toward the spinal cord; 2) the absence of EMG activity at rest indicates that the external anal sphincter is not implicated in the RAIR disturbances observed in spinal patients; 3) the IR is not a spinal reflex but is under voluntary control, because it is not present in spinal humans; 4) in spinal humans the tonic EMG activity of the external anal sphincter does not play a role in the maintenance of the anal pressure at rest."
-How can the expression of ABO(H) antigens and beta-2 microglobulin help predict the response to intravesical BCG treatment in superficial transitional cell carcinoma of the bladder?,"ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin. The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone."
-How does allopurinol (ALLO) mitigate norepinephrine-induced cardiac damage in rabbits?,"Modulation of catecholamine cardiomyopathy by allopurinol. It has been suggested that cardiac injury by catecholamines may be the result of coronary constriction leading to ischemic damage. Allopurinol (ALLO) has been shown to reduce the extent of myocardial necrosis in various systems. Hence the possibility that ALLO might limit norepinephrine (NE) injury was tested. Rabbit hearts were infused with NE (3 micrograms/min/kg) for 90 minutes, with or without ALLO (50 micrograms/min/kg). Control specimens infused with saline solution plus ALLO were also prepared. Hearts were excised 48 hours later and studied as isovolumic isolated heart preparations. Peak systolic pressure, coronary flow, and myocardial oxygen consumption were significantly reduced in the hearts infused with NE but not in the NE + ALLO hearts. Myocardial adenosine triphosphate and glycogen concentrations were 29% and 26% lower in the NE hearts compared with control hearts. These reductions were absent in the NE + ALLO group. Moreover, rates of creatine phosphokinase and lactic dehydrogenase release were sharply elevated in the NE hearts but not in those also given ALLO. These findings are consistent with the changes observed histologically. The amount of myocardial damage was less in the ALLO + NE group compared with the NE group (p less than 0.02). This appears to be the first report to demonstrate that ALLO reduces myocyte damage by NE. Possible mechanisms include decreased free radical production, scavenging of free radicals, and preservation of the adenine nucleotide pool. Because xanthine oxidase activity is absent in the rabbit, the latter two mechanisms are more likely explanations for the findings."
-What is autoerotic asphyxia and how can it lead to fatal consequences?,"A case of autoerotic asphyxia associated with multiplex paraphilia. During the past 20 years, the sensational aspects of autoerotic fatalities have captured the attention of medical examiners, psychiatrists, law enforcement agents, and the public, as well as the individuals themselves who engage in these dangerous practices. Reports of deaths related to sexual asphyxia have been presented numerous times at national and international meetings and have been the topic of discussion on television talk shows and in the press. Autoerotic fatalities and all the sexual curiosities related to these activities have prompted death scene investigators to publish case reports, and even textbooks, on the subject. The case presented herein is one of a multicomponent paraphilia in which self-asphyxiation (autoasphyxiophilia) led to a fatal autoerotic event."
-What was the unusual presentation of the child with a biopterin synthesis defect?,"Paroxysmal tremor and orofacial dyskinesia secondary to a biopterin synthesis defect. We report a child with a systemic biopterin synthesis defect due to an absence of 6-pyruvoyl-tetrahydropterin synthase who had an unusual presentation, with three episodes of coarse ""rubral-like"" tremor in arms and legs orofacial dyskinesia between the ages of 3 and 6 months. Response to levodopa therapy and CSF neurotransmitter metabolite concentrations before and after therapy suggests that his clinical syndrome resulted from a secondary dopamine deficiency."
-How do Quechua highlanders from the Andes demonstrate metabolic efficiency during exercise at high altitudes compared to lowlanders?,"Metabolic and work efficiencies during exercise in Andean natives. Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms."
-What changes in coronary diameter were observed 4 hours after percutaneous transluminal coronary angioplasty (PTCA)?,"Abnormal vasomotor changes early after coronary angioplasty. A quantitative arteriographic study of their time course. BACKGROUND. To study the impact of percutaneous transluminal coronary angioplasty (PTCA) on coronary vasomotion, we prospectively analyzed spontaneous changes in coronary diameter and the response to the cold pressor test and intracoronary nitroglycerin in 11 patients subjected to successful single-vessel PTCA. METHODS AND RESULTS. All antianginal medications were stopped 48 hours before each study. The minimum diameter of the PTCA segment and the diameter of a distal segment in the angioplastied vessel and of a segment in a control vessel not manipulated by the balloon catheter or guide wire were measured by computerized edge detection immediately before PTCA and 5 minutes after, 4 hours after, and 8 days after PTCA. At 4 hours, PTCA and distal segments were constricted by 38 +/- 9% and 16 +/- 5%, respectively, compared with the values at 5 minutes (p less than 0.01). Before angioplasty, the cold pressor test caused vasoconstriction of PTCA and distal segments by 23 +/- 6% (p less than 0.0001) and 15 +/- 4% (p less than 0.008), respectively, but no constrictor response was elicited at 5 minutes or 4 hours after angioplasty. Eight days after PTCA, the basal coronary diameters were similar to those observed 5 minutes after PTCA and the response to the cold pressor test was similar to that observed before PTCA. All segments dilated significantly with nitroglycerin at all times, and no vasoconstriction changes were found in the control segments. CONCLUSIONS. Four hours after PTCA, transient spontaneous vasoconstriction of the PTCA and distal segments occurs, which is so intense that the cold pressor test does not cause any further constriction. These abnormalities resolve within 8 days of PTCA."
-What challenges did the study identify with laser cone biopsy specimens that could interfere with reliable histologic diagnosis?,"The histologic reliability of laser cone biopsy of the cervix. Laser conization of the cervix has been advocated as the technique of choice for the treatment of cervical intraepithelial neoplasia (CIN) in preference to ablative techniques, because it provides a specimen for histologic diagnosis while retaining the advantages of an outpatient procedure with minimal short- and long-term morbidity. To determine whether specimens so obtained are adequate for reliable histologic diagnosis, we reviewed 77 laser conizations performed for lesions confirmed to contain CIN in a colposcopically directed biopsy and satisfying the criteria for local ablation and scored the cones for the presence of epithelial denudation and laser coagulation artifact that interfered with the diagnosis of CIN or the assessment of the margins of excision. Thirty specimens (39%) were negative for CIN. Twenty-eight (36%) showed extensive epithelial denudation, ten (13%) contained coagulation artifact that made recognition of CIN extremely difficult or impossible, and in 11 (14%), assessment of margins was extremely difficult or impossible because of laser coagulation artifact. We conclude that these difficulties with the histologic interpretation of laser cone specimens make it an unsuitable excisional technique when reliable histologic diagnosis of cervical lesions is required."
-What did the study reveal about the relationship between alpha 1 antitrypsin phenotypes and alcoholic pancreatitis?,"Alpha 1 antitrypsin phenotypes and alcoholic pancreatitis. Altered frequencies of alpha 1 antitrypsin phenotypes have been reported in patients with chronic pancreatitis, suggesting a possible genetic basis for individual susceptibility to this disease. Alpha 1 antitrypsin phenotypes, with particular regard to alcoholic pancreatitis, were studied. Patients with alcoholic pancreatitis were compared with alcoholic control subjects with no history of pancreatic disease. Serum alpha 1 antitrypsin concentrations were raised in pancreatitis patients sampled within one month of an acute attack of pancreatitis, but otherwise values were similar to those of control subjects. There were no significant differences in alpha 1 antitrypsin phenotypes between alcoholics with pancreatitis and alcoholic control subjects. This study of alpha 1 antitrypsin phenotypes provides no evidence of an inherited susceptibility to alcoholic pancreatitis."
-What was the main objective of the study regarding ovarian hyperstimulation in patients treated with human menopausal gonadotropin?,"Avoidance of cancellation of potential hyperstimulation cycles by conversion to in vitro fertilization-embryo transfer. OBJECTIVE: The study was undertaken to minimize the rate of ovarian hyperstimulation and to avoid cancellation of human treatment cycles in women treated with human menopausal gonadotropin (hMG) for induction of ovulation. SETTING: Patients were treated in the fertility clinic and in vitro fertilization unit of our institution, which is a government, university-affiliated hospital. PATIENTS: Ninety anovulatory patients were treated with hMG. Of these, 12 were at high risk for ovarian hyperstimulation. The criteria for potential ovarian hyperstimulation syndrome were rising excessive 17 beta-estradiol levels of greater than 1,500 pg/mL in the presence of multiple follicles with a mean diameter greater than 15 mm. These patients were transferred for continuation of treatment to our in vitro fertilization-embryo transfer (IVF-ET) unit. INTERVENTIONS: The patients underwent ova retrieval by the ultrasonically guided transvaginal approach. RESULTS: Of the 12 patients, 5 conceived (41.6%). Two patients had a mild ovarian hyperstimulation syndrome, and 1 had a moderate syndrome and was hospitalized for observation for 48 hours. CONCLUSION: In view of the results, we suggest that IVF-ET should be considered in cases in which ovarian hyperstimulation syndrome is imminent, rather than withhold human chorionic gonadotropin and cancelling the treatment cycle."
-How do the plasma and saliva levels of PGI2 and TXA2 differ in classical migraine patients during an attack-free period?,"Plasma and saliva levels of PGI2 and TXA2 in the headache-free period of classical migraine patients. The effects of nicardipine. The levels of Prostacyclin (PGI2) and Thromboxane A2 (TXA2) were assayed simultaneously (RIA) in the plasma and saliva of 9 patients suffering from classical migraine attacks. The assays were done during an attack-free period. In relation to the control group we observed a significant decrease in the plasma levels of PGI2 together with a sharp increase in TXA2 in saliva. When the patients were treated with nicardipine, a calcium antagonist, the TXA2 increase in saliva did not occur. These results suggest both a systemic and local effect in the classical migraine attacks. We explain and discuss our results by referring to the PGI2: TXA2 equilibrium system. Nicardipine action might be related to its ability to reduce the calcium entry into the cell induced by thromboxane."
-What type of rare neural tumor was observed within the mandibular bone in this case study?,"Unusual intramandibular neural tumor. Neural tumors within the jaw bones are exceptional. We present the histologic observation of a central mandibular tumor of neural origin. Immunohistochemistry confirmed the neural nature of the tumor, which had features of a schwannoma (neurilemmoma) together with ganglion cells as seen in ganglioneuroma. Moreover, the association with an intracranial tumor, possibly a meningioma, is emphasized."
-What percentage of reflux events were simultaneously detected by both scintigraphy and pH monitoring in patients with severe reflux esophagitis?,"Simultaneous esophageal pH monitoring and scintigraphy during the postprandial period in patients with severe reflux esophagitis. To compare reflux events detected by intraesophageal pH monitoring with that of scintigraphy, we simultaneously performed both techniques along with esophageal manometry in nine patients with severe reflux esophagitis. Two hundred eighteen reflux events were detected in the recumbent posture after a meal during a 40-min interval. Both techniques simultaneously detected only 23% of all reflux events. Scintigraphy alone detected 61% of all reflux events as opposed to 16% for pH monitoring. Of those reflux events diagnosed only by scintigraphy, more occurred while the intraesophageal pH was less than 4 (ie, during an acid-clearing interval) than while the intraesophageal pH was greater than 4 (ie, when intragastric contents were neutralized by the meal). Most reflux events occurred during periods of stable, but low LES pressure. While reflux events diagnosed by scintigraphy significantly decreased during the second of two 20-min postprandial intervals, those by pH monitoring tended to increase. That simultaneous scintigraphy and pH monitoring agreed on less than 1/3 of all reflux events not only underscores the fact that both techniques measured different physical components of the esophageal refluxate (ie, volume vs acid concentration, respectively), but also were influenced by different physiologic events such as the ingestion of a meal, gastric emptying, and esophageal acid clearance."
-"What approach do comprehensive multidisciplinary pain centers use to help patients with chronic, disabling pain?","Pain centers--organization and outcome. Pain treatment centers have evolved at a rapid rate, but they differ in their complexity and services provided. Patients, as well as primary care physicians, have difficulty in identifying the appropriate center for a specific problem. Guidelines for pain centers have recently been proposed by the International Association for the Study of Pain, along with an attempt at their accreditation. Outcome studies from pain centers have proliferated, with a wide range of treatment programs being reported. Comprehensive multidisciplinary pain centers using the rehabilitation medicine approach are effective in decreasing disability and increasing the productivity of patients with chronic, disabling pain."
-What differences were observed in motor fiber degeneration and conduction block between the extensor digitorum brevis (EDB) and anterior lateral (AL) compartment muscles in peroneal nerve palsies?,"Quantitation of axon loss and conduction block in peroneal nerve palsies. We compared conduction in motor fibers supplying the extensor digitorum brevis (EDB) and anterior lateral compartment (AL) muscles. The object was to determine whether there were any differences in the relative proportions of degenerated and blocked nerve fibers between the longer EDB and shorter AL fibers. In almost every case the percentage of motor fibers undergoing axonal degeneration was greatest in EDB fibers. Conversely, the percentage of conduction block was greatest in the AL motor fibers. As clinical recovery is dependent on AL muscles rather than EDB, electrophysiological study of the relative proportions of degenerated and blocked fibers in the former should provide a more reliable measure of outcome than similar studies of EDB. Conduction velocity distal to the fibular head was not slowed despite the large loss of EDB motor fibers. Evidence for selective involvement of the larger myelinated fibers is, therefore, lacking. The location of the major conduction abnormalities was in almost every case between the mid-fibular head and popliteal fossa."
-"How are depression, chronic fatigue, and chronic pain interconnected in terms of their psychological and neurobiological factors?","Depression and chronic fatigue in the patient with chronic pain. Chronic benign pain is commonly associated with chronic fatigue and depression. Depression and chronic fatigue syndrome are also associated with each other and often include pain. Psychologic factors are prominent in these conditions, and they may share neurobiologic factors as well. Management requires separately addressing each component of patients' distress and usually includes physical rehabilitation, education, administration of nonhabituating medications and often counseling. Depression may be a favorable prognostic sign, as it suggests a treatable condition and provides incentive for recovery."
-How do DNA methylation patterns change during embryonic development in mice?,"Demethylation of CpG islands in embryonic cells. DNA in differentiated somatic cells has a fixed pattern of methylation, which is faithfully copied after replication. By contrast, the methylation patterns of many tissue-specific and some housekeeping genes are altered during normal development. This modification of DNA methylation in the embryo has also been observed in transgenic mice and in transfection experiments. Here we report the fate in mice of an in vitro-methylated adenine phosphoribosyltransferase transgene. The entire 5' CpG island region became demethylated, whereas the 3' end of the gene remained modified and was even methylated de novo at additional sites. Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences. This suggests that gene sequences can be recognized in the early embryo and imprinted with the correct methylation pattern through a combination of demethylation and de novo methylation."
-What distinguishes Neisseria lactamica from Neisseria meningitidis in laboratory testing?,"Neisseria lactamica meningitis following skull trauma. A woman developed meningitis due to Neisseria lactamica in association with a cribriform plate fracture. Cerebrospinal fluid antigen tests for Neisseria meningitidis were negative. The patient recovered with intravenous penicillin therapy. N. lactamica can be rapidly distinguished from N. meningitidis by the hydrolysis of ONPG (o-nitrophenyl-beta-D-galactopyranoside). In contrast to N. meningitidis and Neisseria gonorrhoeae, N. lactamica lacks virulence properties. As 100% of N. lactamica strains are susceptible to penicillin and all three previously described patients with N. lactamica meningitis have recovered with penicillin treatment, the reason for distinguishing the organisms in this context is primarily to prevent unnecessary anxiety and prophylaxis among contacts."
-How might exclusion criteria in hypertension trials potentially impact the generalizability and statistical power of research findings?,"Potential impact of exclusion criteria on results of hypertension trials. Recent trials of antihypertensive therapy, including the Veterans Administration trials, the Hypertension Detection and Follow-up Program, the Multiple Risk Factor Intervention Trial, the Australian Mild Hypertension Trial, and the British Medical Research Council Trial, are reviewed with a particular emphasis on the criteria leading to the exclusion of potentially eligible participants. The observation of all-cause and cause-specific mortality rates in the group ultimately selected to participate in the trial is suggested as an index to the general applicability of trial results. Because end-point rates are fundamental for determining sample size, substantial reduction in these end-point rates by patient exclusion should be taken into account by the trial design. Some recent trials may have generated end-point-event rates so low that the power of the trial to detect reasonable treatment effects was substantially reduced. Future trials should attempt to take this important factor into account at the design stage."
-What is the association between adult polycystic kidney disease (APKD) and seminal vesicle cysts?,"Seminal vesicle cysts: association with adult polycystic kidney disease. Adult polycystic kidney disease (APKD) is associated with cyst formation in the kidney, liver, pancreas, esophagus, ovary, uterus, and brain. Four patients with APKD (aged 45-65 years) with computed tomographic evidence of seminal vesicle cysts are described. All seminal vesicles contained cystic masses with attenuation values of 0-30 HU. Seminal vesicle thickness was 3-4 cm (normal, 1.5 cm). High-attenuation walls separated the cysts, which were 3-35 mm in diameter. All patients had typical renal stigmata of APKD. None had cysts elsewhere, except one patient with hepatic cysts. Postmortem examination in one patient confirmed the seminal vesicle cysts as well as APKD. It is likely that a basement membrane defect allows cyst formation in multiple organs, presumably including the seminal vesicles. Because of the association of seminal vesicle cysts with ipsilateral urogenital anomalies, and because only 60% of patients with APKD have a relevant familial history, the kidneys of patients with cross-sectional imaging evidence of seminal vesicle cysts should also be studied."
-What treatment method was used to control bleeding from a penetrating atherosclerotic aortic ulcer in this case report?,"Penetrating atherosclerotic aortic ulcer with dissecting hematoma: control of bleeding with percutaneous embolization. A case is presented in which left subpleural hematoma and hemothorax resulted from a penetrating atherosclerotic aortic ulcer with an aortic pseudoaneurysm and intramedial hematoma. Percutaneous transfemoral embolization of the ulcer with use of coils and thrombin resulted in stabilization of the patient's hemodynamic status. The patient died 6 days later of pneumonia. In certain clinical situations, treatment of bleeding from penetrating aortic ulcers with percutaneous embolization may stabilize the patient's condition, allowing elective surgical intervention."
-How does hypoxic exercise affect the levels of atrial natriuretic factor (ANF) and aldosterone in untrained men?,"Effect of hypoxic exercise on atrial natriuretic factor and aldosterone regulation. To evaluate the possible physiologic role of atrial natriuretic factor (ANF) in the observed dissociation of aldosterone secretion from the renin-angiotensin system during hypoxic exercise, 12 untrained men, ages 18 to 24, were studied on two separate days for 30 min during hypoxic (16% O2) and normoxic (room air) exercise on a bicycle ergometer. Workloads were adjusted to produce individual heart rates that remained within 70 to 75% of their previously measured maximum. Hemoglobin saturation decreased during hypoxia from 98 +/- 0.1% to 90 +/- 0.4% (P less than .01). Plasma aldosterone levels increased significantly (P less than .01) under both breathing conditions, yet were on average 36% lower during hypoxia than during normoxia (P less than .001). Plasma ANF levels increased during exercise under both conditions (P less than .01), yet levels were 45% greater during hypoxia than during normoxia (P less than .001). Plasma renin activity, adrenocorticotropic hormone, cortisol, potassium, and systolic blood pressure increased during exercise on both study days (P less than .01, compared to basal level), and showed no difference between normoxic and hypoxic conditions. Plasma pH was slightly higher during hypoxic exercise (P less than .05, compared to normoxia). We conclude that acute hypoxemia is a potent enhancing stimulus for ANF release during dynamic exercise and that ANF is probably a contributing factor in the dissociation of aldosterone secretion from the renin-angiotensin system under these conditions."
-How does technetium-HMPAO SPECT help in evaluating the effectiveness of carotid endarterectomy in patients with internal carotid artery stenosis?,"Use of technetium-HMPAO to demonstrate changes in cerebral blood flow reserve following carotid endarterectomy. Cerebral perfusion through stenosed internal carotid arteries is usually maintained by autoregulation. However, flow reserve may be reduced, suggesting hemodynamically significant stenosis, and such reduction should be improved by carotid endarterectomy. This concept was studied in 20 subjects with unilateral internal carotid artery stenosis (major stenosis greater than or equal to 70%, minor stenosis less than or equal to 50%). Thirteen had experienced recent transient ischemic attacks and seven had no definite focal symptoms. Subjects underwent Tc-HMPAO cerebral SPECT during acetazolamide dysautoregulation before and after internal carotid endarterectomy. Nine (45%) had perfusion defects that improved after surgery, suggesting surgery had improved cerebral flow reserve. Seven had defects that did not improve after surgery. Four had worsened or new defects after surgery, suggesting perioperative infarcts. The relatively large proportion of patients with improved cerebral blood flow reserve after surgery suggests that this technique may have a significant role to play in assessing which patients might benefit from carotid endarterectomy."
-What were the key findings regarding survival times between black and white patients with metastatic breast cancer in the Piedmont Oncology Association study?,"A comparison of treatment outcomes for black patients and white patients with metastatic breast cancer. The Piedmont Oncology Association experience. Prior studies have shown that black patients with breast cancer have poorer survival times compared with white patients even when adjusted for stage. Seventy-four black patients treated on six Piedmont Oncology Association (POA) protocols were compared with 74 randomly selected white patients treated with the same protocols to determine if race had any independent effect on response, time to progression, or survival time. Patients were evenly matched for pretreatment characteristics with the exception that white patients had a significantly higher percentage of bone metastases and significantly less skin involvement. Response rates and median time to progression were similar for black patients and white patients at 31% and 25%, and 9.3 and 9.1 months, respectively. Black patients had poorer survival times even when adjusting for covariables; median survival time was 14.3 months for black patients and 20.3 months for white patients (P less than 0.05). The reason for this survival difference in Stage IV patients is unclear, but is unlikely to be related to treatment. Additional research in this area will be necessary to resolve this issue."
-How does the type of muscle contraction (concentric vs eccentric) and exercise intensity affect exercise-induced muscle soreness?,"Exercise-induced muscle soreness after concentric and eccentric isokinetic contractions. The purpose of this two-part study was to determine whether the amount of exercise-induced muscle soreness differs between subjects who perform concentric and eccentric isokinetic contractions of their quadriceps femoris muscles. In experiment 1, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised at the same power level. In experiment 2, subjects were randomly assigned to either an eccentric or a concentric exercise group and both groups exercised with maximal effort. Muscle soreness ratings, obtained by using a visual analogue scale, were taken immediately before exercise and at 24 and 48 hours postexercise. Changes in muscle soreness ratings between exercise groups from preexercise to postexercise periods were compared in both experiments, using a one-way between-subjects analysis of variance. There was no difference in the change in muscle soreness from preexercise to post-exercise periods between groups exercising at equal power levels. Subjects who exercised using eccentric contractions with maximal effort demonstrated greater increases in muscle soreness than those who performed concentric contractions. The results suggest that exercise intensity, rather than contraction type, may be the dependent factor in producing exercise-induced muscle soreness."
-How can ultrafast MR imaging help differentiate between liver hemangiomas and hepatic metastases?,"Differentiation between hemangiomas and metastases of the liver with ultrafast MR imaging: preliminary results with T2 calculations. We studied the efficacy of T2 measurements at high field strength in distinguishing between liver hemangiomas and hepatic metastases when an ultrafast (single-excitation) MR imaging technique is used. Fourteen patients with known liver tumors were imaged in a 2.0-T prototype ultrafast MR scanner with a spin-echo (infinite TR and TE of 30-340 msec) pulse sequence. Each image was obtained with a total data acquisition time of 20 msec. T2 calculations for hepatic metastases (n = 6) showed a mean of 79.3 +/- 13.5 msec, whereas hemangiomas (n = 8) showed a T2 of 139.8 +/- 18.8 msec (p less than .0001). T2 values of lesions had a smaller relative standard deviation than previously reported, and the range of T2 values of hemangiomas (119-181 msec) and metastases (68-103 msec) did not overlap. Our preliminary results suggest that T2 calculations with ultrafast MR imaging may be useful for differentiating hemangiomas from metastases. We hypothesize that T2 values obtained from ultrafast MR images are more reliable than those obtained from conventional MR images, primarily because of the elimination of T1 information and effects of motion on image signal intensity."
-What is the current status of thrombolytic treatment for patients with unstable angina according to the context?,"Thrombolysis in unstable angina: results of clinical studies. Ample evidence exists to support the major role of intracoronary thrombosis superimposed on a disrupted plaque in unstable angina. Consequently, thrombolytic treatment, already established to be highly beneficial in patients with acute myocardial infarction, might also be indicated in patients with unstable angina. The clinical response to thrombolytic treatment has been evaluated in several small-sized studies with inconsistent and somewhat deceiving results. Thus, the role of thrombolysis in the treatment of unstable angina is still controversial. Two ongoing large-scale, randomized, controlled trials, the Third Thrombolysis in Myocardial Infarction (TIMI III) in the United States testing recombinant tissue-type plasminogen activator and UNASEM in Europe testing anisoylated plasminogen-streptokinase activator complex will, it is hoped, solve the debate. At present, early thrombolysis might be considered for the treatment of the subset of patients with severe rest angina associated with transient ST-T ischemic changes."
-How does oximetry help in detecting sleep apnea syndrome (SAS) and quantifying apneic events?,"Does oximetry contribute to the detection of apneic events? Mathematical processing of the SaO2 signal. The purpose of this study was to assess the ability of continuous nocturnal oximetry to detect sleep apnea syndrome (SAS) and to recognize nonapneic oxyhemoglobin desaturations. Oxygen saturation oscillations, related to successive apneas in SAS or to apneic episodes in COPD or restrictive patients, were quantified using a new index: delta = 1/n sigma 1 n magnitude of delta(SaO2)/delta(t)(12-s intervals) Twenty-six patients (15 SAS, 8 COPD, and 3 restrictive patients) were included in a prospective study comparing nocturnal oximetry and polysomnography over 34 nights. In apneic patients, we found a strong correlation (r2 = 0.73, p less than 0.01) between time spent in apnea and the delta index. In COPD, the number of apneas was also correlated to the delta index (r2 = 0.92, p less than 0.01). A lower threshold for delta of 1.5 is accurate enough to detect apneas if initial SaO2 is greater than 93 percent. If initial SaO2 is greater than 93 percent, the delta threshold should be 0.8 (sensitivity 95 percent). Such a method could contribute to the accurate selection of patients for polysomnography."
-How did antibiotic treatment affect food intake and nutrient absorption in children with Shigella infection during the acute stage of the disease?,"Effect of antibiotics on food intake and absorption of nutrients for children with diarrhea due to Shigella. The effect of antibiotic therapy on intake of food and absorption of nutrients for 19 male children aged 1-5 years with suspected shigella infection was studied. The children were admitted to the hospital with acute diarrhea, high fever, abdominal pain, and greater than or equal to 25 red blood cells and white blood cells per high-power field in the stool. Microbiologic diagnosis was made within 48 hours of admission. On the basis of clinical and microbiologic criteria, children were classified as having mild or severe infection. Ten children with mild infection did not receive antibiotics, whereas nine children with severe infection were treated with ampicillin. After the children were rehydrated, a 72-hour balance study was carried out during the acute stage of infection with Shigella and was repeated 2 weeks after recovery. The levels of consumption of food and absorption of nutrients were estimated. During the acute stage of infection, such levels were higher for the children treated with antibiotics than for the untreated group. During the recovery phase, the levels of intake of food and absorption of nutrients were equal for both groups. Thus, children who are treated with appropriate antibiotics not only may recover from infection with Shigella more rapidly, but they also may be able to absorb nutrients more efficiently."
-How does bronchoscopy via the laryngeal mask provide advantages in assessing patients with malignant tracheal tumors and vocal cord paralysis?,Flexible bronchoscopy via the laryngeal mask: a new technique. Malignant tracheal tumours often cause airway obstruction and this may be aggravated by vocal cord paralysis due to invasion of the recurrent laryngeal nerve. Conventional endoscopic techniques performed under general anaesthesia do not give a simultaneous view of vocal cord function and the distal airways. The technique of bronchoscopy via the laryngeal mask allowed full assessment of the cause of stridor in a patient with a malignant tracheal tumour that was causing airways obstruction and vocal cord paralysis.
-What is the primary factor believed to be responsible for the development of diabetic retinopathy?,"On the pathogenesis of diabetic retinopathy. A 1990 update. Although most investigators now agree that chronic hyperglycemia is the basis for diabetic retinopathy, this has not been proven definitively. Even if chronic hyperglycemia is the initial common pathway leading to retinopathy and other complications of diabetes, it appears to act by different mechanisms in different tissues. The enzyme, aldose reductase, may play a major role in the development of diabetic retinopathy, but contradictory evidence exists. At the present time, results of the only study of aldose reductase inhibition and diabetic retinopathy reported in humans were negative. Another mechanism worthy of consideration is nonenzymatic glycation (glycosylation) of proteins, but there is no direct evidence of a causal role in diabetic retinopathy. Several growth factors have been identified in the retina that may promote neovascularization, and at least two inhibitors may prevent the process. There is evidence to support a role for basic and, perhaps, acidic fibroblast growth factors in retinal vasoproliferation. Transforming growth-factor beta, a peptide produced by capillary pericytes and smooth muscle cells and activated by the interaction of these cells with vascular endothelial cells, appears to be an important inhibitor of neovascularization, as is the vascular basement membrane."
-What characteristic appearance did normal urethras demonstrate on T2-weighted MR images?,"Female urethra: MR imaging. The potential of magnetic resonance (MR) imaging in the evaluation of the female urethra was studied in 64 patients. Spin-echo T1- and T2-weighted images were obtained in all 64 patients, and contrast-enhanced T1-weighted images were also obtained in 27 patients. Urethral pathologic conditions, established with urethroscopy or histologic examination, or both, included urethral diverticula, inflammatory granuloma, and primary and metastatic neoplasms. On T2-weighted images, all normal urethras demonstrated a characteristic targetlike appearance with differentiation among the outer ring of low signal intensity, the middle zone of higher signal intensity, and the center of low signal intensity. After injection of gadopentetate dimeglumine, the targetlike appearance of the normal urethra was seen on the T1-weighted images. Urethral diverticula were detected with MR imaging in all nine patients with that diagnosis, and in each, MR imaging demonstrated urethral expansion, distortion of the zonal anatomy, and presence of fluid in the middle zone. Primary or metastatic urethral neoplasms were also detected with MR imaging in every patient with the diagnosis, but differentiation between benign and malignant disease was not possible. Local staging of primary or metastatic malignant disease was correct in eight of the 11 patients. In three patients, the inflammatory changes could not be differentiated from tumor invasion, resulting in overestimation of tumor extent."
-What is purpura fulminans and how is it related to meningococcemia in this case study?,"Purpura fulminans and adrenal hemorrhage due to group Y meningococcemia in an elderly woman. A 70-year-old previously healthy woman was admitted with a 1-day history of malaise, sore throat, nausea, vomiting, rigors, and confusion. She was found to be in septic shock with purpura fulminans and disseminated intravascular coagulation. She died within 36 hours of admission. Blood cultures grew Neisseria meningitidis group Y. Necropsy revealed evidence of shock and bilateral adrenal hemorrhage."
-What was the relationship between D-dimer plasma concentrations and intracardiac thrombus in patients with mitral stenosis?,"Intracardiac mobile thrombus and D-dimer fragment of fibrin in patients with mitral stenosis. OBJECTIVE--To investigate the relation between intracardiac thrombus and blood coagulability in patients with mitral stenosis. DESIGN--Prospective study. Cross sectional echocardiography and plasma concentrations of the D-dimer fragment of fibrin were used concurrently to detect intracardiac thrombus in patients with mitral stenosis. SETTING--Department of Medicine, National Cardiovascular Centre, Osaka, Japan. PATIENTS--63 patients with mitral stenosis. None of them had been receiving any anticoagulants or antiplatelet agents. MAIN OUTCOME MEASURES--Plasma concentrations of D-dimer in patients with a mobile intracardiac thrombus, those in patients with a non-mobile intracardiac thrombus, and those in patients without an intracardiac thrombus. RESULTS--A mobile intracardiac thrombus was found in 10 patients and a non-mobile thrombus in eight. The remaining 45 patients had no intracardiac thrombi. Plasma concentrations of D-dimer in the 10 patients with a mobile thrombus were all greater than 300 ng/ml (mean 983.3, 95% confidence interval 498.9 to 1467.7 ng/ml) and they were significantly higher than those in the patients with a non-mobile thrombus (226.2, 33.6 to 418.8 ng/ml) and the patients without an intracardiac thrombus (147.2, 110.4 to 184 ng/ml). CONCLUSIONS--A high plasma concentration of D-dimer seemed to reflect a hypercoagulable intracardiac state and may be a helpful indicator of the possible presence of mobile intracardiac thrombus in patients with mitral stenosis."
-What were the two treatment methods compared in this study for managing oesophageal achalasia?,Prospective clinical and manometric study comparing pneumatic dilatation and sublingual nifedipine in the treatment of oesophageal achalasia. A study was carried out in 30 patients affected by a mild or moderate degree of oesophageal achalasia to compare the clinical and manometric effects of sublingual nifedipine and pneumatic dilatation. Sixteen patients were dilated twice with Rider-Moeller dilators and 14 were treated with sublingual nifedipine 10-20 mg 30 minutes before meals. A manometric evaluation was performed before and six months after starting treatment. The clinical evaluation (according to Vantrappen's criteria) was performed every three months for a mean follow up of 21 months. In both groups of patients a significant (p less than 0.001) fall in lower oesophageal sphincter pressure was observed after treatment and excellent or good clinical results were observed in 75% of dilated patients and in 77% of patients treated with nifedipine. One patient could not tolerate nifedipine. No complications were observed after dilatation. It is concluded that longterm treatment with sublingual nifedipine and pneumatic dilatation are equally effective in the treatment of oesophageal achalasia of mild or moderate degree.
-How do p53 gene mutations potentially contribute to the development of lymphoid leukemias?,"Mutations of the p53 gene in lymphoid leukemia. p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase-polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias."
-How did the use of energy-weighted acquisition affect the quantitative analysis of SPECT thallium-201 images?,"Changes in quantitative SPECT thallium-201 results associated with the use of energy-weighted acquisition. The effect of utilizing energy-weighted acquisition on quantitative analysis of SPECT thallium-201 images was evaluated by simultaneously acquiring energy-weighted and windowed projection images in ten patients. The paired image sets were processed identically and evaluated by probability analysis of defect magnitude as indicated by a commercially available software analysis package. It was predicted that defect magnitude would increase as a result of improved image contrast. This was confirmed experimentally. One should be cautious in relying on strict quantitative criteria in cardiac studies with thallium-201, especially when major changes in the imaging system or technique are introduced."
-"What clinical and laboratory features characterize the ""lymphoma syndrome"" in childhood acute lymphoblastic leukemia?","Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure. Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the ""lymphoma syndrome"" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL."
-How does chronic xerostomia affect esophageal acid exposure and potential injury?,"Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury. OBJECTIVE: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency."
-How do insulin and glucagon contribute to liver recovery and cell proliferation in rats with acute hepatic failure?,"Insulin and glucagon therapy of acute hepatic failure. When insulin and glucagon are administered to rats with severe liver injury, survival is enhanced with an attenuation of the liver injury compared to that of untreated controls. In rats with acute liver injury both hormones produce a rapid normalization of hepatic protein content following initiation of DNA synthesis. When rats receive both hormones after partial hepatectomy, the first burst of DNA synthesis reaches a maximum earlier than that seen in controls. Both hormones enhance the increment of hepatic putrescine essential for DNA synthesis through activation of ornithine decaroxylase and/or spermidine-N1-acetyltransferase. The enhancement of putrescine content by each hormone is additive. Putrescine supplementation promotes hepatic DNA synthesis after hepatectomy. Based on these data, we conclude that a combination of insulin and glucagon is effective in the therapy of acute hepatic failure in rats. The restoration of liver function as well as the stimulation of liver cell proliferation via putrescine production may contribute to this effect."
-What are the four common final pathways involved in understanding different types of obesity according to the MONA LISA hypothesis?,"Obesity, a disorder of nutrient partitioning: the MONA LISA hypothesis. The mechanisms underlying different types of obesity have been gradually clarified. Animal models with hypothalamic, genetic or dietary obesity have been examined with a feedback model. Four common final pathways are involved in this model. One of these final common pathways is the sympathetic nervous system. Most Obesities kNown Are Low In Sympathetic Activity states the MONA LISA Hypothesis. A second common pathway is the endocrine system involving adrenal glucocorticosteroids. The third common pathway is hyperphagia. Although not essential for most obesities, hyperphagia may be essential in animals with injury to the hypothalamic paraventricular nucleus. The final pathway is reduced physical activity. The tonic activity of these systems and their response to changes in the diet affect nutrient partitioning between fat and protein. This framework has been used to review genetic obesity, hypothalamic obesity and dietary obesity."
-"What was the main finding of the double-blind, placebo-controlled trial investigating topical PUVA treatment for persistent palmoplantar pustulosis?","A double-blind, placebo-controlled trial of topical PUVA in persistent palmoplantar pustulosis. The effect of topical PUVA was investigated in the treatment of patients with persistent palmoplantar pustulosis (PPP). In this double-blind, placebo-controlled trial of 27 patients with PPP there was an overall improvement of the hands and feet in both the active and placebo-treated areas and little difference between them."
-What was the operative mortality rate and 1-year actual survival rate in the Oregon Liver Transplantation Program during its initial two years?,"Initial two-year results of the Oregon Liver Transplantation Program. During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B."
-How do glomerular hypertrophy and sclerosis contribute to the progression of kidney disease?,"Evidence for a pathogenic linkage between glomerular hypertrophy and sclerosis. Primary renal disease of immunologic or nonimmunologic mechanisms induces loss of substantial nephron population. It is presumed that the initial loss of functioning nephrons causes alterations of function and metabolism in remnant nephrons, which per se are self-inflictive, leading to further loss of nephrons. The ultimate outcome of this vicious cycle is the end-stage kidney. The potential role of various pathophysiologic mechanisms has been explored. These studies have shown a tight link between glomerular hypertrophy and sclerosis. Analysis of individual glomeruli show a biphasic pattern of these two parameters. Early development of glomerular sclerosis takes place along with the hypertrophy of the glomerulus, and further advancement of sclerosis occurs with shrinkage in glomerular size. Thus, we propose that, after initial nephron loss, the remnant glomeruli are exposed to increased growth-promoting factors, which are self-inflictive in nature due to their capacity to produce excessive amounts of extracellular matrix in the mesangial area. When the excessive matrix obliterates the glomerular capillary lumen, a typical sclerotic lesion appears. This is a vicious and accelerating process, since sclerosis induces further reduction in the nephron population, thereby imposing greater influence of growth-promoting factors even on glomeruli that are initially resistant."
-What is endorectal sonography and what diseases can it be used to evaluate?,"Endorectal sonography in the evaluation of rectal and perirectal disease. Endorectal sonography initially was developed for evaluation of the prostate and now has been adapted for evaluation of rectal and perirectal disease. We used endorectal sonography to evaluate a spectrum of diseases, including primary and recurrent rectal carcinoma, metastases, villous adenoma, leiomyosarcoma, endometriosis, sacrococcygeal teratoma, chordoma, retroperitoneal cystic hamartoma, pelvic lipomatosis, diverticulitis, and perirectal abscess. The technique has been useful in localization of perirectal abscesses and in sonographically guided biopsy of perirectal masses. Knowledge of normal sonographic anatomy of the rectum is essential in the evaluation of rectal and perirectal disease. In this essay, we describe the technique of endorectal sonography and illustrate the sonographic findings in a variety of diseases."
-How can quantitative motor performance tests help in early detection of Parkinson's disease?,"Electrophysiologic analysis of early Parkinson's disease. We have been interested in the application of quantitative measures of motor performance as a possible means of early detection of Parkinson's disease. To assess motor function, we have measured movement time (the physiologic correlate of bradykinesia) and reaction time (simple and directional choice) with an upper limb motor task, and tremor with accelerometry and electromyographic recordings. In this report we describe preliminary data from a Parkinson's disease patient group with symptoms of fewer than 2 years' average duration (compared with an age- and gender-matched normal control group) which indicate that precise, quantitative tests of motor function can detect the slight deviations from normal that are present in early Parkinson's disease. It appears that tests of bradykinesia are most sensitive, and detection of rest tremor is most specific. These tests may be applicable in screening individuals who are suspected of having or are ""at risk for"" Parkinson's disease and other related disorders."
-What was the average number of previous operations per joint in the study of elbow replacements for post-traumatic arthritis?,"Total replacement for post-traumatic arthritis of the elbow. Fifty-three of 55 consecutive elbow replacements for post-traumatic arthritis were followed for a minimum of two years (mean 6.3, range 2 to 14.4). The patients presented difficult management problems, having undergone an average of two previous operations per joint; 22 joints had suffered prior complications; 18 had less than 50 degrees of flexion and six were flail. One of three versions of the Coonrad prosthesis was employed in all. During the follow-up period, 10 patients underwent 14 revision procedures for aseptic loosening; 38 elbows are currently without progressive radiolucent lines. In two patients an elbow had to be resected, one for deep infection and the other for bone resorption following a foreign-body reaction to titanium. The current design of the Coonrad prosthesis offers a reliable option for the treatment of post-traumatic arthritis but should be used only in carefully selected patients over the age of 60 years."
-What were the key findings regarding treatment approaches for aortic graft infection in this study?,"Total excision and extra-anatomic bypass for aortic graft infection. Reports of high mortality and amputation rates following total excision and extra-anatomic bypass for aortic graft infection have prompted the use of alternate approaches including local antibiotics, partial resection, in situ revascularization, and graft excision without revascularization. Experience with aortic graft infection was reviewed to establish current morbidity and mortality rates and evaluate our bias in favor of total excision and extra-anatomic bypass. Aortic graft infection was identified in 32 patients, 8 with aortoenteric fistulas. The mean interval between graft placement and infection was 34 months. History of groin exposure (75%) or multiple prior vascular surgery (50%) was common. Clinical signs included fever and/or leukocytosis (23 patients), false aneurysm (9 patients), graft thrombosis (6 patients), groin infection (11 patients), and gastrointestinal hemorrhage (6 patients). Microbiologic data, available in 26 patients, demonstrated gram-positive organisms in 15 patients and gram-negative in 9. Multiple organisms were seen in 11 patients. Patients were treated by partial removal with (8 patients) or without (4 patients) revascularization or total removal with (18 patients) or without (2 patients) revascularization. Revascularization was by an extra-anatomic route, either simultaneous or staged. Overall morbidity/mortality was less in the revascularized groups (p = 0.01), while late complications were seen only after partial removal (p less than 0.01). The best results were found after total excision with revascularization. No patient in this group experienced late infection or amputation during a mean follow-up of 34 months (range: 1 to 168 months). Complications after total excision and extra-anatomic bypass for aortic graft infection are lower than generally appreciated. This approach should remain the standard to which other approaches are compared."
-"What type of cancer did the 77-year-old male develop in his gastric remnant, and how long after his initial gastric resection was it discovered?","Primary squamous cell carcinoma of a gastric remnant. A 77-yr-old male developed primary gastric squamous cell carcinoma 33 yr after gastric resection for peptic ulcer disease. At the time of diagnosis, he was being endoscopically followed for large irregular stomal polyps. Infiltrating squamous cell carcinoma with focal keratinization and stomal polypoid hypertrophic gastritis was found. Previous reports describe adenocarcinoma and adenosquamous carcinoma in gastric remnants. There are various theories as to how such a tumor may arise in this setting."
-How has the introduction of gadolinium-enhanced magnetic resonance imaging (MRI) impacted the diagnosis and treatment of acoustic neuromas?,"Acoustic neuroma: a cost-effective approach. A cost-effective approach to the diagnosis and treatment of acoustic neuromas continues to evolve as diagnostic methods improve. In the past 7 months, since gadolinium-enhanced magnetic resonance imaging (MRI) has become available in our practice, our screening and presurgical workup has changed. The purpose of this article is to outline the current philosophy of the senior authors in relation to acoustic neuroma management on the basis of 72 patients diagnosed from July 1988 to February 1989. With more sensitive diagnostic means, older less sensitive studies may be eliminated from the routine workup, thus maintaining cost-effectiveness while preserving the highest standard of patient care. The body of this article will review our current use of the many available diagnostic options and emphasize a cost-effective approach."
-What were the 4-year actuarial survival rates for patients who underwent aortic valve replacement with Omniscience and Omnicarbon valves?,"Aortic valve replacement with omniscience and omnicarbon valves. Clinical results achieved in 100 cases of aortic valve replacement with the Omniscience (O-S) valve during the period from 1980 to 1985 as well as 100 cases of aortic valve replacement with the Omnicarbon (O-C) valve during the period from 1985 to 1989 were studied. Concomitant surgical procedures including mitral valve replacement were performed in 63 patients in the O-S group and 67 patients in the O-C group. Cumulative follow-up in the two groups was carried out for a total of 559 and 273 patient-years, respectively. The overall 4-year actuarial survival rate was 82% +/- 3.8% in the O-S group and 89.5% +/- 3.2% in the O-C group, the corresponding rates for patients undergoing isolated aortic valve replacement being 82.9% +/- 4.2% in the O-S group and 91.9% +/- 3.5% in the O-C group. The overall 4-year actuarial event-free rate with respect to thromboembolic complications was 88.8% +/- 3.3% in the O-S group and 94.4% +/- 2.8% in the O-C group, as compared with the corresponding rates of 89.2% +/- 3.6% in the O-S group and 95.9% +/- 2.8% in the O-C group for patients undergoing isolated aortic valve replacement. The overall rate of valve-related complications, including thromboembolism, anticoagulant-related hemorrhage, perivalvular leak, infection, and structural failure, was 78.8% +/- 4.2% in the O-S group and 89.3% +/- 3.5% in the O-C group (p less than 0.05), and for isolated aortic valve replacement, 79.7% +/- 4.5% in the O-S group and 89.6% +/- 4.1% in the O-C group."
-What modifications were made to the titanium Greenfield filter to improve its performance compared to the original stainless steel version?,"Results of a multicenter study of the modified hook-titanium Greenfield filter. Initial efforts to modify the stainless steel Greenfield filter for percutaneous insertion led to development of a titanium Greenfield filter, which could be inserted by use of a 12F carrier. This device functioned well as a filter but had an unacceptable 30% rate of migration, tilting, and penetration. Therefore a titanium Greenfield filter with modified hooks was developed and has been tested in 186 patients at 10 institutions. Successful placement occurred in 181 (97%); placement of the remainder was precluded by unfavorable anatomy. A contraindication to anticoagulation was the most frequent indication for insertion (75%). All but two were inserted percutaneously, predominantly via the right femoral vein (70%). Initial incomplete opening was seen in four patients (2%), which was corrected by guide wire manipulation and asymmetry of the legs in 10 (5.4%). Insertion site hematoma occurred in one patient, and apical penetration of the cava during insertion occurred in a second patient. Both events were without sequelae. Follow-up examinations were performed at 30 days at which time 35 deaths had occurred. Recurrent embolism was suspected in six patients (3%) and two of three deaths were confirmed by autopsy. Filter movement greater than 9 mm was seen in 13 patients, (11%) and increase in base diameter greater than or equal to 5 mm was seen in 17 patients (14%). CT scanning showed evidence of caval penetration in only one patient (0.8%). Insertion site venous thrombosis was seen in 4/46 (8.7%) patients screened. The modified hook titanium Greenfield filter is inserted percutaneously or operatively through a sheath, eliminating concern for misplacement from premature discharge."
-What serious medical complications can arise from the use of traditional tribal enemas containing harmful substances like potassium dichromate?,"Colonic complications after toxic tribal enemas. Tribal enemas obtained from traditional healers are used widely in Southern Africa for a variety of indications. Inclusion of injurious substances such as potassium dichromate may cause serious colonic and renal complications. Nine such patients, in seven of whom chromate use was confirmed, presented after a mean delay of 7.3 days. All patients had bloody diarrhoea and vomiting and three underwent major colonic resection, requiring a total of ten procedures. One patient suffered mechanical perforation of the rectum, with subsequent necrotizing fasciitis, necessitating rectal excision. Eight patients had acute renal failure and seven required dialysis. One patient died. At follow-up one patient has chronic renal failure and only three are completely well. Although local medical practitioners are aware of the problem, the challenge of preventing harmful cultural practices remains."
-What are the potential advantages and limitations of intradermal hepatitis B vaccination compared to traditional intramuscular vaccination?,"Intradermal hepatitis B vaccination. The availability of vaccine since 1982 for immunization against hepatitis B virus (HBV) has had minimal impact on the disease; mass immunization has been suggested. Intradermal vaccination, which has precedent in prophylaxis of other infectious diseases, has been investigated as a low-cost alternative to traditional intramuscular HBV vaccination. Results of open and comparative trials indicate similar seroconversion rates for intradermal and intramuscular HBV vaccination routes in healthy adults. However, antibody titers and, presumably, duration of antibody protection appear to be decreased with intradermal HBV vaccination. Limited data suggest that demographic factors such as age and gender may affect vaccine responsiveness to intradermal HBV vaccine. Adverse skin reactions are common but do not represent a deterrent to continued intradermal HBV vaccination. There is a need for large-scale prospective comparative trials to substantiate the value of intradermal HBV vaccination. Nevertheless, the potential economic and epidemiologic benefit of intradermal vaccination justifies continued investigation for prevention of HBV infection."
-What novel diagnostic approach did the authors describe for obtaining tissue samples from Meckel cave lesions?,"Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology. The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction."
-What was the main objective of the study on outpatient pain clinics?,"Audit of outpatients: entering the loop. OBJECTIVE--To develop and test a method for routine data collection to observe current practice in outpatient pain clinics. DESIGN--Prospective questionnaire survey completed by consultants on each patient seen during October 1989 to May 1990. SETTING--Outpatient pain clinics of five teaching and five district general hospitals in Scotland and northern England. MAIN OUTCOME MEASURES--Number of new referrals and their source, and characteristics of pain at presentation. RESULTS--4354 forms were completed by 21 consultants over 29 weeks, corresponding to 2241 patients, of whom 981 were new referrals. The proportion of consultations at which new referrals were seen varied among the 10 clinics from 15% to 34%. The difference could not be accounted for by type of hospital. Sources of new referrals varied widely between the clinics (for example, range 22% to 78% for general practitioner referrals), as did new referrals by the type of pain (range 10.8% to 55.2% for low back pain, 10.5% to 32.5% for pain associated with surgery). However, these differences in types of patients seen could not be accounted for by variations in referral patterns among clinics. Problems identified in performing an audit of outpatients included the difficulty of obtaining firm diagnoses, the need for a method to link successive patient contacts, and the complexity of the presenting problem in many patients. CONCLUSIONS--It is possible to collect data for audit routinely in outpatient clinics. Observation of current practice in the clinics suggested possible unmet need or inappropriate management, which may require changes in practice."
-What were the two techniques used for aortic valve reconstruction in this study?,"Indications and limitations of aortic valve reconstruction. To elucidate the value of conservative operation for aortic regurgitation, all consecutive patients operated on between July 1988 and July 1990 were reviewed. Of 251 patients with aortic regurgitation, 107 (42.6%) had nonprosthetic operation. The mean age was 23 years, and 90 patients (84.1%) were rheumatic. Two techniques were used: repair (annular and leaflet plasties, 69 cases) and cusp extension with glutaraldehyde-treated pericardium (25 bovine, 13 autologous). There were two hospital deaths (1.8%), both in the repair group, and no late deaths or embolic events. Only 5 patients (4.7%) were anticoagulated. In the repair group there were 12 reoperations, four (5.9%) due to aortic and eight to mitral dysfunction. In the cusp extension group there were two reoperations due to mitral dysfunction. Echocardiographic follow-up showed better results with cusp extension. In conclusion, conservative operation for aortic regurgitation is possible in a high percentage of young rheumatic patients and does not require anticoagulation. Cusp extension is more reliable than repair in terms of early results, although its long-term durability is not yet known."
-How does HIV infection impact cell-mediated immunity in patients with chronic D hepatitis?,"Influence of human immunodeficiency virus infection on cell-mediated immunity in chronic D hepatitis. To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication."
-What are the key anatomical features of the infrahyoid portion of the neck that make it suitable for axial imaging and differential diagnosis?,"Differential diagnosis of head and neck lesions based on their space of origin. 2. The infrahyoid portion of the neck. The infrahyoid portion of the neck can be considered as a series of contiguous fascial planes and intervening spaces that lend themselves well to axial imaging. These spaces can serve as a basis on which to formulate differential diagnoses for diseases in this region. This pictorial essay describes the fascia and fascial spaces of the infrahyoid portion of the neck. The contents of each space, the common abnormalities affecting the space, and the characteristic displacements produced by disease in each space are reviewed."
-What were the independent predictors of mortality identified in the multivariate analysis of patients with congestive heart failure?,"Congestive heart failure symptoms in patients with preserved left ventricular systolic function: analysis of the CASS registry. The clinical characteristics and long-term survival of 284 patients from the Coronary Artery Surgery Study (CASS) registry data base who had moderate to severe congestive heart failure symptoms and a left ventricular ejection fraction greater than or equal to 0.45 were studied. A control group consisting of registry patients with an ejection fraction greater than or equal to 0.45 who did not have heart failure was used for comparison. Patients who had heart failure were older and more likely to be female and to have a higher incidence of hypertension, diabetes and chronic lung disease than registry patients who did not have heart failure. As a group, patients with heart failure had more severe angina and were more likely to have had a prior myocardial infarction than were registry patients without heart failure. At 6 year follow-up, 82% of patients in the heart failure group survived compared with 91% of patients in the control group (p less than 0.0001). Multivariate analysis using the Cox proportional hazards model identified the following independent predictors of mortality: regional ventricular systolic dysfunction, number of diseased coronary arteries, advanced age, hypertension, lung disease, diabetes, increased left ventricular end-diastolic pressure and heart failure symptoms. Among patients with heart failure, the 6-year survival rate of those who had three-vessel coronary artery disease was 68% compared with 92% for the group without coronary artery disease. However, the 6-year survival rate for patients with heart failure who underwent surgical revascularization of diseased coronary arteries was not significantly improved compared with that of patients treated medically."
-What were the primary prognostic factors identified in this study of carcinoid tumours in the gastrointestinal tract?,"Carcinoid tumour of the gastrointestinal tract: prognostic factors and disease outcome. This study represents retrospective analysis of 87 patients with a carcinoid tumour of the gastrointestinal tract seen and followed in the British Columbia Cancer Agency (BCCA) from 1960 to 1986. In 49 cases, the primary site was the small bowel. The rest of the cases were distributed as follows: 11 appendix, 10 rectum, 5 stomach, and 7 undetermined. We extrapolated the Dukes' and modified Astler-Coller surgicopathological classifications used for colorectal cancer for use in our cases of carcinoid tumour of the gastrointestinal tract. A strong correlation was found, using this staging, with disease-specific survival. Other prognostic factors included histologic differentiation, the presence of macroscopic residual disease after initial surgery, and level of 5-hydroxyindoleacetic acid (5-HIAA) in urine. Among 51 patients with surgically grossly removed disease, there was a tendency for the development of distant and distant/locoregional recurrence more often than locoregional recurrence alone. The liver was the commonest site of distant recurrence. Analysis of the effect of radiotherapy or chemotherapy on carcinoid tumour of the gastrointestinal tract proved unsuccessful because only a small portion of the patients had this treatment, and it was used mainly for palliation."
-What are the key characteristics and management strategies for neurofibromatosis-2?,"Contemporary management of neurofibromatosis. The neurofibromatoses are two distinct entities with different genetic origins. The phenotypic expressions and required treatments are different. The devastating nature of neurofibromatosis-2 may be more effectively controlled through the application of advanced imaging techniques and contemporary neurotologic procedures. The most common manifestation of neurofibromatosis-2 is that of bilateral acoustic neuromas. The eventual total bilateral sensorineural deafness associated with this condition can be obviated in selected cases if the diagnosis is established early. Follow-up data are reported for three patients in whom hearing was preserved in at least one ear. When removal with hearing preservation is not possible, subtotal tumor removal with decompression of the internal auditory canals may delay progression of hearing loss. A new approach to tumors of the pterygomaxillary fossa that have extended to the middle cranial fossa has been successfully applied and is described."
-What were the most common tumor types observed in the study of children treated for brain tumors?,"Growth hormone deficiency following radiation therapy of primary brain tumors in children. The medical records of 123 patients treated for brain tumors at Children's Hospital and Medical Center, Seattle, Washington, between 1985 and 1987 were reviewed. The endocrinological complications of radiation therapy and the effectiveness of growth hormone (GH) replacement therapy were assessed. These were the first 2 years after synthetic GH became available. The disease pathology was confirmed at craniotomy or biopsy in 108 patients. Ninety-five children completed radiation therapy and 65 of these were alive at the time of review; these 65 children represent the study population. The most common tumor types were medulloblastoma, craniopharyngioma, and ependymoma. Endocrine evaluation was initiated with changes in the patients' growth velocity. Patient workup included skeletal x-ray films for determination of bone and analysis of thyroxin, thyroid-stimulating hormone, and somatomedin-C levels. Following 1-dopa and clonidine stimulation, provocative studies of GH levels were performed. Growth hormone failure and short stature were observed in 26 children, most commonly in the 2nd year after tumor treatment. Eight patients with GH failure were also hypothyroid. Hormone replacement therapy was initiated with recombinant GH, 0.05 mg/kg/day, and all children so treated showed an increase in height, with eight patients experiencing catch-up growth. There were no complications of therapy or tumor recurrence. Studies of baseline bone age and somatomedin-C levels on completion of radiation therapy are recommended. Comprehensive endocrine studies should follow changes in the patients' growth velocity. With early GH replacement, catch-up growth is possible and normal adult heights may be achieved."
-What is the prevalence and characteristics of subarachnoid hemorrhage (SAH) in patients with sickle-cell disease based on the University of Illinois study?,"Subarachnoid hemorrhage in sickle-cell disease. The neurological complications of sickle-cell disease include cerebral intracerebral hemorrhage; subarachnoid hemorrhage (SAH) has been infrequently reported. Among 325 patients with sickle-cell disease followed at the University of Illinois between 1975 and 1989, 11 cases of SAH were identified. Aneurysms were found in 10 of these patients, three of whom had multiple aneurysms. All of the patients had some degree of anemia and nine underwent craniotomy without hematological or neurological complications. From this review it appears that SAH is not uncommon in sickle-cell disease patients and tends to occur at a younger age and with smaller aneurysm size than in the general population. With proper perioperative management, including exchange transfusions to reduce the proportion of hemoglobin S to less than 30%, these patients can undergo angiography and craniotomy without an increased incidence of complications. The techniques used in managing sickle-cell disease patients with SAH are discussed."
-What defines the abnormal B-cell population in peripheral blood from multiple myeloma patients?,"Selective expression of CD45 isoforms defines CALLA+ monoclonal B-lineage cells in peripheral blood from myeloma patients as late stage B cells. The peripheral blood lymphocytes from 42 patients with multiple myeloma (MM) and 13 patients with monoclonal gammopathy of undetermined significance (MGUS) were studied by three-color immunofluorescence (IF) using antibodies directed to a broad range of B-cell markers (CD19, CD20, CD21, CD24), CALLA (CD10), PCA-1 (a plasma cell marker), and to the high and low molecular weight isoforms of the leukocyte common antigen, CD45RA (p205/220) and CD45RO (p 180). CD45RA is expressed on pre-B and B cells, and a transition from CD45RA to CD45RO defines differentiation towards plasma cells. Peripheral blood mononuclear cells (PBMC) from patients with myeloma included a large subset of B-lineage cells (mean of 39% to 45%) that were CALLA+ and PCA-1+ in all patients studied, including newly diagnosed patients and patients undergoing chemotherapy. Southern blot analysis indicated the presence of monoclonal Ig rearrangements in PBMC and a substantial reduction in the germ-line bands consistent with the presence of a large monoclonal B-cell subset. Avoidance of purification methods involving depletion of adherent cells was essential for detection of the abnormal B cells. Phenotypically, this abnormal B-cell population corresponded to late B or early pre-plasma cells (20% to 80% of PBMC), as defined by the concomitant expression of low densities of CD19 and CD20, moderate densities of CALLA and PCA-1, and strong expression of CD45RO on all B cells, with weakly coexpressed CD45RA on a small proportion. Heterogeneity in the expression of CD45RA and CD45RO within the abnormal B-cell population from any given patient suggested multiple differentiation stages. Abnormal B cells similar to those in MM were also detected in MGUS, although as a lower proportion of PBMC (26%). Abnormal B cells from patients with MGUS expressed predominantly the CD45RO isoform, but had a lower proportion of CALLA+ and PCA-1+ cells than were found on B cells from MM. This work indicates that the large subset of circulating monoclonal B lymphocytes from myeloma patients are at a late stage in B-cell differentiation, continuously progressing towards the plasma cell stage."
-What was the most effective body-support system for preventing heel ulcers in bedridden patients according to the study?,"Preventing heel ulcers: a comparison of prophylactic body-support systems. Five commercially available body-support systems used in the prevention of decubitus heel ulcers were objectively compared for their capacity to dissipate or decrease pressure concentration at the most prominent posterior aspect of the heel in bedridden, insensate patients. The Foot Drop Stop, a foam heel suspender, completely eliminated contact between the heel and the bed, and it was the most successful in decreasing pressure concentration. The space boot and foam heel protectors were far more successful than sheepskin rugs or polyester heel protectors, which provided little protection to the prominent heel."
-What are the potential causes of unilateral hydrocephalus identified in this prenatal sonographic study?,"Unilateral hydrocephalus: prenatal sonographic diagnosis. We studied six cases of unilateral hydrocephalus detected prenatally to analyze the sonographic features of the abnormality and to determine the cause and clinical outcome. In all cases, third-trimester sonograms showed marked unilateral lateral ventriculomegaly (mean atrial width, 4.4 cm) and normal contralateral lateral, third, and fourth ventricles. Five of the six cases had marked thinning of the cortical mantle on the affected side and shift of midline structures to the contralateral side. The causes of unilateral hydrocephalus were agenesis or stenosis of the foramen of Monro in three cases, transient obstruction of the foramen in one fetus with an intraventricular hematoma, underlying brain dysplasia in one fetus with a variant of holoprosencephaly, and undetermined in one case. All six neonates had placement of a ventriculoperitoneal shunt catheter; four of these have had normal cognitive development at follow-up. The remaining two infants have moderate to severe developmental impairment. Unilateral hydrocephalus is a rare anomaly that can be recognized by prenatal sonography. Even though unilateral ventriculomegaly may be marked, early diagnosis and treatment may result in a favorable clinical outcome."
-What is ankle arthrodesis and when should it be considered as a treatment option?,"An overview of ankle arthrodesis. Arthrodesis of the ankle can result in a painless, normal walking gait. However, complications in ankle arthrodesis can be major, and can occur when anatomy, deformity, or bony deficiency is not properly addressed. Nonoperative treatment should always be considered first, and, if possible, an open or arthroscopic ankle debridement can provide significant pain relief. Arthrodesis should be considered after conservative treatment fails. Infections, deformity, sensory deficiencies, and bony defects require special consideration. The use of bone graft and internal or external compression will enhance the likelihood of a successful arthrodesis."
-What is a glandular odontogenic cyst and when was it first described?,"Glandular odontogenic cyst: clinicopathologic analysis of three cases. The glandular odontogenic cyst is a rare cyst of odontogenic origin, first described in 1988 by Gardner et al. Three previously unreported glandular odontogenic cysts are presented; none recurred after the initial surgical treatment, and one example was associated with a squamous odontogenic tumor-like proliferation in the wall. Ten similar cases were found in the literature, and their clinical and roentgenographic features, and follow-up, have been compared with the present cases."
-What are the different clinical categories of scleral inflammation and their progression based on the study?,"Progression of scleral disease. The clinical features of 290 patients with scleral inflammation were reviewed to determine whether a classification based on the anatomical site and clinical appearance of the disease at presentation reflected its natural history. The authors' results confirm that the majority of patients remain in the same clinical category throughout the course of their disease. Of the 104 (35.9%) patients who experienced a recurrence of their disease, only 12 had progressed from diffuse to nodular disease, and 10 patients who originally had nodular disease developed scleral necrosis. Patients with necrotizing scleritis were older than patients in the other groups and more frequently had an associated systemic disease than patients with either diffuse or nodular disease; necrotizing scleritis was the most difficult disease to treat. Diffuse anterior scleritis had a lower incidence of visual loss (9%) than either nodular scleritis (26%) or necrotizing disease (74%), and, therefore, the authors consider nodular scleritis a disease of intermediate severity between diffuse scleritis and necrotizing disease. In this series, 12% of patients presented with posterior scleritis, and visual loss was most frequent in this group (84%)."
-How does a prolonged difference in diastolic blood pressure affect the risks of stroke and coronary heart disease?,"Antihypertensive drug treatment. Potential, expected, and observed effects on stroke and on coronary heart disease. The effects of prolonged differences in diastolic blood pressure (DBP) on the risks of stroke and of coronary heart disease (CHD) were estimated from nine major prospective observational studies involving about 420,000 men and women who were followed up for intervals of 6-25 years. The results indicate that a prolonged difference of about 6 mm Hg in DBP was associated with approximately 37% fewer strokes and 23% fewer CHD deaths and nonfatal myocardial infarctions. The effects of equivalent reductions in DBP produced by antihypertensive drug treatment but maintained for only a few years have been estimated in several overviews of randomized trials involving a total of 30,000-40,000 patients. The results of the overviews indicate that treatment reduced the risk of stroke by about 40%, suggesting that most or all the long-term potential benefits for stroke due to lower DBP were achieved within about 3 years of beginning treatment. The risks of nonfatal myocardial infarction and CHD death may have been reduced by about 10% among patients allocated to active treatment; the 95% confidence limits for the difference ranged from about zero to about 20%. Whatever the true effect of treatment on CHD, it would appear somewhat less than the difference in risk estimated from the observational studies for a prolonged difference in DBP of the same size. This apparent shortfall in benefit may reflect a long time-course for changes in DBP to have their full effects on CHD, possible adverse side effects of the principal trial treatments, or both."
-How do soluble and diffusible gases like helium and nitrous oxide affect the size of air emboli in pulmonary arterioles?,"Effect of ventilation with soluble and diffusible gases on the size of air emboli. Pulmonary hypertension resulting from venous air embolism is known to increase after ventilation with highly soluble and diffusible gases. Exacerbation of the hypertension could be due to further blockage of the circulation if the bubbles enlarge as a result of ingress of gas by diffusion. This mechanism has been frequently cited but lacks direct proof. To determine directly whether intravascular air bubbles actually enlarge when highly soluble and diffusible gases are inspired, we used microscopy to measure the size of gas emboli in vivo. When air bubbles were injected into the right atrium, the bubbles that appeared in pulmonary arterioles were larger during ventilation with helium or nitrous oxide than with air. Air bubbles injected into the pulmonary artery enlarged when the inspired gas was changed to helium or nitrous oxide. The direction, magnitude, and timing of changes in bubble size were consistent with a net diffusion of gas into the bubbles. These data support the idea that venous air emboli enlarge during ventilation with soluble and diffusible gases and thereby cause further vascular obstruction."
-How do platelets contribute to the resistance of thrombi to lysis in unstable angina?,"Platelet activation in the pathogenesis of unstable angina: importance in determining the response to plasminogen activators. Unstable angina is a clinical syndrome of recurrent myocardial ischemia. In some cases, this reflects episodic platelet activation and coronary thrombosis. Thus, the biosynthesis of thromboxane A2, which is largely derived from activated platelets, is increased, often coincident with chest pain. The major role of platelets in unstable angina may influence the response to plasminogen activators. Platelets increase the resistance of thrombi to lysis, by inducing clot retraction and cross-linking and by releasing inhibitors. Thus, coronary thrombi in unstable angina may be resistant to lysis. Furthermore, both t-PA and streptokinase cause platelet activation and thrombin formation in vivo, possibly via plasmin. Plasmin can activate platelets and factor V directly. These prothrombotic effects of plasminogen activators may limit their activity in unstable angina. At the very least, their therapeutic efficacy may be highly dependent on the coadministration of potent antiplatelet agents and anticoagulants."
-What are the different types of viruses that can cause hepatitis?,"Viral hepatitis. The new ABC's. Hepatitis may be caused by hepatitis A virus, hepatitis B virus, hepatitis C virus (classic non-A non-B viral hepatitis), hepatitis D virus (delta agent), and hepatitis E virus (epidemic non-A non-B viral hepatitis). Cytomegalovirus, Epstein-Barr virus, and herpes simplex virus may also occasionally cause hepatitis. Some forms of hepatitis carry the risks of chronic infection, cirrhosis, or hepatocellular carcinoma. Treatment options for viral hepatitis are limited and, in many cases, still under investigation. Prophylaxis is available for many forms of hepatitis and should be offered to those at risk."
-How did antibiotic therapy affect vitamin B12 absorption in subjects with atrophic gastritis?,"Reversal of protein-bound vitamin B12 malabsorption with antibiotics in atrophic gastritis. The role of bacteria in the bioavailability of protein-bound vitamin B12 was examined in eight elderly subjects who had atrophic gastritis and in eight normal controls. On separate days and in random order, vitamin B12 absorption tests were performed using either radiolabeled crystalline or protein-bound vitamin B12. At the same time, bacterial samples were collected from the upper gastrointestinal tract. The tests and gastrointestinal aspirates were performed before and during tetracycline therapy. Crystalline vitamin B12 was absorbed to the same extent in the two study groups. Atrophic gastritis subjects absorbed significantly less protein-bound vitamin B12 than normal controls (mean +/- SEM, 0.7% +/- 0.2% vs. 1.9% +/- 0.5%, respectively). However, protein-bound vitamin B12 absorption in these subjects normalized after antibiotic therapy. These results suggest that the small amounts of vitamin B12 released from the protein binders is readily absorbed (as shown in vitro) and/or metabolized by bacteria."
-What is telangiectatic osteosarcoma and how has its prognosis changed over time?,"Telangiectatic osteosarcoma. Telangiectatic osteosarcoma is a rare variant of osteosarcoma. In the original report from the authors' institution, a poor prognosis was noted. The authors have updated their experience with this entity. The prognosis for patients with telangiectatic osteosarcoma has improved remarkably. The prognosis in the present series seems to be the same as that for conventional osteosarcoma. Adjuvant chemotherapy seems to help in salvaging patients with metastatic disease. However, in this small series, survival of patients without metastasis is apparently not influenced by whether they received chemotherapy."
-What medical complications can arise from large vessel occlusion in patients with systemic lupus erythematosus (SLE)?,"Large vessel occlusion with vasculitis in systemic lupus erythematosus. Patients with SLE may have acute large vessel occlusion due to vasculitis and/or circulating antiphospholipid antibodies, as illustrated by the case we have reported. Unfortunately, delayed medical attention led to gangrene of the foot and amputation. Early recognition and appropriate treatment may significantly decrease morbidity and mortality. Medical treatment may include corticosteroids, thrombolysis, anticoagulation, or immunosuppression."
-What are the key hemodynamic effects of ACE inhibitors in treating hypertension?,"Angiotensin converting enzyme inhibitors. Present and future. The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the ""more local"" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents."
-How does the Valsalva maneuver help in detecting left ventricular diastolic function abnormalities in patients with coronary artery disease or systemic hypertension?,"Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler echocardiography in patients with coronary artery disease or systemic hypertension. It has been suggested that changes in left atrial pressure may mask or mimic left ventricular diastolic function abnormalities detected by Doppler echocardiography. The effect of the Valsalva maneuver on the transmitral flow velocity profile was therefore studied in 28 patients without evidence of coronary artery disease (group 1, mean age +/- standard deviation 50 +/- 8 years) and in 94 patients with evidence of coronary artery disease or systemic hypertension (group 2, mean age 54 +/- 10 years). At baseline, group 2 patients had higher peak late diastolic filling velocity (A), lower peak early (E) to late diastolic filling velocity (E/A) ratio and longer isovolumic relaxation time than group 1, whereas heart rate, E velocity and E deceleration time were similar in both groups. During Valsalva, both groups had similar increases in heart rate and similar decreases in E velocity but E/A ratio decreased significantly only in group 2 because of a lesser decrease in A velocity. The E/A ratio was greater than or equal to 1.0 both before and during Valsalva in all but 1 patient in group 1, whereas in group 2, 32 patients had E/A greater than or equal to 1.0 at rest and during Valsalva, 33 patients had E/A greater than or equal to 1.0 at rest but less than 1.0 both at rest and during Valsalva. Using group 1 as controls, prevalence, specificity and positive predictive value of E/A less than 1.0 in group 2 were 31, 100 and 100% at rest and 66, 96 and 98% during Valsalva."
-How does the lipid membrane composition differ in the cerebral tissue of Rett syndrome patients compared to age-matched controls?,"Membrane cerebral lipids in Rett syndrome. The lipid membrane composition of cerebral tissue from 5 patients with classic Rett syndrome, ages 12-30 years, and from 14 age-matched controls was studied. The results demonstrated a selective loss of myelin-associated lipids and an enrichment of gangliosides in temporal white matter. The ganglioside pattern revealed an increase of astroglial cell-associated gangliosides and reduced proportions of gangliosides GD1a and GT1b. This latter finding may be crucial in synaptic function. The fatty acid compositions of ethanolamine phosphoglyceride, choline phosphoglyceride, and galactosylceramide were normal."
-How does inspiratory muscle fatigue affect subsequent high-intensity exercise performance?,"Effect of respiratory muscle fatigue on subsequent exercise performance. The purpose of this study was to determine whether induction of inspiratory muscle fatigue might impair subsequent exercise performance. Ten healthy subjects cycled to volitional exhaustion at 90% of their maximal capacity. Oxygen consumption, breathing pattern, and a visual analogue scale for respiratory effort were measured. Exercise was performed on three separate occasions, once immediately after induction of fatigue, whereas the other two episodes served as controls. Fatigue was achieved by having the subjects breathe against an inspiratory threshold load while generating 80% of their predetermined maximal mouth pressure until they could no longer reach the target pressure. After induction of fatigue, exercise time was reduced compared with control, 238 +/- 69 vs. 311 +/- 96 (SD) s (P less than 0.001). During the last minute of exercise, oxygen consumption and heart rate were lower after induction of fatigue than during control, 2,234 +/- 472 vs. 2,533 +/- 548 ml/min (P less than 0.002) and 167 +/- 15 vs. 177 +/- 12 beats/min (P less than 0.002). At exercise isotime, minutes ventilation and the visual analogue scale for respiratory effort were larger after induction of fatigue than during control. In addition, at exercise isotime, relative tachypnea was observed after induction of fatigue. We conclude that induction of inspiratory muscle fatigue can impair subsequent performance of high-intensity exercise and alter the pattern of breathing during such exercise."
-Does temporary occlusion of hypogastric arteries reduce blood loss during radical retropubic prostatectomy?,"Effect of temporary occlusion of hypogastric arteries on blood loss during radical retropubic prostatectomy. We report on a prospective, partially randomized study of 130 patients, examining the effect of temporary occlusion of the hypogastric arteries on intraoperative blood loss, perioperative blood replacement and change in preoperative to postoperative hematocrit. We observed no significant difference in any of these parameters when comparing patients who did and did not undergo intraoperative occlusion of the hypogastric arteries. These findings suggest that temporary occlusion of the hypogastric arteries during radical prostatectomy does not have a major effect on the blood loss associated with this operation. Extensive collateral circulation to the prostate and a substantial venous component of blood loss may explain these findings. Banking of 3 units of autologous blood preoperatively would have decreased the need for homologous transfusions in the majority of patients."
-What cross-resistance patterns were observed in the ACNU-resistant glioma sublines?,"Cross-resistance patterns in ACNU-resistant glioma sublines in culture. Three ACNU-resistant clones (R1, R3, and R12) were isolated from 9L rat glioma cells under selection pressure of ACNU in vitro. The authors have investigated the mechanisms of resistance and characteristics of these clones at the cellular level by studying cross-resistance patterns to chemical and physical agents. Although these resistant sublines showed complete cross-resistance to methyl-chloroethylnitrosourea (MCNU), no cross-resistance was observed for other alkylating agents, while each of the resistant sublines showed partial cross-resistance to structurally dissimilar toxic agents (vinblastine, Adriamycin, and VP-16). No difference in ACNU uptake was observed between 9L and R3 cells, and resistance patterns among alkylating agents suggested that the mechanism of ACNU resistance was specific to bifunctional nitrosoureas. Based on a transport study, this multidrug resistance could be explained by reduced intracellular uptake of these drugs, but there seemed little possibility that membrane P-glycoprotein, which usually is observed in typical multidrug-resistant cells, was expressed in these ACNU-resistant cells because enhanced drug efflux was not found in ACNU-resistant sublines. Significant collateral sensitivity to L-asparaginase indicated that ACNU might disturb the asparagine synthetic pathways by its mutagenic action. The increased level of total glutathione in the resistant sublines may be one mechanism of radiation or ACNU resistance."
-What are the key differences in management and recurrence rates between suprahyoid and infrahyoid cystic hygromas?,"Cervicofacial cystic hygroma. Patterns of recurrence and management of the difficult case. Cystic hygromas usually present in infancy or early childhood as compressible masses that may rapidly and intermittently enlarge. While they may arise in any anatomic location, hygromas of the head and neck are especially difficult to manage since enlargement may cause serious sequela such as airway obstruction, feeding difficulties, and speech pathology. Complete extirpation of these lesions is often impossible, and recurrence rates are accordingly high. We reviewed our 10-year experience in treating cervicofacial cystic hygromas. Of 34 patients, 21 had lesions cephalad to the hyoid and 13 had lesions caudal to the hyoid. While none of the 13 children with infrahyoid lesions demonstrated feeding or respiratory difficulties, eight of 21 children with suprahyoid involvement presented with dysphagia or airway compromise. The recurrence rates for infrahyoid and suprahyoid lesions were 15% and 81%, respectively. Those children with suprahyoid hygromas also experienced an increased operative complication rate compared with patients with infrahyoid involvement. Principles of management for suprahyoid and infrahyoid lesions are described, including the specific management of lingual, submandibular, parotid, and parotofacial hygromas."
-What is the primary goal of studying the mechanisms behind essential hypertension?,"Can essential hypertension be subclassified with respect to mechanism? Hypertension may result from a variety of abnormalities. The rise in blood pressure may trigger other secondary events that further influence cardiovascular homeostasis. The ability to measure some markers associated with hypertension or the responsiveness of blood pressure to nutritional interventions or to specific therapeutic agents may also have pathogenetic implications. The ultimate goal of further knowledge in this area should be to understand the fundamental abnormalities responsible for hypertension. Such insight would permit more effective treatment and, perhaps, primary prevention of this ubiquitous and multifaceted disorder."
-What was the primary objective of the study on imazodan for treating chronic congestive heart failure?,"Effectiveness of imazodan for treatment of chronic congestive heart failure. The Imazodan Research Group. A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo."
-What is the median weartime for the optimum anal continence plug design in the study?,"The anal continence plug: a disposable device for patients with anorectal incontinence. Anorectal incontinence is most commonly found in the elderly, but colorectal surgeons now see an increasing number of younger patients with this condition. Although medical and surgical treatments are available, a proportion of patients remain refractory to therapy. We investigated the efficacy of three designs of anal continence plug. 8 women and 2 men (mean age, 52 years) who were incontinent to both liquid and solid stool tested each plug for three consecutive weeks. 1 patients withdrew from the study. The median weartime for the optimum plug design was 12 h, and there were no episodes of incontinence in 82% of the periods during which the plug was in place. Patients required a median of eleven plugs per week, and in 82% of cases insertion was as easy as with a suppository. Plugs may have a place in the management of patients with anorectal incontinence."
-What were the survival rates for different stages of cervical cancer when treated with californium-252 neutron brachytherapy?,"A review of californium-252 neutron brachytherapy for cervical cancer. Since 1976 a clinical trial has been conducted to test the feasibility, the potential, and to develop methods for using the neutron-emitting radioactive isotope, californium-252 (Cf-252), for the treatment of cervical cancer. A total of 218 patients were treated in the initial study period from 1976 until 1983. The trials initially treated advanced (Stages III and IV) cervical cancer patients using different doses and schedules; they were extended to include unfavorable presentations of Stages I and II because of favorable results in the initial trials. The authors began to treat patients with Stage IB bulky or barrel-shaped tumors and the majority were treated with both radiation and hysterectomy. Actuarial survival was determined for Stage IB disease and was 87% at 5 years and 82% at 10 years. For those tested with preoperative radiation it was 92% at 5 and 87% at 10 years. For Stage II, it was 62% 5 years and 61% at 10. Survival 5 years after combined radiation and surgical therapy for Stage II disease was 68%. For Stage III, it was 33% at 5 years and 25% at 10. However, 5-year survival using the early neutron implant was 46% versus approximately 19% for delayed Cf-252 or cesium 137. Different schedules and sequences of neutrons and photons greatly altered outcome. Neutron treatment before external photon therapy was better for all stages of disease. Only about 5% of all patients developed complications after neutron therapy. No hematologic or mesenchymal second tumors were observed. Neutron brachytherapy was found to be very effective for producing rapid response and greatly improved local control of bulky, barrel, or advanced cervical cancers. The clinical trial identified and evolved schedules, doses, doses per session, and developed methods different from standard photon therapy but highly effective for local control and cure of cervical cancers of all stages. Clinical and radiobiologic understanding for the use of neutron therapy was greatly advanced by this trial. Future trials will focus on patients with advanced disease and will require evaluation of adjuvant chemotherapy studies and neutron-enhancing chemicals."
-What were the key findings of the study comparing polyamide and polypropylene membranes for plasma separation?,Comparison of polyamide and polypropylene membranes for plasma separation. Plasma separation experiments were made with polyamide experimental prototype hollow-fiber plasma filters with surface areas between 0.025 m2 and 0.1090 m2 using bovine blood collected in acid citrate dextrose (ACD). The maximum filtration velocity rose with the wall shear rate gamma w as gamma w 0.72 +/- 0.02 and decreased with the length of fiber L as L-0.41 with a correlation coefficient of 0.97 +/- 0.02. The results were similar to those with polypropylene fibers. We also investigated the occurrence of hemolysis as a function of shear rate and transmembrane pressure. The free hemoglobin concentration of filtered plasma was checked using a U.V. spectrophotometer. It was concluded that polyamide membrane filters can be safely used for plasma separation from blood.
-How does chemotherapy affect natural killer (NK) cell activity in breast cancer patients?,"The relationship of chemotherapeutic and endocrine intervention on natural killer cell activity in human breast cancer. Peripheral blood natural killer (NK) activity against K562 target tumor cells was monitored in patients with breast cancer receiving no treatment, combination chemotherapy, and/or endocrine therapy. NK activity in untreated Stage I patients with no evidence of disease (ned) was significantly higher than in healthy controls. NK activity was shown to decline in individuals with cytotoxic drug therapy (P equals 0.036). There also were reduction in lymphocyte recoveries concomitant with chemotherapeutic intervention (P less than 0.001). Lymphocyte counts were incorporated in a calculation of absolute NK activity that more accurately reflected the significant reduction in NK activity that occurred in patients with localized and systemic disease on chemotherapy. Different chemotherapeutic agents were found to selectively affect NK activity. Stage II patients on phenylalanine mustard (P)/5-fluorouracil (F) (PF) and cyclophosphamide (C)/methotrexate (M)/5-fluorouracil (F) (CMF) protocols showed significant reductions in overall NK activity relative to healthy controls and Stage I patients with ned. Patients on P/doxorubicin (A)/F/tamoxifen (Tx) (PAFT) protocols showed reduced NK activity relative to Stage I patients. Patients on the short-dose C/A (CA) protocol showed normal levels of overall NK activity. High-risk Stage I patients on methotrexate (M)/F (MF)with sequential leucovorin rescue and patients with metastatic disease on endocrine therapy, i.e., Tx or megestrol acetate (Meg) showed overall NK activities in the range of healthy controls. Patients with systemic disease on CMF, CMF/vincristine/prednisone (CMFVP), vinblastine/A/thiotepa/fluoxymesterone (VATH), mitomycin/mitoxantrone (MtMx), and A regimens showed overall levels of absolute NK that were significantly less than either healthy controls or metastatic patients undergoing endocrine therapy. NK cytolytic data, monitored at multiple effector to target ratios, were subjected to exponential regression analysis. The elevation of NK cell responses in Stage I patients with ned and the decline of NK cell responses with cytotoxic chemotherapy were due to alterations in the maximal plateau levels of NK cell cytotoxicity represented by the A (asymptote) values. The k values obtained on regression analysis and indices of the relative killing capacities of individual NK cells remained unaltered in all populations. These results suggest that the cytolytic lymphocyte NK pool, elevated in Stage I patients with cancer, selectively declines as a result of cytotoxic therapy."
-How does the atrial natriuretic factor (ANF) hormonal system contribute to sodium excretion in dogs with experimental heart failure?,"The atrial natriuretic factor hormonal system in the regulation of sodium excretion in dogs with experimental heart failure. In response to a meat meal containing 125 mEq of sodium, conscious dogs (n = 5) with an arteriovenous (AV) fistula and chronic compensated heart failure exhibited temporally related increases in postprandial plasma immunoreactive atrial natriuretic factor (iANF), right atrial pressure, and sodium excretion. In separate experiments, two weeks of dietary sodium restriction produced similar marked stimulation of renin and aldosterone both in normal dogs (n = 5), and in AV fistula dogs (n = 5) with chronic high circulating levels of ANF. Plasma iANF did not change (P greater than .05) in either group. These results suggest that the ANF system is involved in the postprandial regulation of sodium excretion in the AV fistula dogs with compensated heart failure. In the postabsorptive state, however, the activity of the renin-aldosterone axis is closely related to dietary sodium intake and appears to function independently of the ANF system for the prevention of sodium loss."
-What are the key histologic and clinical characteristics of malignant blue nevus based on the analysis of 12 cases?,"Malignant blue nevus. To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm."
-What paraneoplastic syndrome was observed in the patient with pheochromocytoma and how was it potentially related to interleukin-6?,"Pheochromocytoma with pyrexia and marked inflammatory signs: a paraneoplastic syndrome with possible relation to interleukin-6 production. Pheochromocytoma can cause several paraneoplastic syndromes. We report a patient with pheochromocytoma who exhibited pyrexia and marked inflammatory signs along with an elevated serum interleukin-6 (IL-6) level. All of these abnormalities disappeared and serum IL-6 became undetectable by removal of the tumor. In addition, immunohistochemical analysis revealed the presence of IL-6 in the tumor cells. It is suggested that pyrexia and the elevation of acute phase proteins can be a paraneoplastic syndrome with pheochromocytoma, and that the elaboration of IL-6 from pheochromocytoma may play an important role in the development of the syndrome."
-What was the average cost of averting death or severe disability through neurosurgical intervention in this study?,"Steps towards cost-benefit analysis of regional neurosurgical care OBJECTIVE--To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN--Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING--Wessex Neurological Centre. PATIENTS--1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES--Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS--The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS--In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community."
-How was HLA class I antigen expression evaluated in patients with chronic hepatitis B?,"HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B. HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy."
-What factors were found to potentially delay malaria diagnosis in this urban emergency department study?,"Malaria in an urban emergency department: epidemiology and diagnostic features of 25 cases. This article presents a retrospective study of 25 patients diagnosed with malaria in an urban emergency department (ED) between June 1986 and June 1989. The mean annual case rate of malaria in this study group was more than three times the national rate. This may be ascribed to the notable ethnic diversity of the population. A history of travel to an area endemic for malaria was eventually elicited from all patients. The most common chief complaint was fever (56%) followed by abdominal pain (12%). Temperatures were elevated in 70% of the patients, with a mean temperature of 102.9 degrees F (39 degrees C). Gender was found to play a role in delaying diagnosis, with women accounting for 83% of a group of patients requiring multiple ED visits before diagnosis. The authors conclude that malaria must be considered when diagnosing patients in ethnically diverse populations. Gender may be associated with a delay in diagnosis. A careful travel history and a peripheral smear are aids in rapid diagnosis."
-What did the study reveal about interferon-alpha production in acute versus chronic hepatitis B virus infection?,"Hepatic interferon-alpha gene transcripts and products in liver specimens from acute and chronic hepatitis B virus infection. In this study we have examined the localization of interferon-alpha in liver tissue from acute and chronic hepatitis B virus carriers to establish whether the defect in interferon-alpha production reported in chronic hepatitis B virus infection is at a pretranscriptional or posttranscriptional level using in situ hybridization and immunohistochemical techniques. Interferon-alpha messenger RNA transcripts and the immunoreactive protein were abundant in liver tissue and in particular in hepatocytes from patients with acute hepatitis B virus infection who subsequently recovered. In contrast interferon-alpha polypeptide was present in a significantly lower number of sinusoidal cells, mononuclear cells and hepatocytes in chronic hepatitis B virus carriers. Although a high proportion of patients with chronic hepatitis B virus infection had cells that expressed interferon-alpha messenger RNA transcripts, the number of such cells was significantly less than in acute hepatitis B virus infection, indicating that the defect in the hepatic interferon-alpha synthesis is at the level of gene activation. Furthermore, using double immunohistochemical staining, the number of hepatocytes containing HBcAg correlated inversely with the proportion of neighboring sinusoidal cells expressing interferon-alpha. These data support previous observations that interferon-alpha production is reduced in chronic hepatitis B virus infection and are consistent with the view that this cytokine is important in the clearance of the virus."
-What factors were associated with the embolization of the prosthetic aortic valve in the young woman described in this case report?,"Death by embolization of prosthetic aortic valve. This report describes a case in which a young woman died from embolization of her prosthetic aortic valve. The discussion includes the embolization's association with chronic intravenous narcotism, recurrent bacterial endocarditis, and acute cocaine toxicity."
-What makes flunarizine unique among calcium antagonists in terms of its effects on the brain?,"Flunarizine in migraine: a minireview. Flunarizine is a non-selective calcium antagonist. It distributes preferentially in the adipose tissue and passes the blood brain barrier. Numerous controlled clinical studies have established that flunarizine is efficacious in migraine prophylaxis, including double-blind studies in which the drug was compared with placebo or other antimigraine drugs. To avoid side effects a special schedule or administration is necessary. Flunarizine has no myogenic effect on smooth muscle cells of the vessles. It is said to be the only calcium antagonist able to protect brain cells against hypoxic damage. In addition, the considerable body of information which shows flunarizine capable of directly influencing the central nervous system, suggests that the drug's anti-migraine action may depend on its ability to influence central phenomena."
-What was the primary purpose of this study comparing ondansetron and metoclopramide?,"A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy."
-What was the outcome of thrombolytic therapy in patients with unstable angina in this study?,"Thrombosis and thrombolysis in unstable angina. Pathophysiology of unstable angina involves spasm, plaque rupture, activation of platelets, and coagulation. The incidence and frequency of intracoronary thrombus formation are presently under active assessment in order to establish the potential benefit of thrombolytic therapy. A preliminary study was conducted in patients admitted in our coronary care unit for unstable angina with typical clinical and electrocardiographic criteria and with early coronary angiogram. After exclusion of 4 patients with left main coronary stenosis or contraindications for thrombolysis, 16 patients received thrombolytic infusion and 14 underwent a second coronary angiogram. Seven patients had an intracoronary thrombus (6 nonocclusive, 1 occlusive) and at the second angiogram only 3 nonocclusive thrombi were modified (1 disappeared, 2 were reduced). Moreover, the quantitative Coronary Angiography Analysis System (CAAS) in the 11 cases suitable for analysis did not show any significant changes, especially in the Ambrose type IIB lesions. In-hospital clinical outcome was not influenced by thrombolytic therapy (5 ischemic recurrences, 1 fatal myocardial infarction, 4 emergency and 4 elective revascularization procedures). This short series is in agreement with the literature data. Only one third of patients with active unstable angina remains refractory to conventional therapy. The transient benefit of thrombolysis is limited to patients with demonstrated intracoronary thrombi. Clinical or angiographic improvement are not always in correlation and until now do not seem able to prevent short-term recurrences or the need for revascularization procedures."
-"What is the relationship between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension?","Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system. An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based."
-What was the primary diagnostic challenge in identifying the cause of neurological deterioration in this 1-year-old male infant?,"Intracranial arteriovenous fistula manifesting as progressive neurological deterioration in an infant: case report. This 1-year-old male infant had been diagnosed with cerebral degenerative disease because he developed psychomotor regression, and brain atrophy was demonstrated on computed tomography. He underwent magnetic resonance imaging, which suggested a cerebrovascular malformation. Cerebral angiography disclosed an arteriovenous fistula, fed by an anterior cerebral artery and directly draining into a cortical vein. The occlusion of the feeding artery was followed by a satisfactory recovery. The mechanism of the neurological symptoms in this patient is thought to be caused by a steal phenomenon and compression of the brain stem by venous engorgement in the posterior fossa."
-What was the main finding of the study regarding low power laser biostimulation for chronic oro-facial pain?,Low power laser biostimulation of chronic oro-facial pain. A double-blind placebo controlled cross-over study in 40 patients. The efficacy of low power laser stimulation in the treatment of chronic oro-facial pain conditions was investigated in a double-blind placebo controlled modified cross-over study in 40 patients. The laser was an invisible infrared (IR) diode laser with an emission at 904 nanometer (nm). Treatment effect was evaluated by means of VAS-scales and global assessment of pain. Outcome of treatment was correlated to changes in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). The clinical impression was that placebo was superior to laser stimulation. No statistically significant difference between the analgesic effect of the laser and placebo irradiation was found on VAS-scales. A significant (P = 0.05) increase in 5-HIAA excretion was found in the placebo group. It is concluded that the possibility of a substantial placebo response should be taken into consideration using 904 nm (IR) lasers for pain treatment in patients with this type of chronic oro-facial pain.
-What was the frequency of dysplasia or cancer found in this colonoscopic screening of ulcerative colitis patients with more than 15 years of disease duration?,"Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. Colonoscopic screening for neoplasia was performed in a regional group of ulcerative colitis patients with a disease duration of greater than or equal to 15 years. A total of 121 patients, aged less than 80 years, were invited to participate, of whom 100 (83%) accepted colonoscopy, including biopsies in 15 standard locations of the entire colon, plus additional biopsies from all visible lesions. Unequivocal dysplasia was found in one patient with extensive colitis and a disease duration of 31 years. A polyp with highly differentiated adenocarcinoma was found in the sigmoid colon of a patient with intermittent rectum involvement, 37 years after the ulcerative colitis diagnosis had been made. Biopsy specimens from the remaining 98 patients showed no signs of dysplasia or cancer. Thus the frequency of pre-malignant or malignant changes is very low compared with the results of similar studies, and the rationale for general colonoscopic surveillance programmes for such patients is open to question."
-What types of melanocytic nevi in children and adolescents may indicate an increased risk of malignant melanoma?,"Important melanocytic lesions in childhood and adolescence. Melanocytic nevi are common in children and adolescents, and the preponderance of these lesions are benign. Congenital melanocytic nevi, dysplastic nevi, and large numbers of common acquired nevi, however, may indicate an increased risk of malignant melanoma. With the exception, possibly, of giant congenital nevi, melanoma associated with these lesions generally occurs in adulthood. Nonetheless, some patients can be identified as being at increased risk for the development of melanoma during childhood. The poor prognosis associated with advanced melanoma and the curability of early lesions underscore the importance of prompt recognition of melanoma when it does occur in children. Furthermore, physicians who care for children are in a key position to decrease risk of melanoma throughout the lifespan by encouraging avoidance of excessive sun exposure during childhood."
-What was the dosage and administration method of metoclopramide used in this study for treating gastroparesis?,"Subcutaneous metoclopramide in the treatment of symptomatic gastroparesis: clinical efficacy and pharmacokinetics. We investigated the safety and efficacy of short-term s.c. administration of metoclopramide in the treatment of symptomatic gastric stasis. Ten patients with gastroparesis, documented by abnormal solid phase radionuclide gastric emptying study, were treated with 10 mg (2 ml) of s.c. metoclopramide every 6 hr for 3 days. Patients gave themselves the injections as outpatients. Questionnaires were then completed concerning symptom relief, local side effects and adverse reactions. A repeat gastric emptying study was obtained immediately after the last dose of metoclopramide. Serum metoclopramide concentrations were obtained at trough, 1, 2, 3, 4 and 5 hr postadministration and serum prolactin levels at trough, 1 and 3 hr. Pharmacokinetic analysis showed mean peak metoclopramide concentration at 30 min of 99.7 +/- 47.1 ng/ml with measured levels of 93.9 +/- 106.83 ng/ml at 60 min and return to trough values by 4 hr; trough prolactins remained elevated above normal values. Gastric stasis improved from a base-line retention of 78.7% of radioisotope at 2 hr to 72.5% after 3 days of therapy (P = .65). Eight patients reported significant improvement in symptomology and two patients reported lessening of symptoms such as nausea, vomiting, bloating, abdominal pain, heartburn and vomiting. The side effects were minimal and did not interfere with completion of the protocol. We demonstrated that s.c. administration of metoclopramide was well accepted by patients and resulted in subjective and objective improvement of gastric stasis. In addition, serum metoclopramide concentrations were comparable with other parenteral routes of administration. Furthermore, serum prolactin levels may provide both a bioassay of efficacy and a marker for monitoring compliance."
-"How does 1,25-dihydroxyvitamin D3 affect the interferon-gamma-induced expression of MHC class II antigens on HEp-2 cells?","Differential enhancement of interferon-gamma-induced MHC class II expression of HEp-2 cells by 1,25-dihydroxyvitamin D3. Interferon-gamma (IFN-gamma) induces the expression of MHC class II antigens on non-lymphoid cells. In this study we investigated the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the most active metabolite of vitamin D3, on the IFN-gamma-induced expression of MHC class II antigens on HEp-2 cells. We found that 1,25(OH)2D3 enhanced the IFN-gamma-induced expression of HLA-DR on these cells. Differential effects on the MHC class II antigens HLA-DR, -DQ and -DP were also observed."
-What were the most common late complications following abdominal aortic operation in this study?,"Reoperations for late complications following abdominal aortic operation. Fifty patients were identified who, following abdominal aortic operation, developed late complications affecting the vascular graft or endarterectomy and who underwent their first reoperation between 1979 and 1989. Thrombosis was the commonest complication affecting 28 (56 per cent) patients, followed by false aneurysm in 11 (22 per cent), enteric fistula in nine (18 per cent) and graft infection in two (4 per cent). The 30-day mortality rate for reoperation was 8 per cent; longer follow-up revealed mortality rates of 22, 50 and 63 per cent at 1, 3 and 5 years respectively. Thirty-four complications required reoperation within 5 years of the original surgery. Reoperation was needed for 35 patients whose original pathology was occlusive disease and for 15 whose original pathology was aneurysm. The nature of the complication was related to initial pathology; thrombosis was far commoner in those with occlusive disease, and enteric fistula and false aneurysm were commoner in those with aneurysmal disease."
-What was the cumulative percentage of patients free of arrhythmia after serial drug treatment in this study?,"Serial antiarrhythmic drug treatment to maintain sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. The sequential use of different types of antiarrhythmic drugs may improve arrhythmia prognosis in chronic atrial fibrillation or flutter after successful electrical cardioversion. The rationale for serial treatment is that the arrhythmogenic mechanism may vary between patients, leading to different responses to 1 specific drug. To investigate this issue prospectively, 127 patients having chronic fibrillation or flutter exclusively, underwent serial drug treatment with flecainide (stage I) followed by sotalol or, if contraindicated, quinidine (stage II) and eventually amiodarone (stage III). Stages II and III were entered after electrical recardioversion for a recurrence during stages I or II, respectively. Calculated on an actuarial basis, the 2-year cumulative percentage of patients free of the arrhythmia increased from 31% after stage I to 63% at the end of serial treatment. To reach this result, a mean of 1.8 +/- 0.8 cardioversions per patient were needed, with 53 patients progressing to stage II and 34 to stage III. Sixteen patients stopped serial treatment prematurely and 15 patients were considered to have intractable atrial fibrillation at the end of stage III. Incidence of proarrhythmia was low. Multivariate analysis disclosed that an older age, in combination with a large number of previous episodes of arrhythmia, a long previous duration of arrhythmia and presence of mitral valve disease, were predictive for medical refractoriness during serial treatment. It is concluded that serial treatment may improve arrhythmia prognosis in atrial fibrillation or flutter, with an acceptable incidence of proarrhythmic events."
-How does the p53 gene mutation correlate with the progression of chronic myelocytic leukemia (CML) in this patient's case study?,Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
-What percentage of radiologic modalities showed inaccuracies in assessing lumbar spine fusions in this study?,"Correlation of radiologic assessment of lumbar spine fusions with surgical exploration. Although inspection of posterolateral lumbar fusion is the best method of determining its solidity, routine exploration of the fusion is somewhat impractical because of the morbidity and expense involved. Removal of internal fixation devices or implantable batteries or reoperation for failed back surgery enabled the exploration and assessment of lumbar spine fusions in 214 operations on 175 patients. The preoperative radiologic assessment (plain roentgenographs, polytomography, bending films, and computed tomographic scans) were correlated with surgical findings. This study indicated a significant percentage of inaccuracy of all radiologic modalities used. Noncorrelations were present in 36% of plain roentgenographs, 41% of polytomograms, 38% of bending films, and 43% of computed tomographic scans. Radiologic inaccuracy was manifest on both the positive and negative sides. Computed tomographic scanning presented the lowest percentage of inaccuracy (22%) and bending films the highest percentage (27%). Based on these findings, there exists the need for more accurate noninvasive methods to determine the solidity of spine fusions."
-What are the typical clinical features associated with cervicocranial arterial dissection?,"Cervicocranial arterial dissection. Dissection of the cervicocranial arteries is becoming more frequently recognized as a cause of neurological disorders. Typical clinical features seen with dissection include unilateral headache, oculosympathetic palsy, amaurosis fugax, and symptoms of focal brain ischemia. The diagnosis of carotid or intracranial dissection is usually best confirmed by angiography, although magnetic resonance imaging and computed tomography have been shown to visualize intimal dissection. The prognosis in cases of spontaneous dissection is generally benign unless the initial manifestation involves infarction with substantial deficit. The best approach to treatment appears to be the administration of the anticoagulant, heparin, followed by warfarin or antiplatelet therapy. Surgical intervention is reserved for cases of progressive or recurrent ischemic complication that occurs despite the administration of adequate doses of anticoagulants."
-What factors were significantly associated with an increased risk of cholelithiasis in childhood cancer patients after treatment?,"Cholelithiasis after treatment for childhood cancer. The authors evaluated the risk of development of cholelithiasis in 6050 patients treated at a single hospital for various childhood cancers with different therapeutic modalities, including chemotherapy, surgery, radiation therapy, and bone marrow transplantation, from 1963 to 1989. Patients with underlying chronic hemolytic anemia or preexisting gallstones were excluded. Nine female and seven male patients with a median age of 12.4 years (range, 1.2 to 22.8 years) at diagnosis of primary cancer had gallstones develop 3 months to 17.3 years (median, 3.1 years) after therapy was initiated. Cumulative risks of 0.42% at 10 years and 1.03% at 18 years after diagnosis substantially exceed those reported for the general population of this age group. Treatment-related factors significantly associated with an increased risk of cholelithiasis were ileal conduit, parenteral nutrition, abdominal surgery, and abdominal radiation therapy (relative risks and 95% confidence intervals = 61.6 [27.9-135.9], 23.0 [9.8-54.1], 15.1 [7.1-32.2], and 7.4 [3.2-17.0], respectively). There was no correlation with the type of cancer, nor was the frequency of conventional predisposing features (e.g., family history, obesity, use of oral contraceptives, and pregnancy) any higher among the affected patients in this study than in the general population. Patients with cancer who have risk factors identified here should be monitored for the development of gallstones."
-What were the key findings of the comparison between digital examination and anal endosonography in evaluating anal fistulae?,"Comparison between anal endosonography and digital examination in the evaluation of anal fistulae. A prospective trial was performed comparing the accuracy of digital examination and anal endosonography in defining the anatomy of anal fistulae. Before operation 38 consecutive patients were assessed by the consultant in charge of the case, by a research fellow and by anal endosonography involving two radiologists. These findings were compared with the operative findings. Consultants correctly identified 26 of 33 internal openings, 29 of 34 primary tracks and 15 of 21 secondary tracks. The research fellow correctly identified 26 internal openings, 24 primary tracks and 10 secondary tracks. There was no significant difference between the accuracy of consultants and the research fellow. Anal endosonography identified 10 internal openings based on initial criteria. This rose to 24 when revised ultrasonographic criteria were applied. There was no statistical difference between consultant assessment and anal ultrasonography in correctly identifying intersphincteric and transphincteric tracks. Ultrasonography is unable to assess primary superficial, suprasphincteric and extrasphincteric tracks or secondary supralevator and infralevator tracks. Consultant assessment of secondary supralevator and infralevator tracks was correct in 78 per cent of cases."
-What was the aim of the study in developing a test for gastric emptying and small bowel transit?,"Towards a less costly but accurate test of gastric emptying and small bowel transit. Our aim is to develop a less costly but accurate test of stomach emptying and small bowel transit by utilizing selected scintigraphic observations 1-6 hr after ingestion of a radiolabeled solid meal. These selected data were compared with more detailed analyses that require multiple scans and labor-intensive technical support. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected summaries of scintigraphic transit measurements. We studied 14 patients with motility disorders (eight neuropathic and six myopathic, confirmed by standard gastrointestinal manometry) and 37 healthy subjects. The patient group had abnormal gastric emptying (GE) and small bowel transit time (SBTT). The proportion of radiolabel retained in the stomach from 2 to 4 hr (GE 2 hr, GE 3 hr, GE 4 hr), as well as the proportion filling the colon at 4 and 6 hr (CF 4 hr, CF 6 hr) were individually able to differentiate health from disease (P less than 0.05 for each). From the logistic discriminant model, an estimated sensitivity of 93% resulted in similar specificities for detailed and selected transit parameters for gastric emptying (range: 62-70%). Similarly, combining selected observations, such as GE 4 hr with CF 6 hr, had a specificity of 76%, which was similar to the specificity of combinations of more detailed analyses. Based on the present studies and future confirmation in a larger number of patients, including those with less severe motility disorders, the 2-, 4-, and 6-hr scans with quantitation of proportions of counts in stomach and colon should provide a useful, relatively inexpensive strategy to identify and monitor motility disorders in clinical and epidemiologic studies."
-What was the 10- and 15-year actuarial survival rate for medulloblastoma patients in this study?,"Medulloblastoma: freedom from relapse longer than 8 years--a therapeutic cure? Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (greater than or equal to 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately."
-What was the treatment regimen used for patients with locally advanced paranasal sinus and nasopharynx tumors in this study?,"Locally advanced paranasal sinus and nasopharynx tumors treated with hyperfractionated radiation and concomitant infusion cisplatin. Fourteen patients with paranasal sinus complex and nasopharynx tumors were treated at State University of New York Health Science Center at Brooklyn (Brooklyn, NY) with a regimen of split-course hyperfractionated radiation (120 cGy/fraction) and concomitant cisplatin infusion (5 to 7 mg/m2/24 hours). All of the patients had T4 tumors or massively recurrent disease with base of skull or facial bone involvement. Twelve patients were treated with curative intent receiving total doses of 6000 to 6960 cGy (modal 6750 cGy), whereas two patients were treated with less than 5000 cGy as palliation. Eleven of the 12 patients (92%) achieved a complete response, and 7 of 12 (58%) are alive at 35 to 72 months (mean, 47 months). Five patients are alive with no evidence of disease, and two with a local recurrence. Three patients died of distant disease, and two died from a local recurrence. When the response to treatment was analyzed based on tumor volume and radiation dose, only two of nine lesions measuring between 4 to 10 cm failed locally. The two palliative patients had almost complete local clearance of the disease but died at 2 and 8 months, respectively. In nine patients, the eye or optic nerve was included in the treatment field and received between 2000 to 6960 cGy. Only one of these nine patients had ophthalmic complication and this was confined to the cornea."
-How does iloprost affect microvascular permeability in skeletal muscle after ischemia and reperfusion?,"Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion. Increased vascular permeability is an early and sensitive indicator of ischemic muscle injury, occurring before significant histologic or radionuclide changes are evident. We investigated the effect of iloprost, a stable prostacyclin analog, on microvascular permeability in a rat striated muscle model. In six control and six experimental animals the cremaster muscle was dissected, placed in a closed-flow acrylic chamber, and suffused with a bicarbonate buffer solution. Dextran labeled with fluorescein was injected intravenously as a macromolecular tracer, and microvascular permeability was determined on the basis of clearance of the fluorescent tracer. Two hours of ischemia were followed by 2 hours of reperfusion. In the experimental group iloprost (0.5 microgram/kg/min) was given in a continuous intravenous infusion. Microvascular permeability increased significantly during reperfusion in both control and experimental animals (p less than 0.0001). Treatment with iloprost, however, significantly attenuated this response compared to the control group, 4.8 +/- 0.3 versus 7.3 +/- 0.5 microliters/gm/min, respectively (p less than 0.0001). Iloprost decreases the rise in vascular permeability after ischemia and reperfusion. Experimental clinical use of iloprost under controlled conditions in the treatment of patients with acute skeletal muscle ischemia appears justified."
-How might exercise training potentially influence coronary collateral circulation?,"Exercise training and coronary collateral circulation. This review examines the potential for an exercise-induced increase in coronary collateral circulation, with specific reference to the role and functional significance of collateral vessels, highlighting animal and human studies in particular, and their inherent methodological limitations. Exercise training may enhance myocardial oxygen supply by promoting transient periods of myocardial ischemia, a potent trigger of collateral growth. Some human studies have shown that moderate-to-high intensity training can result in a higher double product at the onset of angina and/or ischemic ST-segment depression, suggesting that myocardial oxygen supply has increased. Attempts to use thallium-201 exercise scintigraphy to assess myocardial perfusion before and after a physical training program have produced conflicting data, whereas angiographic studies in group trials have, without exception, yielded disappointing results. Thus, direct evidence that exercise stimulates collateralization in humans is lacking."
-What percentage of bladder tumors showed positive signals for HPV type 16/18 DNA in this study?,"Detection of human papillomavirus DNA in cancer of the urinary bladder by in situ hybridisation. The association of the human papillomavirus (HPV) with cancer of the urinary bladder was assessed by in situ hybridisation using probes selective for HPV types 6/11 and 16/18 DNA. No hybridisation signal was detected with the type 6/11 probe on 100 formalin-fixed, paraffin-embedded bladder tumours sampled. However, when the same samples were hybridised with the HPV type 16/18 DNA probe, 11 of 66 (16.6%) papillary and 1 of 10 (10%) solid transitional cell carcinomas gave positive signals. These results suggest the involvement of HPV in cancer of the bladder, although the frequency of multiple HPV types in these tumours is uncertain."
-What is the significance of monosomy 7 in the reported case of erythroleukemia?,"Erythroleukemia in a child associated with monosomy 7. A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm."
-What rare condition can cause hypertension with increased renin concentrations in infants?,"Hypertension associated with increased renin concentrations in nephroblastoma. An infant with severe hypertension who had a nephroblastoma which was secreting active renin is described. Nephroblastoma must be included in the differential diagnosis of hypertension associated with increased renin concentrations, even in the absence of an abdominal mass."
-How do the hemodynamic effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) differ in experimental heart failure?,"Differential hemodynamic effects and tolerance properties of nitroglycerin and an S-nitrosothiol in experimental heart failure. S-nitrosothiols are potent in vitro vasodilators, but little is known about their in vivo action. In this study, we compared the effects of S-nitroso N-acetyl penicillamine (SNAP) and nitroglycerin (NTG) on left ventricular (LV) hemodynamics in congestive heart failure rats. By using a twoday crossover design, stepwise i.v. infusions of SNAP or NTG at 3, 5 and 8 micrograms/min were administered for 30 min each, followed by a dose of 10 micrograms/min over the next 10 h. LV end-diastolic and peak-systolic pressures (LVEDP and LVPSP, respectively) were measured at selected intervals. SNAP and NTG produced maximal LVEDP reductions of 46 and 44%, respectively, at the highest infusion rate. However, at the lower doses, greater reductions of LVEDP were seen with SNAP. NTG had a smaller effect on LVPSP (maximum 6% reduction) than SNAP (maximum reduction of 15%). During the 10-h infusion of NTG, LVEDP gradually returned to base-line values, indicating the development of tolerance, despite relatively constant plasma levels of NTG over the infusion period. Tolerance in LVEDP effects was not observed during the 10-h infusion of SNAP. In the presence of NTG tolerance, rats were still responsive to SNAP (mean reduction of LVEDP 24%), suggesting the absence of cross-tolerance between these two nitrovasodilators. These results suggest that SNAP is a more potent in vivo vasodilator than NTG, has more arterial action than NTG and is less prone to produce LV hemodynamic tolerance."
-What is the main focus of the case reports discussed in the context?,"Pattern of arterial involvement of the head, neck, and eyes in giant cell arteritis: three case reports. The findings of two post-mortem examinations and one CT scan of patients with biopsy proved giant cell arteritis (GCA) are presented. The presence or absence of intracranial involvement in GCA is discussed."
-What are coronary artery aneurysms and how are they typically detected?,"Coronary artery aneurysms--a case study and literature review. Coronary artery aneurysms are detected with increasing frequency owing to the advent of coronary angiographies. Although most patients with coronary artery aneurysms are asymptomatic, manifestations of myocardial ischemia may occur. The case described herein serves as a basis for a discussion of the pathogenesis, clinical manifestations, detection, and treatment of coronary artery aneurysms."
-What ethical considerations do physicians face when deciding whether to treat hypercalcemia in patients with advanced malignancy?,"Hypercalcemia of advanced malignancy: decision making and the quality of death. Hypercalcemia is a common complication of certain advanced malignancies and although not therapeutically difficult, its presence raises complex ethical issues. Treatment of this condition is most easily justified when the patient is not terminal, the benefits are tangible, and the patient agrees with therapy. Withholding treatment is defensible medically, legally, and morally when a terminal situation is present, when drawbacks exceed the benefits, and when an informed patient declines therapy. Hypercalcemia is one of a number of conditions of dying that can be controlled by the physician. The physician's decision to treat such a condition, in part, depends upon his or her view of a good death. Further study is needed to clarify and avoid those situations of dying which involve suffering. Physicians must begin this difficult analysis and dialogue if they are to fulfill their obligation to minimize suffering in all patients."
-What evidence suggests that interferon-alpha therapy can cause persistent neurotoxicity in cancer patients?,"Persistent neurotoxicity of systemically administered interferon-alpha. Fourteen cancer patients had evidence of persistent neurotoxicity of interferon-alpha therapy long after their treatment was discontinued. Although most of the cognitive symptoms were mild to moderate in severity, they were incapacitating to these individuals in their usual work. The neuropsychological test abnormalities were not attributable to subsequent therapy, disease status, or other medical problems. The pattern of deficits was consistent with frontal-subcortical dysfunction. Of the four patients who had follow-up assessment, two had improved and two had deteriorated. These findings suggest that in some cases interferon neurotoxicity is not reversible."
-What surgical procedure is described for treating lateral nasal wall neoplasms and what are its key characteristics?,"'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and ""medial maxillectomy,"" an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora."
-What was the overall prevalence of dementia in individuals 65 years and older in the East Baltimore Mental Health Survey?,"Dementia: case ascertainment in a community survey. The three-stage East Baltimore Mental Health Survey, conducted in 1981 as part of the Epidemiological Catchment Area Program, provided an opportunity to assess the prevalence of dementia and specific dementing disorders in a community-based, cross-sectional sample of the population. From the 3,841 households originally sampled, 810 individuals were selected for clinical psychiatric evaluation. Forty-one individuals were given a provisional diagnosis and referred to Stage 3 for differential diagnosis, with 32 individuals completing this evaluation. Thorough clinical evaluation of these cases resulted in an overall prevalence of dementia of 4.5% in those 65 years of age and older. The prevalence of specific dementing disorders was Alzheimer's disease (AD) (2.0%), Multi-Infarct Dementia (MID) (2.0%) and Mixed Dementia (MD) (0.5%). Prevalence increased with age for all dementias: Non-Whites had higher rates of dementia than Whites; females had higher rates of AD while males had higher rates of MID; and the prevalence of AD increased with increasing education, whereas the prevalence of MID decreased with increased education. Although this study includes only a small number of cases, necessitating some caution in interpreting the results, these figures do represent an estimate of the prevalence of severe dementing disorders and provide a basis for further community study."
-What is the key histological finding in the papular mucinosis associated with L-tryptophan-induced eosinophilia-myalgia syndrome?,"Papular mucinosis in L-tryptophan-induced eosinophilia-myalgia syndrome. Five patients with the L-tryptophan-related eosinophilia-myalgia syndrome had a generalized eruption of flesh-colored papules. In all patients, histologic examination revealed a focal accumulation of mucin in the upper mid dermis, associated with increased dermal cellularity. The mucin was composed predominantly of hyaluronic acid, with small amounts of sulfated acid mucopolysaccharides. The cells within the lesion were fibroblasts. The lesions slowly regressed after L-tryptophan was discontinued. Proposed explanations for the L-tryptophan-related eosinophilia-myalgia syndrome have centered on contaminants, chemically related to L-tryptophan, introduced in the manufacturing process. Tryptophan metabolites have been linked with sclerotic cutaneous diseases but have not been previously implicated in cutaneous mucinoses."
-What is fludarabine and in which types of leukemia has it shown potential effectiveness?,"Fludarabine: a review. The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels."
-What were the outcomes of endovascular treatment for brain arteriovenous malformations in this study?,"Endovascular treatment of intracerebral arteriovenous malformations: experience in 49 cases. The authors report the results of treatment in 49 consecutive patients with brain arteriovenous malformations (AVM's) who underwent therapeutic embolization with liquid adhesive agents between 1984 and 1988 at the Toronto Western Hospital. Thirty-three patients had no other treatment and were followed up with angiography at 2 years and clinically from 2 to 6 years. Of the other 16 patients, 10 had adjunctive radiosurgery and six underwent surgical resection following embolization. Seven (14%) of the 49 patients had a morphological cure effected by embolization as evidenced on their 2-year follow-up angiograms: these have remained clinically stable. Twelve patients developed neurological deficits after embolization; eight (16% of the series) were transient and four (8%) were permanent. Two patients (4%) had a delayed hemorrhage after incomplete obliteration of their malformations. Endovascular treatment resulted in clinical improvement in 15 (33%) of the other 46 patients. None of the patients who initially presented with hemorrhage had a rebleed following embolization. It is concluded that endovascular treatment with liquid embolic material can be an integral part of the multidisciplinary treatment protocol for patients with brain AVM's."
-How does nonsteroidal anti-inflammatory drug (NSAID) usage impact upper gastrointestinal lesions in elderly patients?,"Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage. The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer."
-What were the key findings comparing restorative proctocolectomy with and without a covering ileostomy in patients with ulcerative colitis?,"Comparison of restorative proctocolectomy with and without covering ileostomy in ulcerative colitis. The experience of restorative proctocolectomy for ulcerative colitis is reported in 16 consecutive patients with no covering ileostomy (group 2) in comparison with 15 patients with a covering stoma (group 1); in each group a J pouch was constructed. All patients had pre- and postoperative clinical and manometric evaluations of the functional result up to 12 months. There were no deaths or permanent failures. The number of early complications was four in each group. Re-ileostomy was needed in one patient of group 1, and an ileostomy was constructed in three patients of group 2. At 1 year after operation the functional results did not differ between groups 1 and 2 in terms of daily frequency of defaecation (mean 5.6 and 5.4 in 24 h respectively), or in terms of anal basal or maximal squeeze pressures. There was a significant (P less than 0.01) saving in total hospital stay (median 11 days) and in operating theatre time (mean 41 min) in patients with no covering ileostomy. It is concluded that a covering ileostomy may be unnecessary in restorative proctocolectomy, at least in suitable cases with no technical difficulty at the time of operation."
-What percentage of severely hearing impaired adults in the audiology clinic had a mixed hearing impairment in their better hearing ear?,"Characterization of severely and profoundly hearing impaired adults attending an audiology clinic. Despite the fact that around 12 per cent of adult patients attending an audiology department will be severely hearing impaired (pure tone averages of 0.5, 1, 2 and 4 kHz of 70 dB HL or worse in the better hearing ear), their clinical and audiometric characteristics have not been well documented. These characteristics were collected prospectively in 132 adult patients attending a Severe Impairment Clinic, set up to manage their specific problems. The inability to provide sufficient masking makes audiometric assessment of the severity of the impairment uncertain in the poorer hearing ear in 52 per cent of these patients. In addition, the limited bone conduction output makes it almost invariably impossible to assess the masked bone conduction thresholds and hence the air-bone gap in the poorer ear. Hence, accurate characterization is only practical of the better hearing ear in such patients. In 67 per cent of the better hearing ears, there was a mixed hearing impairment, the air-bone gap being 20 dB or greater. The aetiology of the conductive component was almost equally otosclerosis and chronic otitis media. In only 19 per cent was the impairment of a pure sensorineural type, broken down as 6 per cent congenitally acquired, 5 per cent due to meningitis and 9 per cent being adult in onset. In the remaining 14 per cent of patients the type of impairment could not be classified as the bone conductive thresholds were off scale. Having had experience of managing these patients at a special clinic and knowing the workload involved, it is argued that consideration be given to setting up such clinics in most departments."
-What potential complication can cold-reacting autoantibodies cause during cardiac operations?,Agglutination of blood cardioplegia by cold-reacting autoantibodies. Cold-reacting autoantibodies occasionally occur in patients requiring cardiac operations. This report describes the clinical course of 1 patient with cold-reacting autoantibodies and intracoronary agglutination of the blood cardioplegia solution. Observations made in vivo and in vitro are considered in discussing recommendations for the management of extracorporeal circulation and cardioplegic arrest in patients with clinically silent cold-reacting autoantibodies.
-What are the key characteristics of Fibromyalgia Syndrome (FS) according to the context?,"Toward an integrated understanding of fibromyalgia syndrome. I. Medical and pathophysiological aspects. Fibromyalgia syndrome (FS) is a chronic pain disorder characterized by diffuse musculoskeletal soreness, stiffness, non-restorative sleep and psychological disturbance. At present, much about the etiology, pathological mechanisms and course of FS are unknown. Indeed, standardized diagnostic criteria have only been recently agreed upon. The present paper is the first of a two-part series which reviews the extant empirical literature concerning FS, with a view to arriving at an integrated understanding of the syndrome. The present paper describes the clinical presentation of FS and historical conceptualizations of the disorder. Available research on pathophysiological mechanisms in FS is then presented. In this section we have included literature concerning histology of muscle, sleep architecture, neurotransmitter anomalies and neuropeptide involvement in FS symptomatology."
-What is a peripheral ameloblastoma and how rare is this odontogenic tumor?,"Peripheral ameloblastoma: a clinical and histologic study of 11 cases. Peripheral ameloblastoma (PA) is a rare odontogenic tumor. Previously, only 39 cases of PA had been reported in the English literature. In this article 11 additional cases of PA are presented. Concordance with previous cases was evident with regard to race, clinical appearance, and site of predilection. However, differences were observed with regard to age, sex distribution, and predominant histologic pattern. The average age in the current cases is younger, there is no male bias, and the most common histologic pattern is plexiform rather than follicular or acanthomatous. Recurrence following simple excision is rare, but has been reported. Long-term postoperative follow-up is recommended."
-What is primary breast lymphoma (PBL) and how was it treated in the described cases?,"Primary breast lymphoma. Primary breast lymphoma (PBL) is a rare tumor of the breast. Three cases of PBL are being described. All three cases achieved remission following biopsy, chemotherapy, and/or radiotherapy. The literature is extensively reviewed with emphasis on true incidence of PBL and survival rates."
-What are some potential causes of high-attenuation mediastinal masses on unenhanced CT scans?,"High-attenuation mediastinal masses on unenhanced CT. On unenhanced CT scans, a variety of mediastinal masses contain areas with attenuation values higher than the attenuation value of the chest wall musculature. The increased attenuation may be diffuse or focal and may be a result of calcium deposition, high iodine content, or areas of acute hemorrhage. This report illustrates the gamut of high-attenuation mediastinal masses seen on unenhanced CT. Masses that are of high attenuation only on IV contrast-enhanced images (e.g., aberrant vessels) are not included."
-How does subeschar tissue fluid (STF) impact cell-mediated immune function in patients with severe thermal injury?,"Subeschar tissue fluid: a source of cell-mediated immune suppression in victims of severe thermal injury. Thermal injury results in pronounced physiologic alterations in microcirculation at the site of tissue damage. The consequence of these changes is an increase in microvascular permeability, leading to the accumulation of tissue edema, or subeschar tissue fluid (STF). One of the adverse properties of edema is its capacity in vitro to inhibit cell-mediated immune function. Since previous studies evaluated STF collected 5 to 7 days after thermal injury, the present study was designed to determine the time frame during which STF demonstrates its immune suppressive nature. Seven patients with severe thermal injury (30% to 100% total body surface area) were entered into the study. STF was collected in serial fashion, beginning as early as 9 hours after injury and continuing until fascial excision or patient death (maximum of 139 hours after injury). The addition of STF to cultures of lymphocytes obtained from healthy donors resulted in complete inhibition of mitogen-induced lymphocyte proliferation (MILP). Serum collected concomitantly from this group of patients was also capable of inhibiting MILP. From its inception, STF possesses the ability to inhibit MILP; this suppressive nature is stable, persisting for prolonged periods of time. The gradual absorption of STF likely contributes to the serologic evidence of cell-mediated immune suppression documented in victims of severe thermal injury."
-How do TGF alpha and TGF beta influence liver regeneration and hepatocyte proliferation?,"Protooncogenes and growth factors associated with normal and abnormal liver growth. Hepatocyte replication during liver regeneration depends on extrinsic (circulating) and intrinsic (intrahepatic) factors. Two important growth factors produced in the regenerating liver are discussed, TGF alpha, an autocrine, stimulatory growth factor, and TGF beta, a paracrine inhibitory factor. The balance between the activities of these factors is likely to play an important role in regulating hepatocyte proliferation. The expression of some protooncogenes occurs sequentially during the first few hours after partial hepatectomy and is a marker for the entry of hepatocytes into the cell cycle (proliferative competence). As hepatocytes become competent to proliferate, they respond to TGF alpha and other growth factors and enter a proliferative phase. It is possible that TGF beta 1 serves as a stop signal for liver regeneration but the mechanisms by which TGF beta inhibits hepatocyte DNA synthesis are still unknown."
-How did psychopathology levels impact hospital stay length and medical service costs for inpatients in this study?,"Relation of psychopathology in general medical inpatients to use and cost of services. The authors investigated the relation between psychopathology in medically ill inpatients and use and cost of medical care services. Of 455 medical inpatients, the Medical Inpatient Screening Test identified 27.9% as very depressed, 27.5% as very anxious, 20.2% as having cognitive dysfunction, and 8.6% as having high pain levels. Overall, the test identified 51% of the patients as having high levels of psychopathology or pain. These subjects had a 40% longer median length of hospital stay and 35% greater mean hospital costs than those with low levels of psychopathology or pain. Patients with greater psychopathology also had higher hospital charges, more procedures during hospitalization, and more discharge diagnoses but did not differ from the other patients in sex, race, age, diagnosis-related group (DRG) major diagnostic category, or DRG weight."
-How does the presence of blood medium affect the pulsed-dye laser ablation of normal and atherosclerotic human aorta tissues?,"Enhancement of pulsed-dye laser ablation of arterial tissues with blood medium: effects of laser-induced shock waves. The influence of blood medium on tissue ablation by a pulsed dye laser and its selectivity for atheroma were investigated. The role of shock waves on tissue ablation was also evaluated. Normal and atherosclerotic human aortas were irradiated by a 480 nm pulsed dye laser activated at 5 Hz. The laser was coupled with a single 0.2 mm fiber (Uni-guide) (40 mjoules/pulse) or a multifiber catheter (14 x 150 microns) (100 mjoules/pulse). Shock waves were measured using a fluid-filled catheter connected to a strain gauge manometer. With the Uni-guide, pulse-dye lasing resulted in greater ablation of atheroma in blood (11.6 x 10(-3) mm3/joule, p less than 0.001 versus atheroma measured in saline and normal tissue in blood) followed by normal tissue in blood (2.5 x 10(-3)mm3/joule), atheroma in saline (1.71 x 10(-3)mm3/joule, p less than 0.05 versus normal tissue in saline), and normal tissue in saline (0.54 x 10(-3) mm3/joule). With the multifiber catheter, laser ablation was the greatest in atheroma in blood (0.55 +/- 0.26 mm3/joule p less than 0.001 versus atheroma in saline and normal tissue in blood), followed by normal tissue in blood (0.27 +/- 0.12 mm3/joule), atheroma in saline (0.14 +/- 0.15 mm3/joule, p less than 0.001 versus normal tissue in saline), and normal tissue in saline (0 mm3/joule). The ablation efficiency of the multifiber catheter was greater than that of the Uni-guide (p less than 0.0001)."
-What is the significance of the two case studies involving isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma?,Isolated incisional metastases after intraperitoneal radioactive chromic phosphate therapy for ovarian carcinoma. Two women developed apparently isolated recurrences of ovarian carcinoma involving prior incisions after receiving intraperitoneal radioactive chromic phosphate (P-32) adjuvant therapy for early epithelial ovarian carcinoma. Both are alive without evidence of disease at second-look laparotomy after surgical resection of the abdominal wall metastases and cisplatin-based combination chemotherapy. Mechanisms of cutaneous and incisional implantation metastases are discussed. Adjuvant therapy with intraperitoneal P-32 is unable to provide systemic therapy for occult metastatic disease. The favorable outcome in these cases probably reflects limited tumor burden at the time of recurrence and stands in stark contrast to other cases of soft tissue recurrences of ovarian carcinoma reported previously.
-How does blockade of ATP-sensitive potassium channels affect reactive hyperemia in the canine coronary circulation?,"Blockade of the ATP-sensitive potassium channel modulates reactive hyperemia in the canine coronary circulation. The mechanism of reactive hyperemia remains unknown. We hypothesized that reactive hyperemia was related to the opening of ATP-sensitive potassium channels during coronary occlusion. The resulting hyperpolarization of the smooth muscle cell plasma membrane might reduce calcium influx through voltage-dependent calcium channels and result in relaxation of smooth muscle tone and vasodilation. In eight open-chest, anesthetized dogs, 30-second coronary occlusions resulted in an average flow debt repayment of 200 +/- 41%. After low-dose (0.8 mumol/min) and high-dose (3.7 mumol/min) infusion of intracoronary glibenclamide, flow debt repayment fell to 76 +/- 14% and 50 +/- 8%, respectively (p less than 0.05 compared with control for both). The decline in flow debt repayment was due to a significant reduction both in maximum coronary conductance during reactive hyperemia and in its duration. In addition, there was a significant decline in the sensitivity of the coronary circulation to adenosine-induced vasodilation after glibenclamide. While more variable, there was no overall change in the sensitivity of the coronary vasculature to acetylcholine-induced vasodilation after glibenclamide. We conclude that reactive hyperemia is determined in a large part by the ATP-sensitive potassium channel, probably through its effect on membrane potential and voltage-sensitive calcium channels. Because reactive hyperemia was never fully abolished at the highest doses of glibenclamide tested, it is possible that additional mechanisms are involved in the genesis of this complex phenomenon."
-What are the key findings of the study regarding volume tests for chronic venous insufficiency?,"Volume tests for chronic venous insufficiency: an appraisal. Chronic venous disease is increasingly treated surgically with a variety of experimental procedures. Noninvasive volume tests are commonly used before surgery to select patients and after surgery to assess results. Rapid volume changes are considered to indicate regurgitation. Rigorous statistical validation of tests and the confounding nature of unmeasured arterial inflow are seldom considered. Volume changes were measured in 29 control limbs and 35 limbs with venous disease, with mercury-in-silicone rubber strain gauges, for both exercise and elevation. Normalization for arterial flow permitted calculation of the regurgitation rate. Normal (95% confidence) limits for measured and calculated parameters were determined. Specificity was shown by the percent of normal parameter values for control limbs and sensitivity by the percent of abnormal values for extremities with venous disease. Arterial flow significantly altered volume curves. Normalization increased specificity and sensitivity significantly. Calf exercise tests, even normalized, were too insensitive to be reliable. Elevation tests were significantly more sensitive for determining regurgitation. However, exercise tests were useful and supplied important information about the calf muscle pump. We conclude that, as currently used, many limb volume test procedures are unsuitable but could be improved significantly by normalization to reduce the confounding effect of regional arterial flow and use of an elevation test to measure regurgitation."
-What is the significance of the mutation in the porcine ryanodine receptor gene in relation to malignant hyperthermia in swine?,"Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia. Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs."
-What was the main objective of the study on phenytoin overdose?,"Severe oral phenytoin overdose does not cause cardiovascular morbidity. STUDY OBJECTIVE: To evaluate the potential for cardiovascular toxicity from severe oral phenytoin overdose. STUDY POPULATION: Fifty-seven patients admitted during a two-year period to an inner-city hospital for severe oral phenytoin overdose, which is defined as a peak level of 40 micrograms/mL or more. METHODS: Case records were reviewed retrospectively for symptoms and signs of phenytoin toxicity, especially circulatory effects. Baseline and toxic 12-lead ECGs, when available, were reviewed in detail. Continuous variables were compared using either paired or unpaired t tests, as appropriate. Significance was taken as P less than or equal to .05. RESULTS: Mean peak phenytoin level was 49.4 +/- 7.7 micrograms/mL. Continuous single-lead ECG monitoring in 36 patients (63%) for a mean of 26.5 +/- 21.6 hours revealed no incidents of dysrhythmia requiring treatment. ECGs recorded during toxicity in 52 cases (91%) revealed no clinically significant abnormalities attributable to phenytoin. ECGs during toxic and baseline states were available for detailed analysis in 15 cases. Ten patients exhibited an increase in PR interval (mean, 19 +/- 10 ms) when toxic, whereas five had a decrease (mean, 18 +/- 11 ms) compared with nontoxic records. No change in heart rate, QRS duration, or corrected QT interval was observed. There were no circulatory complications and no deaths. CONCLUSION: Cardiovascular toxicity is rarely a manifestation of oral phenytoin overdose. Routine management of stable patients with severe phenytoin overdose in a monitored setting is not mandatory."
-What neurotoxic effects were observed in patients treated with intraventricular alpha-interferon for leptomeningeal disease?,"Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease. Nine patients with leptomeningeal disease are reported who were treated with intraventricular alpha-interferon (alpha-IFN). In seven of these patients, a progressive vegetative state developed during treatment. The patients became unresponsive to verbal commands but opened their eyes with auditory or tactile stimulation. It took an average of 3 weeks for these patients to become verbally responsive after treatment was discontinued. Electroencephalographic findings showed evidence of irritative involvement of the deep midline nuclei in 80% of patients. Periventricular white matter changes developed during treatment in three of six patients who underwent computed tomographic scans. All patients with this severe neurotoxicity received whole-brain irradiation before treatment. Possible mechanisms for the development of this neurotoxic syndrome are discussed. The neurotoxicity of alpha-IFN and brain irradiation may be additive, suggesting a cautious approach when using this combination for treatment."
-How does positive end-expiratory pressure (PEEP) affect splanchnic circulation in experimental peritonitis?,"Effects of positive end-expiratory pressure on splanchnic circulation and function in experimental peritonitis. Splanchnic and central hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in anesthetized pigs using mechanical ventilatory assistance, with or without sepsis (fecal peritonitis). One hour after sepsis, PEEP (10 cm H2O) was applied (n = 6). Another group (n = 6) had sepsis without PEEP. In one group (n = 6) without sepsis, PEEP was applied after 1 hour, while a fourth group (n = 5), without sepsis or PEEP, served as a control. The group with PEEP and sepsis had reduced cardiac index, portal venous blood flow, and liver surface blood flow. The group with PEEP alone had reduced splanchnic circulation by increasing gastrointestinal vascular resistance, while the group with sepsis alone had increased portal vascular resistance. In a separate series with sepsis, intermittent PEEP, and vigorous fluid resuscitation, it was demonstrated that avoiding hypovolemia did not seem to protect from the PEEP effects on the splanchnic circulation. The combination of sepsis and PEEP was not additive on portal blood flow reduction but reduced bile production."
-What factors were associated with higher mortality rates in patients with ruptured abdominal aortic aneurysms in this study?,"Factors affecting survival of patients with ruptured abdominal aortic aneurysm in a West Virginia community. The hospital records for patients treated for ruptured abdominal aortic aneurysms in southern West Virginia during a recent five year period were reviewed. The over-all mortality rate was 62 per cent. Patients with intraperitoneal rupture had a higher mortality rate (97 per cent) than patients with retroperitoneal rupture (25 per cent). Patients at increased risk were more than 80 years of age, presented with syncope, experienced a short duration of symptoms before seeking medical attention, had preoperative systolic blood pressure levels of less than 90 millimeters of mercury and had a preoperative hemoglobin level of less than 8. Other factors associated with death were a delay in beginning surgical treatment, a larger total blood loss and amount of blood transfused. The results of multivariate analysis demonstrated that preoperative blood pressure, preoperative hemoglobin, presence of syncope and the amount of blood loss were, in large part, reflections of the type of rupture and had only slight independent relationship to mortality. The most effective method of preventing fatal outcome is elective resection of the aneurysms before rupture occurs."
-What were the anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A compared to other antiepileptic drugs?,"Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats. The anticonvulsant profiles of two potent and orally active gamma-aminobutyric acid (GABA) uptake inhibitors, 1-(4,4-diphenyl-3-butenyl)-3-piperidine-carboxylic acid hydrochloride (SK&F 89976-A) and 1-(4,4-diphenyl-3-butenyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (SK&F 100330-A), were determined with a battery of well-standardized tests in mice and rats and compared with the profiles of phenytoin (PHT), carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) when subjected to the same tests. ED50 values were calculated and compared with TD50 values for minimal motor impairment to provide protective indexes (PI = TD50/ED50). The anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A were similar and suggest that these compounds raise the threshold for seizure initiation rather than inhibit seizure spread. Like intraperitoneal (i.p.) PHT, CBZ, VPA, and CZP, SK&F 89976-A and SK&F 100330-A inhibited seizures in corneally kindled rats. The profiles of SK&F 89976-A and SK&F 100330-A were most similar to that of CZP and virtually opposite to that of PHT. Intraperitoneal SK&F 100330-A provided complete protection against pentylenetetrazol-induced seizures [subcutaneous (s.c.) PTZ] in mice but was ineffective against seizures induced by maximal electroshock (MES) at doses slightly greater than its TD50. SK&F 100330-A provided complete protection against picrotoxin-induced seizures (s.c. Pic) and against both clonus and forelimb tonic extension induced by NMDA N-methyl-D-aspartate [intracerebral ventricular (i.c.v.)-NMDA] in mice; however, SK&F 100330-A was ineffective against seizures induced by bicuculline (s.c. Bic) and strychnine (s.c. Strych) at doses slightly greater than its TD50. SK&F 89976-A was similar but provided partial protection against NMDA-induced clonus."
-How does substance P protect against the neurodegenerative effects of beta amyloid in the brain?,"An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P. Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta amyloid. Immunoblot analysis showed that beta amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta amyloid. Thus, beta amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P."
-How did technetium-99m-HMPAO labeled leukocyte imaging help in detecting the chronic prosthetic vascular graft infection in the 77-year-old patient?,Chronic prosthetic vascular graft infection visualized with technetium-99m-hexamethylpropyleneamine oxime-labeled leukocytes Technetium-99m-HMPAO labeled leukocytes demonstrated chronic femoro-femoral prosthetic vascular graft infection several times during an 18-mo period in a 77-yr-old man. The intensity and distribution of the uptake in the graft were fluctuating in different imaging occasions possibly indicating the strength and location of the infection. Gallium-67-citrate imaging showed negative results twice. The reason for negative 67Ga results remained obscure. The infected graft was removed and the patient did well 5 mo postoperatively.
-Does zidovudine have an effect on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection?,"No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection. Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity."
-How accurate is pneumothorax CT in evaluating chest wall and mediastinal invasion in lung cancer patients?,"Tumor invasion of the chest wall and mediastinum in lung cancer: evaluation with pneumothorax CT. For preoperative evaluation of chest wall and mediastinal invasion by lung cancer, computed tomography (CT), combined with artificial pneumothorax (pneumothorax CT), was performed in 43 patients with lung cancer in whom conventional CT scans showed that the mass was contiguous to the chest wall (n = 30) and/or mediastinum (n = 25) but without evidence of definite tumor invasion. Invasion was diagnosed on the basis of whether an air space existed between the mass and the adjacent structures. In three patients pneumothorax was not produced. After the procedure, four patients developed symptomatic pneumothorax, and one, subcutaneous emphysema. Comparison of diagnoses based on findings at pneumothorax CT, surgery, and pathologic examination showed that pneumothorax CT is 100% accurate for chest wall invasion and 76% accurate for mediastinal invasion. The authors conclude that this procedure is helpful in accurate evaluation of the T criterion in lung cancer, especially for patients in whom findings at conventional CT suggest tumor invasion of the chest wall and mediastinum."
-What is the relationship between alpha 2 macroglobulin complexes and the severity of acute pancreatitis?,"Alpha 2 macroglobulin state in acute pancreatitis. Raised values of alpha 2 macroglobulin-protease complexes in severe and mild attacks. Plasma values of C reactive protein, alpha 1 proteinase inhibitor, alpha 2 macroglobulin, and complexed alpha 2 macroglobulin have been determined in serial samples from 27 patients with acute pancreatitis. Complexed alpha 2 macroglobulin was measured by a novel enzyme linked immunosorbent assay with a monoclonal antibody specific for the complexed form. Patients with severe illness had lower concentrations of total alpha 2 macroglobulin and higher concentrations of complexed alpha 2 macroglobulin than those with mild illness, and in the majority of severe attacks the abnormal amounts of complexed alpha 2 macroglobulin were present throughout the eight days of the study. The proportion of total alpha 2 macroglobulin in the uncomplexed form, however, was generally greater than 90%, and in 26% of the mild cases completely normal concentrations of uncomplexed alpha 2 macroglobulin (greater than 99% of total) were found throughout the eight days of the study. This suggests that exhaustion of alpha 2 macroglobulin in plasma is unlikely to be a major factor in the pathogenesis of acute pancreatitis."
-How does the depletion of factor XII-dependent fibrinolytic activity relate to the risk of early myocardial reinfarction after rt-PA therapy?,"Depression of factor XII-dependent fibrinolytic activity characterizes patients with early myocardial reinfarction after recombinant tissue-type plasminogen activator therapy. Twenty patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) had endogenous factor XII-dependent fibrinolytic activity levels measured throughout the hospital period and those levels were prospectively correlated with the incidence of recurrent myocardial infarction until 8 weeks after hospital discharge. Within the follow-up period, recurrent myocardial infarction was observed in 8 patients, whereas the remaining 12 patients showed no clinical evidence of recurrence. The patients in the reinfarction group were characterized by a more pronounced depletion of and sustained lower levels of factor XII-dependent fibrinolytic activity than were the patients with no reinfarction (p less than 0.05). The decrease in fibrinolytic activity during rt-PA therapy was significantly associated with a depletion of functional alpha 2-antiplasmin, the primary plasmin inhibitor. These results indicate that, paradoxically, coronary thrombolysis with rt-PA involves depletion of endogenous factor XII-dependent fibrinolytic activity levels, which constitutes a risk for early myocardial reinfarction."
-What is the success rate of arthroscopic stapling for treating superior labral tears in young athletes?,"Arthroscopic stapling for detached superior glenoid labrum. Superior labral tears of the shoulder involve the biceps tendon and labrum complex which may be detached, displaced inferiorly, and interposed between the glenoid and the humeral head. We have treated ten young athletes with painful shoulders due to this lesion by arthroscopic stapling. Arthroscopy at the time of staple removal, after three to six months, showed that all the lesions had been stabilised. Clinical review at over 24 months showed an excellent or good result in 80%. The two relative failures were due in one to residual subacromial bursitis, and the other to multidirectional shoulder instability. Arthroscopic stapling can restore the shoulder anatomy, and it is recommended for active adolescent athletes with this lesion."
-What was the complication rate for intra-aortic balloon pump (IABP) insertion in different clinical scenarios according to the study?,"Percutaneous intra-aortic balloon pump: emphasis on complications. In a review of our 5-year experience with intra-aortic balloon pump (IABP) insertion I examined the complications of percutaneous IABP placement in 93 patients, and compared them with those reported in other studies in the literature. I analyzed several variables that may affect the complication rate. Of 78 patients in our series who had percutaneous IABP cardiac assist, 15 (19%) had complications, which falls into the acceptable range reported by others. Among 15 patients who had surgical placement of an IABP, the complication rate was similar at 20%. The complication rate after IABP insertions done by surgeons primarily in the operating room was compared with that from insertions done by cardiologists in the catheterization laboratory. The overall complication rate was found to be higher in the second group, 28.0% compared with 12.8%. The application of the IABP in cardiogenic shock was associated with a high complication rate (46%). On the other hand, its insertion before cardiac surgery was associated with a relatively low complication rate (9.5%)."
-What were the clinical outcomes for patients who underwent mitral prosthesis insertion with native leaflets left intact?,"Left ventricular outflow obstruction resulting from insertion of mitral prostheses leaving the native leaflets intact: adverse clinical outcome in seven patients. Left ventricular (LV) outflow obstruction may result from retaining the anterior mitral leaflet when a mitral prosthesis is inserted in the mitral anulus. We retrospectively reviewed the echocardiograms (two-dimensional Doppler and Doppler color flow imaging, or transesophageal with color flow imaging) obtained in seven patients with preoperative mitral regurgitation who had a prosthesis implanted with the native mitral leaflets left intact. Systolic anterior motion of the native anterior mitral leaflet, as seen in dynamic LV outflow tract obstruction, was observed in six of seven patients. LV fractional shortening preoperatively was less than or equal to 0.25 in all (mean 0.20 +/- 0.04) and did not significantly (p = ns) increase postoperatively (mean 0.27 +/- 0.12). Color flow imaging revealed disturbed systolic flow in the LV outflow tract in five patients, and all had systolic anterior motion of the native anterior mitral leaflet. Continuous wave Doppler detected significant systolic LV outflow tract jets in five patients averaging 4.1 +/- 0.9 m/sec. Mitral prosthetic function was normal (pressure half-time of 81 +/- 25 msec and mean gradient of 7 +/- 3 mm Hg +/- SD) in five patients. Clinical follow-up revealed that all had died, six of them within 2 months of their operation. Thus systolic anterior motion of the native anterior mitral leaflet occurs commonly after prosthetic mitral valve insertion with the native leaflets left intact. Continuous wave Doppler often demonstrates increased systolic LV outflow tract velocities consistent with dynamic LV outflow obstruction."
-What was the treatment and outcome for the 40-year-old woman with periorbital necrobiotic xanthogranuloma and stage I multiple myeloma?,"Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging. We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma."
-What percentage of patients with failed back surgery syndrome experienced successful outcomes after spinal cord stimulator implantation at 2.2 and 5.0 years follow-up?,"Failed back surgery syndrome: 5-year follow-up after spinal cord stimulator implantation. Spinal cord stimulation, in use for more than 20 years, has evolved into an easily implemented technique, with percutaneous methods for electrode placement. We have reviewed our experience with this technique in treating ""failed back surgery syndrome,"" and have assessed patient and treatment characteristics as predictors of long-term outcome. A series of 50 patients with failed back surgery syndrome (averaging 3.1 previous operations), who underwent spinal cord stimulator implantation, was interviewed by impartial third parties, at mean follow-up intervals of 2.2 years and 5.0 years. Successful outcome (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in 53% of patients at 2.2 years and in 47% of patients at 5.0 years postoperatively. Ten of 40 patients who were disabled preoperatively returned to work. Improvements in activities of daily living were recorded in most patients for most activities; loss of function was rare. Most patients reduced or eliminated analgesic intake. Statistical analysis (including univariate and multivariate logistic regression) of patient characteristics as prognostic factors showed significant advantages for female patients and for those with programmable multi-contact implanted devices. These results, in patients with postsurgical lumbar arachnoid and epidural fibrosis and without surgically remediable lesions, compare favorably with the results in two separate series of patients with failed back surgery syndrome, in whom 1) surgical lesions were diagnosed and repeated operation performed; and 2) monoradicular pain syndromes were diagnosed and dorsal root ganglionectomies performed at our institution. This suggests the need for further assessment of selection criteria, critical analysis of treatment outcome, and prospective study of spinal cord stimulation and alternative approaches to failed back surgery syndrome."
-What clinical benefits did aspirin and heparin demonstrate in the treatment of unstable angina according to the clinical trials?,"Antiplatelet and antithrombotic therapy in unstable angina. In 4 well-controlled clinical trials, aspirin reduced the incidence of coronary events in unstable angina. The benefits were present during the acute, subacute and more chronic phases of the disease and were independent of the doses and of other protocol differences. This benefit of aspirin can be extended to some, but not all, other antiplatelet drugs. In 4 clinical trials, heparin used acutely added substantial benefit to the management of unstable angina, reducing the event rate and also the incidence of refractory angina more than aspirin. The long-term benefit of antithrombin therapy remains to be more thoroughly investigated. Despite these successes, the failure rate of aspirin and of heparin remains high, justifying a continuing search for more potent and safe antiplatelet and antithrombotic drugs."
-What was the primary purpose of using carbon dioxide laser ablation in treating cutaneous metastases from malignant melanoma?,"Carbon dioxide laser ablation of cutaneous metastases from malignant melanoma. Multiple cutaneous and superficial subcutaneous metastases from malignant melanoma in 30 patients were treated palliatively by carbon dioxide laser ablation when lesions were to numerous, too large or recurring too rapidly for multiple local excisions. The number of lesions per patient ranged from three to 250 (median 30). Patients were treated under local or general anaesthetic and as day cases or inpatients. After a median follow-up interval of 8 months fewer than 1 per cent of lasered metastases have recurred locally. Sixteen patients have developed cutaneous metastases at other sites requiring further treatment. Approximately 2000 lesions have been treated on 64 occasions. Patients reported little or no pain after the operation and required only simple dry dressings. Wounds were completely healed in 2-6 weeks with good cosmetic results. This simple and effective treatment is becoming an alternative to isolated limb perfusion."
-How has endoscopy improved the diagnosis and treatment of peptic ulcer disease?,"Use of endoscopy in peptic ulcer disease. The diagnosis and treatment of acute bleeding caused by peptic ulcer disease has been greatly facilitated by fiberoptic endoscopy. The basic differentiation between malignant and benign gastric ulcer requires endoscopic confirmation with biopsy. The management of bleeding from peptic ulceration can be enhanced by endoscopic examination as can the prediction of risk for recurrent bleeding or need for surgical intervention. Various therapeutic maneuvers can be performed endoscopically, including monopolar and multipolar cautery, laser and heater probe therapy, and injection of vasoconstrictors to control bleeding. Endoscopic balloon dilation for the management of gastric outlet obstruction is often effective."
-What is the relationship between optic chiasmal neuritis and multiple sclerosis according to the given context?,"Optic chiasmal neuritis. In four of six patients with clinical optic chiasmal neuritis, MRI demonstrated abnormalities of the chiasm. Optic chiasmal neuritis may be the initial manifestation of multiple sclerosis, a reflection of established CNS demyelination, or an isolated clinical finding."
-What was the overall accuracy of MR imaging in staging endometrial carcinoma according to the NCI cooperative study?,"MR imaging evaluation of endometrial carcinoma: results of an NCI cooperative study. A prospective study to assess the usefulness of magnetic resonance (MR) imaging in the evaluation of endometrial carcinoma was undertaken by five institutions under the auspices of the National Cancer Institute. Six different MR imagers were used, ranging in magnetic field strength from 0.15 T to 1.5 T. For each unit, appropriate T1- and T2-weighted sequences in the transverse plane and T2-weighted sequences in the sagittal plane were used. Initially, 107 patients were entered in the study, but only 88 fulfilled all the criteria and provide the basis for this study. The abnormality within the endometrial cavity was demonstrated with MR imaging in 81% of the patients. The overall accuracy with MR imaging for staging endometrial carcinoma was 85%. In the evaluation of depth of myometrial invasion for stage I disease, overall accuracy with MR imaging was 74%. The accuracy of MR imaging in assessing tumors confined to endometrium or tumor with superficial myometrial invasion was 89% and decreased to 54% in assessing deep myometrial invasion. The results of this prospective study performed by multiple examiners with vastly different equipment demonstrate the inherent value of MR imaging in the evaluation of this neoplasm."
-"How did prazosin treatment affect blood pressure, HDL-cholesterol concentration, and apoprotein-AI/HDL kinetics in patients with mild hypertension?","Effect of prazosin treatment on HDL kinetics in patients with hypertension. The effect of prazosin treatment on blood pressure, plasma HDL-cholesterol concentration, and apoprotein-AI/HDL (apoAI/HDL) kinetics was studied in 11 patients with mild hypertension. Blood pressure (mean +/- SEM) fell from 143 +/- 1/96 +/- 1 to 134 +/- 1/86 +/- 1 mm Hg after 4 to 5 months of prazosin treatment (P less than .001), associated with an increase in plasma HDL-cholesterol concentration from 38 +/- 2 to 46 +/- 2 mg/dL (P less than .001). Both the fractional catabolic rate (FCR) and total synthetic rate of apoAI/HDL, which were higher than previous reported values for normal individuals, decreased from 0.36 +/- 0.02 to 0.30 +/- 0.02 L/day and 17.4 +/- 1.1 to 13.8 +/- 1.1 mg/kg/min, respectively. These changes were statistically significant, and the post-treatment values for both variables were now within the normal range. When the decay curve was further analyzed by nonlinear curve fitting, it was shown that the return to normal of the FCR of apoAI/HDL in patients treated with prazosin was accounted for by the decrease of the decay constants of the second [p(2)] and third [p(3)] components of the 125I-AI/HDL disappearance curve. In conclusion, abnormalities in HDL concentration and HDL kinetics exist in patients with very mild hypertension. These defects were significantly improved with prazosin treatment, and this may render the compound of particular clinical benefit in the treatment of patients with mild hypertension."
-What role does radiotherapy play in the treatment of paediatric haemangiomas?,"Paediatric haemangiomas: the role of radiotherapy. Radiotherapy currently maintains an occasional place in the therapy of complicated haemangiomas of childhood. Eight such childhood benign lesions have been so treated at St Bartholomew's Hospital in the last 10 years. The case histories are presented before being discussed in the context of other therapies available (no treatment, steroids, embolism and surgery), radiation technique used and radiation dose prescription advised."
-What is Human Cyclical Neutropenia and what are its key clinical characteristics?,"Fatal human cyclical neutropenia with unresolving tonsillitis and bilateral cervical abscesses. Human Cyclical Neutropenia is a rare haematological disorder, characterized by periodic oscillations in peripheral neutrophil levels from normal to neutropenic, during which patients experience ulcerative stomatitis, fever, malaise and occasional cutaneous and subcutaneous infections. We present our experience with a fatal case of Human Cyclical Neutropenia together with a brief review of the literature and diagnostic criteria. The paper aims to heighten the clinical awareness of the otolaryngologist to the condition. Close co-operation with the haematologist is essential both for diagnosis and management."
-What surgical procedure is described for treating lateral nasal wall neoplasms and what are its key characteristics?,"'Medial maxillectomy' for lateral nasal wall neoplasms. Lateral rhinotomy and ""medial maxillectomy,"" an en bloc resection of the medial maxillary sinus, ethmoid sinus with the lamina papyracea, medial orbital floor, and lacrimal fossa-duct, have been advocated for lateral nasal wall neoplasma. Experience with 35 (of 41) patients followed up at least 30 months (median, 57 months) postoperatively is reported. There was a 9% recurrence for benign tumors and 15% for malignant neoplasms, the latter only in the patients with nonmelanoma malignant neoplasms not receiving postoperative radiotherapy. The most frequent complications were cavity crusting, epicanthal scarring, and epiphora."
-What was the primary purpose of the study on slow-release nifedipine in patients with variant angina?,"Efficacy of slow-release nifedipine on myocardial ischemic episodes in variant angina pectoris. To evaluate the efficacy of slow-release nifedipine (a single dose of 20 mg given at 10 P.M. or 2 doses of 20 mg at 10 P.M. and 6 A.M.) on ischemic episodes in patients with variant angina, a single-blind crossover study with ambulatory electrocardiographic monitoring was performed in 15 patients (13 men and 2 women, mean age 63 years). In all, there were 646 ischemic episodes detected with ambulatory electrocardiographic monitoring during the study period, and 618 episodes of them occurred during placebo periods with a circadian variation. Sixty-nine percent of the episodes in placebo periods were asymptomatic. The number of anginal attacks, nitroglycerin tablets taken, ST-segment elevation and the total ischemic duration significantly decreased during nifedipine therapy compared with results after the placebo therapy period, respectively (p less than 0.01 or 0.05). Twenty-eight ischemic episodes occurred during nifedipine therapy when the plasma level of nifedipine was low. Thus, asymptomatic ischemic episodes more frequently occur than symptomatic episodes and the administration of slow-release nifedipine is highly effective in suppressing not only symptomatic but also asymptomatic myocardial ischemia in patients with variant angina. The timing of the administration of slow-release nifedipine is an important factor in suppressing ischemic episodes."
-What is the main finding of this study regarding the natural course of hepatic haemangiomas in adults?,"Natural history of hepatic haemangiomas: clinical and ultrasound study. Hepatic haemangiomas are the most common benign tumours of the liver and commonly present as incidental findings on sonographic examination of the abdomen. Since little is known of the natural course of these tumours, we performed a clinical and sonographic follow up of 123 haemangioma patients. Our prospective study investigated clinical and sonographic findings in 158 haemangiomas for periods of 12 to 60 months. Ninety nine haemangiomas measured less than 2 cm and had an echogenic pattern; 40 were between 2 cm and 5 cm with a mainly echogenic structure; 19 measured greater than 5 cm and showed a mixed echo pattern. At the first examination only eight patients, all with giant haemangiomas, presented symptoms which could be attributed to the tumour. During follow up only one haemangioma changed in shape and size. One patient who was symptom free at the first examination experienced right upper abdominal quadrant pain during follow up. No deterioration occurred in any of the patients with symptoms at the first examination, and all had a satisfactory quality of life. No complications arose during the follow up period. This study shows that in adults haemangiomas remain stable in size and echo patterns rarely change. Only haemangiomas greater than 5 cm may cause symptoms. Prolonged clinical and sonographic follow up of small and medium sized haemangiomas is not warranted."
-What recent advances have been made in the treatment of breast cancer?,"Recent advances in the treatment of breast cancer. Multidisciplinary efforts have defined a number of prognostic factors and newer strategies to improve the outcome of patients with breast cancer. Conservative surgery has led to improved functional and cosmetic results. The development of a number of effective adjuvant regimens has led to improved survival. In patients with stage I disease, several biological characteristics of tumor have been identified that are associated with increased risk of relapse. A multimodality approach to patients with locally advanced disease and inflammatory cancer has resulted in improved survival. A number of hormonal and cytotoxic drug contaminations can palliate metastatic disease, with a small fraction of patients remaining in extended remission. Dose-intensive programs may lead to further improvements in survival of selected patients with this disease."
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/opensearch-cluster-simple.yaml b/agentic-apps/strandsdk_agentic_rag_opensearch/opensearch-cluster-simple.yaml
deleted file mode 100644
index 1f63a93d..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/opensearch-cluster-simple.yaml
+++ /dev/null
@@ -1,192 +0,0 @@
-AWSTemplateFormatVersion: '2010-09-09'
-Description: 'Provide by Guidance for Scalable Model Inference and Agentic AI using Efficient and Accelerated Compute on Amazon EKS(solution ID xxxxxx)'
-
-Parameters:
-  ClusterName:
-    Type: String
-    Default: 'strandsdk-rag-opensearch'
-    Description: 'Name of the OpenSearch cluster'
-  
-  ServiceAccountName:
-    Type: String
-    Default: 'strandsdk-rag-service-account'
-    Description: 'Name of the service account that needs access'
-  
-  EKSClusterName:
-    Type: String
-    Default: 'graviton-cluster'
-    Description: 'Name of the EKS cluster for Pod Identity mapping'
-  
-  KubernetesNamespace:
-    Type: String
-    Default: 'default'
-    Description: 'Kubernetes namespace for the service account'
-  
-  OpenSearchVersion:
-    Type: String
-    Default: 'OpenSearch_2.11'
-    Description: 'OpenSearch version'
-    AllowedValues:
-      - 'OpenSearch_2.11'
-      - 'OpenSearch_2.9'
-      - 'OpenSearch_2.7'
-
-Resources:
-  # IAM Role for the service account with full OpenSearch and Bedrock access
-  ServiceAccountRole:
-    Type: AWS::IAM::Role
-    Properties:
-      RoleName: !Sub '${ServiceAccountName}-new'
-      AssumeRolePolicyDocument:
-        Version: '2012-10-17'
-        Statement:
-          - Effect: Allow
-            Principal:
-              Service: pods.eks.amazonaws.com
-            Action: 
-              - sts:AssumeRole
-              - sts:TagSession
-      ManagedPolicyArns:
-        - arn:aws:iam::aws:policy/AmazonBedrockFullAccess
-        - arn:aws:iam::aws:policy/AmazonOpenSearchServiceFullAccess
-
-  # Secrets Manager for OpenSearch master password
-  OpenSearchMasterPassword:
-    Type: AWS::SecretsManager::Secret
-    Properties:
-      Name: !Sub '${ClusterName}-master-password'
-      Description: 'Master password for OpenSearch cluster'
-      GenerateSecretString:
-        SecretStringTemplate: '{"username": "admin"}'
-        GenerateStringKey: 'password'
-        PasswordLength: 16
-        ExcludeCharacters: '"@/\'
-
-  # EKS Pod Identity Association
-  PodIdentityAssociation:
-    Type: AWS::EKS::PodIdentityAssociation
-    Properties:
-      ClusterName: !Ref EKSClusterName
-      Namespace: !Ref KubernetesNamespace
-      ServiceAccount: !Ref ServiceAccountName
-      RoleArn: !GetAtt ServiceAccountRole.Arn
-    DependsOn: ServiceAccountRole
-
-  # OpenSearch Domain
-  OpenSearchDomain:
-    Type: AWS::OpenSearchService::Domain
-    Properties:
-      DomainName: !Ref ClusterName
-      EngineVersion: !Ref OpenSearchVersion
-      
-      # Cluster Configuration
-      ClusterConfig:
-        InstanceType: m7g.large.search
-        InstanceCount: 3
-        DedicatedMasterEnabled: false
-        ZoneAwarenessEnabled: true
-        ZoneAwarenessConfig:
-          AvailabilityZoneCount: 3
-      
-      # EBS Configuration
-      EBSOptions:
-        EBSEnabled: true
-        VolumeType: gp3
-        VolumeSize: 100
-        Iops: 3000
-        Throughput: 125
-      
-      # Network Configuration (Public access)
-      DomainEndpointOptions:
-        EnforceHTTPS: true
-        TLSSecurityPolicy: Policy-Min-TLS-1-2-2019-07
-      
-      # Access Policy - Allow public access with IAM authentication
-      AccessPolicies:
-        Version: '2012-10-17'
-        Statement:
-          - Effect: Allow
-            Principal:
-              AWS: !GetAtt ServiceAccountRole.Arn
-            Action: 'es:*'
-            Resource: !Sub 'arn:aws:es:${AWS::Region}:${AWS::AccountId}:domain/${ClusterName}/*'
-          - Effect: Allow
-            Principal:
-              AWS: '*'
-            Action: 
-              - 'es:ESHttpGet'
-              - 'es:ESHttpPost'
-              - 'es:ESHttpPut'
-              - 'es:ESHttpDelete'
-              - 'es:ESHttpHead'
-            Resource: !Sub 'arn:aws:es:${AWS::Region}:${AWS::AccountId}:domain/${ClusterName}/*'
-            Condition:
-              IpAddress:
-                'aws:SourceIp': '0.0.0.0/0'
-      
-      # Advanced Security Options
-      AdvancedSecurityOptions:
-        Enabled: true
-        InternalUserDatabaseEnabled: true
-        MasterUserOptions:
-          MasterUserName: 'admin'
-          MasterUserPassword: !Sub '{{resolve:secretsmanager:${OpenSearchMasterPassword}:SecretString:password}}'
-      
-      # Node-to-node encryption
-      NodeToNodeEncryptionOptions:
-        Enabled: true
-      
-      # Encryption at rest
-      EncryptionAtRestOptions:
-        Enabled: true
-      
-      Tags:
-        - Key: Name
-          Value: !Ref ClusterName
-        - Key: Environment
-          Value: 'production'
-        - Key: Application
-          Value: 'strandsdk-rag'
-
-Outputs:
-  OpenSearchDomainEndpoint:
-    Description: 'OpenSearch domain endpoint'
-    Value: !GetAtt OpenSearchDomain.DomainEndpoint
-    Export:
-      Name: !Sub '${AWS::StackName}-OpenSearchEndpoint'
-  
-  OpenSearchDomainArn:
-    Description: 'OpenSearch domain ARN'
-    Value: !GetAtt OpenSearchDomain.DomainArn
-    Export:
-      Name: !Sub '${AWS::StackName}-OpenSearchArn'
-  
-  ServiceAccountRoleArn:
-    Description: 'Service account role ARN'
-    Value: !GetAtt ServiceAccountRole.Arn
-    Export:
-      Name: !Sub '${AWS::StackName}-ServiceAccountRoleArn'
-  
-  OpenSearchDashboardsURL:
-    Description: 'OpenSearch Dashboards URL'
-    Value: !Sub 'https://${OpenSearchDomain.DomainEndpoint}/_dashboards'
-  
-  MasterPasswordSecretArn:
-    Description: 'ARN of the secret containing the master password'
-    Value: !Ref OpenSearchMasterPassword
-    Export:
-      Name: !Sub '${AWS::StackName}-MasterPasswordSecret'
-
-  PodIdentityAssociationArn:
-    Description: 'EKS Pod Identity Association ARN'
-    Value: !Ref PodIdentityAssociation
-    Export:
-      Name: !Sub '${AWS::StackName}-PodIdentityAssociation'
-
-  ConfigurationForApp:
-    Description: 'Configuration values for your application'
-    Value: !Sub |
-      Add these to your .env file:
-      OPENSEARCH_ENDPOINT=https://${OpenSearchDomain.DomainEndpoint}
-      AWS_REGION=${AWS::Region}
-      SERVICE_ACCOUNT_ROLE_ARN=${ServiceAccountRole.Arn}
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/pyproject.toml b/agentic-apps/strandsdk_agentic_rag_opensearch/pyproject.toml
deleted file mode 100644
index b62ecf1b..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/pyproject.toml
+++ /dev/null
@@ -1,73 +0,0 @@
-[build-system]
-requires = ["setuptools>=61.0", "wheel"]
-build-backend = "setuptools.build_meta"
-
-[project]
-name = "strandsdk-agentic-rag-opensearch"
-version = "1.0.0"
-description = "Multi-Agent RAG system with MCP and OpenSearch using Strands SDK"
-authors = [
-    {name = "Your Name", email = "your.email@example.com"}
-]
-readme = "README.md"
-requires-python = ">=3.9"
-classifiers = [
-    "Development Status :: 4 - Beta",
-    "Intended Audience :: Developers",
-    "License :: OSI Approved :: MIT License",
-    "Programming Language :: Python :: 3",
-    "Programming Language :: Python :: 3.9",
-    "Programming Language :: Python :: 3.10",
-    "Programming Language :: Python :: 3.11",
-    "Programming Language :: Python :: 3.12",
-]
-dependencies = [
-    "strands-agents>=0.1.0",
-    "strands-tools>=0.1.0",
-    "openai>=1.0.0",
-    "mcp>=1.0.0",
-    "fastmcp>=0.9.0",
-    "boto3>=1.34.0",
-    "opensearch-py>=2.4.0",
-    "aws-requests-auth>=0.4.3",
-    "numpy>=1.24.0",
-    "scikit-learn>=1.3.0",
-    "pandas>=2.0.0",
-    "python-dotenv>=1.0.0",
-    "langfuse>=2.0.0",
-    "pydantic>=2.0.0",
-    "aiofiles>=23.0.0",
-]
-
-[project.optional-dependencies]
-dev = [
-    "pytest>=7.0.0",
-    "pytest-asyncio>=0.21.0",
-    "black>=23.0.0",
-    "isort>=5.12.0",
-    "flake8>=6.0.0",
-    "mypy>=1.0.0",
-]
-
-[project.scripts]
-embed-knowledge = "src.scripts.embed_knowledge:main"
-run-agents = "src.main:main"
-test-agents = "src.test_agents:main"
-
-[tool.setuptools.packages.find]
-where = ["."]
-include = ["src*"]
-
-[tool.black]
-line-length = 88
-target-version = ['py39']
-
-[tool.isort]
-profile = "black"
-line_length = 88
-
-[tool.mypy]
-python_version = "3.9"
-warn_return_any = true
-warn_unused_configs = true
-disallow_untyped_defs = true
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/requirements.txt b/agentic-apps/strandsdk_agentic_rag_opensearch/requirements.txt
deleted file mode 100644
index 78911418..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/requirements.txt
+++ /dev/null
@@ -1,42 +0,0 @@
-# Strands SDK and core dependencies
-strands-agents>=0.1.0
-strands-agents-tools>=0.1.0
-strands-agents[litellm]>=0.1.0
-
-# OpenAI and LLM dependencies
-openai>=1.0.0
-litellm>=1.0.0
-
-# MCP dependencies
-mcp>=1.0.0
-fastmcp>=0.9.0
-fastapi>=0.104.0
-uvicorn>=0.24.0
-
-# AWS and OpenSearch dependencies
-boto3>=1.34.0
-opensearch-py>=2.4.0
-aws-requests-auth>=0.4.3
-langchain-aws>=0.1.0
-
-# RAGAs evaluation dependencies
-ragas>=0.1.0
-langchain>=0.1.0
-langchain-core>=0.1.0
-
-# Vector embeddings and ML
-numpy>=1.24.0
-scikit-learn>=1.3.0
-
-# Data processing
-pandas>=2.0.0
-python-dotenv>=1.0.0
-requests>=2.31.0
-httpx>=0.25.0
-
-# Observability
-langfuse>=2.0.0
-
-# Utilities
-pydantic>=2.0.0
-aiofiles>=23.0.0
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/run_main_clean.py b/agentic-apps/strandsdk_agentic_rag_opensearch/run_main_clean.py
deleted file mode 100644
index b99639b6..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/run_main_clean.py
+++ /dev/null
@@ -1,100 +0,0 @@
-#!/usr/bin/env python3
-"""
-Clean main application runner with complete async error suppression.
-"""
-
-import sys
-import os
-import warnings
-
-# Add current directory to path
-sys.path.insert(0, os.path.dirname(os.path.abspath(__file__)))
-
-class CompleteAsyncErrorFilter:
-    """Complete async error filter that suppresses all async-related output."""
-    
-    def __init__(self):
-        self.original_stderr = sys.__stderr__
-        
-    def write(self, text):
-        """Filter out all async RuntimeErrors and related output."""
-        if not text.strip():
-            return
-            
-        # Comprehensive list of patterns to suppress
-        suppress_patterns = [
-            "RuntimeError",
-            "httpcore",
-            "_synchronization",
-            "asyncio",
-            "anyio",
-            "sniffio",
-            "await",
-            "async",
-            "CancelScope",
-            "shield",
-            "current_task",
-            "get_running_loop",
-            "cancel_shielded_checkpoint",
-            "_anyio_lock",
-            "acquire",
-            "File \"/home/ubuntu/Cost_Effective_and_Scalable_Models_Inference_on_AWS_Graviton/agentic-apps/strandsdk_agentic_rag_opensearch/venv/lib/python3.10/site-packages/httpcore",
-            "File \"/usr/lib/python3.10/asyncio",
-            "raise RuntimeError",
-        ]
-        
-        # Check if this line should be suppressed
-        should_suppress = any(pattern in text for pattern in suppress_patterns)
-        
-        # Also suppress lines that are just punctuation or whitespace
-        if text.strip() in [":", "RuntimeError:", "RuntimeError: ", "RuntimeError", ""]:
-            should_suppress = True
-        
-        # Only write if not suppressed and contains meaningful content
-        if not should_suppress and len(text.strip()) > 1:
-            self.original_stderr.write(text)
-            self.original_stderr.flush()
-        
-    def flush(self):
-        """Flush the original stderr."""
-        self.original_stderr.flush()
-
-def setup_complete_clean_environment():
-    """Set up completely clean environment."""
-    
-    # Suppress all warnings
-    warnings.filterwarnings("ignore")
-    
-    # Install complete error filter
-    sys.stderr = CompleteAsyncErrorFilter()
-    
-    # Try to import and use existing cleanup if available
-    try:
-        from src.utils.global_async_cleanup import setup_global_async_cleanup
-        setup_global_async_cleanup()
-    except ImportError:
-        pass
-
-if __name__ == "__main__":
-    print("🚀 Starting Enhanced RAG System (Ultra Clean Mode)")
-    print("=" * 60)
-    print("Note: All async errors and warnings are completely suppressed")
-    print("=" * 60)
-    
-    # Set up complete clean environment FIRST
-    setup_complete_clean_environment()
-    
-    try:
-        # Import and run the main application
-        from src.main import main
-        main()
-    except KeyboardInterrupt:
-        print("\n\n👋 Application stopped by user")
-    except Exception as e:
-        # Only show truly important errors
-        error_msg = str(e)
-        if not any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            print(f"\n❌ Application error: {e}")
-        sys.exit(1)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/run_single_query_clean.py b/agentic-apps/strandsdk_agentic_rag_opensearch/run_single_query_clean.py
deleted file mode 100644
index ba13a526..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/run_single_query_clean.py
+++ /dev/null
@@ -1,122 +0,0 @@
-#!/usr/bin/env python3
-"""
-Clean single query runner with complete async error suppression.
-"""
-
-import sys
-import os
-import warnings
-
-# Add current directory to path
-sys.path.insert(0, os.path.dirname(os.path.abspath(__file__)))
-
-class CompleteAsyncErrorFilter:
-    """Complete async error filter that suppresses all async-related output."""
-    
-    def __init__(self):
-        self.original_stderr = sys.__stderr__
-        
-    def write(self, text):
-        """Filter out all async RuntimeErrors and related output."""
-        if not text.strip():
-            return
-            
-        # Comprehensive list of patterns to suppress
-        suppress_patterns = [
-            "RuntimeError",
-            "httpcore",
-            "_synchronization",
-            "asyncio",
-            "anyio",
-            "sniffio",
-            "await",
-            "async",
-            "CancelScope",
-            "shield",
-            "current_task",
-            "get_running_loop",
-            "cancel_shielded_checkpoint",
-            "_anyio_lock",
-            "acquire",
-            "File \"/home/ubuntu/Cost_Effective_and_Scalable_Models_Inference_on_AWS_Graviton/agentic-apps/strandsdk_agentic_rag_opensearch/venv/lib/python3.10/site-packages/httpcore",
-            "File \"/usr/lib/python3.10/asyncio",
-            "raise RuntimeError",
-        ]
-        
-        # Check if this line should be suppressed
-        should_suppress = any(pattern in text for pattern in suppress_patterns)
-        
-        # Also suppress lines that are just punctuation or whitespace
-        if text.strip() in [":", "RuntimeError:", "RuntimeError: ", "RuntimeError", ""]:
-            should_suppress = True
-        
-        # Only write if not suppressed and contains meaningful content
-        if not should_suppress and len(text.strip()) > 1:
-            self.original_stderr.write(text)
-            self.original_stderr.flush()
-        
-    def flush(self):
-        """Flush the original stderr."""
-        self.original_stderr.flush()
-
-def setup_complete_clean_environment():
-    """Set up completely clean environment."""
-    
-    # Suppress all warnings
-    warnings.filterwarnings("ignore")
-    
-    # Install complete error filter
-    sys.stderr = CompleteAsyncErrorFilter()
-    
-    # Try to import and use existing cleanup if available
-    try:
-        from src.utils.global_async_cleanup import setup_global_async_cleanup
-        setup_global_async_cleanup()
-    except ImportError:
-        pass
-
-def run_clean_query(query: str):
-    """Run a single query with completely clean output."""
-    print("🚀 Enhanced RAG System - Single Query (Ultra Clean Mode)")
-    print("=" * 60)
-    print(f"Query: {query}")
-    print("=" * 60)
-    print("Note: All async errors and warnings are completely suppressed")
-    print("=" * 60)
-    
-    # Set up complete clean environment FIRST
-    setup_complete_clean_environment()
-    
-    try:
-        from src.agents.supervisor_agent import supervisor_agent
-        
-        print("\n🔍 Processing query...")
-        response = supervisor_agent(query)
-        
-        print("\n📝 Response:")
-        print("-" * 40)
-        print(response)
-        print("-" * 40)
-        print("\n✅ Query completed successfully!")
-        
-        return True
-        
-    except Exception as e:
-        # Only show truly important errors
-        error_msg = str(e)
-        if not any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            print(f"\n❌ Error processing query: {e}")
-        return False
-
-if __name__ == "__main__":
-    # Test with a sample query
-    test_query = "What is Bell's palsy and how is it treated?"
-    
-    if len(sys.argv) > 1:
-        # Use command line argument if provided
-        test_query = " ".join(sys.argv[1:])
-    
-    success = run_clean_query(test_query)
-    sys.exit(0 if success else 1)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/scripts/start_tavily_server.py b/agentic-apps/strandsdk_agentic_rag_opensearch/scripts/start_tavily_server.py
deleted file mode 100755
index a48737bd..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/scripts/start_tavily_server.py
+++ /dev/null
@@ -1,113 +0,0 @@
-#!/usr/bin/env python3
-"""
-Startup script for Tavily MCP Server
-"""
-
-import os
-import sys
-import subprocess
-import time
-import requests
-from pathlib import Path
-from dotenv import load_dotenv
-
-# Add the project root to Python path
-project_root = Path(__file__).parent.parent
-sys.path.insert(0, str(project_root))
-
-# Load environment variables from .env file
-env_file = project_root / ".env"
-if env_file.exists():
-    load_dotenv(env_file)
-    print(f"✅ Loaded environment variables from {env_file}")
-else:
-    print(f"⚠️  No .env file found at {env_file}")
-    print("Please create a .env file with your configuration")
-
-def check_tavily_api_key():
-    """Check if Tavily API key is configured"""
-    api_key = os.getenv("TAVILY_API_KEY")
-    if not api_key:
-        print("❌ TAVILY_API_KEY environment variable is not set!")
-        print("Please get your API key from https://tavily.com and set it in your .env file:")
-        print("TAVILY_API_KEY=your-api-key-here")
-        return False
-    print(f"✅ Tavily API key configured: {api_key[:8]}...")
-    return True
-
-def check_server_health(max_retries=10, delay=2):
-    """Check if the Tavily MCP server is running and healthy"""
-    for attempt in range(max_retries):
-        try:
-            # Try to connect to the MCP server endpoint
-            response = requests.get("http://localhost:8001/", timeout=5)
-            if response.status_code in [200, 404]:  # 404 is OK for MCP server root
-                print("✅ Tavily MCP server is healthy and ready!")
-                return True
-        except requests.exceptions.RequestException:
-            pass
-        
-        if attempt < max_retries - 1:
-            print(f"⏳ Waiting for server to start... (attempt {attempt + 1}/{max_retries})")
-            time.sleep(delay)
-    
-    print("❌ Server health check failed after maximum retries")
-    return False
-
-def start_tavily_server():
-    """Start the Tavily MCP server"""
-    if not check_tavily_api_key():
-        return False
-    
-    print("🚀 Starting Tavily MCP Server...")
-    
-    # Path to the server script
-    server_script = project_root / "src" / "mcp_servers" / "tavily_search_server.py"
-    
-    if not server_script.exists():
-        print(f"❌ Server script not found: {server_script}")
-        return False
-    
-    try:
-        # Start the server as a subprocess
-        process = subprocess.Popen([
-            sys.executable, str(server_script)
-        ], cwd=str(project_root))
-        
-        print(f"📡 Server started with PID: {process.pid}")
-        print("🔗 MCP server available at: http://localhost:8001/mcp")
-        
-        # Wait a moment for server to start
-        time.sleep(3)
-        
-        # Check if server is healthy
-        if check_server_health():
-            print("\n🎉 Tavily MCP Server is ready!")
-            print("\nAvailable tools:")
-            print("  - web_search: General web search with AI-generated answers")
-            print("  - news_search: Recent news and current events search")
-            print("  - health_check: Service health status")
-            print("\n💡 The supervisor agent will automatically use web search when RAG relevance is low (<0.3)")
-            return True
-        else:
-            print("❌ Server failed to start properly")
-            process.terminate()
-            return False
-            
-    except Exception as e:
-        print(f"❌ Failed to start server: {e}")
-        return False
-
-if __name__ == "__main__":
-    success = start_tavily_server()
-    if success:
-        print("\n✨ Server is running! Press Ctrl+C to stop.")
-        try:
-            # Keep the script running
-            while True:
-                time.sleep(1)
-        except KeyboardInterrupt:
-            print("\n🛑 Shutting down server...")
-    else:
-        print("\n❌ Failed to start Tavily MCP Server")
-        sys.exit(1)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/setup.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/setup.sh
deleted file mode 100755
index df43c26c..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/setup.sh
+++ /dev/null
@@ -1,627 +0,0 @@
-#!/bin/bash
-
-# Multi-Agent RAG with Strands SDK and OpenSearch - Setup Script
-# This script automates the complete deployment process
-
-set -e  # Exit on any error
-
-# Colors for output
-RED='\033[0;31m'
-GREEN='\033[0;32m'
-YELLOW='\033[1;33m'
-BLUE='\033[0;34m'
-NC='\033[0m' # No Color
-
-# Function to print colored output
-print_status() {
-    echo -e "${GREEN}[INFO]${NC} $1"
-}
-
-print_warning() {
-    echo -e "${YELLOW}[WARNING]${NC} $1"
-}
-
-print_error() {
-    echo -e "${RED}[ERROR]${NC} $1"
-}
-
-print_header() {
-    echo -e "${BLUE}================================${NC}"
-    echo -e "${BLUE}$1${NC}"
-    echo -e "${BLUE}================================${NC}"
-}
-
-# Function to check if command exists
-command_exists() {
-    command -v "$1" >/dev/null 2>&1
-}
-
-# Function to get user input with default value
-get_input() {
-    local prompt="$1"
-    local default="$2"
-    local var_name="$3"
-    
-    if [ -n "$default" ]; then
-        read -p "$prompt [$default]: " input
-        if [ -z "$input" ]; then
-            input="$default"
-        fi
-    else
-        read -p "$prompt: " input
-        while [ -z "$input" ]; do
-            echo "This field is required."
-            read -p "$prompt: " input
-        done
-    fi
-    
-    eval "$var_name='$input'"
-}
-
-# Function to get sensitive input (hidden)
-get_secret_input() {
-    local prompt="$1"
-    local var_name="$2"
-    
-    read -s -p "$prompt: " input
-    echo  # New line after hidden input
-    while [ -z "$input" ]; do
-        echo "This field is required."
-        read -s -p "$prompt: " input
-        echo
-    done
-    
-    eval "$var_name='$input'"
-}
-
-# Function to encode base64
-encode_base64() {
-    echo -n "$1" | base64
-}
-
-# Function to check existing ingress
-check_existing_ingress() {
-    print_status "Checking for existing ingress resources..."
-    
-    if kubectl get ingress strandsdk-rag-ingress-alb >/dev/null 2>&1; then
-        EXISTING_INGRESS=$(kubectl get ingress strandsdk-rag-ingress-alb -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-        if [ -n "$EXISTING_INGRESS" ]; then
-            print_status "Found existing ingress endpoint: $EXISTING_INGRESS"
-            return 0
-        fi
-    fi
-    return 1
-}
-
-# Function to get LiteLLM ingress endpoint
-get_litellm_ingress() {
-    # Check for ingresses containing "litellm" in the name
-    local litellm_ingresses=$(kubectl get ingress -o jsonpath='{.items[*].metadata.name}' | tr ' ' '\n' | grep -i litellm || echo "")
-    
-    if [ -n "$litellm_ingresses" ]; then
-        for ingress_name in $litellm_ingresses; do
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                echo "http://$endpoint/v1"
-                return 0
-            fi
-        done
-    fi
-    
-    # Fallback: Check for common LiteLLM ingress names
-    local litellm_ingress_names=("litellm-ingress" "litellm-alb" "litellm-loadbalancer" "litellm")
-    
-    for ingress_name in "${litellm_ingress_names[@]}"; do
-        if kubectl get ingress "$ingress_name" >/dev/null 2>&1; then
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                echo "http://$endpoint/v1"
-                return 0
-            fi
-        fi
-    done
-    
-    # Check for services with LoadBalancer type
-    local litellm_services=$(kubectl get svc -o jsonpath='{.items[?(@.spec.type=="LoadBalancer")].metadata.name}' | grep -i litellm || echo "")
-    if [ -n "$litellm_services" ]; then
-        for service in $litellm_services; do
-            local endpoint=$(kubectl get svc "$service" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                echo "http://$endpoint/v1"
-                return 0
-            fi
-        done
-    fi
-    
-    return 1
-}
-
-# Function to log LiteLLM detection
-log_litellm_detection() {
-    print_status "Checking for LiteLLM service ingress..."
-    
-    # Check for ingresses containing "litellm" in the name
-    local litellm_ingresses=$(kubectl get ingress -o jsonpath='{.items[*].metadata.name}' | tr ' ' '\n' | grep -i litellm || echo "")
-    
-    if [ -n "$litellm_ingresses" ]; then
-        for ingress_name in $litellm_ingresses; do
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                print_status "Found LiteLLM ingress '$ingress_name': $endpoint"
-                return 0
-            fi
-        done
-    fi
-    
-    # Check other sources and log appropriately
-    local litellm_ingress_names=("litellm-ingress" "litellm-alb" "litellm-loadbalancer" "litellm")
-    
-    for ingress_name in "${litellm_ingress_names[@]}"; do
-        if kubectl get ingress "$ingress_name" >/dev/null 2>&1; then
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                print_status "Found LiteLLM ingress '$ingress_name': $endpoint"
-                return 0
-            fi
-        fi
-    done
-    
-    local litellm_services=$(kubectl get svc -o jsonpath='{.items[?(@.spec.type=="LoadBalancer")].metadata.name}' | grep -i litellm || echo "")
-    if [ -n "$litellm_services" ]; then
-        for service in $litellm_services; do
-            local endpoint=$(kubectl get svc "$service" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                print_status "Found LiteLLM LoadBalancer service '$service': $endpoint"
-                return 0
-            fi
-        done
-    fi
-    
-    return 1
-}
-
-# Function to get Langfuse ingress endpoint
-get_langfuse_ingress() {
-    # Check for ingresses containing "langfuse" in the name
-    local langfuse_ingresses=$(kubectl get ingress -o jsonpath='{.items[*].metadata.name}' | tr ' ' '\n' | grep -i langfuse || echo "")
-    
-    if [ -n "$langfuse_ingresses" ]; then
-        for ingress_name in $langfuse_ingresses; do
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                echo "http://$endpoint"
-                return 0
-            fi
-        done
-    fi
-    
-    # Fallback: Check for common Langfuse ingress names
-    local langfuse_ingress_names=("langfuse-ingress" "langfuse-alb" "langfuse-loadbalancer" "langfuse")
-    
-    for ingress_name in "${langfuse_ingress_names[@]}"; do
-        if kubectl get ingress "$ingress_name" >/dev/null 2>&1; then
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                echo "http://$endpoint"
-                return 0
-            fi
-        fi
-    done
-    
-    # Check for services with LoadBalancer type
-    local langfuse_services=$(kubectl get svc -o jsonpath='{.items[?(@.spec.type=="LoadBalancer")].metadata.name}' | grep -i langfuse || echo "")
-    if [ -n "$langfuse_services" ]; then
-        for service in $langfuse_services; do
-            local endpoint=$(kubectl get svc "$service" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                echo "http://$endpoint"
-                return 0
-            fi
-        done
-    fi
-    
-    return 1
-}
-
-# Function to log Langfuse detection
-log_langfuse_detection() {
-    print_status "Checking for Langfuse service ingress..."
-    
-    # Check for ingresses containing "langfuse" in the name
-    local langfuse_ingresses=$(kubectl get ingress -o jsonpath='{.items[*].metadata.name}' | tr ' ' '\n' | grep -i langfuse || echo "")
-    
-    if [ -n "$langfuse_ingresses" ]; then
-        for ingress_name in $langfuse_ingresses; do
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                print_status "Found Langfuse ingress '$ingress_name': $endpoint"
-                return 0
-            fi
-        done
-    fi
-    
-    # Check other sources and log appropriately
-    local langfuse_ingress_names=("langfuse-ingress" "langfuse-alb" "langfuse-loadbalancer" "langfuse")
-    
-    for ingress_name in "${langfuse_ingress_names[@]}"; do
-        if kubectl get ingress "$ingress_name" >/dev/null 2>&1; then
-            local endpoint=$(kubectl get ingress "$ingress_name" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                print_status "Found Langfuse ingress '$ingress_name': $endpoint"
-                return 0
-            fi
-        fi
-    done
-    
-    local langfuse_services=$(kubectl get svc -o jsonpath='{.items[?(@.spec.type=="LoadBalancer")].metadata.name}' | grep -i langfuse || echo "")
-    if [ -n "$langfuse_services" ]; then
-        for service in $langfuse_services; do
-            local endpoint=$(kubectl get svc "$service" -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-            if [ -n "$endpoint" ]; then
-                print_status "Found Langfuse LoadBalancer service '$service': $endpoint"
-                return 0
-            fi
-        done
-    fi
-    
-    return 1
-}
-
-
-
-# Function to create knowledge-base ConfigMap
-create_knowledge_base_configmap() {
-    print_status "Creating empty knowledge-base ConfigMap..."
-    
-    # Create temporary knowledge-base configmap file with empty knowledge base
-    cat > /tmp/knowledge-base-configmap.yaml << 'EOF'
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: knowledge-base
-  labels:
-    app: strandsdk-rag
-data:
-  README.md: |
-    # Knowledge Base
-    This ConfigMap contains knowledge base documents for the RAG application.
-    Add your knowledge documents as data entries in this ConfigMap.
-    
-    ## Usage
-    The application will automatically process these documents and create embeddings
-    for retrieval-augmented generation (RAG) functionality.
-    
-    ## Adding Knowledge
-    To add knowledge documents, update this ConfigMap with your files:
-    kubectl patch configmap knowledge-base --patch '{"data":{"your-file.md":"your content here"}}'
-EOF
-    
-    # Apply the knowledge-base ConfigMap
-    kubectl apply -f /tmp/knowledge-base-configmap.yaml
-    rm /tmp/knowledge-base-configmap.yaml
-    print_status "Empty knowledge-base ConfigMap created successfully"
-}
-
-# Function to update configmap
-update_configmap() {
-    local opensearch_endpoint="$1"
-    local litellm_base_url="$2"
-    local embedding_base_url="$3"
-    local langfuse_host="$4"
-    
-    print_status "Updating ConfigMap with provided values..."
-    
-    # Create temporary configmap file based on the existing structure
-    cat > /tmp/configmap-temp.yaml << EOF
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: app-config
-  labels:
-    app: strandsdk-rag
-data:
-  .env: |
-    # LiteLLM Configuration for Reasoning Models
-    LITELLM_BASE_URL=$litellm_base_url
-    REASONING_MODEL=vllm-server-qwen3
-    
-    # Embedding Configuration (separate from reasoning)
-    EMBEDDING_BASE_URL=$embedding_base_url
-    EMBEDDING_MODEL=llamacpp-embedding
-    
-    # AWS Configuration  
-    AWS_REGION=us-east-1
-    OPENSEARCH_ENDPOINT=$opensearch_endpoint
-    
-    # Tavily MCP Service Configuration
-    TAVILY_MCP_SERVICE_URL=http://tavily-mcp-service:8001/mcp
-    
-    # Optional: Langfuse for observability
-    LANGFUSE_HOST=$langfuse_host
-    
-    # Application Settings
-    KNOWLEDGE_DIR=knowledge
-    OUTPUT_DIR=output
-    VECTOR_INDEX_NAME=knowledge-embeddings
-    TOP_K_RESULTS=3
-  
-  # Individual config values for environment variables
-  litellm-base-url: "$litellm_base_url"
-  reasoning-model: "vllm-server-qwen3"
-  embedding-base-url: "$embedding_base_url"
-  embedding-model: "llamacpp-embedding"
-  opensearch-endpoint: "$opensearch_endpoint"
-  aws-region: "us-east-1"
-  vector-index-name: "knowledge-embeddings"
-  tavily-mcp-service-url: "http://tavily-mcp-service:8001/mcp"
-  langfuse-host: "$langfuse_host"
-  knowledge-dir: "knowledge"
-  output-dir: "output"
-  top-k-results: "3"
-EOF
-
-    kubectl apply -f /tmp/configmap-temp.yaml
-    rm /tmp/configmap-temp.yaml
-    print_status "ConfigMap updated successfully"
-    
-    # Create empty knowledge-base ConfigMap
-    create_knowledge_base_configmap
-}
-
-# Function to update secrets
-update_secrets() {
-    local litellm_api_key="$1"
-    local embedding_api_key="$2"
-    local tavily_api_key="$3"
-    local langfuse_public_key="$4"
-    local langfuse_secret_key="$5"
-    
-    print_status "Updating Secrets with provided API keys..."
-    
-    # Create temporary secrets file matching the existing structure
-    cat > /tmp/secrets-temp.yaml << EOF
-apiVersion: v1
-kind: Secret
-metadata:
-  name: app-secrets
-  labels:
-    app: strandsdk-rag
-type: Opaque
-data:
-  # Base64 encoded secrets - replace with your actual base64 encoded values
-  # To encode: echo -n "your-api-key" | base64
-  litellm-api-key: $(encode_base64 "$litellm_api_key")
-  embedding-api-key: $(encode_base64 "$embedding_api_key")
-  tavily-api-key: $(encode_base64 "$tavily_api_key")
-  langfuse-public-key: $(encode_base64 "$langfuse_public_key")
-  langfuse-secret-key: $(encode_base64 "$langfuse_secret_key")
-EOF
-
-    kubectl apply -f /tmp/secrets-temp.yaml
-    rm /tmp/secrets-temp.yaml
-    print_status "Secrets updated successfully"
-}
-
-# Main setup function
-main() {
-    print_header "Multi-Agent RAG System Setup"
-    
-    # Check prerequisites
-    print_status "Checking prerequisites..."
-    
-    if ! command_exists kubectl; then
-        print_error "kubectl is not installed. Please install kubectl first."
-        exit 1
-    fi
-    
-    if ! command_exists aws; then
-        print_error "AWS CLI is not installed. Please install AWS CLI first."
-        exit 1
-    fi
-    
-    if ! command_exists docker; then
-        print_error "Docker is not installed. Please install Docker first."
-        exit 1
-    fi
-    
-    # Check if we can connect to Kubernetes cluster
-    if ! kubectl cluster-info >/dev/null 2>&1; then
-        print_error "Cannot connect to Kubernetes cluster. Please check your kubeconfig."
-        exit 1
-    fi
-    
-    print_status "Prerequisites check passed!"
-    
-    # Step 1: Build and push Docker images
-    print_header "Step 1: Building and Pushing Docker Images"
-    
-    if [ -f "./build-images.sh" ]; then
-        print_status "Running build-images.sh..."
-        chmod +x ./build-images.sh
-        ./build-images.sh
-        print_status "Docker images built and pushed successfully!"
-    else
-        print_warning "build-images.sh not found. Skipping image build step."
-        echo "Please ensure your container images are available in ECR."
-        read -p "Press Enter to continue..."
-    fi
-    
-    # Step 2: Deploy OpenSearch
-    print_header "Step 2: Deploying OpenSearch Cluster"
-    
-    get_input "Enter OpenSearch stack name" "strandsdk-rag-opensearch-stack" STACK_NAME
-    get_input "Enter AWS region" "us-east-1" AWS_REGION
-    get_input "Enter Kubernetes namespace" "default" NAMESPACE
-    
-    if [ -f "./deploy-opensearch.sh" ]; then
-        print_status "Running deploy-opensearch.sh..."
-        chmod +x ./deploy-opensearch.sh
-        ./deploy-opensearch.sh "$STACK_NAME" "$AWS_REGION" "$NAMESPACE"
-        print_status "OpenSearch cluster deployed successfully!"
-        
-        # Get OpenSearch endpoint from CloudFormation stack
-        print_status "Retrieving OpenSearch endpoint..."
-        OPENSEARCH_ENDPOINT=$(aws cloudformation describe-stacks \
-            --stack-name "$STACK_NAME" \
-            --region "$AWS_REGION" \
-            --query 'Stacks[0].Outputs[?OutputKey==`OpenSearchEndpoint`].OutputValue' \
-            --output text 2>/dev/null || echo "")
-        
-        if [ -n "$OPENSEARCH_ENDPOINT" ]; then
-            print_status "OpenSearch endpoint: $OPENSEARCH_ENDPOINT"
-        else
-            print_warning "Could not retrieve OpenSearch endpoint automatically."
-            get_input "Please enter the OpenSearch endpoint manually" "" OPENSEARCH_ENDPOINT
-        fi
-    else
-        print_warning "deploy-opensearch.sh not found. Skipping OpenSearch deployment."
-        get_input "Please enter your existing OpenSearch endpoint" "" OPENSEARCH_ENDPOINT
-    fi
-    
-    # Step 3: Configure application settings
-    print_header "Step 3: Configuring Application Settings"
-    
-    # Auto-detect LiteLLM endpoint
-    print_status "Auto-detecting service endpoints..."
-    LITELLM_DEFAULT=""
-    if LITELLM_DETECTED=$(get_litellm_ingress); then
-        LITELLM_DEFAULT="$LITELLM_DETECTED"
-        log_litellm_detection
-        print_status "Auto-detected LiteLLM endpoint: $LITELLM_DEFAULT"
-    else
-        print_warning "Could not auto-detect LiteLLM endpoint"
-        LITELLM_DEFAULT="https://api.openai.com/v1"
-    fi
-    
-    # Auto-detect Langfuse endpoint
-    LANGFUSE_DEFAULT=""
-    if LANGFUSE_DETECTED=$(get_langfuse_ingress); then
-        LANGFUSE_DEFAULT="$LANGFUSE_DETECTED"
-        log_langfuse_detection
-        print_status "Auto-detected Langfuse endpoint: $LANGFUSE_DEFAULT"
-    else
-        print_warning "Could not auto-detect Langfuse endpoint"
-        LANGFUSE_DEFAULT="https://cloud.langfuse.com"
-    fi
-    
-    # Get user input with auto-detected defaults
-    get_input "Enter LiteLLM base URL" "$LITELLM_DEFAULT" LITELLM_BASE_URL
-    
-    # For embedding, use the same base URL but with /embeddings endpoint
-    EMBEDDING_DEFAULT="${LITELLM_BASE_URL%/v1}/v1/embeddings"
-    get_input "Enter Embedding service base URL" "$EMBEDDING_DEFAULT" EMBEDDING_BASE_URL
-    
-    get_input "Enter Langfuse host" "$LANGFUSE_DEFAULT" LANGFUSE_HOST
-    
-    # Step 4: Configure secrets
-    print_header "Step 4: Configuring API Keys and Secrets"
-    
-    print_status "Please provide the following API keys:"
-    
-    # Required API keys
-    get_secret_input "Enter LiteLLM API key" LITELLM_API_KEY
-    get_secret_input "Enter Embedding service API key (can be same as LiteLLM)" EMBEDDING_API_KEY
-    get_secret_input "Enter Tavily API key (for web search functionality)" TAVILY_API_KEY
-    
-    echo
-    print_status "Optional Langfuse keys for observability (press Enter to skip):"
-    read -s -p "Enter Langfuse public key (optional): " LANGFUSE_PUBLIC_KEY
-    echo
-    read -s -p "Enter Langfuse secret key (optional): " LANGFUSE_SECRET_KEY
-    echo
-    
-    # Set defaults for empty Langfuse keys
-    LANGFUSE_PUBLIC_KEY=${LANGFUSE_PUBLIC_KEY:-""}
-    LANGFUSE_SECRET_KEY=${LANGFUSE_SECRET_KEY:-""}
-    
-    # Validate required fields
-    if [ -z "$LITELLM_API_KEY" ] || [ -z "$EMBEDDING_API_KEY" ] || [ -z "$TAVILY_API_KEY" ]; then
-        print_error "Required API keys are missing. Please provide all required keys."
-        exit 1
-    fi
-    
-    # Step 5: Apply Kubernetes resources
-    print_header "Step 5: Applying Kubernetes Resources"
-    
-    # Update ConfigMap
-    update_configmap "$OPENSEARCH_ENDPOINT" "$LITELLM_BASE_URL" "$EMBEDDING_BASE_URL" "$LANGFUSE_HOST"
-    
-    # Update Secrets
-    update_secrets "$LITELLM_API_KEY" "$EMBEDDING_API_KEY" "$TAVILY_API_KEY" "$LANGFUSE_PUBLIC_KEY" "$LANGFUSE_SECRET_KEY"
-    
-    # Apply remaining Kubernetes resources
-    print_status "Applying Kubernetes manifests..."
-    
-    if [ -f "k8s/service-account.yaml" ]; then
-        kubectl apply -f k8s/service-account.yaml
-        print_status "Service account applied"
-    else
-        print_warning "k8s/service-account.yaml not found"
-    fi
-    
-    if [ -f "k8s/tavily-mcp-deployment.yaml" ]; then
-        kubectl apply -f k8s/tavily-mcp-deployment.yaml
-        print_status "Tavily MCP deployment applied"
-    else
-        print_warning "k8s/tavily-mcp-deployment.yaml not found"
-    fi
-    
-    if [ -f "k8s/main-app-deployment.yaml" ]; then
-        kubectl apply -f k8s/main-app-deployment.yaml
-        print_status "Main application deployment applied"
-    else
-        print_warning "k8s/main-app-deployment.yaml not found"
-    fi
-    
-    # Step 6: Verify deployment
-    print_header "Step 6: Verifying Deployment"
-    
-    print_status "Checking pod status..."
-    kubectl get pods -l app=tavily-mcp-server
-    kubectl get pods -l app=strandsdk-rag-app
-    
-    print_status "Checking services..."
-    kubectl get svc
-    
-    print_status "Checking ingress..."
-    kubectl get ingress
-    
-    # Get final ALB endpoint
-    print_status "Waiting for ALB endpoint to be ready..."
-    sleep 30
-    
-    ALB_ENDPOINT=$(kubectl get ingress strandsdk-rag-ingress-alb -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-    
-    if [ -n "$ALB_ENDPOINT" ]; then
-        print_header "Deployment Complete!"
-        echo -e "${GREEN}Your Multi-Agent RAG system is now deployed!${NC}"
-        echo
-        echo -e "${BLUE}Configuration Summary:${NC}"
-        echo "• OpenSearch Endpoint: $OPENSEARCH_ENDPOINT"
-        echo "• LiteLLM Base URL: $LITELLM_BASE_URL"
-        echo "• Embedding Base URL: $EMBEDDING_BASE_URL"
-        echo "• Langfuse Host: $LANGFUSE_HOST"
-        echo "• Application Load Balancer: http://$ALB_ENDPOINT"
-        echo
-        echo -e "${BLUE}Test endpoints:${NC}"
-        echo "Health check: curl -X GET \"http://$ALB_ENDPOINT/health\""
-        echo "Embed knowledge: curl -X POST \"http://$ALB_ENDPOINT/embed\" -H \"Content-Type: application/json\" -d '{\"force_refresh\": false}'"
-        echo "Complex query: curl -i -X POST \"http://$ALB_ENDPOINT/query\" -H \"Content-Type: application/json\" -d '{\"question\": \"Find information about \\\"What was the purpose of the study on encainide and flecainide in patients with supraventricular arrhythmias\\\". Summarize this information and create a comprehensive story.Save the story and important information to a file named \\\"test1.md\\\" in the output directory as a beautiful markdown file.\", \"top_k\": 3}' --max-time 600"
-        echo
-        echo -e "${YELLOW}Note: It may take a few minutes for the ALB to become fully available.${NC}"
-        echo -e "${YELLOW}If services were auto-detected, verify the endpoints are correct for your setup.${NC}"
-    else
-        print_warning "ALB endpoint not yet available. Check 'kubectl get ingress' in a few minutes."
-        echo
-        echo -e "${BLUE}Configuration Summary:${NC}"
-        echo "• OpenSearch Endpoint: $OPENSEARCH_ENDPOINT"
-        echo "• LiteLLM Base URL: $LITELLM_BASE_URL"
-        echo "• Embedding Base URL: $EMBEDDING_BASE_URL"
-        echo "• Langfuse Host: $LANGFUSE_HOST"
-    fi
-    
-    print_status "Setup completed successfully!"
-}
-
-# Run main function
-main "$@"
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/setup_opensearch_index.py b/agentic-apps/strandsdk_agentic_rag_opensearch/setup_opensearch_index.py
deleted file mode 100755
index ca0c8783..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/setup_opensearch_index.py
+++ /dev/null
@@ -1,382 +0,0 @@
-#!/usr/bin/env python3
-"""
-OpenSearch Index Setup Script
-Creates a vector index for embeddings with proper mapping
-"""
-
-import os
-import json
-import logging
-import time
-from opensearchpy import OpenSearch, RequestsHttpConnection
-from opensearchpy.exceptions import ConnectionError, ConnectionTimeout
-import boto3
-from requests_aws4auth import AWS4Auth
-
-# Configure logging
-logging.basicConfig(level=logging.INFO, format='%(asctime)s - %(name)s - %(levelname)s - %(message)s')
-logger = logging.getLogger(__name__)
-
-def update_role_trust_policy(service_account_role_arn):
-    """Update the service account role trust policy to allow the current role to assume it"""
-    try:
-        iam = boto3.client('iam')
-        sts = boto3.client('sts')
-        
-        # Get current identity
-        identity = sts.get_caller_identity()
-        current_arn = identity['Arn']
-        
-        # Extract the base role ARN from assumed role ARN
-        if ':assumed-role/' in current_arn:
-            # Convert from arn:aws:sts::account:assumed-role/role-name/session-name
-            # to arn:aws:iam::account:role/role-name
-            parts = current_arn.split(':')
-            account = parts[4]
-            role_info = parts[5].split('/')
-            role_name = role_info[1]  # Get role name from assumed-role/role-name/session-name
-            current_role_arn = f"arn:aws:iam::{account}:role/{role_name}"
-        else:
-            current_role_arn = current_arn
-            
-        logger.info(f"Current role ARN: {current_role_arn}")
-        
-        # Extract role name from service account ARN
-        role_name = service_account_role_arn.split('/')[-1]
-        
-        # Define the updated trust policy
-        trust_policy = {
-            "Version": "2012-10-17",
-            "Statement": [
-                {
-                    "Effect": "Allow",
-                    "Principal": {
-                        "Service": "pods.eks.amazonaws.com"
-                    },
-                    "Action": [
-                        "sts:AssumeRole",
-                        "sts:TagSession"
-                    ]
-                },
-                {
-                    "Effect": "Allow",
-                    "Principal": {
-                        "AWS": current_role_arn
-                    },
-                    "Action": "sts:AssumeRole"
-                }
-            ]
-        }
-        
-        # Update the role trust policy
-        response = iam.update_assume_role_policy(
-            RoleName=role_name,
-            PolicyDocument=json.dumps(trust_policy)
-        )
-        logger.info(f"Successfully updated role trust policy for {role_name}")
-        logger.info(f"Added permission for {current_role_arn} to assume the role")
-        return True
-        
-    except Exception as e:
-        logger.warning(f"Failed to update role trust policy: {e}")
-        return False
-
-def update_opensearch_access_policy(domain_name, region, service_account_role_arn):
-    """Update OpenSearch domain access policy to include the service account role"""
-    try:
-        opensearch_client = boto3.client('opensearch', region_name=region)
-        
-        # Get current domain configuration
-        response = opensearch_client.describe_domain(DomainName=domain_name)
-        domain_config = response['DomainStatus']
-        
-        # Create updated access policy
-        access_policy = {
-            "Version": "2012-10-17",
-            "Statement": [
-                {
-                    "Effect": "Allow",
-                    "Principal": {
-                        "AWS": service_account_role_arn
-                    },
-                    "Action": "es:*",
-                    "Resource": f"arn:aws:es:{region}:{boto3.client('sts').get_caller_identity()['Account']}:domain/{domain_name}/*"
-                },
-                {
-                    "Effect": "Allow",
-                    "Principal": {
-                        "AWS": "*"
-                    },
-                    "Action": [
-                        "es:ESHttpGet",
-                        "es:ESHttpPost",
-                        "es:ESHttpPut",
-                        "es:ESHttpDelete",
-                        "es:ESHttpHead"
-                    ],
-                    "Resource": f"arn:aws:es:{region}:{boto3.client('sts').get_caller_identity()['Account']}:domain/{domain_name}/*",
-                    "Condition": {
-                        "IpAddress": {
-                            "aws:SourceIp": "0.0.0.0/0"
-                        }
-                    }
-                }
-            ]
-        }
-        
-        # Update the domain access policy
-        update_response = opensearch_client.update_domain_config(
-            DomainName=domain_name,
-            AccessPolicies=json.dumps(access_policy)
-        )
-        
-        logger.info(f"Successfully updated OpenSearch domain access policy for {domain_name}")
-        return True
-        
-    except Exception as e:
-        logger.warning(f"Failed to update OpenSearch domain access policy: {e}")
-        return False
-
-def configure_opensearch_iam_access(domain_name, region, service_account_role_arn):
-    """Configure fine-grained access control to use IAM instead of internal user database"""
-    try:
-        opensearch_client = boto3.client('opensearch', region_name=region)
-        
-        # Update domain configuration to disable internal user database and enable IAM
-        update_response = opensearch_client.update_domain_config(
-            DomainName=domain_name,
-            AdvancedSecurityOptions={
-                'Enabled': True,
-                'InternalUserDatabaseEnabled': False,
-                'MasterUserOptions': {
-                    'MasterUserARN': service_account_role_arn
-                }
-            }
-        )
-        
-        logger.info(f"Successfully configured IAM-based access for {domain_name}")
-        logger.info(f"Set master user to: {service_account_role_arn}")
-        logger.info("Domain update initiated - this may take several minutes to complete")
-        return True
-        
-    except Exception as e:
-        logger.warning(f"Failed to configure IAM-based access: {e}")
-        return False
-
-def create_opensearch_client(endpoint, region, service_account_role_arn=None):
-    """Create OpenSearch client with AWS authentication"""
-    try:
-        # Parse endpoint to get host
-        host = endpoint.replace('https://', '').replace('http://', '')
-        
-        # Get AWS credentials - either assume the service account role or use current credentials
-        if service_account_role_arn:
-            logger.info(f"Assuming role: {service_account_role_arn}")
-            sts_client = boto3.client('sts', region_name=region)
-            
-            try:
-                # Assume the service account role
-                response = sts_client.assume_role(
-                    RoleArn=service_account_role_arn,
-                    RoleSessionName='opensearch-index-setup'
-                )
-                
-                # Create session with assumed role credentials
-                session = boto3.Session(
-                    aws_access_key_id=response['Credentials']['AccessKeyId'],
-                    aws_secret_access_key=response['Credentials']['SecretAccessKey'],
-                    aws_session_token=response['Credentials']['SessionToken'],
-                    region_name=region
-                )
-                credentials = session.get_credentials()
-                logger.info("Successfully assumed service account role")
-                
-            except Exception as e:
-                logger.warning(f"Failed to assume role {service_account_role_arn}: {e}")
-                logger.info("Falling back to current credentials")
-                session = boto3.Session()
-                credentials = session.get_credentials()
-        else:
-            # Use current credentials
-            session = boto3.Session()
-            credentials = session.get_credentials()
-        
-        # Create AWS4Auth for authentication
-        awsauth = AWS4Auth(
-            credentials.access_key,
-            credentials.secret_key,
-            region,
-            'es',
-            session_token=credentials.token
-        )
-        
-        # Create OpenSearch client
-        client = OpenSearch(
-            hosts=[{'host': host, 'port': 443}],
-            http_auth=awsauth,
-            use_ssl=True,
-            verify_certs=True,
-            connection_class=RequestsHttpConnection,
-            timeout=30,
-            max_retries=3,
-            retry_on_timeout=True
-        )
-        
-        return client
-    except Exception as e:
-        logger.error(f"Failed to create OpenSearch client: {e}")
-        raise
-
-def create_opensearch_index(endpoint, region, index_name, dimension=384, service_account_role_arn=None):
-    """Create OpenSearch index with vector mapping"""
-    max_retries = 3
-    retry_delay = 10
-    
-    for attempt in range(max_retries):
-        try:
-            logger.info(f"Connection attempt {attempt + 1}/{max_retries}")
-            
-            # Create client
-            client = create_opensearch_client(endpoint, region, service_account_role_arn)
-            
-            # Test connection
-            logger.info("Testing connection to OpenSearch...")
-            cluster_info = client.info()
-            logger.info(f"Connected to OpenSearch cluster: {cluster_info['cluster_name']}")
-            
-            # Check if index already exists
-            if client.indices.exists(index=index_name):
-                logger.info(f"Index '{index_name}' already exists")
-                return True
-            
-            # Create index with vector mapping
-            index_mapping = {
-                "settings": {
-                    "index": {
-                        "number_of_shards": 1,
-                        "number_of_replicas": 0,
-                        "knn": True,
-                        "knn.algo_param.ef_search": 100
-                    }
-                },
-                "mappings": {
-                    "properties": {
-                        "content": {
-                            "type": "text",
-                            "analyzer": "standard"
-                        },
-                        "embedding": {
-                            "type": "knn_vector",
-                            "dimension": dimension,
-                            "method": {
-                                "name": "hnsw",
-                                "space_type": "cosinesimil",
-                                "engine": "nmslib",
-                                "parameters": {
-                                    "ef_construction": 128,
-                                    "m": 24
-                                }
-                            }
-                        },
-                        "metadata": {
-                            "type": "object",
-                            "properties": {
-                                "source": {"type": "keyword"},
-                                "chunk_id": {"type": "keyword"},
-                                "timestamp": {"type": "date"}
-                            }
-                        }
-                    }
-                }
-            }
-            
-            logger.info(f"Creating index '{index_name}' with {dimension}-dimensional vectors...")
-            response = client.indices.create(index=index_name, body=index_mapping)
-            logger.info(f"Index created successfully: {response}")
-            
-            return True
-            
-        except (ConnectionError, ConnectionTimeout) as e:
-            logger.warning(f"Connection attempt {attempt + 1} failed: {e}. Retrying in {retry_delay} seconds...")
-            if attempt < max_retries - 1:
-                time.sleep(retry_delay)
-            else:
-                logger.error(f"Failed to create index after {max_retries} attempts")
-                logger.error(f"Full traceback: {e}")
-                raise e
-        except Exception as e:
-            logger.error(f"Unexpected error: {e}")
-            raise e
-
-def main():
-    # Get configuration from environment
-    endpoint = os.getenv('OPENSEARCH_ENDPOINT')
-    region = os.getenv('AWS_REGION', 'us-east-1')
-    index_name = os.getenv('VECTOR_INDEX_NAME', 'knowledge-embeddings')
-    dimension = int(os.getenv('EMBEDDING_DIMENSION', '384'))
-    service_account_role_arn = os.getenv('SERVICE_ACCOUNT_ROLE_ARN')
-    
-    if not endpoint:
-        logger.error("OPENSEARCH_ENDPOINT environment variable is required")
-        return False
-    
-    print(f"🔧 Setting up OpenSearch index...")
-    print(f"   Endpoint: {endpoint}")
-    print(f"   Region: {region}")
-    print(f"   Index: {index_name}")
-    print(f"   Dimension: {dimension}")
-    if service_account_role_arn:
-        print(f"   Using Role: {service_account_role_arn}")
-        
-        # Update the role trust policy to allow current role to assume it
-        print("🔐 Updating role trust policy...")
-        if update_role_trust_policy(service_account_role_arn):
-            print("✅ Role trust policy updated successfully")
-            # Wait a moment for the policy to propagate
-            time.sleep(5)
-        else:
-            print("⚠️  Failed to update role trust policy, will try without role assumption")
-            service_account_role_arn = None
-            
-        # Update OpenSearch domain access policy
-        if service_account_role_arn:
-            print("🔐 Updating OpenSearch domain access policy...")
-            # Extract domain name from CloudFormation stack (it should be 'strandsdk-rag-opensearch')
-            domain_name = 'strandsdk-rag-opensearch'
-            if update_opensearch_access_policy(domain_name, region, service_account_role_arn):
-                print("✅ OpenSearch domain access policy updated successfully")
-                # Wait a moment for the policy to propagate
-                time.sleep(5)
-            else:
-                print("⚠️  Failed to update OpenSearch domain access policy")
-                
-            # Configure fine-grained access control to use IAM instead of internal user database
-            print("🔐 Configuring fine-grained access control for IAM...")
-            if configure_opensearch_iam_access(domain_name, region, service_account_role_arn):
-                print("✅ Fine-grained access control configured for IAM successfully")
-                print("⏳ Waiting for domain configuration to update (this may take 10-15 minutes)...")
-                # Wait longer for the domain configuration to update
-                time.sleep(30)
-            else:
-                print("⚠️  Failed to configure fine-grained access control for IAM")
-    print()
-    
-    try:
-        success = create_opensearch_index(endpoint, region, index_name, dimension, service_account_role_arn)
-        if success:
-            print("✅ OpenSearch index created successfully!")
-            print(f"   Index name: {index_name}")
-            print(f"   Vector dimension: {dimension}")
-            print(f"   Endpoint: {endpoint}")
-            return True
-        else:
-            print("❌ Failed to create OpenSearch index")
-            return False
-    except Exception as e:
-        print("❌ Failed to create OpenSearch index")
-        print(f"   Check the logs above for details")
-        return False
-
-if __name__ == "__main__":
-    success = main()
-    exit(0 if success else 1)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/__init__.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/__init__.py
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diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/__init__.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/__init__.py
deleted file mode 100644
index 8dc67aa3..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/__init__.py
+++ /dev/null
@@ -1,11 +0,0 @@
-"""Multi-agent system using Strands SDK with built-in tracing."""
-
-from .supervisor_agent import supervisor_agent
-from .knowledge_agent import knowledge_agent
-from .mcp_agent import mcp_agent
-
-__all__ = [
-    "supervisor_agent",
-    "knowledge_agent", 
-    "mcp_agent"
-]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/knowledge_agent.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/knowledge_agent.py
deleted file mode 100644
index f56d5f10..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/knowledge_agent.py
+++ /dev/null
@@ -1,217 +0,0 @@
-"""Knowledge Agent using Strands SDK patterns."""
-
-import os
-import json
-import hashlib
-import logging
-from typing import Dict, List, Any, Optional
-from datetime import datetime
-from pathlib import Path
-import pandas as pd
-from strands import Agent, tool
-from strands_tools import file_read, file_write
-from ..tools.embedding_retriever import EmbeddingRetriever
-from ..config import config
-from ..utils.logging import log_title
-from ..utils.model_providers import get_reasoning_model
-from ..utils.strands_langfuse_integration import create_traced_agent, setup_tracing_environment
-
-logger = logging.getLogger(__name__)
-
-# Set up tracing environment
-setup_tracing_environment()
-
-@tool
-def scan_knowledge_directory() -> str:
-    """
-    Scan the knowledge directory for files and return metadata.
-    
-    Returns:
-        JSON string with file metadata
-    """
-    try:
-        knowledge_dir = Path(config.KNOWLEDGE_DIR)
-        if not knowledge_dir.exists():
-            result = json.dumps({"error": "Knowledge directory does not exist"})
-            return result
-        
-        files_info = []
-        for file_path in knowledge_dir.rglob("*"):
-            if file_path.is_file() and file_path.suffix in [".md", ".txt", ".json", ".csv"]:
-                stat = file_path.stat()
-                files_info.append({
-                    "path": str(file_path.relative_to(knowledge_dir)),
-                    "size": stat.st_size,
-                    "modified": stat.st_mtime,
-                    "type": file_path.suffix[1:]
-                })
-        
-        result = json.dumps({
-            "success": True,
-            "files": files_info,
-            "total_files": len(files_info)
-        })
-        
-        logger.info(f"Scanned knowledge directory: {len(files_info)} files found")
-        return result
-        
-    except Exception as e:
-        logger.error(f"Error scanning knowledge directory: {e}")
-        return json.dumps({"error": str(e), "success": False})
-        
-        return error_result
-
-@tool
-@tool
-def embed_knowledge_files() -> str:
-    """
-    Process and embed all knowledge files.
-    
-    Returns:
-        JSON string with embedding results
-    """
-    try:
-        knowledge_dir = Path(config.KNOWLEDGE_DIR)
-        retriever = EmbeddingRetriever()
-        
-        embedded_count = 0
-        total_files = 0
-        total_rows = 0  # For CSV files
-        processed_files = []
-        
-        for file_path in knowledge_dir.rglob("*"):
-            if file_path.is_file() and file_path.suffix in [".md", ".txt", ".json", ".csv"]:
-                total_files += 1
-                try:
-                    # Special handling for CSV files
-                    if file_path.suffix.lower() == ".csv":
-                        logger.info(f"Processing CSV file: {file_path}")
-                        try:
-                            # Read the CSV file
-                            df = pd.read_csv(file_path)
-                            logger.info(f"CSV file has {len(df)} rows and {len(df.columns)} columns")
-                            
-                            # Process each row
-                            csv_success_count = 0
-                            for index, row in df.iterrows():
-                                try:
-                                    # Check if the CSV has question and context columns
-                                    if 'question' in df.columns and 'context' in df.columns:
-                                        question = row.get('question', '')
-                                        context = row.get('context', '')
-                                        
-                                        if not question or not context:
-                                            logger.warning(f"Row {index} is missing question or context, skipping")
-                                            continue
-                                        
-                                        # Create document content
-                                        document = f"Question: {question}\nContext: {context}"
-                                    else:
-                                        # If not a Q&A format, just concatenate all columns
-                                        document = "\n".join([f"{col}: {row[col]}" for col in df.columns])
-                                    
-                                    # Add metadata
-                                    metadata = {
-                                        'source': str(file_path.relative_to(knowledge_dir)),
-                                        'row_index': int(index),
-                                        'type': 'csv_row',
-                                    }
-                                    
-                                    # Add question as identifier if available
-                                    if 'question' in df.columns:
-                                        metadata['question'] = row['question'][:100]  # First 100 chars
-                                    
-                                    # Add to retriever
-                                    row_success = retriever.add_document(
-                                        content=document,
-                                        metadata=metadata
-                                    )
-                                    
-                                    if row_success:
-                                        csv_success_count += 1
-                                    
-                                    total_rows += 1
-                                    
-                                except Exception as e:
-                                    logger.error(f"Error processing CSV row {index}: {e}")
-                            
-                            logger.info(f"Successfully embedded {csv_success_count} out of {len(df)} rows from {file_path}")
-                            
-                            if csv_success_count > 0:
-                                embedded_count += 1
-                                processed_files.append(str(file_path.relative_to(knowledge_dir)))
-                                
-                        except Exception as e:
-                            logger.error(f"Error processing CSV file {file_path}: {e}")
-                    else:
-                        # Standard processing for non-CSV files
-                        # Read file content
-                        with open(file_path, 'r', encoding='utf-8') as f:
-                            content = f.read()
-                        
-                        # Add to retriever
-                        success = retriever.add_document(
-                            content=content,
-                            metadata={
-                                "source": str(file_path.relative_to(knowledge_dir)),
-                                "type": file_path.suffix[1:],
-                                "size": len(content)
-                            }
-                        )
-                        
-                        if success:
-                            embedded_count += 1
-                            processed_files.append(str(file_path.relative_to(knowledge_dir)))
-                    
-                except Exception as e:
-                    logger.error(f"Error processing file {file_path}: {e}")
-        
-        result = json.dumps({
-            "success": True,
-            "embedded_count": embedded_count,
-            "total_files": total_files,
-            "total_csv_rows": total_rows,
-            "message": f"Successfully embedded {embedded_count} out of {total_files} files" + 
-                      (f" ({total_rows} CSV rows)" if total_rows > 0 else "")
-        })
-        
-        logger.info(f"Embedding completed: {embedded_count}/{total_files} files processed")
-        return result
-        
-    except Exception as e:
-        logger.error(f"Error embedding knowledge files: {e}")
-        return json.dumps({"error": str(e), "success": False})
-
-# Create the knowledge agent with tracing
-knowledge_agent = create_traced_agent(
-    Agent,
-    model=get_reasoning_model(),
-    tools=[scan_knowledge_directory, embed_knowledge_files, file_read, file_write],
-    system_prompt="""
-You are KnowledgeKeeper, a specialized agent for managing knowledge base operations. Your capabilities include:
-
-1. **File Management**: Scan and monitor knowledge directory for files
-2. **Content Processing**: Process markdown, text, JSON, and CSV files
-3. **Embedding Operations**: Generate embeddings for knowledge documents
-4. **Status Reporting**: Provide detailed reports on knowledge base status
-
-**Available Tools:**
-- scan_knowledge_directory: Scan the knowledge directory and return file metadata
-- embed_knowledge_files: Process and embed all knowledge files
-- file_read: Read content from specific files
-- file_write: Write content to files
-
-**Instructions:**
-- Use scan_knowledge_directory to check what files are available
-- Use embed_knowledge_files to process and embed all knowledge documents
-- Provide detailed status reports and handle errors gracefully
-- Focus on maintaining an up-to-date and well-organized knowledge base
-
-Your goal is to ensure the knowledge base is current, properly indexed, and ready for retrieval operations.
-""",
-    session_id="knowledge-session",
-    user_id="system"
-)
-
-# Export the agent
-__all__ = ["knowledge_agent"]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/mcp_agent.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/mcp_agent.py
deleted file mode 100644
index 850398e5..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/mcp_agent.py
+++ /dev/null
@@ -1,162 +0,0 @@
-"""MCP Agent using Strands SDK patterns."""
-
-import logging
-from typing import Dict, List, Any, Optional
-from datetime import datetime
-from strands import Agent, tool
-import strands_tools.file_read as file_read
-import strands_tools.file_write as file_write_module
-import strands_tools.shell as shell
-from strands.tools.mcp import MCPClient
-from mcp import stdio_client, StdioServerParameters
-from ..config import config
-from ..utils.logging import log_title
-from ..utils.model_providers import get_reasoning_model
-from ..utils.strands_langfuse_integration import create_traced_agent, setup_tracing_environment
-
-logger = logging.getLogger(__name__)
-
-# Set up tracing environment
-setup_tracing_environment()
-
-@tool
-def file_write(content: str, path: str = None, filename: str = None) -> str:
-    """
-    Write content to a file without confirmation prompt. Either path or filename must be provided.
-    When filename is provided, file is automatically saved to the output directory.
-    
-    Args:
-        content: Content to write to the file
-        path: Full path to the file (including filename)
-        filename: Name of the file (will be saved in the output directory)
-        
-    Returns:
-        Result of the file write operation
-    """
-    import os
-    from pathlib import Path
-    
-    if path is None and filename is None:
-        return "Error: Either path or filename must be provided"
-    
-    if path is None and filename is not None:
-        # Use the output directory from config
-        output_dir = getattr(config, "OUTPUT_DIR", "output")
-        path = f"{output_dir}/{filename}"
-    
-    try:
-        # Ensure the directory exists
-        file_path = Path(path)
-        file_path.parent.mkdir(parents=True, exist_ok=True)
-        
-        # Write the content directly to the file
-        with open(file_path, 'w', encoding='utf-8') as f:
-            f.write(content)
-        
-        # Get file size for confirmation
-        file_size = file_path.stat().st_size
-        
-        logger.info(f"File written successfully: {path} ({file_size} bytes)")
-        
-        return f"✅ File written successfully to {path} ({file_size} bytes)"
-        
-    except Exception as e:
-        logger.error(f"Error writing to file: {e}")
-        return f"❌ Error writing to file: {str(e)}"
-
-@tool
-def execute_with_mcp_tools(task_description: str, context: str = "") -> str:
-    """
-    Execute tasks using available MCP tools.
-    
-    Args:
-        task_description: Description of the task to execute
-        context: Additional context for the task
-        
-    Returns:
-        Result of the task execution
-    """
-    # Create Langfuse span for MCP tool execution
-    mcp_span = langfuse_config.create_span(
-        trace=None,
-        name="mcp-tool-execution",
-        input_data={
-            "task_description": task_description,
-            "context_length": len(context)
-        }
-    )
-    
-    try:
-        # For now, use built-in tools since MCP server setup requires external process
-        # In production, this would connect to actual MCP servers
-        
-        result = ""
-        if "file" in task_description.lower() and "create" in task_description.lower():
-            # Handle file creation tasks
-            result = f"Task: {task_description}\nContext: {context}\n\nI can help create files using the file_write tool. Please specify the filename and content."
-        
-        elif "summary" in task_description.lower() or "summarize" in task_description.lower():
-            # Handle summarization tasks
-            result = f"Based on the context provided:\n{context}\n\nI can create a summary. Please specify what aspects you'd like me to focus on."
-        
-        else:
-            result = f"Task received: {task_description}\nContext length: {len(context)} characters\n\nI'm ready to help with various tasks using available tools."
-        
-        # Update Langfuse span with results
-        if mcp_span and langfuse_config.is_enabled:
-            mcp_span.end(output={
-                "task_type": "file_creation" if "file" in task_description.lower() else "general",
-                "result_length": len(result),
-                "success": True
-            })
-        
-        return result
-            
-    except Exception as e:
-        logger.error(f"Error executing MCP task: {e}")
-        error_result = f"Error executing task: {str(e)}"
-        
-        # Update Langfuse span with error
-        if mcp_span and langfuse_config.is_enabled:
-            mcp_span.end(output={
-                "error": str(e),
-                "success": False
-            })
-        
-        return error_result
-
-# Create the MCP agent with tracing
-mcp_agent = create_traced_agent(
-    Agent,
-    model=get_reasoning_model(),
-    tools=[execute_with_mcp_tools, file_write],
-    system_prompt="""
-You are ToolMaster, a specialized agent for executing tasks using various tools including MCP (Model Context Protocol) tools. Your capabilities include:
-
-1. **Task Execution**: Process user requests and execute them using available tools
-2. **File Operations**: Create, read, and modify files as needed
-3. **Shell Commands**: Execute system commands when appropriate
-4. **Context Integration**: Use provided context to inform your actions
-
-**Available Tools:**
-- execute_with_mcp_tools: Execute tasks using MCP tool capabilities
-- file_read: Read content from files
-- file_write: Write content to files (requires path or filename)
-- shell: Execute shell commands
-
-**Instructions:**
-- Analyze the user's request and determine the best tools to use
-- Use the provided context to inform your responses
-- Create files, summaries, or other outputs as requested
-- When using file_write, always provide either path or filename parameter
-- Handle errors gracefully and provide helpful feedback
-- Be thorough and accurate in your task execution
-
-Your goal is to complete user tasks effectively using the available tools and context.
-""",
-    session_id="mcp-session",
-    user_id="system"
-)
-
-# Export the agent
-__all__ = ["mcp_agent", "file_write"]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/rag_agent.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/rag_agent.py
deleted file mode 100644
index 90dbc2ce..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/rag_agent.py
+++ /dev/null
@@ -1,2 +0,0 @@
-# This file has been removed - RAG functionality is now integrated into the supervisor_agent.py
-# The supervisor agent now directly uses the search_knowledge_base tool for RAG operations
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent copy.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent copy.py
deleted file mode 100644
index 5ff21cc3..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent copy.py	
+++ /dev/null
@@ -1,843 +0,0 @@
-"""Supervisor Agent using Strands SDK patterns with Tavily Web Search integration and RAG relevance evaluation."""
-
-# Import global async cleanup FIRST
-from ..utils.global_async_cleanup import setup_global_async_cleanup
-
-import asyncio
-import re
-import logging
-import json
-from typing import Dict, List, Any, Optional
-from datetime import datetime
-from strands import Agent, tool
-from strands_tools import file_read
-from mcp.client.streamable_http import streamablehttp_client
-from strands.tools.mcp.mcp_client import MCPClient
-from langchain_aws import ChatBedrockConverse
-from ragas import SingleTurnSample
-from ragas.metrics import LLMContextPrecisionWithoutReference
-from ragas.llms import LangchainLLMWrapper
-from ..config import config
-from ..utils.logging import log_title
-from ..utils.model_providers import get_reasoning_model
-from ..utils.strands_langfuse_integration import create_traced_agent, setup_tracing_environment
-from ..utils.async_cleanup import suppress_async_warnings, setup_async_environment
-from ..tools.embedding_retriever import EmbeddingRetriever
-from .mcp_agent import file_write  # Use the wrapped file_write from mcp_agent
-
-logger = logging.getLogger(__name__)
-
-# Set up tracing environment and async cleanup
-setup_tracing_environment()
-setup_async_environment()
-
-# Evaluation model configuration for RAGAs
-eval_modelId = 'us.anthropic.claude-3-7-sonnet-20250219-v1:0'
-thinking_params = {
-    "thinking": {
-        "type": "disabled"
-    }
-}
-llm_for_evaluation = ChatBedrockConverse(model_id=eval_modelId, additional_model_request_fields=thinking_params)
-llm_for_evaluation = LangchainLLMWrapper(llm_for_evaluation)
-
-# Initialize Tavily MCP client
-tavily_mcp_client = None
-
-def get_tavily_mcp_client():
-    """Get or create Tavily MCP client"""
-    global tavily_mcp_client
-    if tavily_mcp_client is None:
-        try:
-            # Use config for MCP service URL
-            mcp_url = config.TAVILY_MCP_SERVICE_URL
-            tavily_mcp_client = MCPClient(lambda: streamablehttp_client(mcp_url))
-            logger.info(f"Tavily MCP client initialized successfully with URL: {mcp_url}")
-        except Exception as e:
-            logger.warning(f"Failed to initialize Tavily MCP client: {e}")
-            tavily_mcp_client = None
-    return tavily_mcp_client
-
-def calculate_relevance_score(results: List[Dict], query: str) -> float:
-    """
-    Calculate relevance score with content validation to prevent false positives.
-    
-    Args:
-        results: List of search results with scores
-        query: Original search query for semantic validation
-        
-    Returns:
-        float: Validated relevance score (0.0 to 1.0)
-    """
-    if not results:
-        return 0.0
-    
-    # Extract scores and validate content relevance
-    scores = []
-    query_lower = query.lower()
-    query_keywords = set(query_lower.split())
-    
-    for result in results:
-        # Get the similarity score
-        score = None
-        if isinstance(result, dict):
-            score = result.get('score') or result.get('_score')
-            if score is None and 'metadata' in result:
-                score = result['metadata'].get('score')
-        
-        if score is not None:
-            # Validate content relevance by checking keyword overlap
-            content = result.get('content', '').lower()
-            content_keywords = set(content.split())
-            
-            # Calculate keyword overlap ratio
-            overlap = len(query_keywords.intersection(content_keywords))
-            overlap_ratio = overlap / len(query_keywords) if query_keywords else 0
-            
-            # Penalize results with very low keyword overlap
-            if overlap_ratio < 0.1:  # Less than 10% keyword overlap
-                score = score * 0.2  # Heavily penalize
-            elif overlap_ratio < 0.3:  # Less than 30% keyword overlap
-                score = score * 0.5  # Moderately penalize
-            
-            scores.append(float(score))
-    
-    if not scores:
-        return 0.0
-    
-    # Calculate average and apply additional validation
-    avg_score = sum(scores) / len(scores)
-    
-    # Additional semantic validation for common mismatches
-    if any(keyword in query_lower for keyword in ['weather', 'temperature', 'forecast']):
-        # For weather queries, check if results contain weather-related terms
-        weather_terms = ['weather', 'temperature', 'rain', 'sunny', 'cloudy', 'forecast', 'celsius', 'fahrenheit']
-        has_weather_content = False
-        
-        for result in results:
-            content = result.get('content', '').lower()
-            if any(term in content for term in weather_terms):
-                has_weather_content = True
-                break
-        
-        if not has_weather_content:
-            avg_score = avg_score * 0.1  # Heavily penalize non-weather content for weather queries
-    
-    return min(avg_score, 1.0)
-
-# Create tools for the supervisor agent
-def _run_async_evaluation_safe(scorer, sample):
-    """
-    Helper function to run async evaluation with proper cleanup and error handling.
-    
-    Args:
-        scorer: RAGAs scorer instance
-        sample: SingleTurnSample for evaluation
-        
-    Returns:
-        float: Evaluation score
-    """
-    import asyncio
-    import threading
-    import queue
-    
-    def run_evaluation():
-        """Run the evaluation in a clean async environment."""
-        async def evaluate():
-            try:
-                # Set a shorter timeout for the evaluation
-                score = await asyncio.wait_for(
-                    scorer.single_turn_ascore(sample), 
-                    timeout=20.0  # 20 second timeout
-                )
-                return score
-            except asyncio.TimeoutError:
-                raise TimeoutError("RAGAs evaluation timed out")
-            except Exception as e:
-                raise Exception(f"RAGAs evaluation failed: {str(e)}")
-        
-        # Create and run in a new event loop with proper cleanup
-        loop = asyncio.new_event_loop()
-        asyncio.set_event_loop(loop)
-        
-        try:
-            score = loop.run_until_complete(evaluate())
-            result_queue.put(('success', score))
-        except Exception as e:
-            result_queue.put(('error', str(e)))
-        finally:
-            # Properly close the loop and clean up
-            try:
-                # Cancel all remaining tasks
-                pending = asyncio.all_tasks(loop)
-                for task in pending:
-                    task.cancel()
-                
-                # Wait for tasks to complete cancellation with timeout
-                if pending:
-                    try:
-                        loop.run_until_complete(
-                            asyncio.wait_for(
-                                asyncio.gather(*pending, return_exceptions=True),
-                                timeout=2.0
-                            )
-                        )
-                    except asyncio.TimeoutError:
-                        pass  # Ignore timeout during cleanup
-                
-                # Close the loop
-                loop.close()
-            except Exception:
-                pass  # Ignore cleanup errors
-    
-    # Use a queue to communicate between threads
-    result_queue = queue.Queue()
-    
-    # Run in a separate thread to avoid event loop conflicts
-    thread = threading.Thread(target=run_evaluation, daemon=True)
-    thread.start()
-    thread.join(timeout=25)  # Give extra time for cleanup
-    
-    if thread.is_alive():
-        raise TimeoutError("Evaluation thread timed out")
-    
-    try:
-        result_type, result_value = result_queue.get_nowait()
-        if result_type == 'error':
-            raise Exception(result_value)
-        return result_value
-    except queue.Empty:
-        raise Exception("No result received from evaluation")
-
-@tool
-def check_chunks_relevance(results: str, question: str):
-    """
-    Evaluates the relevance of retrieved chunks to the user question using RAGAs.
-
-    Args:
-        results (str): Retrieval output as a string with 'Score:' and 'Content:' patterns.
-        question (str): Original user question.
-
-    Returns:
-        dict: A binary score ('yes' or 'no') and the numeric relevance score, or an error message.
-    """
-    # Use the async warning suppression context
-    with suppress_async_warnings():
-        try:
-            if not results or not isinstance(results, str):
-                raise ValueError("Invalid input: 'results' must be a non-empty string.")
-            if not question or not isinstance(question, str):
-                raise ValueError("Invalid input: 'question' must be a non-empty string.")
-
-            # Extract content chunks using regex with improved error handling
-            patterns_to_try = [
-                r"Score:.*?\nContent:\s*(.*?)(?=\n\nScore:|\Z)",  # Handle double newlines
-                r"Score:.*?\nContent:\s*(.*?)(?=Score:|\Z)",      # Original pattern
-                r"Score:\s*[\d.]+\s*\nContent:\s*(.*?)(?=\n\nScore:|\Z)",  # More specific score pattern
-            ]
-            
-            docs = []
-            pattern_used = None
-            
-            for i, pattern in enumerate(patterns_to_try):
-                try:
-                    docs = [chunk.strip() for chunk in re.findall(pattern, results, re.DOTALL) if chunk.strip()]
-                    if docs:
-                        pattern_used = f"Pattern {i+1}"
-                        logger.debug(f"Successfully extracted {len(docs)} chunks using pattern {i+1}")
-                        break
-                except Exception as e:
-                    logger.warning(f"Pattern {i+1} failed: {e}")
-                    continue
-            
-            # If no patterns worked, try a more flexible approach
-            if not docs:
-                logger.warning("Standard patterns failed, trying flexible extraction...")
-                flexible_pattern = r"Content:\s*([^\n]+(?:\n(?!Score:)[^\n]*)*)"
-                try:
-                    docs = [chunk.strip() for chunk in re.findall(flexible_pattern, results, re.MULTILINE) if chunk.strip()]
-                    if docs:
-                        pattern_used = "Flexible pattern"
-                        logger.info(f"Flexible extraction found {len(docs)} chunks")
-                except Exception as e:
-                    logger.error(f"Flexible extraction also failed: {e}")
-
-            if not docs:
-                # Provide detailed debugging information
-                debug_info = {
-                    "results_length": len(results),
-                    "contains_score": "Score:" in results,
-                    "contains_content": "Content:" in results,
-                    "results_preview": results[:200] if len(results) > 200 else results
-                }
-                logger.error(f"No valid content chunks found. Debug info: {debug_info}")
-                raise ValueError(f"No valid content chunks found in 'results'. Debug: {debug_info}")
-
-            # Limit the number of chunks to avoid timeout
-            if len(docs) > 3:
-                docs = docs[:3]  # Take only first 3 chunks
-                logger.info(f"Limited evaluation to first 3 chunks out of {len(docs)} total")
-
-            # Generate a proper answer from the context for RAGAs evaluation
-            # This is necessary because LLMContextPrecisionWithoutReference evaluates
-            # whether the context was useful in arriving at the given answer
-            try:
-                context_for_answer = "\n\n".join(docs[:2])  # Use first 2 chunks
-                answer_prompt = f"""Based on the following context, provide a brief answer to the question.
-
-Question: {question}
-Context: {context_for_answer}
-
-Answer:"""
-                
-                # Use a simple model call to generate the answer
-                from langchain_aws import ChatBedrockConverse
-                answer_llm = ChatBedrockConverse(model_id='us.anthropic.claude-3-7-sonnet-20250219-v1:0')
-                answer_response = answer_llm.invoke(answer_prompt)
-                generated_answer = answer_response.content.strip()
-                
-                logger.debug(f"Generated answer for RAGAs evaluation: {generated_answer[:100]}...")
-                
-            except Exception as e:
-                logger.warning(f"Failed to generate answer for RAGAs evaluation: {e}")
-                generated_answer = "Unable to generate answer from context"
-
-            # Prepare evaluation sample with proper answer
-            sample = SingleTurnSample(
-                user_input=question,
-                response=generated_answer,  # Use generated answer instead of placeholder
-                retrieved_contexts=docs
-            )
-
-            # Evaluate using context precision metric with safe async handling
-            scorer = LLMContextPrecisionWithoutReference(llm=llm_for_evaluation)
-            
-            print("------------------------")
-            print("Context evaluation (RAGAs)")
-            print("------------------------")
-            print(f"Evaluating {len(docs)} chunks...")
-            
-            # Use the safe evaluation helper
-            score = _run_async_evaluation_safe(scorer, sample)
-
-            print(f"chunk_relevance_score: {score}")
-            print("------------------------")
-
-            return {
-                "chunk_relevance_score": "yes" if score > 0.5 else "no",
-                "chunk_relevance_value": score
-            }
-
-        except Exception as e:
-            logger.error(f"Error in chunk relevance evaluation: {e}")
-            # Provide a fallback based on simple heuristics
-            try:
-                # Simple fallback: check if question keywords appear in results
-                question_words = set(question.lower().split())
-                results_words = set(results.lower().split())
-                overlap = len(question_words.intersection(results_words))
-                fallback_score = min(overlap / len(question_words), 1.0) if question_words else 0.0
-                
-                logger.info(f"Using fallback relevance score: {fallback_score}")
-                
-                return {
-                    "chunk_relevance_score": "yes" if fallback_score > 0.3 else "no",
-                    "chunk_relevance_value": fallback_score,
-                    "evaluation_method": "fallback_heuristic",
-                    "note": f"RAGAs evaluation failed, using keyword overlap heuristic"
-                }
-            except Exception as fallback_error:
-                logger.error(f"Fallback evaluation also failed: {fallback_error}")
-                return {
-                    "error": f"Both RAGAs and fallback evaluation failed: {str(e)}",
-                    "chunk_relevance_score": "unknown",
-                    "chunk_relevance_value": None
-                }
-
-@tool
-def search_knowledge_base(query: str, top_k: int = 3) -> str:  
-    """
-    Search the knowledge base for relevant information.
-    
-    Args:
-        query (str): The search query - REQUIRED
-        top_k (int): Number of top results to return (default: 3)
-        
-    Returns:
-        str: JSON string with search results and relevance metadata
-    """
-    if not query or not isinstance(query, str):
-        return '{"error": "Query parameter is required and must be a non-empty string", "results": [], "relevance_score": 0.0}'
-    
-    try:
-        retriever = EmbeddingRetriever()
-        results = retriever.search(query, top_k=top_k)
-        
-        # Calculate relevance score with content validation
-        relevance_score = calculate_relevance_score(results, query)
-        
-        # Remove duplicate results
-        seen_content = set()
-        unique_results = []
-        for result in results:
-            content_hash = hash(result['content'][:100])  # Use first 100 chars as hash
-            if content_hash not in seen_content:
-                seen_content.add(content_hash)
-                unique_results.append(result)
-        
-        # Format results for RAGAs evaluation (with Score: and Content: patterns)
-        formatted_for_evaluation = ""
-        for result in unique_results[:top_k]:
-            formatted_for_evaluation += f"Score: {result.get('score', result.get('_score', 0.0))}\n"
-            formatted_for_evaluation += f"Content: {result['content']}\n\n"
-        
-        # Format results as compact JSON for response
-        formatted_results = []
-        for result in unique_results[:top_k]:  # Ensure we don't exceed top_k after deduplication
-            # Limit content length to reduce tokens
-            content = result['content']
-            if len(content) > 200:  
-                content = content[:200] + "..."
-                
-            formatted_results.append({
-                "source": result['metadata'].get('source', 'Unknown'),
-                "content": content,
-                "score": result.get('score', result.get('_score', 0.0))
-            })
-        
-        # Create response with relevance metadata and validation info
-        response_data = {
-            "results": formatted_results,
-            "relevance_score": relevance_score,
-            "total_results": len(unique_results),
-            "duplicates_removed": len(results) - len(unique_results),
-            "query": query,
-            "validation_note": "Relevance score includes content validation to prevent false positives",
-            "formatted_for_evaluation": formatted_for_evaluation  # Add this for RAGAs evaluation
-        }
-        
-        # Convert to JSON string
-        response = json.dumps(response_data, indent=2)
-        
-        # Log successful search with debug info
-        logger.info(f"Knowledge base search completed: {len(unique_results)} unique results (removed {len(results) - len(unique_results)} duplicates), relevance: {relevance_score:.2f}")
-        
-        # Debug logging for relevance issues
-        if relevance_score < 0.3:
-            logger.debug(f"Low relevance detected for query '{query}': {relevance_score:.2f}")
-            for i, result in enumerate(formatted_results[:2]):  # Log first 2 results for debugging
-                logger.debug(f"Result {i+1}: {result['content'][:50]}... (score: {result['score']:.2f})")
-        
-        return f"<search_results>\n{response}\n</search_results>"
-        
-    except Exception as e:
-        logger.error(f"Error searching knowledge base: {e}")
-        error_response = {
-            "error": f"Error searching knowledge base: {str(e)}",
-            "results": [],
-            "relevance_score": 0.0,
-            "query": query
-        }
-        return json.dumps(error_response)
-
-@tool
-def check_knowledge_status() -> str:
-    """
-    Check the status of the knowledge base.
-    
-    Returns:
-        str: JSON string with knowledge base status
-    """
-    try:
-        retriever = EmbeddingRetriever()
-        count = retriever.get_document_count()
-        
-        # Format as compact JSON to reduce token usage
-        status_data = {
-            "status": "ready" if count > 0 else "empty",
-            "document_count": count,
-            "last_updated": datetime.now().strftime("%Y-%m-%d")
-        }
-        response = json.dumps(status_data)
-        
-        # Log successful status check
-        logger.info(f"Knowledge base status checked: {count} documents")
-        
-        return response
-        
-    except Exception as e:
-        logger.error(f"Error checking knowledge status: {e}")
-        error_msg = f'{{"error": "Failed to check knowledge status: {str(e)}", "status": "error"}}'
-        return error_msg
-
-# Create the supervisor agent with tracing and enhanced tools including MCP tools
-def create_supervisor_agent_with_mcp():
-    """Create supervisor agent with MCP tools integrated using proper context manager"""
-    
-    # Get MCP client
-    mcp_client = get_tavily_mcp_client()
-    
-    if mcp_client:
-        # Use the MCP client context manager as per Strands SDK documentation
-        with mcp_client:
-            # Get the tools from the MCP server
-            mcp_tools = mcp_client.list_tools_sync()
-            logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server")
-            
-            # Combine local tools with MCP tools
-            all_tools = [
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ] + mcp_tools
-            
-            # Create agent within the MCP context
-            return create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=all_tools,
-                system_prompt="""
-You are a RAG system with web search capabilities. Answer questions using retrieved info and real-time web data.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with relevance_score)
-3. Check the relevance_score: if < 0.3 OR for time-sensitive queries (weather, news, "today", "current"): use web_search
-4. If relevance_score >= 0.3 and not time-sensitive: use RAG results
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with relevance_score)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. For weather/news/current events: use web_search directly
-3. For other queries: search knowledge base first, check relevance_score
-4. If relevance_score < 0.3: use web_search for better results
-5. If relevance_score >= 0.3: use RAG results
-6. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-""",
-                session_id="supervisor-session",
-                user_id="system"
-            )
-    else:
-        # Fallback: create agent without MCP tools
-        logger.warning("Creating agent without MCP tools due to client unavailability")
-        return create_traced_agent(
-            Agent,
-            model=get_reasoning_model(),
-            tools=[
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ],
-            system_prompt="""
-You are a RAG system with advanced relevance evaluation. Answer questions using retrieved information from the knowledge base.
-
-ENHANCED WORKFLOW WITH RAG EVALUATION:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with formatted_for_evaluation field)
-3. EVALUATE RELEVANCE: Use check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-   - This returns {"chunk_relevance_score": "yes"/"no", "chunk_relevance_value": float}
-4. DECISION POINT:
-   - If chunk_relevance_score is "yes" (score > 0.5): Use RAG results to answer
-   - If chunk_relevance_score is "no" (score <= 0.5): Inform user that results may not be relevant
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly and mention evaluation results
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with formatted_for_evaluation field)
-- check_chunks_relevance(results, question): Evaluate relevance using RAGAs (use formatted_for_evaluation field)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-ENHANCED DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. SECOND: search_knowledge_base(query) to get results with formatted_for_evaluation
-3. THIRD: check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-4. DECISION:
-   - If chunk_relevance_score is "yes": Use RAG results confidently
-   - If chunk_relevance_score is "no": Mention low relevance and provide best available information
-5. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS evaluate chunk relevance before providing answers
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-- Be transparent about relevance evaluation results
-
-FORMAT: Be concise, cite sources, use bullets when helpful, mention evaluation results
-""",
-            session_id="supervisor-session",
-            user_id="system"
-        )
-
-# Create a wrapper class to handle MCP context properly
-class SupervisorAgentWrapper:
-    """Wrapper to handle MCP client context for supervisor agent"""
-    
-    def __init__(self):
-        self.mcp_client = get_tavily_mcp_client()
-        self.agent = None
-        self._create_agent()
-    
-    def _create_agent(self):
-        """Create the agent with proper MCP context"""
-        if self.mcp_client:
-            with self.mcp_client:
-                # Get the tools from the MCP server
-                mcp_tools = self.mcp_client.list_tools_sync()
-                logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server")
-                
-                # Combine local tools with MCP tools
-                all_tools = [
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ] + mcp_tools
-                
-                # Create agent within the MCP context
-                self.agent = create_traced_agent(
-                    Agent,
-                    model=get_reasoning_model(),
-                    tools=all_tools,
-                    system_prompt="""
-You are a RAG system with web search capabilities. Answer questions using retrieved info and real-time web data.
-
-WORKFLOW:
-1. check_knowledge_status() - verify knowledge base
-2. search_knowledge_base(query="terms") - search internal data
-4. If recommendation is "USE_WEB_SEARCH": use web_search or news_search MCP tools
-5. If recommendation is "USE_RAG_RESULTS": use the RAG results
-6. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, path): Write files
-
-DECISION LOGIC:
-1. Always search knowledge base first
-3. Follow the recommendation (USE_WEB_SEARCH or USE_RAG_RESULTS)
-4. For weather, news, or current events: prefer web search
-5. For established knowledge: prefer RAG results
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                    session_id="supervisor-session",
-                    user_id="system"
-                )
-        else:
-            # Fallback: create agent without MCP tools
-            logger.warning("Creating agent without MCP tools due to client unavailability")
-            self.agent = create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=[
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ],
-                system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                session_id="supervisor-session",
-                user_id="system"
-            )
-    
-    def __call__(self, query: str):
-        """Call the agent with proper MCP context"""
-        if self.mcp_client:
-            with self.mcp_client:
-                return self.agent(query)
-        else:
-            return self.agent(query)
-
-# Create the default supervisor agent
-supervisor_agent = SupervisorAgentWrapper()
-
-def create_fresh_supervisor_agent():
-    """
-    Create a fresh supervisor agent instance with no conversation history.
-    This ensures each query starts with a clean context window.
-    """
-    import uuid
-    
-    # Create a unique session ID for each fresh agent
-    fresh_session_id = f"supervisor-{uuid.uuid4().hex[:8]}"
-    
-    # Return a fresh wrapper instance
-    class FreshSupervisorAgentWrapper:
-        """Fresh wrapper to handle MCP client context for supervisor agent"""
-        
-        def __init__(self, session_id):
-            self.mcp_client = get_tavily_mcp_client()
-            self.agent = None
-            self.session_id = session_id
-            self._create_agent()
-        
-        def _create_agent(self):
-            """Create the agent with proper MCP context"""
-            if self.mcp_client:
-                    with self.mcp_client:
-                        # Get the tools from the MCP server
-                        mcp_tools = self.mcp_client.list_tools_sync()
-                        logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server for fresh agent")
-                        
-                        # Combine local tools with MCP tools
-                        all_tools = [
-                            check_chunks_relevance,
-                            search_knowledge_base, 
-                            check_knowledge_status, 
-                            file_read, 
-                            file_write
-                        ] + mcp_tools
-                        
-                        # Create agent within the MCP context
-                        self.agent = create_traced_agent(
-                            Agent,
-                            model=get_reasoning_model(),
-                            tools=all_tools,
-                            system_prompt="""
-You are a RAG system with web search capabilities and advanced relevance evaluation. Answer questions using retrieved info and real-time web data.
-
-ENHANCED WORKFLOW WITH RAG EVALUATION:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with formatted_for_evaluation field)
-3. EVALUATE RELEVANCE: Use check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-   - This returns {"chunk_relevance_score": "yes"/"no", "chunk_relevance_value": float}
-4. DECISION POINT:
-   - If chunk_relevance_score is "yes" (score > 0.5): Use RAG results to answer
-   - If chunk_relevance_score is "no" (score <= 0.5): Use web_search for better results
-   - For time-sensitive queries (weather, news, "today", "current"): Always use web_search
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly and mention which evaluation method was used
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with formatted_for_evaluation field)
-- check_chunks_relevance(results, question): Evaluate relevance using RAGAs (use formatted_for_evaluation field)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-ENHANCED DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. SECOND: search_knowledge_base(query) to get results with formatted_for_evaluation
-3. THIRD: check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-4. DECISION:
-   - If chunk_relevance_score is "yes": Use RAG results
-   - If chunk_relevance_score is "no": Use web_search
-   - For weather/news/current events: Skip evaluation, use web_search directly
-5. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-FORMAT: Be concise, cite sources, use bullets when helpful, mention evaluation results
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS evaluate chunk relevance before deciding between RAG and web search
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-- Be transparent about which source provided the information and the relevance evaluation results
-""",
-                        session_id=self.session_id,
-                        user_id="system"
-                    )
-            else:
-                # Fallback: create agent without MCP tools
-                logger.warning("Creating fresh agent without MCP tools due to client unavailability")
-                self.agent = create_traced_agent(
-                    Agent,
-                    model=get_reasoning_model(),
-                    tools=[
-                        check_chunks_relevance,
-                        search_knowledge_base, 
-                        check_knowledge_status, 
-                        file_read, 
-                        file_write
-                    ],
-                    system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                    session_id=self.session_id,
-                    user_id="system"
-                )
-        
-        def __call__(self, query: str):
-            """Call the agent with proper MCP context"""
-            if self.mcp_client:
-                with self.mcp_client:
-                    return self.agent(query)
-            else:
-                return self.agent(query)
-    
-    return FreshSupervisorAgentWrapper(fresh_session_id)
-
-# The supervisor_agent now has built-in tracing via Strands SDK and proper MCP integration
-# Export the agent and the fresh agent creator
-__all__ = ["supervisor_agent", "create_fresh_supervisor_agent"]
\ No newline at end of file
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent.py
deleted file mode 100644
index 67b16c17..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent.py
+++ /dev/null
@@ -1,889 +0,0 @@
-"""Supervisor Agent using Strands SDK patterns with Tavily Web Search integration and RAG relevance evaluation."""
-
-# Import global async cleanup FIRST
-from ..utils.global_async_cleanup import setup_global_async_cleanup
-
-import asyncio
-import re
-import logging
-import json
-import uuid
-from typing import Dict, List, Any, Optional
-from datetime import datetime
-from strands import Agent, tool
-from strands_tools import file_read
-from mcp.client.streamable_http import streamablehttp_client
-from strands.tools.mcp.mcp_client import MCPClient
-from langchain_aws import ChatBedrockConverse
-from ragas import SingleTurnSample
-from ragas.metrics import LLMContextPrecisionWithoutReference
-from ragas.llms import LangchainLLMWrapper
-from ..config import config
-from ..utils.logging import log_title
-from ..utils.model_providers import get_reasoning_model
-from ..utils.strands_langfuse_integration import create_traced_agent, setup_tracing_environment
-from ..utils.async_cleanup import suppress_async_warnings, setup_async_environment
-from ..tools.embedding_retriever import EmbeddingRetriever
-from .mcp_agent import file_write  # Use the wrapped file_write from mcp_agent
-
-logger = logging.getLogger(__name__)
-
-# Set up tracing environment and async cleanup
-setup_tracing_environment()
-setup_async_environment()
-
-# Evaluation model configuration for RAGAs
-eval_modelId = 'us.anthropic.claude-3-7-sonnet-20250219-v1:0'
-thinking_params = {
-    "thinking": {
-        "type": "disabled"
-    }
-}
-llm_for_evaluation = ChatBedrockConverse(model_id=eval_modelId, additional_model_request_fields=thinking_params)
-llm_for_evaluation = LangchainLLMWrapper(llm_for_evaluation)
-
-# Initialize Tavily MCP client
-tavily_mcp_client = None
-
-def get_tavily_mcp_client():
-    """Get or create Tavily MCP client with proper session management"""
-    global tavily_mcp_client
-    
-    if tavily_mcp_client is None:
-        try:
-            # Use config for MCP service URL
-            mcp_url = config.TAVILY_MCP_SERVICE_URL
-            tavily_mcp_client = MCPClient(lambda: streamablehttp_client(mcp_url))
-            logger.info(f"Tavily MCP client initialized successfully with URL: {mcp_url}")
-        except Exception as e:
-            logger.warning(f"Failed to initialize Tavily MCP client: {e}")
-            tavily_mcp_client = None
-    
-    return tavily_mcp_client
-
-def calculate_relevance_score(results: List[Dict], query: str) -> float:
-    """
-    Calculate relevance score with content validation to prevent false positives.
-    
-    Args:
-        results: List of search results with scores
-        query: Original search query for semantic validation
-        
-    Returns:
-        float: Validated relevance score (0.0 to 1.0)
-    """
-    if not results:
-        return 0.0
-    
-    # Extract scores and validate content relevance
-    scores = []
-    query_lower = query.lower()
-    query_keywords = set(query_lower.split())
-    
-    for result in results:
-        # Get the similarity score
-        score = None
-        if isinstance(result, dict):
-            score = result.get('score') or result.get('_score')
-            if score is None and 'metadata' in result:
-                score = result['metadata'].get('score')
-        
-        if score is not None:
-            # Validate content relevance by checking keyword overlap
-            content = result.get('content', '').lower()
-            content_keywords = set(content.split())
-            
-            # Calculate keyword overlap ratio
-            overlap = len(query_keywords.intersection(content_keywords))
-            overlap_ratio = overlap / len(query_keywords) if query_keywords else 0
-            
-            # Penalize results with very low keyword overlap
-            if overlap_ratio < 0.1:  # Less than 10% keyword overlap
-                score = score * 0.2  # Heavily penalize
-            elif overlap_ratio < 0.3:  # Less than 30% keyword overlap
-                score = score * 0.5  # Moderately penalize
-            
-            scores.append(float(score))
-    
-    if not scores:
-        return 0.0
-    
-    # Calculate average and apply additional validation
-    avg_score = sum(scores) / len(scores)
-    
-    # Additional semantic validation for common mismatches
-    if any(keyword in query_lower for keyword in ['weather', 'temperature', 'forecast']):
-        # For weather queries, check if results contain weather-related terms
-        weather_terms = ['weather', 'temperature', 'rain', 'sunny', 'cloudy', 'forecast', 'celsius', 'fahrenheit']
-        has_weather_content = False
-        
-        for result in results:
-            content = result.get('content', '').lower()
-            if any(term in content for term in weather_terms):
-                has_weather_content = True
-                break
-        
-        if not has_weather_content:
-            avg_score = avg_score * 0.1  # Heavily penalize non-weather content for weather queries
-    
-    return min(avg_score, 1.0)
-
-# Create tools for the supervisor agent
-def _run_async_evaluation_safe(scorer, sample):
-    """
-    Helper function to run async evaluation with proper cleanup and error handling.
-    
-    Args:
-        scorer: RAGAs scorer instance
-        sample: SingleTurnSample for evaluation
-        
-    Returns:
-        float: Evaluation score
-    """
-    import asyncio
-    import threading
-    import queue
-    
-    def run_evaluation():
-        """Run the evaluation in a clean async environment."""
-        async def evaluate():
-            try:
-                # Set a shorter timeout for the evaluation
-                score = await asyncio.wait_for(
-                    scorer.single_turn_ascore(sample), 
-                    timeout=20.0  # 20 second timeout
-                )
-                return score
-            except asyncio.TimeoutError:
-                raise TimeoutError("RAGAs evaluation timed out")
-            except Exception as e:
-                raise Exception(f"RAGAs evaluation failed: {str(e)}")
-        
-        # Create and run in a new event loop with proper cleanup
-        loop = asyncio.new_event_loop()
-        asyncio.set_event_loop(loop)
-        
-        try:
-            score = loop.run_until_complete(evaluate())
-            result_queue.put(('success', score))
-        except Exception as e:
-            result_queue.put(('error', str(e)))
-        finally:
-            # Properly close the loop and clean up
-            try:
-                # Cancel all remaining tasks
-                pending = asyncio.all_tasks(loop)
-                for task in pending:
-                    task.cancel()
-                
-                # Wait for tasks to complete cancellation with timeout
-                if pending:
-                    try:
-                        loop.run_until_complete(
-                            asyncio.wait_for(
-                                asyncio.gather(*pending, return_exceptions=True),
-                                timeout=2.0
-                            )
-                        )
-                    except asyncio.TimeoutError:
-                        pass  # Ignore timeout during cleanup
-                
-                # Close the loop
-                loop.close()
-            except Exception:
-                pass  # Ignore cleanup errors
-    
-    # Use a queue to communicate between threads
-    result_queue = queue.Queue()
-    
-    # Run in a separate thread to avoid event loop conflicts
-    thread = threading.Thread(target=run_evaluation, daemon=True)
-    thread.start()
-    thread.join(timeout=25)  # Give extra time for cleanup
-    
-    if thread.is_alive():
-        raise TimeoutError("Evaluation thread timed out")
-    
-    try:
-        result_type, result_value = result_queue.get_nowait()
-        if result_type == 'error':
-            raise Exception(result_value)
-        return result_value
-    except queue.Empty:
-        raise Exception("No result received from evaluation")
-
-@tool
-def check_chunks_relevance(results: str, question: str):
-    """
-    Evaluates the relevance of retrieved chunks to the user question using RAGAs.
-
-    Args:
-        results (str): Retrieval output as a string with 'Score:' and 'Content:' patterns.
-        question (str): Original user question.
-
-    Returns:
-        dict: A binary score ('yes' or 'no') and the numeric relevance score, or an error message.
-    """
-    # Use the async warning suppression context
-    with suppress_async_warnings():
-        try:
-            if not results or not isinstance(results, str):
-                raise ValueError("Invalid input: 'results' must be a non-empty string.")
-            if not question or not isinstance(question, str):
-                raise ValueError("Invalid input: 'question' must be a non-empty string.")
-
-            # Extract content chunks using regex with improved error handling
-            patterns_to_try = [
-                r"Score:.*?\nContent:\s*(.*?)(?=\n\nScore:|\Z)",  # Handle double newlines
-                r"Score:.*?\nContent:\s*(.*?)(?=Score:|\Z)",      # Original pattern
-                r"Score:\s*[\d.]+\s*\nContent:\s*(.*?)(?=\n\nScore:|\Z)",  # More specific score pattern
-            ]
-            
-            docs = []
-            pattern_used = None
-            
-            for i, pattern in enumerate(patterns_to_try):
-                try:
-                    docs = [chunk.strip() for chunk in re.findall(pattern, results, re.DOTALL) if chunk.strip()]
-                    if docs:
-                        pattern_used = f"Pattern {i+1}"
-                        logger.debug(f"Successfully extracted {len(docs)} chunks using pattern {i+1}")
-                        break
-                except Exception as e:
-                    logger.warning(f"Pattern {i+1} failed: {e}")
-                    continue
-            
-            # If no patterns worked, try a more flexible approach
-            if not docs:
-                logger.warning("Standard patterns failed, trying flexible extraction...")
-                flexible_pattern = r"Content:\s*([^\n]+(?:\n(?!Score:)[^\n]*)*)"
-                try:
-                    docs = [chunk.strip() for chunk in re.findall(flexible_pattern, results, re.MULTILINE) if chunk.strip()]
-                    if docs:
-                        pattern_used = "Flexible pattern"
-                        logger.info(f"Flexible extraction found {len(docs)} chunks")
-                except Exception as e:
-                    logger.error(f"Flexible extraction also failed: {e}")
-
-            if not docs:
-                # Provide detailed debugging information
-                debug_info = {
-                    "results_length": len(results),
-                    "contains_score": "Score:" in results,
-                    "contains_content": "Content:" in results,
-                    "results_preview": results[:200] if len(results) > 200 else results
-                }
-                logger.error(f"No valid content chunks found. Debug info: {debug_info}")
-                raise ValueError(f"No valid content chunks found in 'results'. Debug: {debug_info}")
-
-            # Limit the number of chunks to avoid timeout
-            if len(docs) > 3:
-                docs = docs[:3]  # Take only first 3 chunks
-                logger.info(f"Limited evaluation to first 3 chunks out of {len(docs)} total")
-
-            # Generate a proper answer from the context for RAGAs evaluation
-            # This is necessary because LLMContextPrecisionWithoutReference evaluates
-            # whether the context was useful in arriving at the given answer
-            try:
-                context_for_answer = "\n\n".join(docs[:2])  # Use first 2 chunks
-                answer_prompt = f"""Based on the following context, provide a brief answer to the question.
-
-Question: {question}
-Context: {context_for_answer}
-
-Answer:"""
-                
-                # Use a simple model call to generate the answer
-                from langchain_aws import ChatBedrockConverse
-                answer_llm = ChatBedrockConverse(model_id='us.anthropic.claude-3-7-sonnet-20250219-v1:0')
-                answer_response = answer_llm.invoke(answer_prompt)
-                generated_answer = answer_response.content.strip()
-                
-                logger.debug(f"Generated answer for RAGAs evaluation: {generated_answer[:100]}...")
-                
-            except Exception as e:
-                logger.warning(f"Failed to generate answer for RAGAs evaluation: {e}")
-                generated_answer = "Unable to generate answer from context"
-
-            # Prepare evaluation sample with proper answer
-            sample = SingleTurnSample(
-                user_input=question,
-                response=generated_answer,  # Use generated answer instead of placeholder
-                retrieved_contexts=docs
-            )
-
-            # Evaluate using context precision metric with safe async handling
-            scorer = LLMContextPrecisionWithoutReference(llm=llm_for_evaluation)
-            
-            print("------------------------")
-            print("Context evaluation (RAGAs)")
-            print("------------------------")
-            print(f"Evaluating {len(docs)} chunks...")
-            
-            # Use the safe evaluation helper
-            score = _run_async_evaluation_safe(scorer, sample)
-
-            print(f"chunk_relevance_score: {score}")
-            print("------------------------")
-
-            return {
-                "chunk_relevance_score": "yes" if score > 0.5 else "no",
-                "chunk_relevance_value": score
-            }
-
-        except Exception as e:
-            logger.error(f"Error in chunk relevance evaluation: {e}")
-            # Provide a fallback based on simple heuristics
-            try:
-                # Simple fallback: check if question keywords appear in results
-                question_words = set(question.lower().split())
-                results_words = set(results.lower().split())
-                overlap = len(question_words.intersection(results_words))
-                fallback_score = min(overlap / len(question_words), 1.0) if question_words else 0.0
-                
-                logger.info(f"Using fallback relevance score: {fallback_score}")
-                
-                return {
-                    "chunk_relevance_score": "yes" if fallback_score > 0.3 else "no",
-                    "chunk_relevance_value": fallback_score,
-                    "evaluation_method": "fallback_heuristic",
-                    "note": f"RAGAs evaluation failed, using keyword overlap heuristic"
-                }
-            except Exception as fallback_error:
-                logger.error(f"Fallback evaluation also failed: {fallback_error}")
-                return {
-                    "error": f"Both RAGAs and fallback evaluation failed: {str(e)}",
-                    "chunk_relevance_score": "unknown",
-                    "chunk_relevance_value": None
-                }
-
-@tool
-def search_knowledge_base(query: str, top_k: int = 3) -> str:  
-    """
-    Search the knowledge base for relevant information.
-    
-    Args:
-        query (str): The search query - REQUIRED
-        top_k (int): Number of top results to return (default: 3)
-        
-    Returns:
-        str: JSON string with search results and relevance metadata
-    """
-    if not query or not isinstance(query, str):
-        return '{"error": "Query parameter is required and must be a non-empty string", "results": [], "relevance_score": 0.0}'
-    
-    try:
-        retriever = EmbeddingRetriever()
-        results = retriever.search(query, top_k=top_k)
-        
-        # Calculate relevance score with content validation
-        relevance_score = calculate_relevance_score(results, query)
-        
-        # Remove duplicate results
-        seen_content = set()
-        unique_results = []
-        for result in results:
-            content_hash = hash(result['content'][:100])  # Use first 100 chars as hash
-            if content_hash not in seen_content:
-                seen_content.add(content_hash)
-                unique_results.append(result)
-        
-        # Format results for RAGAs evaluation (with Score: and Content: patterns)
-        formatted_for_evaluation = ""
-        for result in unique_results[:top_k]:
-            formatted_for_evaluation += f"Score: {result.get('score', result.get('_score', 0.0))}\n"
-            formatted_for_evaluation += f"Content: {result['content']}\n\n"
-        
-        # Format results as compact JSON for response
-        formatted_results = []
-        for result in unique_results[:top_k]:  # Ensure we don't exceed top_k after deduplication
-            # Limit content length to reduce tokens
-            content = result['content']
-            if len(content) > 200:  
-                content = content[:200] + "..."
-                
-            formatted_results.append({
-                "source": result['metadata'].get('source', 'Unknown'),
-                "content": content,
-                "score": result.get('score', result.get('_score', 0.0))
-            })
-        
-        # Create response with relevance metadata and validation info
-        response_data = {
-            "results": formatted_results,
-            "relevance_score": relevance_score,
-            "total_results": len(unique_results),
-            "duplicates_removed": len(results) - len(unique_results),
-            "query": query,
-            "validation_note": "Relevance score includes content validation to prevent false positives",
-            "formatted_for_evaluation": formatted_for_evaluation  # Add this for RAGAs evaluation
-        }
-        
-        # Convert to JSON string
-        response = json.dumps(response_data, indent=2)
-        
-        # Log successful search with debug info
-        logger.info(f"Knowledge base search completed: {len(unique_results)} unique results (removed {len(results) - len(unique_results)} duplicates), relevance: {relevance_score:.2f}")
-        
-        # Debug logging for relevance issues
-        if relevance_score < 0.3:
-            logger.debug(f"Low relevance detected for query '{query}': {relevance_score:.2f}")
-            for i, result in enumerate(formatted_results[:2]):  # Log first 2 results for debugging
-                logger.debug(f"Result {i+1}: {result['content'][:50]}... (score: {result['score']:.2f})")
-        
-        return f"<search_results>\n{response}\n</search_results>"
-        
-    except Exception as e:
-        logger.error(f"Error searching knowledge base: {e}")
-        error_response = {
-            "error": f"Error searching knowledge base: {str(e)}",
-            "results": [],
-            "relevance_score": 0.0,
-            "query": query
-        }
-        return json.dumps(error_response)
-
-@tool
-def check_knowledge_status() -> str:
-    """
-    Check the status of the knowledge base.
-    
-    Returns:
-        str: JSON string with knowledge base status
-    """
-    try:
-        retriever = EmbeddingRetriever()
-        count = retriever.get_document_count()
-        
-        # Format as compact JSON to reduce token usage
-        status_data = {
-            "status": "ready" if count > 0 else "empty",
-            "document_count": count,
-            "last_updated": datetime.now().strftime("%Y-%m-%d")
-        }
-        response = json.dumps(status_data)
-        
-        # Log successful status check
-        logger.info(f"Knowledge base status checked: {count} documents")
-        
-        return response
-        
-    except Exception as e:
-        logger.error(f"Error checking knowledge status: {e}")
-        error_msg = f'{{"error": "Failed to check knowledge status: {str(e)}", "status": "error"}}'
-        return error_msg
-
-# Create the supervisor agent with tracing and enhanced tools including MCP tools
-def create_supervisor_agent_with_mcp():
-    """Create supervisor agent with MCP tools integrated using proper context manager"""
-    
-    # Get MCP client
-    mcp_client = get_tavily_mcp_client()
-    
-    if mcp_client:
-        # Use the MCP client context manager as per Strands SDK documentation
-        with mcp_client:
-            # Get the tools from the MCP server
-            mcp_tools = mcp_client.list_tools_sync()
-            logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server")
-            
-            # Combine local tools with MCP tools
-            all_tools = [
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ] + mcp_tools
-            
-            # Create agent within the MCP context
-            return create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=all_tools,
-                system_prompt="""
-You are a RAG system with web search capabilities. Answer questions using retrieved info and real-time web data.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with relevance_score)
-3. Check the relevance_score: if < 0.3 OR for time-sensitive queries (weather, news, "today", "current"): use web_search
-4. If relevance_score >= 0.3 and not time-sensitive: use RAG results
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with relevance_score)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. For weather/news/current events: use web_search directly
-3. For other queries: search knowledge base first, check relevance_score
-4. If relevance_score < 0.3: use web_search for better results
-5. If relevance_score >= 0.3: use RAG results
-6. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-""",
-                session_id="supervisor-session",
-                user_id="system"
-            )
-    else:
-        # Fallback: create agent without MCP tools
-        logger.warning("Creating agent without MCP tools due to client unavailability")
-        return create_traced_agent(
-            Agent,
-            model=get_reasoning_model(),
-            tools=[
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ],
-            system_prompt="""
-You are a RAG system with advanced relevance evaluation. Answer questions using retrieved information from the knowledge base.
-
-ENHANCED WORKFLOW WITH RAG EVALUATION:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with formatted_for_evaluation field)
-3. EVALUATE RELEVANCE: Use check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-   - This returns {"chunk_relevance_score": "yes"/"no", "chunk_relevance_value": float}
-4. DECISION POINT:
-   - If chunk_relevance_score is "yes" (score > 0.5): Use RAG results to answer
-   - If chunk_relevance_score is "no" (score <= 0.5): Inform user that results may not be relevant
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly and mention evaluation results
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with formatted_for_evaluation field)
-- check_chunks_relevance(results, question): Evaluate relevance using RAGAs (use formatted_for_evaluation field)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-ENHANCED DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. SECOND: search_knowledge_base(query) to get results with formatted_for_evaluation
-3. THIRD: check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-4. DECISION:
-   - If chunk_relevance_score is "yes": Use RAG results confidently
-   - If chunk_relevance_score is "no": Mention low relevance and provide best available information
-5. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS evaluate chunk relevance before providing answers
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-- Be transparent about relevance evaluation results
-
-FORMAT: Be concise, cite sources, use bullets when helpful, mention evaluation results
-""",
-            session_id="supervisor-session",
-            user_id="system"
-        )
-
-# Create a wrapper class to handle MCP context properly
-class SupervisorAgentWrapper:
-    """Wrapper to handle MCP client context for supervisor agent"""
-    
-    def __init__(self):
-        self.mcp_client = None
-        self.agent = None
-        self._initialized = False
-    
-    def _ensure_initialized(self):
-        """Ensure the agent is initialized, with lazy loading"""
-        if not self._initialized:
-            try:
-                self.mcp_client = get_tavily_mcp_client()
-                self._create_agent()
-                self._initialized = True
-            except Exception as e:
-                logger.error(f"Failed to initialize supervisor agent: {e}")
-                logger.warning("Creating agent without MCP tools due to initialization failure")
-                self.mcp_client = None
-                self._create_agent_without_mcp()
-                self._initialized = True
-    
-    def _create_agent(self):
-        """Prepare for agent creation - actual creation happens in __call__ within MCP context"""
-        if not self.mcp_client:
-            self._create_agent_without_mcp()
-    
-    def _create_agent_without_mcp(self):
-        """Create agent without MCP tools"""
-        logger.warning("Creating supervisor agent without MCP tools")
-        self.agent = create_traced_agent(
-            Agent,
-            model=get_reasoning_model(),
-            tools=[
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ],
-            system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-            session_id="supervisor-session",
-            user_id="system"
-        )
-    
-    def __call__(self, query: str):
-        """Call the agent with proper MCP context"""
-        self._ensure_initialized()
-        if self.mcp_client:
-            # Use context manager for the entire agent lifecycle
-            with self.mcp_client:
-                # Create agent within context if needed
-                if not hasattr(self, '_agent_created_in_context'):
-                    # Get the tools from the MCP server within the context
-                    mcp_tools = self.mcp_client.list_tools_sync()
-                    logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server")
-                    
-                    # Combine local tools with MCP tools
-                    all_tools = [
-                        check_chunks_relevance,
-                        search_knowledge_base, 
-                        check_knowledge_status, 
-                        file_read, 
-                        file_write
-                    ] + mcp_tools
-                    
-                    # Create agent with all tools within the MCP context
-                    self.agent = create_traced_agent(
-                        Agent,
-                        model=get_reasoning_model(),
-                        tools=all_tools,
-                        system_prompt="""You are a RAG system with web search capabilities. Answer questions using retrieved info and real-time web data.
-
-WORKFLOW:
-1. check_knowledge_status() - verify knowledge base
-2. search_knowledge_base(query="terms") - search internal data
-4. If recommendation is "USE_WEB_SEARCH": use web_search or news_search MCP tools
-5. If recommendation is "USE_RAG_RESULTS": use the RAG results
-6. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, path): Write files
-
-DECISION LOGIC:
-1. Always search knowledge base first
-3. Follow the recommendation (USE_WEB_SEARCH or USE_RAG_RESULTS)
-4. For weather, news, or current events: prefer web search
-5. For established knowledge: prefer RAG results
-
-FORMAT: Be concise, cite sources, use bullets when helpful""",
-                        session_id="supervisor-session",
-                        user_id="system"
-                    )
-                    self._agent_created_in_context = True
-                
-                # Execute the agent within the MCP context
-                return self.agent(query)
-        else:
-            return self.agent(query)
-
-# Create the default supervisor agent
-supervisor_agent = SupervisorAgentWrapper()
-
-def create_fresh_supervisor_agent():
-    """
-    Create a fresh supervisor agent instance with no conversation history.
-    This ensures each query starts with a clean context window.
-    """
-    import uuid
-    
-    # Create a unique session ID for each fresh agent
-    fresh_session_id = f"supervisor-{uuid.uuid4().hex[:8]}"
-    
-    # Return a fresh wrapper instance
-def create_fresh_supervisor_agent(fresh_session_id: str = None):
-    """Create a fresh supervisor agent with a new session ID and proper MCP context management"""
-    if fresh_session_id is None:
-        fresh_session_id = f"fresh-supervisor-{uuid.uuid4().hex[:8]}"
-    
-    class FreshSupervisorAgentWrapper:
-        """Fresh wrapper to handle MCP client context for supervisor agent"""
-        
-        def __init__(self, session_id):
-            self.mcp_client = None
-            self.agent = None
-            self.session_id = session_id
-            self._initialized = False
-        
-        def _ensure_initialized(self):
-            """Ensure the agent is initialized, with lazy loading"""
-            if not self._initialized:
-                try:
-                    self.mcp_client = get_tavily_mcp_client()
-                    self._create_agent()
-                    self._initialized = True
-                except Exception as e:
-                    logger.error(f"Failed to create fresh agent with MCP tools: {e}")
-                    logger.warning("Creating fresh agent without MCP tools due to MCP failure")
-                    self.mcp_client = None
-                    self._create_agent_without_mcp()
-                    self._initialized = True
-        
-        def _create_agent(self):
-            """Prepare for agent creation - actual creation happens in __call__ within MCP context"""
-            if not self.mcp_client:
-                self._create_agent_without_mcp()
-        
-        def _create_agent_without_mcp(self):
-            """Create agent without MCP tools"""
-            logger.warning("Creating fresh agent without MCP tools due to client unavailability")
-            self.agent = create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=[
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ],
-                system_prompt="""You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful""",
-                session_id=self.session_id,
-                user_id="system"
-            )
-        
-        def __call__(self, query: str):
-            """Call the agent with proper MCP context"""
-            self._ensure_initialized()
-            if self.mcp_client:
-                # Use context manager for the entire agent lifecycle
-                with self.mcp_client:
-                    # Create agent within context if needed
-                    if not hasattr(self, '_agent_created_in_context'):
-                        # Get the tools from the MCP server within the context
-                        mcp_tools = self.mcp_client.list_tools_sync()
-                        logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server for fresh agent")
-                        
-                        # Combine local tools with MCP tools
-                        all_tools = [
-                            check_chunks_relevance,
-                            search_knowledge_base, 
-                            check_knowledge_status, 
-                            file_read, 
-                            file_write
-                        ] + mcp_tools
-                        
-                        # Create agent with all tools within the MCP context
-                        self.agent = create_traced_agent(
-                            Agent,
-                            model=get_reasoning_model(),
-                            tools=all_tools,
-                            system_prompt="""You are a RAG system with web search capabilities and advanced relevance evaluation. Answer questions using retrieved info and real-time web data.
-
-ENHANCED WORKFLOW WITH RAG EVALUATION:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with formatted_for_evaluation field)
-3. EVALUATE RELEVANCE: Use check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-   - This returns {"chunk_relevance_score": "yes"/"no", "chunk_relevance_value": float}
-4. DECISION POINT:
-   - If chunk_relevance_score is "yes" (score > 0.5): Use RAG results to answer
-   - If chunk_relevance_score is "no" (score <= 0.5): Use web_search for better results
-   - For time-sensitive queries (weather, news, "today", "current"): Always use web_search
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly and mention which evaluation method was used
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with formatted_for_evaluation field)
-- check_chunks_relevance(results, question): Evaluate relevance using RAGAs (use formatted_for_evaluation field)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-ENHANCED DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. SECOND: search_knowledge_base(query) to get results with formatted_for_evaluation
-3. THIRD: check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-4. DECISION:
-   - If chunk_relevance_score is "yes": Use RAG results
-   - If chunk_relevance_score is "no": Use web_search
-   - For weather/news/current events: Skip evaluation, use web_search directly
-5. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-FORMAT: Be concise, cite sources, use bullets when helpful, mention evaluation results
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS evaluate chunk relevance before deciding between RAG and web search
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-- Be transparent about which source provided the information and the relevance evaluation results""",
-                            session_id=self.session_id,
-                            user_id="system"
-                        )
-                        self._agent_created_in_context = True
-                    
-                    # Execute the agent within the MCP context
-                    return self.agent(query)
-            else:
-                return self.agent(query)
-    
-    return FreshSupervisorAgentWrapper(fresh_session_id)
-
-# The supervisor_agent now has built-in tracing via Strands SDK and proper MCP integration
-# Export the agent and the fresh agent creator
-__all__ = ["supervisor_agent", "create_fresh_supervisor_agent"]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent.py.backup b/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent.py.backup
deleted file mode 100644
index 3eec7d6d..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/agents/supervisor_agent.py.backup
+++ /dev/null
@@ -1,967 +0,0 @@
-"""Supervisor Agent using Strands SDK patterns with Tavily Web Search integration and RAG relevance evaluation."""
-
-# Import global async cleanup FIRST
-from ..utils.global_async_cleanup import setup_global_async_cleanup
-
-import asyncio
-import re
-import logging
-import json
-from typing import Dict, List, Any, Optional
-from datetime import datetime
-from strands import Agent, tool
-from strands_tools import file_read
-from mcp.client.streamable_http import streamablehttp_client
-from strands.tools.mcp.mcp_client import MCPClient
-from langchain_aws import ChatBedrockConverse
-from ragas import SingleTurnSample
-from ragas.metrics import LLMContextPrecisionWithoutReference
-from ragas.llms import LangchainLLMWrapper
-from ..config import config
-from ..utils.logging import log_title
-from ..utils.model_providers import get_reasoning_model
-from ..utils.strands_langfuse_integration import create_traced_agent, setup_tracing_environment
-from ..utils.async_cleanup import suppress_async_warnings, setup_async_environment
-from ..tools.embedding_retriever import EmbeddingRetriever
-from .mcp_agent import file_write  # Use the wrapped file_write from mcp_agent
-
-logger = logging.getLogger(__name__)
-
-# Set up tracing environment and async cleanup
-setup_tracing_environment()
-setup_async_environment()
-
-# Evaluation model configuration for RAGAs
-eval_modelId = 'us.anthropic.claude-3-7-sonnet-20250219-v1:0'
-thinking_params = {
-    "thinking": {
-        "type": "disabled"
-    }
-}
-llm_for_evaluation = ChatBedrockConverse(model_id=eval_modelId, additional_model_request_fields=thinking_params)
-llm_for_evaluation = LangchainLLMWrapper(llm_for_evaluation)
-
-# Initialize Tavily MCP client
-tavily_mcp_client = None
-
-def get_tavily_mcp_client():
-    """Get or create Tavily MCP client"""
-    global tavily_mcp_client
-    if tavily_mcp_client is None:
-        try:
-            # Use config for MCP service URL
-            mcp_url = config.TAVILY_MCP_SERVICE_URL
-            tavily_mcp_client = MCPClient(lambda: streamablehttp_client(mcp_url))
-            logger.info(f"Tavily MCP client initialized successfully with URL: {mcp_url}")
-        except Exception as e:
-            logger.warning(f"Failed to initialize Tavily MCP client: {e}")
-            tavily_mcp_client = None
-    return tavily_mcp_client
-
-def calculate_relevance_score(results: List[Dict], query: str) -> float:
-    """
-    Calculate relevance score with content validation to prevent false positives.
-    
-    Args:
-        results: List of search results with scores
-        query: Original search query for semantic validation
-        
-    Returns:
-        float: Validated relevance score (0.0 to 1.0)
-    """
-    if not results:
-        return 0.0
-    
-    # Extract scores and validate content relevance
-    scores = []
-    query_lower = query.lower()
-    query_keywords = set(query_lower.split())
-    
-    for result in results:
-        # Get the similarity score
-        score = None
-        if isinstance(result, dict):
-            score = result.get('score') or result.get('_score')
-            if score is None and 'metadata' in result:
-                score = result['metadata'].get('score')
-        
-        if score is not None:
-            # Validate content relevance by checking keyword overlap
-            content = result.get('content', '').lower()
-            content_keywords = set(content.split())
-            
-            # Calculate keyword overlap ratio
-            overlap = len(query_keywords.intersection(content_keywords))
-            overlap_ratio = overlap / len(query_keywords) if query_keywords else 0
-            
-            # Penalize results with very low keyword overlap
-            if overlap_ratio < 0.1:  # Less than 10% keyword overlap
-                score = score * 0.2  # Heavily penalize
-            elif overlap_ratio < 0.3:  # Less than 30% keyword overlap
-                score = score * 0.5  # Moderately penalize
-            
-            scores.append(float(score))
-    
-    if not scores:
-        return 0.0
-    
-    # Calculate average and apply additional validation
-    avg_score = sum(scores) / len(scores)
-    
-    # Additional semantic validation for common mismatches
-    if any(keyword in query_lower for keyword in ['weather', 'temperature', 'forecast']):
-        # For weather queries, check if results contain weather-related terms
-        weather_terms = ['weather', 'temperature', 'rain', 'sunny', 'cloudy', 'forecast', 'celsius', 'fahrenheit']
-        has_weather_content = False
-        
-        for result in results:
-            content = result.get('content', '').lower()
-            if any(term in content for term in weather_terms):
-                has_weather_content = True
-                break
-        
-        if not has_weather_content:
-            avg_score = avg_score * 0.1  # Heavily penalize non-weather content for weather queries
-    
-    return min(avg_score, 1.0)
-
-# Create tools for the supervisor agent
-def _run_async_evaluation_safe(scorer, sample):
-    """
-    Helper function to run async evaluation with proper cleanup and error handling.
-    
-    Args:
-        scorer: RAGAs scorer instance
-        sample: SingleTurnSample for evaluation
-        
-    Returns:
-        float: Evaluation score
-    """
-    import asyncio
-    import threading
-    import queue
-    
-    def run_evaluation():
-        """Run the evaluation in a clean async environment."""
-        async def evaluate():
-            try:
-                # Set a shorter timeout for the evaluation
-                score = await asyncio.wait_for(
-                    scorer.single_turn_ascore(sample), 
-                    timeout=20.0  # 20 second timeout
-                )
-                return score
-            except asyncio.TimeoutError:
-                raise TimeoutError("RAGAs evaluation timed out")
-            except Exception as e:
-                raise Exception(f"RAGAs evaluation failed: {str(e)}")
-        
-        # Create and run in a new event loop with proper cleanup
-        loop = asyncio.new_event_loop()
-        asyncio.set_event_loop(loop)
-        
-        try:
-            score = loop.run_until_complete(evaluate())
-            result_queue.put(('success', score))
-        except Exception as e:
-            result_queue.put(('error', str(e)))
-        finally:
-            # Properly close the loop and clean up
-            try:
-                # Cancel all remaining tasks
-                pending = asyncio.all_tasks(loop)
-                for task in pending:
-                    task.cancel()
-                
-                # Wait for tasks to complete cancellation with timeout
-                if pending:
-                    try:
-                        loop.run_until_complete(
-                            asyncio.wait_for(
-                                asyncio.gather(*pending, return_exceptions=True),
-                                timeout=2.0
-                            )
-                        )
-                    except asyncio.TimeoutError:
-                        pass  # Ignore timeout during cleanup
-                
-                # Close the loop
-                loop.close()
-            except Exception:
-                pass  # Ignore cleanup errors
-    
-    # Use a queue to communicate between threads
-    result_queue = queue.Queue()
-    
-    # Run in a separate thread to avoid event loop conflicts
-    thread = threading.Thread(target=run_evaluation, daemon=True)
-    thread.start()
-    thread.join(timeout=25)  # Give extra time for cleanup
-    
-    if thread.is_alive():
-        raise TimeoutError("Evaluation thread timed out")
-    
-    try:
-        result_type, result_value = result_queue.get_nowait()
-        if result_type == 'error':
-            raise Exception(result_value)
-        return result_value
-    except queue.Empty:
-        raise Exception("No result received from evaluation")
-
-@tool
-def check_chunks_relevance(results: str, question: str):
-    """
-    Evaluates the relevance of retrieved chunks to the user question using RAGAs.
-
-    Args:
-        results (str): Retrieval output as a string with 'Score:' and 'Content:' patterns.
-        question (str): Original user question.
-
-    Returns:
-        dict: A binary score ('yes' or 'no') and the numeric relevance score, or an error message.
-    """
-    # Use the async warning suppression context
-    with suppress_async_warnings():
-        try:
-            if not results or not isinstance(results, str):
-                raise ValueError("Invalid input: 'results' must be a non-empty string.")
-            if not question or not isinstance(question, str):
-                raise ValueError("Invalid input: 'question' must be a non-empty string.")
-
-            # Extract content chunks using regex with improved error handling
-            patterns_to_try = [
-                r"Score:.*?\nContent:\s*(.*?)(?=\n\nScore:|\Z)",  # Handle double newlines
-                r"Score:.*?\nContent:\s*(.*?)(?=Score:|\Z)",      # Original pattern
-                r"Score:\s*[\d.]+\s*\nContent:\s*(.*?)(?=\n\nScore:|\Z)",  # More specific score pattern
-            ]
-            
-            docs = []
-            pattern_used = None
-            
-            for i, pattern in enumerate(patterns_to_try):
-                try:
-                    docs = [chunk.strip() for chunk in re.findall(pattern, results, re.DOTALL) if chunk.strip()]
-                    if docs:
-                        pattern_used = f"Pattern {i+1}"
-                        logger.debug(f"Successfully extracted {len(docs)} chunks using pattern {i+1}")
-                        break
-                except Exception as e:
-                    logger.warning(f"Pattern {i+1} failed: {e}")
-                    continue
-            
-            # If no patterns worked, try a more flexible approach
-            if not docs:
-                logger.warning("Standard patterns failed, trying flexible extraction...")
-                flexible_pattern = r"Content:\s*([^\n]+(?:\n(?!Score:)[^\n]*)*)"
-                try:
-                    docs = [chunk.strip() for chunk in re.findall(flexible_pattern, results, re.MULTILINE) if chunk.strip()]
-                    if docs:
-                        pattern_used = "Flexible pattern"
-                        logger.info(f"Flexible extraction found {len(docs)} chunks")
-                except Exception as e:
-                    logger.error(f"Flexible extraction also failed: {e}")
-
-            if not docs:
-                # Provide detailed debugging information
-                debug_info = {
-                    "results_length": len(results),
-                    "contains_score": "Score:" in results,
-                    "contains_content": "Content:" in results,
-                    "results_preview": results[:200] if len(results) > 200 else results
-                }
-                logger.error(f"No valid content chunks found. Debug info: {debug_info}")
-                raise ValueError(f"No valid content chunks found in 'results'. Debug: {debug_info}")
-
-            # Limit the number of chunks to avoid timeout
-            if len(docs) > 3:
-                docs = docs[:3]  # Take only first 3 chunks
-                logger.info(f"Limited evaluation to first 3 chunks out of {len(docs)} total")
-
-            # Generate a proper answer from the context for RAGAs evaluation
-            # This is necessary because LLMContextPrecisionWithoutReference evaluates
-            # whether the context was useful in arriving at the given answer
-            try:
-                context_for_answer = "\n\n".join(docs[:2])  # Use first 2 chunks
-                answer_prompt = f"""Based on the following context, provide a brief answer to the question.
-
-Question: {question}
-Context: {context_for_answer}
-
-Answer:"""
-                
-                # Use a simple model call to generate the answer
-                from langchain_aws import ChatBedrockConverse
-                answer_llm = ChatBedrockConverse(model_id='us.anthropic.claude-3-7-sonnet-20250219-v1:0')
-                answer_response = answer_llm.invoke(answer_prompt)
-                generated_answer = answer_response.content.strip()
-                
-                logger.debug(f"Generated answer for RAGAs evaluation: {generated_answer[:100]}...")
-                
-            except Exception as e:
-                logger.warning(f"Failed to generate answer for RAGAs evaluation: {e}")
-                generated_answer = "Unable to generate answer from context"
-
-            # Prepare evaluation sample with proper answer
-            sample = SingleTurnSample(
-                user_input=question,
-                response=generated_answer,  # Use generated answer instead of placeholder
-                retrieved_contexts=docs
-            )
-
-            # Evaluate using context precision metric with safe async handling
-            scorer = LLMContextPrecisionWithoutReference(llm=llm_for_evaluation)
-            
-            print("------------------------")
-            print("Context evaluation (RAGAs)")
-            print("------------------------")
-            print(f"Evaluating {len(docs)} chunks...")
-            
-            # Use the safe evaluation helper
-            score = _run_async_evaluation_safe(scorer, sample)
-
-            print(f"chunk_relevance_score: {score}")
-            print("------------------------")
-
-            return {
-                "chunk_relevance_score": "yes" if score > 0.5 else "no",
-                "chunk_relevance_value": score
-            }
-
-        except Exception as e:
-            logger.error(f"Error in chunk relevance evaluation: {e}")
-            # Provide a fallback based on simple heuristics
-            try:
-                # Simple fallback: check if question keywords appear in results
-                question_words = set(question.lower().split())
-                results_words = set(results.lower().split())
-                overlap = len(question_words.intersection(results_words))
-                fallback_score = min(overlap / len(question_words), 1.0) if question_words else 0.0
-                
-                logger.info(f"Using fallback relevance score: {fallback_score}")
-                
-                return {
-                    "chunk_relevance_score": "yes" if fallback_score > 0.3 else "no",
-                    "chunk_relevance_value": fallback_score,
-                    "evaluation_method": "fallback_heuristic",
-                    "note": f"RAGAs evaluation failed, using keyword overlap heuristic"
-                }
-            except Exception as fallback_error:
-                logger.error(f"Fallback evaluation also failed: {fallback_error}")
-                return {
-                    "error": f"Both RAGAs and fallback evaluation failed: {str(e)}",
-                    "chunk_relevance_score": "unknown",
-                    "chunk_relevance_value": None
-                }
-
-@tool
-def search_knowledge_base(query: str, top_k: int = 3) -> str:  
-    """
-    Search the knowledge base for relevant information.
-    
-    Args:
-        query (str): The search query - REQUIRED
-        top_k (int): Number of top results to return (default: 3)
-        
-    Returns:
-        str: JSON string with search results and relevance metadata
-    """
-    if not query or not isinstance(query, str):
-        return '{"error": "Query parameter is required and must be a non-empty string", "results": [], "relevance_score": 0.0}'
-    
-    try:
-        retriever = EmbeddingRetriever()
-        results = retriever.search(query, top_k=top_k)
-        
-        # Calculate relevance score with content validation
-        relevance_score = calculate_relevance_score(results, query)
-        
-        # Remove duplicate results
-        seen_content = set()
-        unique_results = []
-        for result in results:
-            content_hash = hash(result['content'][:100])  # Use first 100 chars as hash
-            if content_hash not in seen_content:
-                seen_content.add(content_hash)
-                unique_results.append(result)
-        
-        # Format results for RAGAs evaluation (with Score: and Content: patterns)
-        formatted_for_evaluation = ""
-        for result in unique_results[:top_k]:
-            formatted_for_evaluation += f"Score: {result.get('score', result.get('_score', 0.0))}\n"
-            formatted_for_evaluation += f"Content: {result['content']}\n\n"
-        
-        # Format results as compact JSON for response
-        formatted_results = []
-        for result in unique_results[:top_k]:  # Ensure we don't exceed top_k after deduplication
-            # Limit content length to reduce tokens
-            content = result['content']
-            if len(content) > 200:  
-                content = content[:200] + "..."
-                
-            formatted_results.append({
-                "source": result['metadata'].get('source', 'Unknown'),
-                "content": content,
-                "score": result.get('score', result.get('_score', 0.0))
-            })
-        
-        # Create response with relevance metadata and validation info
-        response_data = {
-            "results": formatted_results,
-            "relevance_score": relevance_score,
-            "total_results": len(unique_results),
-            "duplicates_removed": len(results) - len(unique_results),
-            "query": query,
-            "validation_note": "Relevance score includes content validation to prevent false positives",
-            "formatted_for_evaluation": formatted_for_evaluation  # Add this for RAGAs evaluation
-        }
-        
-        # Convert to JSON string
-        response = json.dumps(response_data, indent=2)
-        
-        # Log successful search with debug info
-        logger.info(f"Knowledge base search completed: {len(unique_results)} unique results (removed {len(results) - len(unique_results)} duplicates), relevance: {relevance_score:.2f}")
-        
-        # Debug logging for relevance issues
-        if relevance_score < 0.3:
-            logger.debug(f"Low relevance detected for query '{query}': {relevance_score:.2f}")
-            for i, result in enumerate(formatted_results[:2]):  # Log first 2 results for debugging
-                logger.debug(f"Result {i+1}: {result['content'][:50]}... (score: {result['score']:.2f})")
-        
-        return f"<search_results>\n{response}\n</search_results>"
-        
-    except Exception as e:
-        logger.error(f"Error searching knowledge base: {e}")
-        error_response = {
-            "error": f"Error searching knowledge base: {str(e)}",
-            "results": [],
-            "relevance_score": 0.0,
-            "query": query
-        }
-        return json.dumps(error_response)
-
-@tool
-def check_knowledge_status() -> str:
-    """
-    Check the status of the knowledge base.
-    
-    Returns:
-        str: JSON string with knowledge base status
-    """
-    try:
-        retriever = EmbeddingRetriever()
-        count = retriever.get_document_count()
-        
-        # Format as compact JSON to reduce token usage
-        status_data = {
-            "status": "ready" if count > 0 else "empty",
-            "document_count": count,
-            "last_updated": datetime.now().strftime("%Y-%m-%d")
-        }
-        response = json.dumps(status_data)
-        
-        # Log successful status check
-        logger.info(f"Knowledge base status checked: {count} documents")
-        
-        return response
-        
-    except Exception as e:
-        logger.error(f"Error checking knowledge status: {e}")
-        error_msg = f'{{"error": "Failed to check knowledge status: {str(e)}", "status": "error"}}'
-        return error_msg
-
-# Create the supervisor agent with tracing and enhanced tools including MCP tools
-def create_supervisor_agent_with_mcp():
-    """Create supervisor agent with MCP tools integrated using proper context manager"""
-    
-    # Get MCP client
-    mcp_client = get_tavily_mcp_client()
-    
-    if mcp_client:
-        # Use the MCP client context manager as per Strands SDK documentation
-        with mcp_client:
-            # Get the tools from the MCP server
-            mcp_tools = mcp_client.list_tools_sync()
-            logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server")
-            
-            # Combine local tools with MCP tools
-            all_tools = [
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ] + mcp_tools
-            
-            # Create agent within the MCP context
-            return create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=all_tools,
-                system_prompt="""
-You are a RAG system with web search capabilities. Answer questions using retrieved info and real-time web data.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with relevance_score)
-3. Check the relevance_score: if < 0.3 OR for time-sensitive queries (weather, news, "today", "current"): use web_search
-4. If relevance_score >= 0.3 and not time-sensitive: use RAG results
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with relevance_score)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. For weather/news/current events: use web_search directly
-3. For other queries: search knowledge base first, check relevance_score
-4. If relevance_score < 0.3: use web_search for better results
-5. If relevance_score >= 0.3: use RAG results
-6. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-""",
-                session_id="supervisor-session",
-                user_id="system"
-            )
-    else:
-        # Fallback: create agent without MCP tools
-        logger.warning("Creating agent without MCP tools due to client unavailability")
-        return create_traced_agent(
-            Agent,
-            model=get_reasoning_model(),
-            tools=[
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ],
-            system_prompt="""
-You are a RAG system with advanced relevance evaluation. Answer questions using retrieved information from the knowledge base.
-
-ENHANCED WORKFLOW WITH RAG EVALUATION:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with formatted_for_evaluation field)
-3. EVALUATE RELEVANCE: Use check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-   - This returns {"chunk_relevance_score": "yes"/"no", "chunk_relevance_value": float}
-4. DECISION POINT:
-   - If chunk_relevance_score is "yes" (score > 0.5): Use RAG results to answer
-   - If chunk_relevance_score is "no" (score <= 0.5): Inform user that results may not be relevant
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly and mention evaluation results
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with formatted_for_evaluation field)
-- check_chunks_relevance(results, question): Evaluate relevance using RAGAs (use formatted_for_evaluation field)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-ENHANCED DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. SECOND: search_knowledge_base(query) to get results with formatted_for_evaluation
-3. THIRD: check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-4. DECISION:
-   - If chunk_relevance_score is "yes": Use RAG results confidently
-   - If chunk_relevance_score is "no": Mention low relevance and provide best available information
-5. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS evaluate chunk relevance before providing answers
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-- Be transparent about relevance evaluation results
-
-FORMAT: Be concise, cite sources, use bullets when helpful, mention evaluation results
-""",
-            session_id="supervisor-session",
-            user_id="system"
-        )
-
-# Create a wrapper class to handle MCP context properly
-class SupervisorAgentWrapper:
-    """Wrapper to handle MCP client context for supervisor agent"""
-    
-    def __init__(self):
-        self.mcp_client = None
-        self.agent = None
-        self._initialized = False
-    
-    def _ensure_initialized(self):
-        """Ensure the agent is initialized, with lazy loading"""
-        if not self._initialized:
-            try:
-                self.mcp_client = get_tavily_mcp_client()
-                self._create_agent()
-                self._initialized = True
-            except Exception as e:
-                logger.error(f"Failed to initialize supervisor agent: {e}")
-                logger.warning("Creating agent without MCP tools due to initialization failure")
-                self.mcp_client = None
-                self._create_agent_without_mcp()
-                self._initialized = True
-    
-    def _create_agent(self):
-        """Create the agent with proper MCP context"""
-        if self.mcp_client:
-            try:
-                with self.mcp_client:
-                    # Get the tools from the MCP server
-                    mcp_tools = self.mcp_client.list_tools_sync()
-                    logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server")
-                    
-                    # Combine local tools with MCP tools
-                all_tools = [
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ] + mcp_tools
-                
-                # Create agent within the MCP context
-                self.agent = create_traced_agent(
-                    Agent,
-                    model=get_reasoning_model(),
-                    tools=all_tools,
-                    system_prompt="""
-You are a RAG system with web search capabilities. Answer questions using retrieved info and real-time web data.
-
-WORKFLOW:
-1. check_knowledge_status() - verify knowledge base
-2. search_knowledge_base(query="terms") - search internal data
-4. If recommendation is "USE_WEB_SEARCH": use web_search or news_search MCP tools
-5. If recommendation is "USE_RAG_RESULTS": use the RAG results
-6. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, path): Write files
-
-DECISION LOGIC:
-1. Always search knowledge base first
-3. Follow the recommendation (USE_WEB_SEARCH or USE_RAG_RESULTS)
-4. For weather, news, or current events: prefer web search
-5. For established knowledge: prefer RAG results
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                    session_id="supervisor-session",
-                    user_id="system"
-                )
-            except Exception as e:
-                logger.error(f"Failed to create agent with MCP tools: {e}")
-                logger.warning("Creating agent without MCP tools due to MCP failure")
-                self.mcp_client = None  # Disable MCP client for this instance
-                self._create_agent_without_mcp()
-        else:
-            # Fallback: create agent without MCP tools
-            logger.warning("Creating agent without MCP tools due to client unavailability")
-            self.agent = create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=[
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ],
-                system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                session_id="supervisor-session",
-                user_id="system"
-            )
-    
-    def _create_agent_without_mcp(self):
-        """Create agent without MCP tools"""
-        logger.warning("Creating supervisor agent without MCP tools")
-        self.agent = create_traced_agent(
-            Agent,
-            model=get_reasoning_model(),
-            tools=[
-                check_chunks_relevance,
-                search_knowledge_base, 
-                check_knowledge_status, 
-                file_read, 
-                file_write
-            ],
-            system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-            session_id="supervisor-session",
-            user_id="system"
-        )
-    
-    def __call__(self, query: str):
-        """Call the agent with proper MCP context"""
-        self._ensure_initialized()
-        if self.mcp_client:
-            with self.mcp_client:
-                return self.agent(query)
-        else:
-            return self.agent(query)
-
-# Create the default supervisor agent
-supervisor_agent = SupervisorAgentWrapper()
-
-def create_fresh_supervisor_agent():
-    """
-    Create a fresh supervisor agent instance with no conversation history.
-    This ensures each query starts with a clean context window.
-    """
-    import uuid
-    
-    # Create a unique session ID for each fresh agent
-    fresh_session_id = f"supervisor-{uuid.uuid4().hex[:8]}"
-    
-    # Return a fresh wrapper instance
-    class FreshSupervisorAgentWrapper:
-        """Fresh wrapper to handle MCP client context for supervisor agent"""
-        
-        def __init__(self, session_id):
-            self.mcp_client = None
-            self.agent = None
-            self.session_id = session_id
-            self._initialized = False
-        
-        def _ensure_initialized(self):
-            """Ensure the agent is initialized, with lazy loading"""
-            if not self._initialized:
-                try:
-                    self.mcp_client = get_tavily_mcp_client()
-                    self._create_agent()
-                    self._initialized = True
-                except Exception as e:
-                    logger.error(f"Failed to create fresh agent with MCP tools: {e}")
-                    logger.warning("Creating fresh agent without MCP tools due to MCP failure")
-                    self.mcp_client = None
-                    self._create_agent_without_mcp()
-                    self._initialized = True
-        
-        def _create_agent(self):
-            """Create the agent with proper MCP context"""
-            if self.mcp_client:
-                try:
-                    with self.mcp_client:
-                        # Get the tools from the MCP server
-                        mcp_tools = self.mcp_client.list_tools_sync()
-                        logger.info(f"Loaded {len(mcp_tools)} MCP tools from Tavily server for fresh agent")
-                        
-                        # Combine local tools with MCP tools
-                        all_tools = [
-                            check_chunks_relevance,
-                            search_knowledge_base, 
-                            check_knowledge_status, 
-                            file_read, 
-                            file_write
-                        ] + mcp_tools
-                        
-                        # Create agent within the MCP context
-                        self.agent = create_traced_agent(
-                            Agent,
-                            model=get_reasoning_model(),
-                            tools=all_tools,
-                            system_prompt="""
-You are a RAG system with web search capabilities and advanced relevance evaluation. Answer questions using retrieved info and real-time web data.
-
-ENHANCED WORKFLOW WITH RAG EVALUATION:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data (returns JSON with formatted_for_evaluation field)
-3. EVALUATE RELEVANCE: Use check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-   - This returns {"chunk_relevance_score": "yes"/"no", "chunk_relevance_value": float}
-4. DECISION POINT:
-   - If chunk_relevance_score is "yes" (score > 0.5): Use RAG results to answer
-   - If chunk_relevance_score is "no" (score <= 0.5): Use web_search for better results
-   - For time-sensitive queries (weather, news, "today", "current"): Always use web_search
-5. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-6. Cite sources clearly and mention which evaluation method was used
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns JSON with formatted_for_evaluation field)
-- check_chunks_relevance(results, question): Evaluate relevance using RAGAs (use formatted_for_evaluation field)
-- web_search(query, max_results, search_depth, include_answer): MCP tool for web search
-- news_search(query, max_results, days_back): MCP tool for news search
-- health_check(): MCP tool to check Tavily service status
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-ENHANCED DECISION LOGIC:
-1. FIRST: Always call check_knowledge_status()
-2. SECOND: search_knowledge_base(query) to get results with formatted_for_evaluation
-3. THIRD: check_chunks_relevance(results=formatted_for_evaluation, question=original_query)
-4. DECISION:
-   - If chunk_relevance_score is "yes": Use RAG results
-   - If chunk_relevance_score is "no": Use web_search
-   - For weather/news/current events: Skip evaluation, use web_search directly
-5. FINAL: When saving files, use file_write(content, filename) - files go to output directory automatically
-
-FORMAT: Be concise, cite sources, use bullets when helpful, mention evaluation results
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS evaluate chunk relevance before deciding between RAG and web search
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-- Be transparent about which source provided the information and the relevance evaluation results
-""",
-                        session_id=self.session_id,
-                        user_id="system"
-                    )
-                except Exception as e:
-                    logger.error(f"Failed to create fresh agent with MCP tools: {e}")
-                    logger.warning("Creating fresh agent without MCP tools due to MCP failure")
-                    self.mcp_client = None  # Disable MCP client for this instance
-                    self._create_agent_without_mcp()
-            else:
-                self._create_agent_without_mcp()
-        
-        def _create_agent_without_mcp(self):
-            """Create agent without MCP tools"""
-            # Fallback: create agent without MCP tools
-            logger.warning("Creating fresh agent without MCP tools due to client unavailability")
-            self.agent = create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=[
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ],
-                system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                    session_id=self.session_id,
-                    user_id="system"
-                )
-        
-        def _create_agent_without_mcp(self):
-            """Create agent without MCP tools"""
-            logger.warning("Creating fresh agent without MCP tools due to client unavailability")
-            self.agent = create_traced_agent(
-                Agent,
-                model=get_reasoning_model(),
-                tools=[
-                    check_chunks_relevance,
-                    search_knowledge_base, 
-                    check_knowledge_status, 
-                    file_read, 
-                    file_write
-                ],
-                system_prompt="""
-You are a RAG system. Answer questions using retrieved information from the knowledge base.
-
-WORKFLOW:
-1. ALWAYS start with check_knowledge_status() - verify knowledge base first
-2. search_knowledge_base(query="terms") - search internal data
-3. Use the retrieved information to answer questions
-4. When writing files, ALWAYS use the output directory - call file_write with filename parameter only
-5. Cite sources clearly
-
-TOOLS AVAILABLE:
-- check_knowledge_status(): Check KB status - ALWAYS CALL THIS FIRST
-- search_knowledge_base(query): Search KB (returns relevance_score)
-- file_read(path): Read files
-- file_write(content, filename): Write files to output directory (use filename parameter, not path)
-
-IMPORTANT: 
-- ALWAYS start with check_knowledge_status()
-- ALWAYS use filename parameter (not path) for file_write to save to output directory
-
-FORMAT: Be concise, cite sources, use bullets when helpful
-""",
-                session_id=self.session_id,
-                user_id="system"
-            )
-        
-        def __call__(self, query: str):
-            """Call the agent with proper MCP context"""
-            self._ensure_initialized()
-            if self.mcp_client:
-                with self.mcp_client:
-                    return self.agent(query)
-            else:
-                return self.agent(query)
-    
-    return FreshSupervisorAgentWrapper(fresh_session_id)
-
-# The supervisor_agent now has built-in tracing via Strands SDK and proper MCP integration
-# Export the agent and the fresh agent creator
-__all__ = ["supervisor_agent", "create_fresh_supervisor_agent"]
\ No newline at end of file
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/config.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/config.py
deleted file mode 100644
index e9e5ab0e..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/config.py
+++ /dev/null
@@ -1,68 +0,0 @@
-"""Configuration management for the multi-agent RAG system."""
-
-import os
-from typing import Optional
-from dotenv import load_dotenv
-
-# Load environment variables
-load_dotenv()
-
-class Config:
-    """Configuration class for the application."""
-    
-    # LiteLLM Configuration for Reasoning Models
-    LITELLM_API_KEY: str = os.getenv("LITELLM_API_KEY", os.getenv("OPENAI_API_KEY", ""))
-    LITELLM_BASE_URL: str = os.getenv("LITELLM_BASE_URL", os.getenv("OPENAI_BASE_URL", "https://api.openai.com/v1"))
-    REASONING_MODEL: str = os.getenv("REASONING_MODEL", "qwen-qwq-32b-preview")
-    
-    # Embedding Configuration (separate from reasoning)
-    EMBEDDING_API_KEY: str = os.getenv("EMBEDDING_API_KEY", os.getenv("OPENAI_API_KEY", ""))
-    EMBEDDING_BASE_URL: str = os.getenv("EMBEDDING_BASE_URL", os.getenv("OPENAI_BASE_URL", "https://api.openai.com/v1"))
-    EMBEDDING_MODEL: str = os.getenv("EMBEDDING_MODEL", "llamacpp-embedding")
-    
-    # Legacy OpenAI Configuration (for backward compatibility)
-    OPENAI_API_KEY: str = os.getenv("OPENAI_API_KEY", "")
-    OPENAI_BASE_URL: str = os.getenv("OPENAI_BASE_URL", "https://api.openai.com/v1")
-    DEFAULT_MODEL: str = os.getenv("DEFAULT_MODEL", os.getenv("REASONING_MODEL", "qwen-qwq-32b-preview"))
-    
-    # AWS Configuration
-    AWS_REGION: str = os.getenv("AWS_REGION", "us-east-1")
-    OPENSEARCH_ENDPOINT: str = os.getenv("OPENSEARCH_ENDPOINT", "")
-    
-    # Tavily MCP Configuration
-    TAVILY_MCP_SERVICE_URL: str = os.getenv("TAVILY_MCP_SERVICE_URL", "http://localhost:8001/mcp")
-    
-    # Langfuse Configuration
-    LANGFUSE_HOST: str = os.getenv("LANGFUSE_HOST", "")
-    LANGFUSE_PUBLIC_KEY: str = os.getenv("LANGFUSE_PUBLIC_KEY", "")
-    LANGFUSE_SECRET_KEY: str = os.getenv("LANGFUSE_SECRET_KEY", "")
-    
-    # Application Configuration
-    KNOWLEDGE_DIR: str = os.getenv("KNOWLEDGE_DIR", "knowledge")
-    OUTPUT_DIR: str = os.getenv("OUTPUT_DIR", "output")
-    EMBEDDING_ENDPOINT: str = os.getenv("EMBEDDING_ENDPOINT", "")
-    
-    # Vector Search Configuration
-    VECTOR_INDEX_NAME: str = os.getenv("VECTOR_INDEX_NAME", "knowledge-embeddings")
-    TOP_K_RESULTS: int = int(os.getenv("TOP_K_RESULTS", "5"))
-    
-    @classmethod
-    def is_langfuse_enabled(cls) -> bool:
-        """Check if Langfuse is properly configured."""
-        return bool(cls.LANGFUSE_HOST and cls.LANGFUSE_PUBLIC_KEY and cls.LANGFUSE_SECRET_KEY)
-    
-    @classmethod
-    def validate_config(cls) -> None:
-        """Validate required configuration."""
-        required_vars = [
-            ("LITELLM_API_KEY", cls.LITELLM_API_KEY),
-            ("OPENSEARCH_ENDPOINT", cls.OPENSEARCH_ENDPOINT),
-        ]
-        
-        missing_vars = [name for name, value in required_vars if not value]
-        
-        if missing_vars:
-            raise ValueError(f"Missing required environment variables: {', '.join(missing_vars)}")
-
-# Global config instance
-config = Config()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/main.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/main.py
deleted file mode 100644
index d6236395..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/main.py
+++ /dev/null
@@ -1,163 +0,0 @@
-#!/usr/bin/env python3
-"""
-Multi-Agent RAG System with MCP and OpenSearch using Strands SDK
-
-A sophisticated multi-agent system that combines:
-- Knowledge management with change detection
-- RAG (Retrieval Augmented Generation) with OpenSearch
-- MCP (Model Context Protocol) tool integration
-- Strands SDK agent orchestration
-- Langfuse observability integration
-"""
-
-# Import global async cleanup FIRST to suppress warnings
-from .utils.global_async_cleanup import setup_global_async_cleanup
-
-import sys
-import logging
-from typing import Optional
-from .config import config
-from .utils.logging import setup_logging, log_title
-from .agents.supervisor_agent import supervisor_agent
-from .agents.knowledge_agent import knowledge_agent
-from .agents.mcp_agent import mcp_agent
-
-def main():
-    """Main application entry point."""
-    # Setup logging
-    setup_logging()
-    logger = logging.getLogger(__name__)
-    
-    try:
-        # Validate configuration
-        config.validate_config()
-        
-        log_title("MULTI-AGENT RAG SYSTEM STARTUP")
-        logger.info("Starting Multi-Agent RAG System with Strands SDK")
-        logger.info(f"OpenSearch Endpoint: {config.OPENSEARCH_ENDPOINT}")
-        logger.info(f"Knowledge Directory: {config.KNOWLEDGE_DIR}")
-        logger.info(f"Reasoning Model: {config.REASONING_MODEL}")
-        logger.info(f"Embedding Model: {config.EMBEDDING_MODEL}")
-        logger.info(f"LiteLLM Endpoint: {config.LITELLM_BASE_URL}")
-        logger.info(f"Langfuse Enabled: {config.is_langfuse_enabled()}")
-        
-        # Interactive mode
-        run_interactive_mode()
-        
-    except KeyboardInterrupt:
-        print("\n\nExiting gracefully...")
-        sys.exit(0)
-    except Exception as e:
-        logger.error(f"Application startup failed: {e}")
-        sys.exit(1)
-
-def run_interactive_mode():
-    """Run the application in interactive mode."""
-    logger = logging.getLogger(__name__)  # Add logger definition
-    
-    log_title("INTERACTIVE MODE")
-    print("🤖 Multi-Agent RAG System Ready!")
-    print("Ask questions and I'll use my specialized agents to help you.")
-    print("Type 'exit', 'quit', or press Ctrl+C to exit.\n")
-    
-    while True:
-        try:
-            # Get user input
-            user_input = input("❓ Your question: ").strip()
-            
-            # Check for exit commands
-            if user_input.lower() in ['exit', 'quit', 'bye']:
-                print("\n👋 Goodbye!")
-                break
-            
-            if not user_input:
-                print("Please enter a question or type 'exit' to quit.")
-                continue
-            
-            # Process the query using the supervisor agent
-            print("\n🔄 Processing your request...")
-            
-            try:
-                # Limit query length to avoid context window issues
-                if len(user_input) > 500:
-                    print("⚠️ Query is too long, truncating to 500 characters...")
-                    user_input = user_input[:500]
-                
-                # Add debug logging
-                logger.info(f"Starting agent processing for query: {user_input[:50]}...")
-                
-                # Create a fresh agent instance for each query to avoid context accumulation
-                from .agents.supervisor_agent import create_fresh_supervisor_agent
-                fresh_agent = create_fresh_supervisor_agent()
-                
-                # Use the fresh agent instance (no conversation history)
-                response = fresh_agent(user_input)
-                
-                logger.info("Agent processing completed")
-                
-                # Ensure response is fully processed before displaying
-                if response is None:
-                    response = "No response received from agent."
-                
-                response_str = str(response).strip()
-                if not response_str:
-                    response_str = "Agent completed processing but returned empty response."
-                
-                print(f"\n🤖 Response:\n{response_str}")
-                
-                # Add a small delay to ensure all background processes complete
-                import time
-                time.sleep(0.5)
-                
-                logger.info("Response display completed, ready for next input")
-                
-            except KeyboardInterrupt:
-                print("\n⚠️ Processing interrupted by user.")
-                break
-            except Exception as e:
-                print(f"\n❌ Error: {e}")
-                logger.error(f"Error processing query: {e}")
-            
-            print("\n" + "="*60 + "\n")
-            
-        except KeyboardInterrupt:
-            print("\n\nExiting...")
-            break
-        except EOFError:
-            print("\n\nInput stream closed. Exiting...")
-            break
-        except Exception as e:
-            print(f"\n❌ An error occurred: {e}")
-            print("Please try again with a different question.\n")
-            logger.error(f"Unexpected error in interactive mode: {e}")
-
-def run_single_query(query: str) -> Optional[str]:
-    """Run a single query and return the result."""
-    try:
-        config.validate_config()
-        
-        # Limit query length to avoid context window issues
-        if len(query) > 500:
-            logging.warning("Query too long, truncating to 500 characters")
-            query = query[:500]
-        
-        # Create a fresh agent instance for this single query
-        from .agents.supervisor_agent import create_fresh_supervisor_agent
-        fresh_agent = create_fresh_supervisor_agent()
-        
-        # Use the fresh agent (no conversation history)
-        response = fresh_agent(query)
-            
-        # Limit response length if needed
-        response_str = str(response)
-        if len(response_str) > 4000:
-            logging.warning("Response too long, truncating to 4000 characters")
-            response_str = response_str[:4000] + "... [Response truncated due to length]"
-            
-        return response_str
-    except Exception as e:
-        logging.error(f"Single query execution failed: {e}")
-        return f"Error processing query: {str(e)}"
-
-if __name__ == "__main__":
-    main()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_server_standalone.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_server_standalone.py
deleted file mode 100644
index 6ed8a237..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_server_standalone.py
+++ /dev/null
@@ -1,126 +0,0 @@
-#!/usr/bin/env python3
-"""
-Standalone Tavily MCP Server for Kubernetes deployment.
-This runs as a separate service that the main application connects to.
-"""
-
-import sys
-import os
-import warnings
-import logging
-from dotenv import load_dotenv
-
-# Add current directory to path
-sys.path.insert(0, os.path.dirname(os.path.dirname(os.path.abspath(__file__))))
-
-class CompleteAsyncErrorFilter:
-    """Complete async error filter that suppresses all async-related output."""
-    
-    def __init__(self):
-        self.original_stderr = sys.__stderr__
-        
-    def write(self, text):
-        """Filter out all async RuntimeErrors and related output."""
-        if not text.strip():
-            return
-            
-        # Comprehensive list of patterns to suppress
-        suppress_patterns = [
-            "RuntimeError",
-            "httpcore",
-            "_synchronization",
-            "asyncio",
-            "anyio",
-            "sniffio",
-            "await",
-            "async",
-            "CancelScope",
-            "shield",
-            "current_task",
-            "get_running_loop",
-            "cancel_shielded_checkpoint",
-            "_anyio_lock",
-            "acquire",
-            "raise RuntimeError",
-        ]
-        
-        # Check if this line should be suppressed
-        should_suppress = any(pattern in text for pattern in suppress_patterns)
-        
-        # Also suppress lines that are just punctuation or whitespace
-        if text.strip() in [":", "RuntimeError:", "RuntimeError: ", "RuntimeError", ""]:
-            should_suppress = True
-        
-        # Only write if not suppressed and contains meaningful content
-        if not should_suppress and len(text.strip()) > 1:
-            self.original_stderr.write(text)
-            self.original_stderr.flush()
-        
-    def flush(self):
-        """Flush the original stderr."""
-        self.original_stderr.flush()
-
-def setup_complete_clean_environment():
-    """Set up completely clean environment."""
-    
-    # Suppress all warnings
-    warnings.filterwarnings("ignore")
-    
-    # Install complete error filter
-    sys.stderr = CompleteAsyncErrorFilter()
-    
-    # Try to import and use existing cleanup if available
-    try:
-        from src.utils.global_async_cleanup import setup_global_async_cleanup
-        setup_global_async_cleanup()
-    except ImportError:
-        pass
-
-def main():
-    """Main entry point for standalone MCP server."""
-    print("🚀 Starting Standalone Tavily MCP Server (Clean Mode)")
-    print("=" * 60)
-    print("Note: All async errors and warnings are suppressed")
-    print("=" * 60)
-    
-    # Set up clean environment FIRST
-    setup_complete_clean_environment()
-    
-    # Load environment variables from ConfigMap or local .env file
-    if os.path.exists("/app/config/.env"):
-        print("Loading environment variables from ConfigMap .env file...")
-        load_dotenv("/app/config/.env")
-        print("Environment variables loaded successfully from ConfigMap")
-    elif os.path.exists("/app/.env"):
-        print("Loading environment variables from local .env file...")
-        load_dotenv("/app/.env")
-        print("Environment variables loaded successfully from local file")
-    else:
-        print("WARNING: No .env file found. Using environment variables from Kubernetes.")
-    
-    # Verify Tavily API key
-    tavily_api_key = os.getenv("TAVILY_API_KEY")
-    if not tavily_api_key:
-        print("ERROR: TAVILY_API_KEY is not set")
-        sys.exit(1)
-    
-    print("Tavily API key verified")
-    
-    try:
-        # Import and run the Tavily MCP server
-        from src.mcp_servers.tavily_search_server import mcp
-        print("Starting Tavily MCP Server on port 8001...")
-        mcp.run(transport="streamable-http", port=8001)
-    except KeyboardInterrupt:
-        print("\n👋 Tavily MCP Server stopped by user")
-    except Exception as e:
-        # Filter out async-related errors
-        error_msg = str(e)
-        if not any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            print(f"❌ Tavily MCP Server error: {e}")
-        sys.exit(1)
-
-if __name__ == "__main__":
-    main()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_servers/mcp_filesystem_server.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_servers/mcp_filesystem_server.py
deleted file mode 100644
index 27da4c98..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_servers/mcp_filesystem_server.py
+++ /dev/null
@@ -1,192 +0,0 @@
-#!/usr/bin/env python3
-"""
-Simple MCP Filesystem Server
-
-This server provides basic filesystem operations through the Model Context Protocol.
-It demonstrates how to create MCP tools that can be used by the Strands agents.
-"""
-
-import os
-import json
-from pathlib import Path
-from typing import Any, Dict
-from mcp.server import FastMCP
-
-# Create MCP server
-mcp = FastMCP("Filesystem Server")
-
-@mcp.tool(description="Read the contents of a file")
-def read_file(file_path: str) -> str:
-    """Read and return the contents of a file.
-    
-    Args:
-        file_path: Path to the file to read
-        
-    Returns:
-        The contents of the file as a string
-    """
-    try:
-        path = Path(file_path)
-        if not path.exists():
-            return f"Error: File {file_path} does not exist"
-        
-        if not path.is_file():
-            return f"Error: {file_path} is not a file"
-        
-        with open(path, 'r', encoding='utf-8') as f:
-            content = f.read()
-        
-        return content
-    except Exception as e:
-        return f"Error reading file {file_path}: {str(e)}"
-
-@mcp.tool(description="Write content to a file")
-def write_file(file_path: str, content: str, append: bool = False) -> str:
-    """Write content to a file.
-    
-    Args:
-        file_path: Path to the file to write
-        content: Content to write to the file
-        append: Whether to append to the file (default: False, overwrites)
-        
-    Returns:
-        Success or error message
-    """
-    try:
-        path = Path(file_path)
-        
-        # Create parent directories if they don't exist
-        path.parent.mkdir(parents=True, exist_ok=True)
-        
-        mode = 'a' if append else 'w'
-        with open(path, mode, encoding='utf-8') as f:
-            f.write(content)
-        
-        action = "appended to" if append else "written to"
-        return f"Successfully {action} {file_path}"
-    except Exception as e:
-        return f"Error writing to file {file_path}: {str(e)}"
-
-@mcp.tool(description="List files and directories in a path")
-def list_directory(dir_path: str = ".") -> str:
-    """List the contents of a directory.
-    
-    Args:
-        dir_path: Path to the directory to list (default: current directory)
-        
-    Returns:
-        A formatted list of directory contents
-    """
-    try:
-        path = Path(dir_path)
-        if not path.exists():
-            return f"Error: Directory {dir_path} does not exist"
-        
-        if not path.is_dir():
-            return f"Error: {dir_path} is not a directory"
-        
-        items = []
-        for item in sorted(path.iterdir()):
-            if item.is_dir():
-                items.append(f"📁 {item.name}/")
-            else:
-                size = item.stat().st_size
-                items.append(f"📄 {item.name} ({size} bytes)")
-        
-        if not items:
-            return f"Directory {dir_path} is empty"
-        
-        return f"Contents of {dir_path}:\n" + "\n".join(items)
-    except Exception as e:
-        return f"Error listing directory {dir_path}: {str(e)}"
-
-@mcp.tool(description="Create a new directory")
-def create_directory(dir_path: str) -> str:
-    """Create a new directory.
-    
-    Args:
-        dir_path: Path to the directory to create
-        
-    Returns:
-        Success or error message
-    """
-    try:
-        path = Path(dir_path)
-        path.mkdir(parents=True, exist_ok=True)
-        return f"Successfully created directory {dir_path}"
-    except Exception as e:
-        return f"Error creating directory {dir_path}: {str(e)}"
-
-@mcp.tool(description="Delete a file or directory")
-def delete_path(path_to_delete: str) -> str:
-    """Delete a file or directory.
-    
-    Args:
-        path_to_delete: Path to the file or directory to delete
-        
-    Returns:
-        Success or error message
-    """
-    try:
-        path = Path(path_to_delete)
-        if not path.exists():
-            return f"Error: Path {path_to_delete} does not exist"
-        
-        if path.is_file():
-            path.unlink()
-            return f"Successfully deleted file {path_to_delete}"
-        elif path.is_dir():
-            # Only delete empty directories for safety
-            try:
-                path.rmdir()
-                return f"Successfully deleted directory {path_to_delete}"
-            except OSError:
-                return f"Error: Directory {path_to_delete} is not empty. Only empty directories can be deleted."
-        else:
-            return f"Error: {path_to_delete} is neither a file nor a directory"
-    except Exception as e:
-        return f"Error deleting {path_to_delete}: {str(e)}"
-
-@mcp.tool(description="Get file or directory information")
-def get_path_info(path_to_check: str) -> str:
-    """Get information about a file or directory.
-    
-    Args:
-        path_to_check: Path to check
-        
-    Returns:
-        Information about the path
-    """
-    try:
-        path = Path(path_to_check)
-        if not path.exists():
-            return f"Path {path_to_check} does not exist"
-        
-        stat = path.stat()
-        info = {
-            "path": str(path.absolute()),
-            "name": path.name,
-            "type": "directory" if path.is_dir() else "file",
-            "size": stat.st_size if path.is_file() else "N/A",
-            "modified": stat.st_mtime,
-            "permissions": oct(stat.st_mode)[-3:]
-        }
-        
-        return json.dumps(info, indent=2)
-    except Exception as e:
-        return f"Error getting info for {path_to_check}: {str(e)}"
-
-if __name__ == "__main__":
-    print("Starting MCP Filesystem Server on http://localhost:8001")
-    print("Available tools:")
-    print("- read_file: Read file contents")
-    print("- write_file: Write content to file")
-    print("- list_directory: List directory contents")
-    print("- create_directory: Create new directory")
-    print("- delete_path: Delete file or empty directory")
-    print("- get_path_info: Get file/directory information")
-    print("\nPress Ctrl+C to stop the server")
-    
-    mcp = FastMCP("my mcp", port=8001)
-    # Run the server with Streamable HTTP transport
-    mcp.run(transport="streamable-http")
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_servers/tavily_search_server.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_servers/tavily_search_server.py
deleted file mode 100644
index 4eae0c6a..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/mcp_servers/tavily_search_server.py
+++ /dev/null
@@ -1,307 +0,0 @@
-#!/usr/bin/env python3
-"""
-Tavily Web Search MCP Server
-
-This MCP server provides web search capabilities using the Tavily API.
-It's designed to be called when RAG retrieval relevance is low.
-"""
-
-import os
-import json
-import time
-import asyncio
-from typing import Dict, List, Any, Optional
-from pathlib import Path
-from fastmcp import FastMCP
-import httpx
-from pydantic import BaseModel
-from dotenv import load_dotenv
-
-# Load environment variables from .env file
-project_root = Path(__file__).parent.parent.parent
-env_file = project_root / ".env"
-if env_file.exists():
-    load_dotenv(env_file)
-    print(f"✅ Loaded environment variables from {env_file}")
-else:
-    print(f"⚠️  No .env file found at {env_file}")
-
-class TavilySearchResult(BaseModel):
-    """Model for Tavily search results"""
-    title: str
-    url: str
-    content: str
-    score: float
-    published_date: Optional[str] = None
-
-class TavilySearchResponse(BaseModel):
-    """Model for complete Tavily response"""
-    query: str
-    results: List[TavilySearchResult]
-    answer: Optional[str] = None
-    follow_up_questions: Optional[List[str]] = None
-
-# Initialize FastMCP server
-mcp = FastMCP("Tavily Web Search Server")
-
-class TavilyClient:
-    """Client for interacting with Tavily API"""
-    
-    def __init__(self, api_key: str):
-        self.api_key = api_key
-        self.base_url = "https://api.tavily.com"
-        
-    async def search(
-        self, 
-        query: str, 
-        search_depth: str = "basic",
-        max_results: int = 5,
-        include_answer: bool = True,
-        include_raw_content: bool = False,
-        include_domains: Optional[List[str]] = None,
-        exclude_domains: Optional[List[str]] = None
-    ) -> TavilySearchResponse:
-        """
-        Perform web search using Tavily API
-        
-        Args:
-            query: Search query
-            search_depth: "basic" or "advanced"
-            max_results: Maximum number of results (1-20)
-            include_answer: Whether to include AI-generated answer
-            include_raw_content: Whether to include raw HTML content
-            include_domains: List of domains to include
-            exclude_domains: List of domains to exclude
-            
-        Returns:
-            TavilySearchResponse with search results
-        """
-        
-        payload = {
-            "api_key": self.api_key,
-            "query": query,
-            "search_depth": search_depth,
-            "max_results": min(max_results, 20),
-            "include_answer": include_answer,
-            "include_raw_content": include_raw_content,
-        }
-        
-        if include_domains:
-            payload["include_domains"] = include_domains
-        if exclude_domains:
-            payload["exclude_domains"] = exclude_domains
-            
-        async with httpx.AsyncClient(timeout=30.0) as client:
-            try:
-                response = await client.post(
-                    f"{self.base_url}/search",
-                    json=payload,
-                    headers={"Content-Type": "application/json"}
-                )
-                response.raise_for_status()
-                
-                data = response.json()
-                
-                # Parse results
-                results = []
-                for result in data.get("results", []):
-                    results.append(TavilySearchResult(
-                        title=result.get("title", ""),
-                        url=result.get("url", ""),
-                        content=result.get("content", ""),
-                        score=result.get("score", 0.0),
-                        published_date=result.get("published_date")
-                    ))
-                
-                return TavilySearchResponse(
-                    query=query,
-                    results=results,
-                    answer=data.get("answer"),
-                    follow_up_questions=data.get("follow_up_questions", [])
-                )
-                
-            except httpx.HTTPStatusError as e:
-                raise Exception(f"Tavily API error: {e.response.status_code} - {e.response.text}")
-            except Exception as e:
-                raise Exception(f"Search failed: {str(e)}")
-
-# Initialize Tavily client
-tavily_client = None
-
-def get_tavily_client() -> TavilyClient:
-    """Get or create Tavily client"""
-    global tavily_client
-    if tavily_client is None:
-        api_key = os.getenv("TAVILY_API_KEY")
-        if not api_key:
-            raise ValueError("TAVILY_API_KEY environment variable is required")
-        tavily_client = TavilyClient(api_key)
-    return tavily_client
-
-@mcp.tool(description="Search the web for real-time information using Tavily API")
-async def web_search(
-    query: str,
-    max_results: int = 5,
-    search_depth: str = "basic",
-    include_answer: bool = True
-) -> str:
-    """
-    Search the web for real-time information when RAG retrieval relevance is low.
-    
-    Args:
-        query: The search query
-        max_results: Maximum number of results to return (1-10)
-        search_depth: Search depth - "basic" or "advanced"
-        include_answer: Whether to include AI-generated answer summary
-        
-    Returns:
-        JSON string containing search results and answer
-    """
-    try:
-        client = get_tavily_client()
-        
-        # Perform search
-        response = await client.search(
-            query=query,
-            max_results=min(max_results, 10),
-            search_depth=search_depth,
-            include_answer=include_answer
-        )
-        
-        # Format response for the agent
-        formatted_response = {
-            "query": response.query,
-            "answer": response.answer,
-            "results": [
-                {
-                    "title": result.title,
-                    "url": result.url,
-                    "content": result.content[:500] + "..." if len(result.content) > 500 else result.content,
-                    "score": result.score,
-                    "published_date": result.published_date
-                }
-                for result in response.results
-            ],
-            "follow_up_questions": response.follow_up_questions or []
-        }
-        
-        return json.dumps(formatted_response, indent=2)
-        
-    except Exception as e:
-        error_response = {
-            "error": f"Web search failed: {str(e)}",
-            "query": query,
-            "results": [],
-            "answer": None
-        }
-        return json.dumps(error_response, indent=2)
-
-@mcp.tool(description="Search for recent news and current events")
-async def news_search(
-    query: str,
-    max_results: int = 5,
-    days_back: int = 7
-) -> str:
-    """
-    Search for recent news and current events.
-    
-    Args:
-        query: The news search query
-        max_results: Maximum number of results to return
-        days_back: How many days back to search for news
-        
-    Returns:
-        JSON string containing recent news results
-    """
-    try:
-        client = get_tavily_client()
-        
-        # Add time constraint to query for recent news
-        time_constrained_query = f"{query} recent news last {days_back} days"
-        
-        response = await client.search(
-            query=time_constrained_query,
-            max_results=min(max_results, 10),
-            search_depth="basic",
-            include_answer=True
-        )
-        
-        # Filter for more recent results and news sources
-        news_domains = ["reuters.com", "bbc.com", "cnn.com", "ap.org", "npr.org", "bloomberg.com"]
-        
-        formatted_response = {
-            "query": response.query,
-            "answer": response.answer,
-            "news_results": [
-                {
-                    "title": result.title,
-                    "url": result.url,
-                    "content": result.content[:400] + "..." if len(result.content) > 400 else result.content,
-                    "score": result.score,
-                    "published_date": result.published_date,
-                    "is_news_source": any(domain in result.url for domain in news_domains)
-                }
-                for result in response.results
-            ],
-            "follow_up_questions": response.follow_up_questions or []
-        }
-        
-        return json.dumps(formatted_response, indent=2)
-        
-    except Exception as e:
-        error_response = {
-            "error": f"News search failed: {str(e)}",
-            "query": query,
-            "news_results": [],
-            "answer": None
-        }
-        return json.dumps(error_response, indent=2)
-
-@mcp.tool(description="Get health check status of the Tavily search service")
-async def health_check() -> str:
-    """
-    Check if the Tavily API service is available and working.
-    
-    Returns:
-        JSON string with health status
-    """
-    try:
-        client = get_tavily_client()
-        
-        # Perform a simple test search
-        response = await client.search(
-            query="test",
-            max_results=1,
-            include_answer=False
-        )
-        
-        status = {
-            "status": "healthy",
-            "service": "Tavily Web Search",
-            "api_accessible": True,
-            "test_query_successful": len(response.results) > 0,
-            "timestamp": time.time()
-        }
-        
-        return json.dumps(status, indent=2)
-        
-    except Exception as e:
-        status = {
-            "status": "unhealthy",
-            "service": "Tavily Web Search",
-            "api_accessible": False,
-            "error": str(e),
-            "timestamp": time.time()
-        }
-        return json.dumps(status, indent=2)
-
-if __name__ == "__main__":
-    # Run the MCP server
-    print("Starting Tavily Web Search MCP Server...")
-    print("Available tools:")
-    print("- web_search: General web search with AI-generated answers")
-    print("- news_search: Recent news and current events search")
-    print("- health_check: Service health status")
-    print("\nMCP server will be available at http://localhost:8001/mcp")
-    
-    mcp.run(transport="streamable-http", port=8001)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/scripts/__init__.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/scripts/__init__.py
deleted file mode 100644
index e69de29b..00000000
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/scripts/embed_knowledge.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/scripts/embed_knowledge.py
deleted file mode 100644
index b4f91bb3..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/scripts/embed_knowledge.py
+++ /dev/null
@@ -1,86 +0,0 @@
-#!/usr/bin/env python3
-"""
-Knowledge Embedding Script
-
-This script processes all documents in the knowledge directory and creates
-embeddings for them in the OpenSearch vector store.
-"""
-
-import sys
-import logging
-from pathlib import Path
-from ..config import config
-from ..utils.logging import setup_logging, log_title
-from ..agents.knowledge_agent import knowledge_agent
-
-def main():
-    """Main function for embedding knowledge."""
-    # Setup logging
-    setup_logging()
-    logger = logging.getLogger(__name__)
-    
-    try:
-        # Validate configuration
-        config.validate_config()
-        
-        log_title("KNOWLEDGE EMBEDDING SCRIPT")
-        logger.info("Starting knowledge embedding process")
-        logger.info(f"Knowledge Directory: {config.KNOWLEDGE_DIR}")
-        logger.info(f"OpenSearch Endpoint: {config.OPENSEARCH_ENDPOINT}")
-        logger.info(f"Vector Index: {config.VECTOR_INDEX_NAME}")
-        
-        # Check if knowledge directory exists
-        knowledge_path = Path(config.KNOWLEDGE_DIR)
-        if not knowledge_path.exists():
-            logger.error(f"Knowledge directory does not exist: {config.KNOWLEDGE_DIR}")
-            sys.exit(1)
-        
-        # Get knowledge statistics before embedding
-        print("\n📊 Getting knowledge statistics...")
-        stats_result = knowledge_agent("get_stats")
-        if stats_result.get("success"):
-            stats = stats_result.get("stats", {})
-            print(f"Total files: {stats.get('total_files', 0)}")
-            print(f"File types: {stats.get('file_types', {})}")
-            print(f"Current vector store count: {stats.get('vector_store_count', 0)}")
-        
-        # Check for changes
-        print("\n🔍 Checking for knowledge changes...")
-        check_result = knowledge_agent("check_changes")
-        
-        if not check_result.get("success"):
-            logger.error(f"Failed to check for changes: {check_result.get('message')}")
-            sys.exit(1)
-        
-        has_changes = check_result.get("has_changes", False)
-        print(f"Changes detected: {has_changes}")
-        
-        # Embed knowledge (force embedding regardless of changes)
-        print("\n🚀 Starting knowledge embedding...")
-        embed_result = knowledge_agent("embed_knowledge")
-        
-        if embed_result.get("success"):
-            print("✅ Knowledge embedding completed successfully!")
-            
-            # Get updated statistics
-            print("\n📊 Updated knowledge statistics...")
-            updated_stats_result = knowledge_agent("get_stats")
-            if updated_stats_result.get("success"):
-                updated_stats = updated_stats_result.get("stats", {})
-                print(f"Vector store count after embedding: {updated_stats.get('vector_store_count', 0)}")
-        else:
-            print(f"❌ Knowledge embedding failed: {embed_result.get('message')}")
-            sys.exit(1)
-        
-        print("\n🎉 Knowledge embedding process completed!")
-        
-    except KeyboardInterrupt:
-        print("\n\nProcess interrupted by user.")
-        sys.exit(0)
-    except Exception as e:
-        logger.error(f"Knowledge embedding failed: {e}")
-        print(f"❌ Error: {e}")
-        sys.exit(1)
-
-if __name__ == "__main__":
-    main()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/server.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/server.py
deleted file mode 100644
index 6a498e14..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/server.py
+++ /dev/null
@@ -1,471 +0,0 @@
-#!/usr/bin/env python3
-"""
-FastAPI Server for Multi-Agent RAG System with MCP and OpenSearch using Strands SDK
-
-A REST API server that provides HTTP endpoints for the multi-agent system.
-Uses clean execution pattern to suppress async warnings.
-"""
-
-import sys
-import os
-import warnings
-import logging
-import asyncio
-from typing import Optional, Dict, Any
-from contextlib import asynccontextmanager
-
-# Add current directory to path
-sys.path.insert(0, os.path.dirname(os.path.dirname(os.path.abspath(__file__))))
-
-class CompleteAsyncErrorFilter:
-    """Complete async error filter that suppresses all async-related output."""
-    
-    def __init__(self):
-        self.original_stderr = sys.__stderr__
-        
-    def write(self, text):
-        """Filter out all async RuntimeErrors and related output."""
-        if not text.strip():
-            return
-            
-        # Comprehensive list of patterns to suppress
-        suppress_patterns = [
-            "RuntimeError",
-            "httpcore",
-            "_synchronization",
-            "asyncio",
-            "anyio",
-            "sniffio",
-            "await",
-            "async",
-            "CancelScope",
-            "shield",
-            "current_task",
-            "get_running_loop",
-            "cancel_shielded_checkpoint",
-            "_anyio_lock",
-            "acquire",
-            "File \"/home/ubuntu/Cost_Effective_and_Scalable_Models_Inference_on_AWS_Graviton/agentic-apps/strandsdk_agentic_rag_opensearch/venv/lib/python3.10/site-packages/httpcore",
-            "File \"/usr/lib/python3.10/asyncio",
-            "raise RuntimeError",
-        ]
-        
-        # Check if this line should be suppressed
-        should_suppress = any(pattern in text for pattern in suppress_patterns)
-        
-        # Also suppress lines that are just punctuation or whitespace
-        if text.strip() in [":", "RuntimeError:", "RuntimeError: ", "RuntimeError", ""]:
-            should_suppress = True
-        
-        # Only write if not suppressed and contains meaningful content
-        if not should_suppress and len(text.strip()) > 1:
-            self.original_stderr.write(text)
-            self.original_stderr.flush()
-        
-    def flush(self):
-        """Flush the original stderr."""
-        self.original_stderr.flush()
-
-def setup_complete_clean_environment():
-    """Set up completely clean environment."""
-    
-    # Suppress all warnings
-    warnings.filterwarnings("ignore")
-    
-    # Install complete error filter
-    sys.stderr = CompleteAsyncErrorFilter()
-    
-    # Try to import and use existing cleanup if available
-    try:
-        from src.utils.global_async_cleanup import setup_global_async_cleanup
-        setup_global_async_cleanup()
-    except ImportError:
-        pass
-
-# Set up clean environment FIRST before any other imports
-setup_complete_clean_environment()
-
-from fastapi import FastAPI, HTTPException, BackgroundTasks
-from fastapi.middleware.cors import CORSMiddleware
-from fastapi.responses import JSONResponse
-from pydantic import BaseModel, Field
-import uvicorn
-
-from src.config import config
-from src.utils.logging import setup_logging, log_title
-from src.agents.supervisor_agent import supervisor_agent, create_fresh_supervisor_agent
-from src.agents.knowledge_agent import knowledge_agent
-from src.agents.mcp_agent import mcp_agent
-
-# Pydantic models for request/response
-class QueryRequest(BaseModel):
-    question: str = Field(..., description="The question to ask the multi-agent system", max_length=1000)
-    session_id: Optional[str] = Field(None, description="Optional session ID for conversation tracking")
-
-class QueryResponse(BaseModel):
-    response: str = Field(..., description="The response from the multi-agent system")
-    session_id: Optional[str] = Field(None, description="Session ID if provided")
-    processing_time: float = Field(..., description="Processing time in seconds")
-    status: str = Field(default="success", description="Response status")
-
-class HealthResponse(BaseModel):
-    status: str = Field(default="healthy", description="Health status")
-    version: str = Field(default="1.0.0", description="Application version")
-    services: Dict[str, str] = Field(..., description="Status of various services")
-
-class EmbedRequest(BaseModel):
-    force_refresh: bool = Field(default=False, description="Force refresh of all embeddings")
-
-# Global variables for service status
-tavily_server_process = None
-service_status = {
-    "tavily_mcp_server": "starting",
-    "opensearch": "unknown",
-    "knowledge_base": "unknown"
-}
-
-@asynccontextmanager
-async def lifespan(app: FastAPI):
-    """Application lifespan manager."""
-    global tavily_server_process, service_status
-    
-    # Startup
-    logger = logging.getLogger(__name__)
-    log_title("FASTAPI SERVER STARTUP (CLEAN MODE)")
-    
-    try:
-        # Validate configuration
-        config.validate_config()
-        logger.info("Configuration validated successfully")
-        
-        # Check Tavily MCP Server connectivity (Kubernetes service)
-        logger.info("Checking Tavily MCP Server connectivity...")
-        tavily_accessible = await check_tavily_server()
-        if tavily_accessible:
-            service_status["tavily_mcp_server"] = "connected"
-            logger.info("Tavily MCP Server is accessible via Kubernetes service")
-        else:
-            service_status["tavily_mcp_server"] = "disconnected"
-            logger.warning("Tavily MCP Server is not accessible")
-        
-        # Check OpenSearch connectivity
-        try:
-            from src.utils.opensearch_client import OpenSearchClient
-            client = OpenSearchClient(config)
-            # Simple connectivity test
-            info = client.client.info()
-            service_status["opensearch"] = "connected"
-            logger.info(f"OpenSearch connected: {info.get('version', {}).get('number', 'unknown')}")
-        except Exception as e:
-            service_status["opensearch"] = "disconnected"
-            logger.warning(f"OpenSearch connection failed: {e}")
-        
-        # Check knowledge base status
-        try:
-            from src.utils.opensearch_client import OpenSearchClient
-            client = OpenSearchClient(config)
-            if client.client.indices.exists(index=config.VECTOR_INDEX_NAME):
-                count = client.client.count(index=config.VECTOR_INDEX_NAME)
-                doc_count = count['count']
-                service_status["knowledge_base"] = f"ready ({doc_count} documents)"
-                logger.info(f"Knowledge base ready with {doc_count} documents")
-            else:
-                service_status["knowledge_base"] = "no_index"
-                logger.warning("Knowledge base index does not exist")
-        except Exception as e:
-            service_status["knowledge_base"] = "error"
-            logger.warning(f"Knowledge base check failed: {e}")
-        
-        # Initialize MCP client during startup to avoid blocking during requests
-        try:
-            from src.agents.supervisor_agent import get_tavily_mcp_client
-            mcp_client = get_tavily_mcp_client()
-            if mcp_client:
-                # Test MCP client connectivity
-                with mcp_client:
-                    tools = mcp_client.list_tools_sync()
-                    service_status["mcp_tools"] = f"ready ({len(tools)} tools)"
-                    logger.info(f"MCP client initialized successfully with {len(tools)} tools")
-            else:
-                service_status["mcp_tools"] = "unavailable"
-                logger.warning("MCP client initialization failed")
-        except Exception as e:
-            service_status["mcp_tools"] = "error"
-            logger.warning(f"MCP client initialization failed: {e}")
-        
-        logger.info("FastAPI server startup completed")
-        
-        yield
-        
-    except Exception as e:
-        # Filter out async-related errors in startup
-        error_msg = str(e)
-        if not any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            logger.error(f"Startup failed: {e}")
-        raise
-    
-    # Shutdown
-    logger.info("Shutting down FastAPI server...")
-    # No need to terminate Tavily server as it's running in a separate Kubernetes service
-
-async def check_tavily_server():
-    """Check if the Tavily MCP server is accessible via Kubernetes service."""
-    try:
-        import httpx
-        
-        # Get Tavily service URL from environment or use default Kubernetes service name
-        tavily_service_url = os.getenv("TAVILY_MCP_SERVICE_URL", "http://tavily-mcp-service:8001")
-        
-        async with httpx.AsyncClient(timeout=5.0) as client:
-            # Try to connect to the MCP endpoint with proper headers
-            response = await client.post(
-                f"{tavily_service_url}/mcp/",
-                headers={
-                    "Content-Type": "application/json",
-                    "Accept": "application/json, text/event-stream"
-                },
-                json={
-                    "jsonrpc": "2.0",
-                    "method": "initialize",
-                    "id": "health-check",
-                    "params": {
-                        "protocolVersion": "2024-11-05",
-                        "capabilities": {},
-                        "clientInfo": {
-                            "name": "health-check",
-                            "version": "1.0.0"
-                        }
-                    }
-                }
-            )
-            # If we get any response (even an error), the service is accessible
-            return response.status_code in [200, 400, 406]  # Accept various response codes as "accessible"
-    except Exception as e:
-        # Filter out async-related errors
-        error_msg = str(e)
-        if not any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            logging.error(f"Failed to check Tavily server: {e}")
-        return False
-
-# Create FastAPI app
-app = FastAPI(
-    title="Multi-Agent RAG System API",
-    description="REST API for the Strands SDK Multi-Agent RAG System with OpenSearch (Clean Mode)",
-    version="1.0.0",
-    lifespan=lifespan
-)
-
-# Add CORS middleware
-app.add_middleware(
-    CORSMiddleware,
-    allow_origins=["*"],  # Configure appropriately for production
-    allow_credentials=True,
-    allow_methods=["*"],
-    allow_headers=["*"],
-)
-
-# Setup logging
-setup_logging()
-logger = logging.getLogger(__name__)
-
-@app.get("/health", response_model=HealthResponse)
-async def health_check():
-    """Health check endpoint."""
-    return HealthResponse(
-        status="healthy",
-        version="1.0.0",
-        services=service_status
-    )
-
-@app.get("/")
-async def root():
-    """Root endpoint."""
-    return {
-        "message": "Multi-Agent RAG System API (Clean Mode)",
-        "version": "1.0.0",
-        "mode": "clean",
-        "endpoints": {
-            "health": "/health",
-            "query": "/query",
-            "embed": "/embed",
-            "status": "/status",
-            "docs": "/docs"
-        }
-    }
-
-@app.post("/query", response_model=QueryResponse)
-async def process_query(request: QueryRequest, background_tasks: BackgroundTasks):
-    """Process a query using the multi-agent system."""
-    import time
-    start_time = time.time()
-    
-    try:
-        logger.info(f"Processing query: {request.question[:50]}...")
-        
-        # Validate query length
-        if len(request.question.strip()) == 0:
-            raise HTTPException(status_code=400, detail="Question cannot be empty")
-        
-        # Limit query length to avoid context window issues
-        query = request.question
-        if len(query) > 1000:
-            logger.warning("Query too long, truncating to 1000 characters")
-            query = query[:1000]
-        
-        # Create a fresh agent instance for each query to avoid context accumulation
-        fresh_agent = create_fresh_supervisor_agent()
-        
-        # Process the query
-        response = fresh_agent(query)
-        
-        # Ensure response is properly formatted
-        if response is None:
-            response = "No response received from agent."
-        
-        response_str = str(response).strip()
-        if not response_str:
-            response_str = "Agent completed processing but returned empty response."
-        
-        # Limit response length if needed
-        if len(response_str) > 4000:
-            logger.warning("Response too long, truncating to 4000 characters")
-            response_str = response_str[:4000] + "... [Response truncated due to length]"
-        
-        processing_time = time.time() - start_time
-        logger.info(f"Query processed successfully in {processing_time:.2f}s")
-        
-        return QueryResponse(
-            response=response_str,
-            session_id=request.session_id,
-            processing_time=processing_time,
-            status="success"
-        )
-        
-    except Exception as e:
-        processing_time = time.time() - start_time
-        
-        # Always log the error for debugging, but filter display for async-related errors
-        error_msg = str(e)
-        logger.error(f"Error processing query: {e}", exc_info=True)
-        
-        # Filter display message for async-related errors
-        if any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            display_error = "Internal processing error (async-related)"
-        else:
-            display_error = str(e) if str(e) else "Unknown error occurred"
-        
-        return QueryResponse(
-            response=f"Error processing query: {display_error}",
-            session_id=request.session_id,
-            processing_time=processing_time,
-            status="error"
-        )
-
-@app.post("/embed")
-async def embed_knowledge(request: EmbedRequest, background_tasks: BackgroundTasks):
-    """Embed knowledge documents into the vector database."""
-    try:
-        logger.info("Starting knowledge embedding process...")
-        
-        # Run embedding in background to avoid timeout
-        def run_embedding():
-            try:
-                if request.force_refresh:
-                    result = knowledge_agent('Please refresh and embed all knowledge files')
-                else:
-                    result = knowledge_agent('Please embed all knowledge files')
-                
-                # Update service status
-                global service_status
-                try:
-                    from src.utils.opensearch_client import OpenSearchClient
-                    client = OpenSearchClient(config)
-                    if client.client.indices.exists(index=config.VECTOR_INDEX_NAME):
-                        count = client.client.count(index=config.VECTOR_INDEX_NAME)
-                        doc_count = count['count']
-                        service_status["knowledge_base"] = f"ready ({doc_count} documents)"
-                except Exception:
-                    pass
-                
-                logger.info("Knowledge embedding completed successfully")
-                return result
-            except Exception as e:
-                # Filter out async-related errors
-                error_msg = str(e)
-                if not any(keyword in error_msg.lower() for keyword in [
-                    "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-                ]):
-                    logger.error(f"Knowledge embedding failed: {e}")
-                service_status["knowledge_base"] = "error"
-                raise
-        
-        background_tasks.add_task(run_embedding)
-        
-        return {
-            "message": "Knowledge embedding started in background",
-            "status": "processing"
-        }
-        
-    except Exception as e:
-        # Filter out async-related errors
-        error_msg = str(e)
-        if not any(keyword in error_msg.lower() for keyword in [
-            "runtimeerror", "httpcore", "asyncio", "anyio", "await", "async"
-        ]):
-            logger.error(f"Error starting embedding process: {e}")
-            raise HTTPException(status_code=500, detail=f"Failed to start embedding: {str(e)}")
-
-@app.get("/status")
-async def get_status():
-    """Get detailed system status."""
-    return {
-        "mode": "clean",
-        "services": service_status,
-        "config": {
-            "opensearch_endpoint": config.OPENSEARCH_ENDPOINT,
-            "knowledge_dir": config.KNOWLEDGE_DIR,
-            "vector_index": config.VECTOR_INDEX_NAME,
-            "reasoning_model": config.REASONING_MODEL,
-            "embedding_model": config.EMBEDDING_MODEL
-        }
-    }
-
-def run_server():
-    """Run the FastAPI server."""
-    print("🚀 Starting Multi-Agent RAG System API Server (Clean Mode)")
-    print("=" * 60)
-    print("Note: All async errors and warnings are suppressed")
-    print("=" * 60)
-    
-    # Load environment variables from ConfigMap or local file
-    if os.path.exists("/app/config/.env"):
-        print("Loading environment variables from ConfigMap...")
-        from dotenv import load_dotenv
-        load_dotenv("/app/config/.env")
-        print("Environment variables loaded from ConfigMap")
-    elif os.path.exists("/app/.env"):
-        print("Loading environment variables from local file...")
-        from dotenv import load_dotenv
-        load_dotenv("/app/.env")
-        print("Environment variables loaded from local file")
-    
-    uvicorn.run(
-        "src.server:app",
-        host="0.0.0.0",
-        port=8000,
-        reload=False,
-        log_level="info",
-        timeout_keep_alive=900,  # 15 minutes keep-alive timeout
-        timeout_graceful_shutdown=30,  # 30 seconds graceful shutdown
-        limit_max_requests=1000,  # Limit max requests per worker
-        limit_concurrency=100  # Limit concurrent connections
-    )
-
-if __name__ == "__main__":
-    run_server()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/test_agents.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/test_agents.py
deleted file mode 100644
index 39037452..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/test_agents.py
+++ /dev/null
@@ -1,100 +0,0 @@
-#!/usr/bin/env python3
-"""
-Agent Testing Script
-
-This script tests the multi-agent system with various queries to ensure
-all components are working correctly, including Langfuse integration.
-"""
-
-import sys
-import logging
-from typing import List, Dict, Any
-from .config import config
-from .utils.logging import setup_logging, log_title
-from .agents.supervisor_agent import supervisor_agent, supervisor_agent_with_langfuse
-from .agents.knowledge_agent import knowledge_agent, knowledge_agent_with_langfuse
-from .agents.mcp_agent import mcp_agent, mcp_agent_with_langfuse
-
-def main():
-    """Main function for testing agents."""
-    # Setup logging
-    setup_logging()
-    logger = logging.getLogger(__name__)
-    
-    try:
-        # Validate configuration
-        config.validate_config()
-        
-        log_title("AGENT TESTING SCRIPT")
-        logger.info("Starting agent testing process")
-        
-        # Test individual agents first
-        test_individual_agents()
-        
-        # Test supervisor agent
-        test_supervisor_agent()
-        
-        print("\n🎉 All tests completed!")
-        
-    except KeyboardInterrupt:
-        print("\n\nTesting interrupted by user.")
-        sys.exit(0)
-    except Exception as e:
-        logger.error(f"Agent testing failed: {e}")
-        print(f"❌ Error: {e}")
-        sys.exit(1)
-
-def test_individual_agents():
-    """Test individual agents."""
-    log_title("INDIVIDUAL AGENT TESTS")
-    
-    # Test Knowledge Agent
-    print("🧠 Testing Knowledge Agent...")
-    try:
-        if config.is_langfuse_enabled():
-            knowledge_response = knowledge_agent_with_langfuse("Please scan the knowledge directory and report what files are available.")
-            print(f"✅ Knowledge Agent Response (with Langfuse): {str(knowledge_response)[:200]}...")
-        else:
-            knowledge_response = knowledge_agent("Please scan the knowledge directory and report what files are available.")
-            print(f"✅ Knowledge Agent Response: {str(knowledge_response)[:200]}...")
-    except Exception as e:
-        print(f"❌ Knowledge Agent failed: {e}")
-    
-    # Test MCP Agent
-    print("\n🔧 Testing MCP Agent...")
-    try:
-        if config.is_langfuse_enabled():
-            mcp_response = mcp_agent_with_langfuse("Please help me understand what tools are available for file operations.")
-            print(f"✅ MCP Agent Response (with Langfuse): {str(mcp_response)[:200]}...")
-        else:
-            mcp_response = mcp_agent("Please help me understand what tools are available for file operations.")
-            print(f"✅ MCP Agent Response: {str(mcp_response)[:200]}...")
-    except Exception as e:
-        print(f"❌ MCP Agent failed: {e}")
-
-def test_supervisor_agent():
-    """Test the supervisor agent with various queries."""
-    log_title("SUPERVISOR AGENT TESTS")
-    
-    test_queries = [
-        "What is the status of the knowledge base?",
-        "Can you help me understand what files are in the knowledge directory?",
-        "Please search for information about Bell's palsy if available."
-    ]
-    
-    for i, query in enumerate(test_queries, 1):
-        print(f"\n🧪 Test {i}: {query}")
-        
-        try:
-            if config.is_langfuse_enabled():
-                response = supervisor_agent_with_langfuse(query)
-                print(f"✅ Success (with Langfuse): {str(response)[:300]}...")
-            else:
-                response = supervisor_agent(query)
-                print(f"✅ Success: {str(response)[:300]}...")
-                
-        except Exception as e:
-            print(f"❌ Error: {e}")
-
-if __name__ == "__main__":
-    main()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/test_web_search_integration.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/test_web_search_integration.py
deleted file mode 100644
index 6c2ab76e..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/test_web_search_integration.py
+++ /dev/null
@@ -1,215 +0,0 @@
-#!/usr/bin/env python3
-"""
-Test script for Web Search Integration with Tavily MCP Server
-"""
-
-import os
-import sys
-import json
-import time
-import asyncio
-from pathlib import Path
-
-# Add project root to path
-project_root = Path(__file__).parent.parent
-sys.path.insert(0, str(project_root))
-
-from src.agents.supervisor_agent import supervisor_agent
-from src.utils.logging import setup_logging
-
-def test_rag_relevance_scoring():
-    """Test RAG relevance scoring and web search triggering"""
-    print("🧪 Testing RAG Relevance Scoring and Web Search Integration")
-    print("=" * 60)
-    
-    # Test cases with expected low relevance (should trigger web search)
-    low_relevance_queries = [
-        "What happened in the news today?",
-        "Current stock market prices",
-        "Latest AI developments in 2024",
-        "Recent weather updates"
-    ]
-    
-    # Test cases with expected high relevance (should use RAG)
-    high_relevance_queries = [
-        "What is Bell's palsy?",  # Assuming medical knowledge is in the knowledge base
-        "Symptoms of facial paralysis",
-        "Treatment for neurological conditions"
-    ]
-    
-    print("\n📊 Testing Low Relevance Queries (Should Trigger Web Search):")
-    print("-" * 50)
-    
-    for query in low_relevance_queries:
-        print(f"\n🔍 Query: {query}")
-        try:
-            result = supervisor_agent(query)
-            print(f"✅ Response received (length: {len(result)} chars)")
-            
-            # Check if web search was mentioned in the response
-            if "web" in result.lower() or "search" in result.lower():
-                print("🌐 Web search likely used")
-            else:
-                print("📚 RAG likely used")
-                
-        except Exception as e:
-            print(f"❌ Error: {e}")
-        
-        time.sleep(2)  # Rate limiting
-    
-    print("\n📚 Testing High Relevance Queries (Should Use RAG):")
-    print("-" * 50)
-    
-    for query in high_relevance_queries:
-        print(f"\n🔍 Query: {query}")
-        try:
-            result = supervisor_agent(query)
-            print(f"✅ Response received (length: {len(result)} chars)")
-            
-            # Check source indicators
-            if "knowledge base" in result.lower() or "retrieved" in result.lower():
-                print("📚 RAG likely used")
-            elif "web" in result.lower():
-                print("🌐 Web search used (unexpected for this query)")
-            else:
-                print("❓ Source unclear")
-                
-        except Exception as e:
-            print(f"❌ Error: {e}")
-        
-        time.sleep(2)  # Rate limiting
-
-def test_direct_web_search():
-    """Test direct web search functionality"""
-    print("\n🌐 Testing Direct Web Search Tools")
-    print("=" * 40)
-    
-    # Test web search tool directly
-    test_queries = [
-        "Latest developments in artificial intelligence",
-        "Current events in technology",
-        "Recent scientific discoveries"
-    ]
-    
-    for query in test_queries:
-        print(f"\n🔍 Testing web search for: {query}")
-        try:
-            # This should trigger web search regardless of RAG relevance
-            prompt = f"Use web search to find information about: {query}"
-            result = supervisor_agent(prompt)
-            print(f"✅ Web search result received (length: {len(result)} chars)")
-            
-            # Look for web search indicators
-            if any(indicator in result.lower() for indicator in ["url", "http", "web", "search"]):
-                print("🌐 Web search successfully used")
-            else:
-                print("❓ Web search usage unclear")
-                
-        except Exception as e:
-            print(f"❌ Error: {e}")
-        
-        time.sleep(2)
-
-def test_news_search():
-    """Test news search functionality"""
-    print("\n📰 Testing News Search")
-    print("=" * 30)
-    
-    news_queries = [
-        "Recent technology news",
-        "Latest AI breakthroughs",
-        "Current events in science"
-    ]
-    
-    for query in news_queries:
-        print(f"\n📰 Testing news search for: {query}")
-        try:
-            prompt = f"Find recent news about: {query}"
-            result = supervisor_agent(prompt)
-            print(f"✅ News search result received (length: {len(result)} chars)")
-            
-            # Look for news indicators
-            if any(indicator in result.lower() for indicator in ["news", "recent", "published", "article"]):
-                print("📰 News search successfully used")
-            else:
-                print("❓ News search usage unclear")
-                
-        except Exception as e:
-            print(f"❌ Error: {e}")
-        
-        time.sleep(2)
-
-def test_hybrid_responses():
-    """Test hybrid responses combining RAG and web search"""
-    print("\n🔄 Testing Hybrid RAG + Web Search Responses")
-    print("=" * 45)
-    
-    hybrid_queries = [
-        "What is machine learning and what are the latest developments?",
-        "Explain neural networks and recent breakthroughs",
-        "What are the current trends in AI research?"
-    ]
-    
-    for query in hybrid_queries:
-        print(f"\n🔄 Testing hybrid query: {query}")
-        try:
-            result = supervisor_agent(query)
-            print(f"✅ Hybrid response received (length: {len(result)} chars)")
-            
-            # Check for both RAG and web search indicators
-            has_rag = any(indicator in result.lower() for indicator in ["knowledge", "retrieved", "database"])
-            has_web = any(indicator in result.lower() for indicator in ["web", "search", "recent", "current"])
-            
-            if has_rag and has_web:
-                print("🎯 Hybrid response detected (RAG + Web)")
-            elif has_rag:
-                print("📚 RAG-only response")
-            elif has_web:
-                print("🌐 Web-only response")
-            else:
-                print("❓ Response source unclear")
-                
-        except Exception as e:
-            print(f"❌ Error: {e}")
-        
-        time.sleep(2)
-
-def main():
-    """Run all web search integration tests"""
-    print("🚀 Starting Web Search Integration Tests")
-    print("=" * 50)
-    
-    # Setup logging
-    setup_logging()
-    
-    # Check if Tavily API key is configured
-    if not os.getenv("TAVILY_API_KEY"):
-        print("⚠️  Warning: TAVILY_API_KEY not found in environment")
-        print("Web search functionality may not work properly")
-        print("Please set TAVILY_API_KEY in your .env file")
-        return
-    
-    try:
-        # Run tests
-        test_rag_relevance_scoring()
-        test_direct_web_search()
-        test_news_search()
-        test_hybrid_responses()
-        
-        print("\n🎉 All tests completed!")
-        print("\n📋 Test Summary:")
-        print("- RAG relevance scoring and automatic web search triggering")
-        print("- Direct web search functionality")
-        print("- News search capabilities")
-        print("- Hybrid RAG + web search responses")
-        
-    except Exception as e:
-        print(f"\n❌ Test suite failed: {e}")
-        return False
-    
-    return True
-
-if __name__ == "__main__":
-    success = main()
-    if not success:
-        sys.exit(1)
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diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/tools/embedding_retriever.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/tools/embedding_retriever.py
deleted file mode 100644
index 639c3cee..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/tools/embedding_retriever.py
+++ /dev/null
@@ -1,291 +0,0 @@
-"""Embedding retriever for RAG functionality."""
-
-import logging
-import math
-import random
-from typing import List, Dict, Any, Optional
-import requests
-from .opensearch_vector_store import OpenSearchVectorStore
-from ..config import config
-from ..utils.logging import log_title
-
-logger = logging.getLogger(__name__)
-
-class EmbeddingRetriever:
-    """Handles embedding generation and retrieval operations."""
-    
-    def __init__(self, embedding_model: str = None):
-        self.embedding_model = embedding_model or config.EMBEDDING_MODEL
-        self.vector_store = OpenSearchVectorStore()
-        self.embedding_endpoint = config.EMBEDDING_BASE_URL
-        self.api_key = config.EMBEDDING_API_KEY
-        self.target_dimension = 384  # Target dimension for embeddings
-    
-    def embed_document(self, document: str) -> List[float]:
-        """Embed a document and add it to the vector store."""
-        log_title('EMBEDDING DOCUMENT')
-        embedding = self.embed(document)
-        self.vector_store.add_embedding(embedding, document)
-        return embedding
-    
-    def embed_query(self, query: str) -> List[float]:
-        """Embed a query for search."""
-        log_title('EMBEDDING QUERY')
-        return self.embed(query)
-    
-    def generate_random_embedding(self) -> List[float]:
-        """Generate a random embedding as fallback."""
-        return [random.uniform(-1, 1) for _ in range(self.target_dimension)]
-    
-    def normalize_vector(self, vector: List[float]) -> List[float]:
-        """Normalize a vector to unit length."""
-        magnitude = math.sqrt(sum(val * val for val in vector))
-        if magnitude == 0:
-            return vector
-        return [val / magnitude for val in vector]
-    
-    def resize_embedding(self, embedding: List[float]) -> List[float]:
-        """Resize embedding to target dimension."""
-        if len(embedding) == self.target_dimension:
-            return embedding
-        
-        result = [0.0] * self.target_dimension
-        ratio = len(embedding) / self.target_dimension
-        
-        for i in range(self.target_dimension):
-            start = int(i * ratio)
-            end = int((i + 1) * ratio)
-            if end > len(embedding):
-                end = len(embedding)
-            
-            if start < end:
-                sum_val = sum(embedding[j] for j in range(start, end))
-                result[i] = sum_val / (end - start)
-        
-        return self.normalize_vector(result)
-    
-    def embed(self, text: str) -> List[float]:
-        """Generate embedding for text."""
-        try:
-            logger.info(f"Sending embedding request to endpoint: {self.embedding_endpoint}")
-            logger.info(f"Using model: {self.embedding_model}")
-            logger.info(f"Text length: {len(text)} characters")
-            
-            # Prepare request
-            headers = {
-                'Content-Type': 'application/json',
-                'Authorization': f'Bearer {self.api_key}'
-            }
-            
-            data = {
-                'model': self.embedding_model,
-                'input': text
-            }
-            
-            # Make request
-            # Check if the endpoint already ends with /embeddings
-            endpoint = self.embedding_endpoint
-            if endpoint.endswith('/embeddings'):
-                request_url = endpoint
-            else:
-                request_url = f"{endpoint}/embeddings"
-                
-            response = requests.post(
-                request_url,
-                headers=headers,
-                json=data,
-                timeout=30
-            )
-            
-            if not response.ok:
-                logger.warning(f"HTTP error! Status: {response.status_code}")
-                logger.warning(f"Error response: {response.text}")
-                return self.generate_random_embedding()
-            
-            response_data = response.json()
-            
-            # Check if we got a valid embedding in the expected OpenAI format
-            if (not response_data or 
-                not response_data.get('data') or 
-                not response_data['data'][0] or 
-                not response_data['data'][0].get('embedding')):
-                logger.warning("Warning: Embedding API didn't return a valid embedding")
-                logger.warning(f"Response: {response_data}")
-                return self.generate_random_embedding()
-            
-            # Get the embedding array from the OpenAI-compatible format
-            embedding = response_data['data'][0]['embedding']
-            
-            # Ensure we have the target dimensional vector
-            resized_embedding = self.resize_embedding(embedding)
-            
-            logger.info(f"Successfully processed embedding with {len(resized_embedding)} dimensions")
-            return resized_embedding
-            
-        except Exception as e:
-            logger.error(f"Error fetching embedding from endpoint: {e}")
-            return self.generate_random_embedding()
-    
-    def generate_embedding(self, text: str) -> List[float]:
-        """Generate embedding for a given text."""
-        return self.embed(text)
-    
-    def generate_embeddings_batch(self, texts: List[str]) -> List[List[float]]:
-        """Generate embeddings for a batch of texts."""
-        embeddings = []
-        for text in texts:
-            embedding = self.embed(text)
-            embeddings.append(embedding)
-        return embeddings
-    
-    def add_documents(self, documents: List[Dict[str, Any]]) -> bool:
-        """Add documents with embeddings to the vector store."""
-        try:
-            # Generate embeddings for documents
-            texts = [doc["content"] for doc in documents]
-            embeddings = self.generate_embeddings_batch(texts)
-            
-            # Prepare documents with embeddings
-            embedded_docs = []
-            for i, doc in enumerate(documents):
-                embedded_doc = {
-                    "id": doc.get("id"),
-                    "content": doc["content"],
-                    "vector": embeddings[i],
-                    "metadata": doc.get("metadata", {}),
-                    "timestamp": doc.get("timestamp")
-                }
-                embedded_docs.append(embedded_doc)
-            
-            # Add to vector store
-            return self.vector_store.add_documents(embedded_docs)
-            
-        except Exception as e:
-            logger.error(f"Failed to add documents: {e}")
-            return False
-    
-    def retrieve_similar_documents(
-        self, 
-        query: str, 
-        k: int = None, 
-        filter_dict: Optional[Dict[str, Any]] = None
-    ) -> List[Dict[str, Any]]:
-        """Retrieve similar documents for a query."""
-        try:
-            # Generate query embedding
-            query_embedding = self.embed(query)
-            
-            # Search for similar documents
-            results = self.vector_store.similarity_search(
-                query_vector=query_embedding,
-                k=k,
-                filter_dict=filter_dict
-            )
-            
-            return results
-            
-        except Exception as e:
-            logger.error(f"Failed to retrieve similar documents: {e}")
-            return []
-    
-    def search(self, query: str, top_k: int = 3) -> List[Dict[str, Any]]:
-        """
-        Search for similar documents using the query.
-        
-        Args:
-            query: The search query
-            top_k: Number of top results to return
-            
-        Returns:
-            List of documents with content and metadata
-        """
-        try:
-            # Generate query embedding
-            query_embedding = self.embed(query)
-            
-            # Search using the vector store
-            results = self.vector_store.similarity_search(
-                query_vector=query_embedding,
-                k=top_k
-            )
-            
-            # Truncate content to reduce token usage
-            for result in results:
-                if len(result['content']) > 500:
-                    result['content'] = result['content'][:500]
-            
-            logger.info(f"Found {len(results)} similar documents for query: {query[:50]}...")
-            return results
-            
-        except Exception as e:
-            logger.error(f"Failed to search documents: {e}")
-            return []
-
-    def add_document(self, content: str, metadata: Dict[str, Any] = None) -> bool:
-        """
-        Add a single document to the vector store.
-        
-        Args:
-            content: Document content
-            metadata: Document metadata
-            
-        Returns:
-            True if successful, False otherwise
-        """
-        try:
-            # Generate embedding for the document
-            embedding = self.embed(content)
-            
-            # Prepare document
-            doc = {
-                "content": content,
-                "vector": embedding,
-                "metadata": metadata or {}
-            }
-            
-            # Add to vector store
-            return self.vector_store.add_documents([doc])
-            
-        except Exception as e:
-            logger.error(f"Failed to add document: {e}")
-            return False
-    
-    def retrieve_context(self, query: str, k: int = None) -> str:
-        """Retrieve and format context for a query."""
-        try:
-            # Get similar documents
-            similar_docs = self.retrieve_similar_documents(query, k)
-            
-            if not similar_docs:
-                return "No relevant context found."
-            
-            # Format context
-            context_parts = []
-            for i, doc in enumerate(similar_docs, 1):
-                metadata = doc.get("metadata", {})
-                source = metadata.get("source", "Unknown")
-                
-                context_part = f"[Context {i} - Source: {source}]\n{doc['content']}\n"
-                context_parts.append(context_part)
-            
-            context = "\n".join(context_parts)
-            logger.info(f"Retrieved context with {len(similar_docs)} documents, total length: {len(context)} characters")
-            
-            return context
-            
-        except Exception as e:
-            logger.error(f"Failed to retrieve context: {e}")
-            return "Error retrieving context."
-    
-    def initialize_index(self, dimension: int = 384) -> bool:
-        """Initialize the vector store index."""
-        return self.vector_store.create_index(dimension)
-    
-    def get_document_count(self) -> int:
-        """Get the number of documents in the vector store."""
-        return self.vector_store.get_document_count()
-    
-    def close(self) -> None:
-        """Close the vector store connection."""
-        if self.vector_store:
-            self.vector_store.close()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/tools/opensearch_vector_store.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/tools/opensearch_vector_store.py
deleted file mode 100644
index 4ad69fae..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/tools/opensearch_vector_store.py
+++ /dev/null
@@ -1,339 +0,0 @@
-from datetime import datetime
-import json
-import logging
-from typing import List, Dict, Any, Optional, Tuple
-import numpy as np
-from opensearchpy import OpenSearch, RequestsHttpConnection
-from aws_requests_auth.aws_auth import AWSRequestsAuth
-import boto3
-from ..config import config
-
-logger = logging.getLogger(__name__)
-
-class OpenSearchVectorStore:
-    """Vector store implementation using OpenSearch."""
-    
-    def __init__(self, index_name: str = None):
-        self.index_name = index_name or config.VECTOR_INDEX_NAME
-        self.client: Optional[OpenSearch] = None
-        self.dimension = 384  # Default dimension for embeddings
-        self._initialize_client()
-    
-    def _initialize_client(self) -> None:
-        """Initialize OpenSearch client with AWS authentication."""
-        try:
-            # Get AWS credentials
-            session = boto3.Session()
-            credentials = session.get_credentials()
-            
-            if not credentials:
-                raise ValueError("AWS credentials not found")
-            
-            # Parse endpoint to get host
-            endpoint_url = config.OPENSEARCH_ENDPOINT
-            if endpoint_url.startswith('https://'):
-                host = endpoint_url.replace('https://', '')
-            else:
-                host = endpoint_url
-            
-            # Create AWS auth
-            awsauth = AWSRequestsAuth(
-                aws_access_key=credentials.access_key,
-                aws_secret_access_key=credentials.secret_key,
-                aws_token=credentials.token,
-                aws_host=host,
-                aws_region=config.AWS_REGION,
-                aws_service='es'
-            )
-            
-            # Initialize OpenSearch client
-            self.client = OpenSearch(
-                hosts=[{'host': host, 'port': 443}],
-                http_auth=awsauth,
-                use_ssl=True,
-                verify_certs=True,
-                connection_class=RequestsHttpConnection
-            )
-            
-            logger.info("OpenSearch client initialized successfully")
-            
-        except Exception as e:
-            logger.error(f"Failed to initialize OpenSearch client: {e}")
-            raise
-    
-    def create_index(self, dimension: int = 384) -> bool:
-        """Create the vector index if it doesn't exist."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        self.dimension = dimension
-        
-        try:
-            # Check if index exists
-            if self.client.indices.exists(index=self.index_name):
-                logger.info(f"Index {self.index_name} already exists")
-                return True
-            
-            # Create index with vector mapping
-            index_body = {
-                "settings": {
-                    "index": {
-                        "knn": True,
-                        "knn.space_type": "cosinesimil"
-                    }
-                },
-                "mappings": {
-                    "properties": {
-                        "embedding": {
-                            "type": "knn_vector",
-                            "dimension": dimension,
-                            "method": {
-                                "name": "hnsw",
-                                "space_type": "cosinesimil",
-                                "engine": "nmslib",
-                                "parameters": {
-                                    "ef_construction": 128,
-                                    "m": 16
-                                }
-                            }
-                        },
-                        "document": {
-                            "type": "text",
-                            "store": True
-                        },
-                        "metadata": {
-                            "type": "object"
-                        },
-                        "timestamp": {
-                            "type": "date"
-                        }
-                    }
-                }
-            }
-            
-            response = self.client.indices.create(
-                index=self.index_name,
-                body=index_body
-            )
-            
-            logger.info(f"Created index {self.index_name}: {response}")
-            return True
-            
-        except Exception as e:
-            logger.error(f"Failed to create index: {e}")
-            return False
-    
-    def add_embedding(self, embedding: List[float], document: str, metadata: Optional[Dict[str, Any]] = None) -> bool:
-        """Add a single document with embedding to the vector store."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        try:
-            from datetime import datetime
-            
-            doc_body = {
-                "embedding": embedding,
-                "document": document,
-                "metadata": metadata or {},
-                "timestamp": datetime.now().isoformat()
-            }
-            
-            response = self.client.index(
-                index=self.index_name,
-                body=doc_body,
-                refresh=True  # Make immediately searchable
-            )
-            
-            logger.debug(f"Document added to OpenSearch: {response['_id']}")
-            return True
-            
-        except Exception as e:
-            logger.error(f"Failed to add embedding: {e}")
-            return False
-    
-    def add_documents(self, documents: List[Dict[str, Any]]) -> bool:
-        """Add multiple documents with embeddings to the vector store."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        try:
-            # Prepare bulk operations
-            bulk_body = []
-            
-            for doc in documents:
-                # Index operation
-                bulk_body.append({
-                    "index": {
-                        "_index": self.index_name,
-                        "_id": doc.get("id", None)
-                    }
-                })
-                
-                # Document data
-                bulk_body.append({
-                    "embedding": doc["vector"],
-                    "document": doc["content"],
-                    "metadata": doc.get("metadata", {}),
-                    "timestamp": doc.get("timestamp", datetime.now().isoformat())
-                })
-            
-            # Execute bulk operation
-            response = self.client.bulk(body=bulk_body, refresh=True)
-            
-            # Check for errors
-            if response.get("errors"):
-                logger.error(f"Bulk indexing errors: {response}")
-                return False
-            
-            logger.info(f"Successfully indexed {len(documents)} documents")
-            return True
-            
-        except Exception as e:
-            logger.error(f"Failed to add documents: {e}")
-            return False
-    
-    def search(self, query_embedding: List[float], top_k: int = 3) -> List[str]:
-        """Search for similar documents using vector similarity."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        try:
-            search_body = {
-                "size": top_k,
-                "query": {
-                    "knn": {
-                        "embedding": {
-                            "vector": query_embedding,
-                            "k": top_k
-                        }
-                    }
-                },
-                "_source": ["document"]
-            }
-            
-            response = self.client.search(
-                index=self.index_name,
-                body=search_body
-            )
-            
-            # Extract documents from search results
-            hits = response["hits"]["hits"]
-            documents = [hit["_source"]["document"] for hit in hits]
-            
-            logger.debug(f"Found {len(documents)} similar documents")
-            return documents
-            
-        except Exception as e:
-            logger.error(f"Failed to search: {e}")
-            return []
-    
-    def similarity_search(
-        self, 
-        query_vector: List[float], 
-        k: int = None, 
-        filter_dict: Optional[Dict[str, Any]] = None
-    ) -> List[Dict[str, Any]]:
-        """Perform similarity search using vector with detailed results."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        k = k or config.TOP_K_RESULTS
-        
-        try:
-            # Build query with source filtering to reduce response size
-            query = {
-                "size": k,
-                "query": {
-                    "knn": {
-                        "embedding": {
-                            "vector": query_vector,
-                            "k": k
-                        }
-                    }
-                },
-                "_source": ["document", "metadata"]  # Only return necessary fields
-            }
-            
-            # Add filters if provided
-            if filter_dict:
-                query["query"] = {
-                    "bool": {
-                        "must": [query["query"]],
-                        "filter": [
-                            {"term": {key: value}} for key, value in filter_dict.items()
-                        ]
-                    }
-                }
-            
-            # Execute search
-            response = self.client.search(
-                index=self.index_name,
-                body=query
-            )
-            
-            # Process results - keep metadata minimal
-            results = []
-            for hit in response["hits"]["hits"]:
-                # Extract only essential metadata to reduce token usage
-                metadata = {}
-                if "metadata" in hit["_source"]:
-                    source_metadata = hit["_source"]["metadata"]
-                    # Only keep essential metadata fields
-                    if isinstance(source_metadata, dict):
-                        metadata = {
-                            "source": source_metadata.get("source", "Unknown")
-                        }
-                
-                results.append({
-                    "content": hit["_source"]["document"],
-                    "metadata": metadata,
-                    "score": hit["_score"],
-                    "id": hit["_id"]
-                })
-            
-            logger.info(f"Found {len(results)} similar documents")
-            return results
-            
-        except Exception as e:
-            logger.error(f"Failed to perform similarity search: {e}")
-            return []
-    
-    def delete_index(self) -> bool:
-        """Delete the vector index."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        try:
-            if self.client.indices.exists(index=self.index_name):
-                response = self.client.indices.delete(index=self.index_name)
-                logger.info(f"Deleted index {self.index_name}: {response}")
-                return True
-            else:
-                logger.info(f"Index {self.index_name} does not exist")
-                return True
-                
-        except Exception as e:
-            logger.error(f"Failed to delete index: {e}")
-            return False
-    
-    def get_document_count(self) -> int:
-        """Get the number of documents in the index."""
-        if not self.client:
-            raise RuntimeError("OpenSearch client not initialized")
-        
-        try:
-            response = self.client.count(index=self.index_name)
-            return response["count"]
-        except Exception as e:
-            logger.error(f"Failed to get document count: {e}")
-            return 0
-    
-    def close(self) -> None:
-        """Close the OpenSearch connection."""
-        if self.client:
-            try:
-                # OpenSearch client doesn't have explicit close method
-                # Connection will be closed automatically
-                logger.info("OpenSearch connection closed")
-            except Exception as e:
-                logger.error(f"Error closing OpenSearch connection: {e}")
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__init__.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__init__.py
deleted file mode 100644
index 010ebb1b..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__init__.py
+++ /dev/null
@@ -1,6 +0,0 @@
-"""Utility functions and helpers."""
-
-from .logging import log_title, setup_logging
-from .langfuse_config import LangfuseConfig, langfuse_config
-
-__all__ = ["log_title", "setup_logging", "LangfuseConfig", "langfuse_config"]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__pycache__/__init__.cpython-310.pyc b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__pycache__/__init__.cpython-310.pyc
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diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__pycache__/strands_langfuse_integration.cpython-310.pyc b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/__pycache__/strands_langfuse_integration.cpython-310.pyc
deleted file mode 100644
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diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/async_cleanup.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/async_cleanup.py
deleted file mode 100644
index d73a0865..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/async_cleanup.py
+++ /dev/null
@@ -1,88 +0,0 @@
-"""
-Utility functions for handling async cleanup and suppressing warnings.
-"""
-
-import warnings
-import sys
-import logging
-from contextlib import contextmanager
-
-# Configure logging to suppress specific async warnings
-logging.getLogger("httpcore").setLevel(logging.ERROR)
-logging.getLogger("httpx").setLevel(logging.ERROR)
-logging.getLogger("anyio").setLevel(logging.ERROR)
-
-@contextmanager
-def suppress_async_warnings():
-    """Context manager to suppress async-related warnings during RAGAs evaluation."""
-    
-    # Store original warning filters
-    original_filters = warnings.filters[:]
-    
-    # Store original stderr
-    original_stderr = sys.stderr
-    
-    try:
-        # Suppress specific async warnings
-        warnings.filterwarnings("ignore", category=RuntimeWarning, message=".*async generator ignored GeneratorExit.*")
-        warnings.filterwarnings("ignore", category=RuntimeWarning, message=".*coroutine.*was never awaited.*")
-        warnings.filterwarnings("ignore", category=RuntimeWarning, message=".*Attempted to exit cancel scope.*")
-        warnings.filterwarnings("ignore", category=RuntimeWarning, message=".*no running event loop.*")
-        
-        # Suppress HTTP connection warnings
-        warnings.filterwarnings("ignore", message=".*HTTP11ConnectionByteStream.*")
-        warnings.filterwarnings("ignore", message=".*HTTP11Connection.*")
-        
-        # Create a custom stderr that filters out specific error messages
-        class FilteredStderr:
-            def __init__(self, original_stderr):
-                self.original_stderr = original_stderr
-                
-            def write(self, text):
-                # Filter out specific async error messages
-                if any(phrase in text for phrase in [
-                    "async generator ignored GeneratorExit",
-                    "Attempted to exit cancel scope",
-                    "no running event loop",
-                    "HTTP11ConnectionByteStream",
-                    "coroutine object HTTP11ConnectionByteStream.aclose"
-                ]):
-                    return  # Don't write these messages
-                
-                self.original_stderr.write(text)
-                
-            def flush(self):
-                self.original_stderr.flush()
-                
-            def __getattr__(self, name):
-                return getattr(self.original_stderr, name)
-        
-        # Replace stderr temporarily
-        sys.stderr = FilteredStderr(original_stderr)
-        
-        yield
-        
-    finally:
-        # Restore original settings
-        warnings.filters[:] = original_filters
-        sys.stderr = original_stderr
-
-def setup_async_environment():
-    """Set up the environment to minimize async warnings."""
-    
-    # Configure logging levels
-    loggers_to_quiet = [
-        "httpcore",
-        "httpx", 
-        "anyio",
-        "asyncio",
-        "urllib3.connectionpool"
-    ]
-    
-    for logger_name in loggers_to_quiet:
-        logger = logging.getLogger(logger_name)
-        logger.setLevel(logging.ERROR)
-        
-    # Set global warning filters
-    warnings.filterwarnings("ignore", category=RuntimeWarning, message=".*async generator ignored GeneratorExit.*")
-    warnings.filterwarnings("ignore", category=RuntimeWarning, message=".*coroutine.*was never awaited.*")
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/global_async_cleanup.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/global_async_cleanup.py
deleted file mode 100644
index 0622e4e0..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/global_async_cleanup.py
+++ /dev/null
@@ -1,116 +0,0 @@
-"""
-Global async cleanup and warning suppression for the entire application.
-This module should be imported at the very beginning of the main application.
-"""
-
-import warnings
-import sys
-import logging
-import os
-from contextlib import redirect_stderr
-from io import StringIO
-
-def setup_global_async_cleanup():
-    """Set up global async cleanup and warning suppression."""
-    
-    # Suppress all async-related warnings globally
-    warnings.filterwarnings("ignore", category=RuntimeWarning)
-    warnings.filterwarnings("ignore", category=DeprecationWarning)
-    warnings.filterwarnings("ignore", message=".*async.*")
-    warnings.filterwarnings("ignore", message=".*coroutine.*")
-    warnings.filterwarnings("ignore", message=".*HTTP.*")
-    warnings.filterwarnings("ignore", message=".*Exception ignored.*")
-    
-    # Configure logging to suppress noisy libraries
-    loggers_to_quiet = [
-        "httpcore",
-        "httpx", 
-        "anyio",
-        "asyncio",
-        "urllib3.connectionpool",
-        "mcp.client.streamable_http"
-    ]
-    
-    for logger_name in loggers_to_quiet:
-        logger = logging.getLogger(logger_name)
-        logger.setLevel(logging.CRITICAL)  # Only show critical errors
-    
-    # Set environment variables to reduce async noise
-    os.environ.setdefault("PYTHONWARNINGS", "ignore")
-
-class AsyncWarningFilter:
-    """Custom stderr filter to remove async warnings while preserving other messages."""
-    
-    def __init__(self, original_stderr):
-        self.original_stderr = original_stderr
-        self.buffer = []
-        self.in_async_traceback = False
-        
-    def write(self, text):
-        # Check if we're starting an async exception block
-        if "Exception ignored in:" in text:
-            self.in_async_traceback = True
-            return
-        
-        # Check if we're in an async traceback
-        if self.in_async_traceback:
-            # Look for patterns that indicate end of traceback
-            if (text.strip() == "" or 
-                not any(pattern in text for pattern in [
-                    "Traceback", "File ", "RuntimeError", "yield", "await", 
-                    "async", "coroutine", "HTTP", "anyio", "httpcore"
-                ])):
-                self.in_async_traceback = False
-            else:
-                return  # Skip this line as it's part of async traceback
-        
-        # Filter out specific async error patterns
-        async_patterns = [
-            "async generator ignored GeneratorExit",
-            "Attempted to exit cancel scope",
-            "no running event loop",
-            "HTTP11ConnectionByteStream",
-            "coroutine object",
-            "RuntimeError: async generator",
-            "Exception ignored in:",
-            "httpcore/_async/",
-            "anyio/_backends/",
-            "RuntimeError:",
-            "Traceback (most recent call last):",
-            "yield part",
-            "await self._connection",
-            "async with self._state_lock"
-        ]
-        
-        # Check if this line contains async warning patterns
-        if any(pattern in text for pattern in async_patterns):
-            return  # Don't write async warning messages
-        
-        # Write non-async messages to original stderr
-        self.original_stderr.write(text)
-        
-    def flush(self):
-        self.original_stderr.flush()
-        
-    def __getattr__(self, name):
-        return getattr(self.original_stderr, name)
-
-def install_global_stderr_filter():
-    """Install global stderr filter to suppress async warnings."""
-    if not hasattr(sys.stderr, '_original_stderr'):
-        sys.stderr._original_stderr = sys.stderr
-        sys.stderr = AsyncWarningFilter(sys.stderr._original_stderr)
-
-def remove_global_stderr_filter():
-    """Remove global stderr filter and restore original stderr."""
-    if hasattr(sys.stderr, '_original_stderr'):
-        original = sys.stderr._original_stderr
-        sys.stderr = original
-
-# Apply global setup when module is imported
-setup_global_async_cleanup()
-install_global_stderr_filter()
-
-# Ensure cleanup on exit
-import atexit
-atexit.register(remove_global_stderr_filter)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/langfuse_config.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/langfuse_config.py
deleted file mode 100644
index 21218508..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/langfuse_config.py
+++ /dev/null
@@ -1,106 +0,0 @@
-"""Langfuse configuration and utilities."""
-
-from typing import Optional, Dict, Any
-from ..config import config
-
-try:
-    from langfuse import Langfuse
-    LANGFUSE_AVAILABLE = True
-except ImportError:
-    LANGFUSE_AVAILABLE = False
-    Langfuse = None
-
-class LangfuseSpanWrapper:
-    """Wrapper for Langfuse spans to handle API differences."""
-    def __init__(self, span):
-        self.span = span
-    
-    def end(self, **kwargs):
-        """End the span, handling different API versions."""
-        try:
-            # For Langfuse 3.x
-            if hasattr(self.span, 'end'):
-                # Just call end without parameters
-                self.span.end()
-        except Exception as e:
-            print(f"Warning: Failed to end span: {e}")
-
-class LangfuseConfig:
-    """Langfuse configuration and trace management."""
-    
-    def __init__(self):
-        self.client: Optional[Langfuse] = None
-        self._initialize_client()
-    
-    def _initialize_client(self) -> None:
-        """Initialize Langfuse client if available and configured."""
-        if not LANGFUSE_AVAILABLE:
-            print("Langfuse not available. Install with: pip install langfuse")
-            return
-        
-        if not config.is_langfuse_enabled():
-            print("Langfuse not configured. Skipping initialization.")
-            return
-        
-        try:
-            self.client = Langfuse(
-                host=config.LANGFUSE_HOST,
-                public_key=config.LANGFUSE_PUBLIC_KEY,
-                secret_key=config.LANGFUSE_SECRET_KEY
-            )
-            print("Langfuse initialized successfully")
-        except Exception as e:
-            print(f"Failed to initialize Langfuse: {e}")
-            self.client = None
-    
-    def create_trace(self, name: str, input_data: Dict[str, Any], metadata: Optional[Dict[str, Any]] = None):
-        """Create a new trace."""
-        if not self.client:
-            return None
-        
-        try:
-            # For Langfuse 3.x
-            trace_id = self.client.create_trace_id()
-            # Use start_span without trace_id parameter
-            trace = self.client.start_span(
-                name=name,
-                input=input_data,
-                metadata=metadata or {}
-            )
-            return LangfuseSpanWrapper(trace)
-        except Exception as e:
-            print(f"Failed to create trace: {e}")
-            return None
-    
-    def create_span(self, trace, name: str, input_data: Dict[str, Any], metadata: Optional[Dict[str, Any]] = None):
-        """Create a new span within a trace."""
-        if not self.client:
-            return None
-        
-        try:
-            # For Langfuse 3.x
-            span = self.client.start_span(
-                name=name,
-                input=input_data,
-                metadata=metadata or {}
-            )
-            return LangfuseSpanWrapper(span)
-        except Exception as e:
-            print(f"Failed to create span: {e}")
-            return None
-    
-    def flush(self) -> None:
-        """Flush pending traces."""
-        if self.client:
-            try:
-                self.client.flush()
-            except Exception as e:
-                print(f"Failed to flush Langfuse: {e}")
-    
-    @property
-    def is_enabled(self) -> bool:
-        """Check if Langfuse is enabled and available."""
-        return self.client is not None
-
-# Global Langfuse instance
-langfuse_config = LangfuseConfig()
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/logging.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/logging.py
deleted file mode 100644
index b505cb2d..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/logging.py
+++ /dev/null
@@ -1,22 +0,0 @@
-"""Logging utilities for the application."""
-
-import logging
-import sys
-from typing import Optional
-
-def setup_logging(level: str = "INFO") -> None:
-    """Setup logging configuration."""
-    logging.basicConfig(
-        level=getattr(logging, level.upper()),
-        format="%(asctime)s - %(name)s - %(levelname)s - %(message)s",
-        handlers=[
-            logging.StreamHandler(sys.stdout),
-        ]
-    )
-
-def log_title(title: str, width: int = 60) -> None:
-    """Print a formatted title for logging."""
-    border = "=" * width
-    padding = (width - len(title) - 2) // 2
-    formatted_title = f"{border}\n{' ' * padding} {title} {' ' * padding}\n{border}"
-    print(formatted_title)
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/model_providers.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/model_providers.py
deleted file mode 100644
index 369a104f..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/model_providers.py
+++ /dev/null
@@ -1,30 +0,0 @@
-"""Model provider configurations for Strands agents."""
-
-from strands.models.openai import OpenAIModel
-from ..config import config
-
-def create_openai_reasoning_model():
-    """Create an OpenAI model instance for reasoning tasks."""
-    return OpenAIModel(
-        client_args={
-            "api_key": config.LITELLM_API_KEY,
-            "base_url": config.LITELLM_BASE_URL,
-        },
-        model_id=config.REASONING_MODEL,
-        params={
-            "temperature": 0.7,
-            "max_tokens": 4096,
-        }
-    )
-
-def get_reasoning_model():
-    """Get the configured reasoning model for agents."""
-    try:
-        # Try to use OpenAI client
-        return create_openai_reasoning_model()
-    except ImportError:
-        # Fallback to string model ID
-        return config.REASONING_MODEL
-    except Exception as e:
-        print(f"Warning: Failed to create OpenAI model, falling back to string ID: {e}")
-        return config.REASONING_MODEL
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/opensearch_client.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/opensearch_client.py
deleted file mode 100644
index add2e335..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/opensearch_client.py
+++ /dev/null
@@ -1,90 +0,0 @@
-"""OpenSearch client wrapper for the multi-agent RAG system."""
-
-import logging
-from typing import Optional, Dict, Any
-from ..tools.opensearch_vector_store import OpenSearchVectorStore
-
-logger = logging.getLogger(__name__)
-
-class OpenSearchClient:
-    """OpenSearch client wrapper that provides compatibility with server.py expectations."""
-    
-    def __init__(self, config):
-        """Initialize OpenSearch client with configuration."""
-        self.config = config
-        self._vector_store = None
-        self.client = None
-        self._initialize_client()
-    
-    def _initialize_client(self) -> None:
-        """Initialize OpenSearch client using the existing vector store."""
-        try:
-            # Use the existing OpenSearchVectorStore implementation
-            self._vector_store = OpenSearchVectorStore()
-            
-            # Expose the underlying client for compatibility
-            if self._vector_store and self._vector_store.client:
-                self.client = self._vector_store.client
-                logger.info("OpenSearch client initialized successfully via vector store")
-            else:
-                logger.warning("OpenSearch vector store client not available")
-                self.client = None
-                
-        except Exception as e:
-            logger.error(f"Failed to initialize OpenSearch client: {e}")
-            self.client = None
-    
-    def is_connected(self) -> bool:
-        """Check if the client is connected and can reach OpenSearch."""
-        if not self.client:
-            return False
-        
-        try:
-            info = self.client.info()
-            return True
-        except Exception as e:
-            logger.debug(f"OpenSearch connection check failed: {e}")
-            return False
-    
-    def get_info(self) -> Optional[Dict[str, Any]]:
-        """Get OpenSearch cluster information."""
-        if not self.client:
-            return None
-        
-        try:
-            return self.client.info()
-        except Exception as e:
-            logger.error(f"Failed to get OpenSearch info: {e}")
-            return None
-    
-    def index_exists(self, index_name: str) -> bool:
-        """Check if an index exists."""
-        if not self.client:
-            return False
-        
-        try:
-            return self.client.indices.exists(index=index_name)
-        except Exception as e:
-            logger.error(f"Failed to check if index exists: {e}")
-            return False
-    
-    def get_document_count(self, index_name: str) -> int:
-        """Get the number of documents in an index."""
-        if not self.client:
-            return 0
-        
-        try:
-            response = self.client.count(index=index_name)
-            return response.get("count", 0)
-        except Exception as e:
-            logger.error(f"Failed to get document count: {e}")
-            return 0
-    
-    def close(self) -> None:
-        """Close the OpenSearch connection."""
-        if self._vector_store:
-            try:
-                self._vector_store.close()
-                logger.info("OpenSearch connection closed")
-            except Exception as e:
-                logger.error(f"Error closing OpenSearch connection: {e}")
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/strands_langfuse_integration.py b/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/strands_langfuse_integration.py
deleted file mode 100644
index c9af420a..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/src/utils/strands_langfuse_integration.py
+++ /dev/null
@@ -1,152 +0,0 @@
-"""
-Strands SDK tracing integration with Langfuse support.
-
-This module provides tracing capabilities using Strands SDK's native OpenTelemetry
-integration, with optional Langfuse export for enhanced observability.
-"""
-
-import logging
-import os
-from typing import Dict, Any, Optional
-from ..config import config
-
-try:
-    from strands.telemetry.tracer import get_tracer
-    STRANDS_TRACING_AVAILABLE = True
-except ImportError:
-    STRANDS_TRACING_AVAILABLE = False
-    get_tracer = None
-
-logger = logging.getLogger(__name__)
-
-class StrandsTracingIntegration:
-    """Strands SDK tracing integration with Langfuse support."""
-    
-    def __init__(self):
-        self.tracer = None
-        self.tracing_enabled = False
-        self._initialize_tracing()
-    
-    def _initialize_tracing(self) -> None:
-        """Initialize Strands tracing with optional Langfuse export."""
-        if not STRANDS_TRACING_AVAILABLE:
-            logger.warning("Strands tracing not available. Install latest Strands SDK.")
-            return
-        
-        try:
-            # Configure tracing based on environment or config
-            otlp_endpoint = None
-            otlp_headers = {}
-            enable_console = False
-            
-            # Check if Langfuse is configured and set up OTLP endpoint
-            if config.is_langfuse_enabled():
-                # For Langfuse, we can use their OTLP endpoint if available
-                # Or set up console export for development
-                enable_console = True
-                logger.info("Langfuse configured - enabling console tracing for development")
-            
-            # Check for explicit OTLP configuration
-            if os.getenv("OTEL_EXPORTER_OTLP_ENDPOINT"):
-                otlp_endpoint = os.getenv("OTEL_EXPORTER_OTLP_ENDPOINT")
-                
-            if os.getenv("OTEL_EXPORTER_OTLP_HEADERS"):
-                headers_str = os.getenv("OTEL_EXPORTER_OTLP_HEADERS")
-                otlp_headers = dict(h.split("=") for h in headers_str.split(","))
-            
-            if os.getenv("STRANDS_OTEL_ENABLE_CONSOLE_EXPORT", "").lower() == "true":
-                enable_console = True
-            
-            # Initialize the tracer
-            self.tracer = get_tracer(
-                service_name="strands-agentic-rag",
-                otlp_endpoint=otlp_endpoint,
-                otlp_headers=otlp_headers,
-                enable_console_export=enable_console
-            )
-            
-            self.tracing_enabled = True
-            logger.info("Strands tracing initialized successfully")
-            
-        except Exception as e:
-            logger.error(f"Failed to initialize Strands tracing: {e}")
-            self.tracer = None
-            self.tracing_enabled = False
-    
-    @property
-    def is_enabled(self) -> bool:
-        """Check if tracing is enabled."""
-        return self.tracing_enabled
-    
-    def create_agent_with_tracing(self, agent_class, trace_attributes: Optional[Dict[str, Any]] = None, **agent_kwargs):
-        """
-        Create a Strands Agent with built-in tracing enabled.
-        
-        Args:
-            agent_class: Strands Agent class
-            trace_attributes: Custom attributes to add to traces
-            **agent_kwargs: Arguments for agent initialization
-            
-        Returns:
-            Agent instance with tracing enabled
-        """
-        # Add trace attributes if provided
-        if trace_attributes and self.tracing_enabled:
-            agent_kwargs["trace_attributes"] = trace_attributes
-        
-        # Create and return the agent (tracing is automatic in Strands SDK)
-        return agent_class(**agent_kwargs)
-    
-    def setup_environment_for_tracing(self):
-        """Set up environment variables for optimal tracing."""
-        if not self.tracing_enabled:
-            return
-        
-        # Enable console export for development if not already set
-        if not os.getenv("STRANDS_OTEL_ENABLE_CONSOLE_EXPORT"):
-            os.environ["STRANDS_OTEL_ENABLE_CONSOLE_EXPORT"] = "true"
-        
-        # Set sampling if not configured (sample 100% for development)
-        if not os.getenv("OTEL_TRACES_SAMPLER"):
-            os.environ["OTEL_TRACES_SAMPLER"] = "always_on"
-        
-        logger.info("Tracing environment configured")
-
-# Global instance
-strands_tracing = StrandsTracingIntegration()
-
-# Convenience functions
-def create_traced_agent(agent_class, session_id: Optional[str] = None, 
-                       user_id: Optional[str] = None, **kwargs):
-    """Create a Strands Agent with tracing enabled."""
-    trace_attributes = {}
-    
-    if session_id:
-        trace_attributes["session.id"] = session_id
-    if user_id:
-        trace_attributes["user.id"] = user_id
-    
-    # Add default attributes
-    trace_attributes.update({
-        "service.name": "agentic-rag-opensearch",
-        "service.version": "1.0.0",
-        "tags": ["RAG", "OpenSearch", "Multi-Agent"]
-    })
-    
-    return strands_tracing.create_agent_with_tracing(
-        agent_class, 
-        trace_attributes=trace_attributes,
-        **kwargs
-    )
-
-def setup_tracing_environment():
-    """Set up the tracing environment."""
-    strands_tracing.setup_environment_for_tracing()
-
-# Export main components
-__all__ = [
-    "StrandsTracingIntegration",
-    "strands_tracing", 
-    "create_traced_agent",
-    "setup_tracing_environment"
-]
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/startup-main.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/startup-main.sh
deleted file mode 100755
index 91938998..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/startup-main.sh
+++ /dev/null
@@ -1,58 +0,0 @@
-#!/bin/bash
-set -e
-
-echo "Starting Strands SDK Agentic RAG Main Application (Clean Mode)..."
-
-# Load environment variables from ConfigMap or local file
-if [ -f "/app/config/.env" ]; then
-    echo "Loading environment variables from ConfigMap .env file..."
-    export $(grep -v '^#' /app/config/.env | xargs)
-    echo "Environment variables loaded successfully from ConfigMap"
-elif [ -f "/app/.env" ]; then
-    echo "Loading environment variables from local .env file..."
-    export $(grep -v '^#' /app/.env | xargs)
-    echo "Environment variables loaded successfully from local file"
-else
-    echo "WARNING: No .env file found. Using environment variables from Kubernetes."
-fi
-
-# Verify critical environment variables
-echo "Verifying critical environment variables..."
-if [ -z "$LITELLM_API_KEY" ] && [ -z "$OPENAI_API_KEY" ]; then
-    echo "ERROR: Neither LITELLM_API_KEY nor OPENAI_API_KEY is set"
-    exit 1
-fi
-
-if [ -z "$OPENSEARCH_ENDPOINT" ]; then
-    echo "ERROR: OPENSEARCH_ENDPOINT is not set"
-    exit 1
-fi
-
-if [ -z "$AWS_REGION" ]; then
-    echo "ERROR: AWS_REGION is not set"
-    exit 1
-fi
-
-echo "Critical environment variables verified"
-
-echo "Starting FastAPI server with clean mode..."
-echo "Server will be available on port 8000"
-echo "API Documentation available at http://localhost:8000/docs"
-
-# Load .env and run the server
-python -c "
-from dotenv import load_dotenv
-import os
-
-# Try to load from ConfigMap first, then fallback to local
-if os.path.exists('/app/config/.env'):
-    load_dotenv('/app/config/.env')
-    print('Loaded environment from ConfigMap')
-elif os.path.exists('/app/.env'):
-    load_dotenv('/app/.env')
-    print('Loaded environment from local file')
-
-# Now run the server
-from src.server import run_server
-run_server()
-"
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/startup-mcp.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/startup-mcp.sh
deleted file mode 100755
index 7845a69a..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/startup-mcp.sh
+++ /dev/null
@@ -1,47 +0,0 @@
-#!/bin/bash
-set -e
-
-echo "Starting Strands SDK Tavily MCP Server (Clean Mode)..."
-
-# Load environment variables from ConfigMap or local file
-if [ -f "/app/config/.env" ]; then
-    echo "Loading environment variables from ConfigMap .env file..."
-    export $(grep -v '^#' /app/config/.env | xargs)
-    echo "Environment variables loaded successfully from ConfigMap"
-elif [ -f "/app/.env" ]; then
-    echo "Loading environment variables from local .env file..."
-    export $(grep -v '^#' /app/.env | xargs)
-    echo "Environment variables loaded successfully from local file"
-else
-    echo "WARNING: No .env file found. Using environment variables from Kubernetes."
-fi
-
-# Verify critical environment variables
-echo "Verifying critical environment variables..."
-if [ -z "$TAVILY_API_KEY" ]; then
-    echo "ERROR: TAVILY_API_KEY is not set"
-    exit 1
-fi
-
-echo "Critical environment variables verified"
-
-echo "Starting Tavily MCP Server..."
-echo "Server will be available on port 8001"
-
-# Load .env and run the MCP server
-python -c "
-from dotenv import load_dotenv
-import os
-
-# Try to load from ConfigMap first, then fallback to local
-if os.path.exists('/app/config/.env'):
-    load_dotenv('/app/config/.env')
-    print('Loaded environment from ConfigMap')
-elif os.path.exists('/app/.env'):
-    load_dotenv('/app/.env')
-    print('Loaded environment from local file')
-
-# Now run the MCP server
-from src.mcp_server_standalone import main
-main()
-"
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/update-k8s-config.sh b/agentic-apps/strandsdk_agentic_rag_opensearch/update-k8s-config.sh
deleted file mode 100755
index 5ba12dcd..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/update-k8s-config.sh
+++ /dev/null
@@ -1,34 +0,0 @@
-#!/bin/bash
-
-# Interactive Kubernetes ConfigMap Update Script
-# Updates k8s/configmap.yaml with your actual service endpoints and API keys
-
-echo "🚀 Starting Kubernetes ConfigMap Update Tool..."
-echo ""
-
-# Check if Python 3 is available
-if ! command -v python3 &> /dev/null; then
-    echo "❌ Python 3 is required but not found"
-    echo "Please install Python 3 and try again"
-    exit 1
-fi
-
-# Check if k8s directory exists
-if [ ! -d "k8s" ]; then
-    echo "❌ k8s directory not found"
-    echo "Please run this script from the project root directory"
-    exit 1
-fi
-
-# Check if configmap.yaml exists
-if [ ! -f "k8s/configmap.yaml" ]; then
-    echo "❌ k8s/configmap.yaml not found"
-    echo "Please ensure the ConfigMap file exists"
-    exit 1
-fi
-
-# Run the Python script
-python3 ./update_k8s_config.py
-
-echo ""
-echo "✅ ConfigMap update completed!"
diff --git a/agentic-apps/strandsdk_agentic_rag_opensearch/update_k8s_config.py b/agentic-apps/strandsdk_agentic_rag_opensearch/update_k8s_config.py
deleted file mode 100755
index 8dbafea6..00000000
--- a/agentic-apps/strandsdk_agentic_rag_opensearch/update_k8s_config.py
+++ /dev/null
@@ -1,281 +0,0 @@
-#!/usr/bin/env python3
-"""
-Interactive script to update Kubernetes ConfigMap and Secrets
-for the Strands SDK RAG application with OpenSearch
-"""
-
-import os
-import sys
-import base64
-import yaml
-from typing import Dict, Any
-
-def get_user_input(prompt: str, default: str = "", required: bool = True) -> str:
-    """Get user input with optional default value"""
-    if default:
-        full_prompt = f"{prompt} [{default}]: "
-    else:
-        full_prompt = f"{prompt}: "
-    
-    while True:
-        value = input(full_prompt).strip()
-        if value:
-            return value
-        elif default:
-            return default
-        elif not required:
-            return ""
-        else:
-            print("This field is required. Please enter a value.")
-
-def encode_base64(value: str) -> str:
-    """Encode string to base64"""
-    if not value:
-        return "<BASE64_ENCODED_VALUE>"
-    return base64.b64encode(value.encode('utf-8')).decode('utf-8')
-
-def get_opensearch_info_from_deployment():
-    """Try to extract OpenSearch info from previous deployment"""
-    try:
-        # Try to get from AWS CLI if available
-        import subprocess
-        result = subprocess.run([
-            'aws', 'cloudformation', 'describe-stacks',
-            '--stack-name', 'strandsdk-rag-opensearch-stack',
-            '--region', 'us-east-1',
-            '--query', 'Stacks[0].Outputs[?OutputKey==`OpenSearchDomainEndpoint`].OutputValue',
-            '--output', 'text'
-        ], capture_output=True, text=True, timeout=10)
-        
-        if result.returncode == 0 and result.stdout.strip():
-            endpoint = result.stdout.strip()
-            return f"https://{endpoint}"
-    except:
-        pass
-    
-    return None
-
-def main():
-    print("🔧 Kubernetes ConfigMap and Secrets Update Tool")
-    print("=" * 50)
-    print("This script will help you update the k8s/configmap.yaml file")
-    print("with your actual service endpoints and API keys.\n")
-    
-    # Get OpenSearch endpoint from deployment if possible
-    opensearch_endpoint = get_opensearch_info_from_deployment()
-    if opensearch_endpoint:
-        print(f"✅ Found OpenSearch endpoint from deployment: {opensearch_endpoint}")
-    
-    # Collect configuration values
-    print("📋 Configuration Values")
-    print("-" * 25)
-    
-    config = {}
-    
-    # LiteLLM Configuration
-    print("\n🤖 LiteLLM Configuration (for reasoning models):")
-    config['litellm_base_url'] = get_user_input(
-        "LiteLLM Base URL", 
-        "http://your-litellm-loadbalancer.us-east-1.elb.amazonaws.com/v1"
-    )
-    config['reasoning_model'] = get_user_input(
-        "Reasoning Model Name", 
-        "vllm-server-qwen3"
-    )
-    
-    # Embedding Configuration
-    print("\n🔤 Embedding Configuration:")
-    config['embedding_base_url'] = get_user_input(
-        "Embedding Base URL", 
-        config['litellm_base_url'].replace('/v1', '/v1/embeddings')
-    )
-    config['embedding_model'] = get_user_input(
-        "Embedding Model Name", 
-        "llamacpp-embedding"
-    )
-    
-    # AWS Configuration
-    print("\n☁️  AWS Configuration:")
-    config['aws_region'] = get_user_input("AWS Region", "us-east-1")
-    config['opensearch_endpoint'] = get_user_input(
-        "OpenSearch Endpoint", 
-        opensearch_endpoint or "https://your-opensearch-domain.us-east-1.es.amazonaws.com"
-    )
-    
-    # Optional Langfuse Configuration
-    print("\n📊 Langfuse Configuration (optional):")
-    config['langfuse_host'] = get_user_input(
-        "Langfuse Host URL", 
-        "http://your-langfuse-loadbalancer.us-east-1.elb.amazonaws.com",
-        required=False
-    )
-    
-    # Application Settings
-    print("\n⚙️  Application Settings:")
-    config['vector_index_name'] = get_user_input("Vector Index Name", "knowledge-embeddings")
-    config['top_k_results'] = get_user_input("Top K Results", "3")
-    config['knowledge_dir'] = get_user_input("Knowledge Directory", "knowledge")
-    config['output_dir'] = get_user_input("Output Directory", "output")
-    
-    # Collect secrets
-    print("\n🔐 API Keys and Secrets")
-    print("-" * 25)
-    print("Note: Leave empty to keep placeholder values")
-    
-    secrets = {}
-    
-    secrets['litellm_api_key'] = get_user_input("LiteLLM API Key", required=False)
-    secrets['embedding_api_key'] = get_user_input("Embedding API Key", required=False)
-    secrets['tavily_api_key'] = get_user_input("Tavily API Key (for web search)", required=False)
-    
-    if config['langfuse_host']:
-        secrets['langfuse_public_key'] = get_user_input("Langfuse Public Key", required=False)
-        secrets['langfuse_secret_key'] = get_user_input("Langfuse Secret Key", required=False)
-    else:
-        secrets['langfuse_public_key'] = ""
-        secrets['langfuse_secret_key'] = ""
-    
-    # Generate the updated ConfigMap
-    print("\n🔄 Generating updated ConfigMap...")
-    
-    # Create the .env content
-    env_content = f"""# LiteLLM Configuration for Reasoning Models
-LITELLM_BASE_URL={config['litellm_base_url']}
-REASONING_MODEL={config['reasoning_model']}
-
-# Embedding Configuration (separate from reasoning)
-EMBEDDING_BASE_URL={config['embedding_base_url']}
-EMBEDDING_MODEL={config['embedding_model']}
-
-# AWS Configuration  
-AWS_REGION={config['aws_region']}
-OPENSEARCH_ENDPOINT={config['opensearch_endpoint']}
-
-# Tavily MCP Service Configuration
-TAVILY_MCP_SERVICE_URL=http://tavily-mcp-service:8001/mcp
-
-# Optional: Langfuse for observability
-LANGFUSE_HOST={config['langfuse_host']}
-
-# Application Settings
-KNOWLEDGE_DIR={config['knowledge_dir']}
-OUTPUT_DIR={config['output_dir']}
-VECTOR_INDEX_NAME={config['vector_index_name']}
-TOP_K_RESULTS={config['top_k_results']}"""
-    
-    # Create the full YAML content as a string to preserve formatting
-    yaml_content = f"""apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: app-config
-  labels:
-    app: strandsdk-rag
-data:
-  .env: |
-{env_content}
-  
-  # Individual config values for environment variables
-  litellm-base-url: "{config['litellm_base_url']}"
-  reasoning-model: "{config['reasoning_model']}"
-  embedding-base-url: "{config['embedding_base_url']}"
-  embedding-model: "{config['embedding_model']}"
-  opensearch-endpoint: "{config['opensearch_endpoint']}"
-  aws-region: "{config['aws_region']}"
-  vector-index-name: "{config['vector_index_name']}"
-  tavily-mcp-service-url: "http://tavily-mcp-service:8001/mcp"
-  langfuse-host: "{config['langfuse_host']}"
-  knowledge-dir: "{config['knowledge_dir']}"
-  output-dir: "{config['output_dir']}"
-  top-k-results: "{config['top_k_results']}"
----
-apiVersion: v1
-kind: Secret
-metadata:
-  name: app-secrets
-  labels:
-    app: strandsdk-rag
-type: Opaque
-data:
-  # Base64 encoded secrets - replace with your actual base64 encoded values
-  # To encode: echo -n "your-api-key" | base64
-  litellm-api-key: {encode_base64(secrets['litellm_api_key'])}
-  embedding-api-key: {encode_base64(secrets['embedding_api_key'])}
-  tavily-api-key: {encode_base64(secrets['tavily_api_key'])}
-  langfuse-public-key: {encode_base64(secrets['langfuse_public_key'])}
-  langfuse-secret-key: {encode_base64(secrets['langfuse_secret_key'])}"""
-    
-    # Write the updated ConfigMap file
-    output_file = 'k8s/configmap.yaml'
-    backup_file = 'k8s/configmap.yaml.backup'
-    
-    # Create backup
-    if os.path.exists(output_file):
-        print(f"📁 Creating backup: {backup_file}")
-        import shutil
-        shutil.copy2(output_file, backup_file)
-    
-    # Write new file
-    with open(output_file, 'w') as f:
-        f.write(yaml_content)
-    
-    print(f"✅ Updated ConfigMap written to: {output_file}")
-    
-    # Show summary
-    print("\n📋 Configuration Summary:")
-    print("-" * 30)
-    print(f"LiteLLM Base URL: {config['litellm_base_url']}")
-    print(f"Reasoning Model: {config['reasoning_model']}")
-    print(f"Embedding Base URL: {config['embedding_base_url']}")
-    print(f"Embedding Model: {config['embedding_model']}")
-    print(f"OpenSearch Endpoint: {config['opensearch_endpoint']}")
-    print(f"AWS Region: {config['aws_region']}")
-    print(f"Vector Index: {config['vector_index_name']}")
-    if config['langfuse_host']:
-        print(f"Langfuse Host: {config['langfuse_host']}")
-    
-    secrets_count = len([k for k, v in secrets.items() if v])
-    print(f"\n🔐 Secrets configured: {secrets_count}/{len(secrets)}")
-    
-    if secrets_count == 0:
-        print("⚠️  No API keys provided - placeholder values will be used")
-        print("   You can update secrets later with: kubectl edit secret app-secrets")
-    
-    print("\n🚀 Next Steps:")
-    print("1. Review the generated k8s/configmap.yaml file")
-    print("2. Apply the ConfigMap to your cluster:")
-    print("   kubectl apply -f k8s/configmap.yaml")
-    print("3. Deploy your application:")
-    print("   kubectl apply -f k8s/")
-    
-    # Show how to encode secrets manually if needed
-    if secrets_count < len(secrets):
-        print("\n💡 To encode API keys manually:")
-        print("   echo -n 'your-api-key' | base64")
-        print("   Then update the secret with: kubectl edit secret app-secrets")
-    
-    # Offer to apply directly
-    apply_now = input("\n❓ Would you like to apply the ConfigMap now? (y/N): ").strip().lower()
-    if apply_now in ['y', 'yes']:
-        try:
-            import subprocess
-            result = subprocess.run(['kubectl', 'apply', '-f', output_file], 
-                                  capture_output=True, text=True)
-            if result.returncode == 0:
-                print("✅ ConfigMap applied successfully!")
-                print(result.stdout)
-            else:
-                print("❌ Failed to apply ConfigMap:")
-                print(result.stderr)
-        except Exception as e:
-            print(f"❌ Error applying ConfigMap: {e}")
-            print("Please apply manually with: kubectl apply -f k8s/configmap.yaml")
-
-if __name__ == "__main__":
-    try:
-        main()
-    except KeyboardInterrupt:
-        print("\n\n❌ Operation cancelled by user")
-        sys.exit(1)
-    except Exception as e:
-        print(f"\n❌ Error: {e}")
-        sys.exit(1)
diff --git a/app.py b/app.py
new file mode 100644
index 00000000..ec8efe80
--- /dev/null
+++ b/app.py
@@ -0,0 +1,131 @@
+# Copyright Amazon.com, Inc. or its affiliates. All Rights Reserved.
+# SPDX-License-Identifier: MIT-0
+
+# Adapted from https://github.com/kyopark2014/strands-agent
+# SPDX-License-Identifier: MIT
+
+import logging
+import sys
+
+import streamlit as st
+
+import health_agent_async
+
+logging.basicConfig(
+    level=logging.INFO,  # Default to INFO level
+    format="%(filename)s:%(lineno)d | %(message)s",
+    handlers=[logging.StreamHandler(sys.stderr)],
+)
+logger = logging.getLogger("streamlit")
+
+# title
+st.set_page_config(
+    page_title="Clinical Decision Support AI Assistant",
+    page_icon="🏥",
+    layout="centered",
+    initial_sidebar_state="auto",
+    menu_items=None,
+)
+
+with st.sidebar:
+    st.title("Clinical Assistant Menu")
+
+    st.markdown(
+        "**Clinical Decision Support AI Assistant** with access to patient data through MCP healthcare server. "
+        "This assistant helps healthcare professionals with diagnostic reasoning and clinical decision-making. "
+    )
+
+    
+    # Healthcare-specific information
+    st.markdown("### Available Patient Data")
+    st.markdown("""
+    **Sample Patient IDs:**
+    - PAT001, PAT002, PAT003
+    
+    **Available Tools:**
+    - Patient Demographics
+    - Medical History
+    - Lab Results
+    - Patient Search
+    - Risk Assessment
+    """)
+    
+    st.markdown("---")
+    
+    st.markdown("### ⚠️ Important Notice")
+    st.markdown("""
+    This is a **clinical decision support tool** for healthcare professionals only. 
+    
+    - Not a replacement for clinical judgment
+    - Final decisions must be made by qualified healthcare professionals
+    - Maintains HIPAA compliance principles
+    """)
+
+    clear_button = st.button("Reset Conversation", key="clear")
+
+st.title("🏥 Clinical Decision Support AI Assistant")
+
+# Initialize chat history
+if "messages" not in st.session_state:
+    st.session_state.messages = []
+    st.session_state.greetings = False
+
+# Display chat messages from history on app rerun
+def display_chat_messages():
+    """Print message history
+    @returns None
+    """
+    for message in st.session_state.messages:
+        with st.chat_message(message["role"]):
+            if "images" in message:
+                for url in message["images"]:
+                    logger.info(f"url: {url}")
+                    file_name = url[url.rfind("/") + 1 :]
+                    st.image(url, caption=file_name, use_container_width=True)
+            st.markdown(message["content"])
+
+display_chat_messages()
+
+# Greet user
+if not st.session_state.greetings:
+    with st.chat_message("assistant"):
+        intro = """👋 Welcome to the Clinical Decision Support AI Assistant!
+
+I'm here to help healthcare professionals with:
+- **Diagnostic reasoning** and differential diagnoses
+- **Patient data analysis** using our MCP healthcare server
+- **Clinical insights** based on medical guidelines
+- **Treatment recommendations** considering patient history
+- **Lab result interpretation** and clinical findings
+
+I have access to patient data for sample patients (PAT001, PAT002, PAT003) and can help with clinical decision-making.
+
+**Important:** I'm a support tool for healthcare professionals, not a replacement for clinical judgment. All recommendations are for clinical decision support only.
+
+How can I assist you with your clinical analysis today?"""
+        
+        st.markdown(intro)
+        # Add assistant response to chat history
+        st.session_state.messages.append({"role": "assistant", "content": intro})
+        st.session_state.greetings = True
+
+if clear_button or "messages" not in st.session_state:
+    st.session_state.messages = []
+    st.session_state.greetings = False
+    st.rerun()
+
+# Always show the chat input
+if prompt := st.chat_input("Enter your clinical question or patient case..."):
+    with st.chat_message("user"):  # display user message in chat message container
+        st.markdown(prompt)
+
+    st.session_state.messages.append(
+        {"role": "user", "content": prompt}
+    )  # add user message to chat history
+    prompt = prompt.replace('"', "").replace("'", "")
+    logger.info(f"Clinical prompt: {prompt}")
+
+    with st.chat_message("assistant"):
+        response = health_agent_async.run_health_agent(prompt, st)
+
+    st.session_state.messages.append({"role": "assistant", "content": response})
diff --git a/base_eks_setup/install_operators.sh b/base_eks_setup/install_operators.sh
deleted file mode 100755
index 28c25c4a..00000000
--- a/base_eks_setup/install_operators.sh
+++ /dev/null
@@ -1,353 +0,0 @@
-#!/bin/bash
-
-# Script to validate existing EKS cluster and install KubeRay and NVIDIA GPU operators
-#
-# Storage Class Configuration:
-# - Creates GP3 storage class with 'Immediate' binding mode instead of 'WaitForFirstConsumer'
-# - This prevents volume binding timeout issues that can occur with StatefulSets
-# - Immediate binding ensures PVs are created immediately when PVCs are created
-# - Compatible with both simple deployments and complex StatefulSet configurations
-
-set -e
-
-# Color codes for better readability
-GREEN='\033[0;32m'
-BLUE='\033[0;34m'
-RED='\033[0;31m'
-YELLOW='\033[0;33m'
-NC='\033[0m' # No Color
-
-# Export current EKS cluster name
-export CLUSTER_NAME=$(kubectl config current-context | cut -d'/' -f2)
-
-# Function to display messages with timestamp
-log() {
-  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
-}
-
-warn() {
-  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
-}
-
-error() {
-  echo -e "${RED}[$(date '+%Y-%m-%d %H:%M:%S')] ERROR:${NC} $1"
-  exit 1
-}
-
-success() {
-  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
-}
-
-# Check prerequisites
-check_prerequisites() {
-  log "Checking prerequisites..."
-  
-  # Install gettext if not available
-  if ! command -v envsubst &> /dev/null; then
-    log "Installing gettext package for envsubst..."
-    if [[ "$OSTYPE" == "darwin"* ]]; then
-      # macOS
-      if command -v brew &> /dev/null; then
-        brew install gettext
-        # Add gettext to PATH for current session
-        export PATH="/usr/local/opt/gettext/bin:$PATH"
-        # For Apple Silicon Macs
-        if [[ -d "/opt/homebrew/opt/gettext/bin" ]]; then
-          export PATH="/opt/homebrew/opt/gettext/bin:$PATH"
-        fi
-      else
-        error "Homebrew is not installed. Please install Homebrew first or install gettext manually."
-      fi
-    elif command -v apt-get &> /dev/null; then
-      # Ubuntu/Debian
-      sudo apt-get update && sudo apt-get install -y gettext
-    elif command -v yum &> /dev/null; then
-      # RHEL/CentOS/Amazon Linux
-      sudo yum install -y gettext
-    elif command -v dnf &> /dev/null; then
-      # Fedora
-      sudo dnf install -y gettext
-    else
-      error "Cannot install gettext. Please install it manually for your distribution."
-    fi
-    success "gettext installed successfully."
-  fi
-  
-  # Check AWS CLI
-  if ! command -v aws &> /dev/null; then
-    error "AWS CLI is not installed. Please install it first."
-  fi
-  
-  # Check kubectl
-  if ! command -v kubectl &> /dev/null; then
-    error "kubectl is not installed. Please install it first."
-  fi
-  
-  # Check helm
-  if ! command -v helm &> /dev/null; then
-    error "Helm is not installed. Please install it first."
-  fi
-  
-  # Check AWS credentials
-  if ! aws sts get-caller-identity &> /dev/null; then
-    error "AWS credentials not configured or invalid. Please configure AWS CLI."
-  fi
-  
-  success "All prerequisites satisfied."
-}
-
-# Validate existing EKS cluster
-validate_eks_cluster() {
-  log "Validating existing EKS cluster..."
-  
-  # Check if kubectl is configured to access a cluster
-  if ! kubectl cluster-info &> /dev/null; then
-    error "Cannot access Kubernetes cluster. Please check your kubeconfig."
-  fi
-  
-  # Get cluster info
-  CLUSTER_INFO=$(kubectl cluster-info)
-  log "Connected to Kubernetes cluster:"
-  echo "$CLUSTER_INFO"
-  
-  # Check nodes
-  log "Checking cluster nodes..."
-  NODE_COUNT=$(kubectl get nodes --no-headers | wc -l)
-  if [ "$NODE_COUNT" -lt 1 ]; then
-    error "No nodes found in the cluster. Please check your EKS cluster."
-  fi
-  
-  log "Found $NODE_COUNT nodes in the cluster:"
-  kubectl get nodes
-  
-  # Check for GPU nodes (optional)
-  if kubectl get nodes -o=custom-columns=NAME:.metadata.name,GPU:.status.capacity.nvidia\\.com\\/gpu --no-headers | grep -v "<none>" &> /dev/null; then
-    log "GPU nodes detected in the cluster."
-  else
-    warn "No GPU nodes detected. NVIDIA GPU operator will still be installed but may not be utilized."
-  fi
-  
-  success "EKS cluster validation completed successfully!"
-}
-
-# Install KubeRay operator
-install_kuberay_operator() {
-  log "Installing KubeRay operator..."
-  
-  # Create namespace for KubeRay
-  kubectl create namespace kuberay --dry-run=client -o yaml | kubectl apply -f -
-  
-  # Add KubeRay Helm repository
-  helm repo add kuberay https://ray-project.github.io/kuberay-helm/
-  helm repo update
-  
-  # Check if KubeRay operator is already installed
-  if helm list -n kuberay | grep kuberay-operator &> /dev/null; then
-    warn "KubeRay operator is already installed. Upgrading..."
-    helm upgrade kuberay-operator kuberay/kuberay-operator -n kuberay
-  else
-    # Install KubeRay operator
-    helm install kuberay-operator kuberay/kuberay-operator -n kuberay
-  fi
-  
-  # Wait for the operator to be ready
-  log "Waiting for KubeRay operator to be ready..."
-  kubectl wait --for=condition=available --timeout=300s deployment/kuberay-operator -n kuberay
-  
-  success "KubeRay operator installed successfully!"
-}
-
-# Install NVIDIA Device Plugin (standalone)
-install_nvidia_device_plugin() {
-  log "Installing NVIDIA Device Plugin..."
-  
-  # Check if NVIDIA Device Plugin is already installed
-  if kubectl get daemonset nvidia-device-plugin-daemonset -n kube-system &> /dev/null; then
-    warn "NVIDIA Device Plugin is already installed. Skipping..."
-    return
-  fi
-  
-  # Install NVIDIA Device Plugin
-  kubectl apply -f https://raw.githubusercontent.com/NVIDIA/k8s-device-plugin/v0.17.2/deployments/static/nvidia-device-plugin.yml
-  
-  # Wait for device plugin to be ready
-  log "Waiting for NVIDIA Device Plugin to be ready..."
-  kubectl rollout status daemonset/nvidia-device-plugin-daemonset -n kube-system --timeout=300s
-  
-  # Verify installation
-  if kubectl get pods -n kube-system | grep nvidia-device-plugin | grep Running > /dev/null; then
-    success "NVIDIA Device Plugin is running successfully!"
-  else
-    warn "NVIDIA Device Plugin may still be starting up..."
-  fi
-  
-  success "NVIDIA Device Plugin installation completed!"
-}
-
-# Install NVIDIA GPU operator
-install_nvidia_gpu_operator() {
-  log "Installing NVIDIA GPU operator..."
-  
-  # Create namespace for GPU operator
-  kubectl create namespace gpu-operator --dry-run=client -o yaml | kubectl apply -f -
-  
-  # Add NVIDIA Helm repository
-  helm repo add nvidia https://helm.ngc.nvidia.com/nvidia
-  helm repo update
-  
-  # Check if NVIDIA GPU operator is already installed
-  if helm list -n gpu-operator | grep gpu-operator &> /dev/null; then
-    warn "NVIDIA GPU operator is already installed. Upgrading..."
-    helm upgrade -n gpu-operator $(helm list -n gpu-operator | grep gpu-operator | awk '{print $1}') nvidia/gpu-operator
-  else
-    # Install NVIDIA GPU operator
-    helm install --wait --generate-name \
-      -n gpu-operator \
-      nvidia/gpu-operator
-  fi
-  
-  # Wait for the operator to be ready
-  log "Waiting for NVIDIA GPU operator to be ready..."
-  kubectl wait --for=condition=available --timeout=600s -n gpu-operator deployment/gpu-operator-node-feature-discovery-master 2>/dev/null || true
-  kubectl wait --for=condition=available --timeout=600s -n gpu-operator deployment/gpu-operator 2>/dev/null || true
-  
-  success "NVIDIA GPU operator installed successfully!"
-}
-
-# Install GP3 storage class with Immediate binding mode
-# Note: Using Immediate binding mode instead of WaitForFirstConsumer to avoid
-# volume binding timeout issues that can occur with StatefulSets and complex scheduling
-install_gp3_storage() {
-  log "Installing GP3 storage class with Immediate binding mode..."
-  
-  if kubectl get storageclass gp3 &> /dev/null; then
-    warn "GP3 storage class already exists. Checking configuration..."
-    
-    # Check if the existing storage class has the correct binding mode
-    BINDING_MODE=$(kubectl get storageclass gp3 -o jsonpath='{.volumeBindingMode}')
-    if [ "$BINDING_MODE" != "Immediate" ]; then
-      warn "Existing GP3 storage class uses '$BINDING_MODE' binding mode."
-      warn "For optimal compatibility, consider updating to 'Immediate' binding mode."
-      warn "You can delete the existing storage class and rerun this script to update it."
-    else
-      success "GP3 storage class already configured with Immediate binding mode."
-    fi
-  else
-    kubectl apply -f gp3.yaml
-    
-    # Validate the storage class was created correctly
-    if kubectl get storageclass gp3 &> /dev/null; then
-      BINDING_MODE=$(kubectl get storageclass gp3 -o jsonpath='{.volumeBindingMode}')
-      PROVISIONER=$(kubectl get storageclass gp3 -o jsonpath='{.provisioner}')
-      success "GP3 storage class installed successfully!"
-      log "  - Binding Mode: $BINDING_MODE"
-      log "  - Provisioner: $PROVISIONER"
-      log "  - Default: $(kubectl get storageclass gp3 -o jsonpath='{.metadata.annotations.storageclass\.kubernetes\.io/is-default-class}')"
-    else
-      error "Failed to create GP3 storage class"
-    fi
-  fi
-}
-
-# Install Karpenter node pools
-install_karpenter_nodepools() {
-  log "Installing Karpenter node pools..."
-  
-  # Install all node pool configurations with environment variable substitution
-  for nodepool_file in karpenter_nodepool/*.yaml; do
-    if [ -f "$nodepool_file" ]; then
-      log "Installing node pool: $(basename "$nodepool_file") with cluster name: $CLUSTER_NAME"
-      envsubst < "$nodepool_file" | kubectl apply -f -
-    fi
-  done
-  
-  success "All Karpenter node pools installed successfully!"
-}
-
-# Verify installations
-verify_installations() {
-  log "Verifying KubeRay operator installation..."
-  kubectl get all -n kuberay
-  
-  log "Verifying NVIDIA GPU operator installation..."
-  kubectl get all -n gpu-operator
-  
-  log "Verifying NVIDIA Device Plugin installation..."
-  if kubectl get daemonset nvidia-device-plugin-daemonset -n kube-system &> /dev/null; then
-    success "NVIDIA Device Plugin daemonset is installed."
-    kubectl get pods -n kube-system | grep nvidia-device-plugin || true
-  else
-    warn "NVIDIA Device Plugin daemonset not found."
-  fi
-  
-  log "Checking for RayCluster CRD..."
-  if kubectl get crd rayclusters.ray.io &> /dev/null; then
-    success "RayCluster CRD is installed."
-  else
-    warn "RayCluster CRD not found. KubeRay operator might not be functioning correctly."
-  fi
-  
-  log "Checking for NVIDIA GPU operator components..."
-  if kubectl get pods -n gpu-operator | grep -q "nvidia-device-plugin"; then
-    success "NVIDIA device plugin found."
-  else
-    warn "NVIDIA device plugin not found. GPU operator might still be initializing."
-  fi
-  
-  log "Checking for GPU resources on nodes..."
-  if kubectl get nodes -o=custom-columns=NAME:.metadata.name,GPU:.status.capacity.nvidia\\.com\\/gpu --no-headers | grep -v "<none>" &> /dev/null; then
-    success "GPU resources detected on nodes:"
-    kubectl get nodes -o=custom-columns=NAME:.metadata.name,GPU:.status.capacity.nvidia\\.com\\/gpu --no-headers | grep -v "<none>"
-  else
-    warn "No GPU resources found yet. This is normal if no GPU nodes are currently provisioned."
-  fi
-  
-  log "Verifying GP3 storage class configuration..."
-  if kubectl get storageclass gp3 &> /dev/null; then
-    BINDING_MODE=$(kubectl get storageclass gp3 -o jsonpath='{.volumeBindingMode}')
-    PROVISIONER=$(kubectl get storageclass gp3 -o jsonpath='{.provisioner}')
-    IS_DEFAULT=$(kubectl get storageclass gp3 -o jsonpath='{.metadata.annotations.storageclass\.kubernetes\.io/is-default-class}')
-    
-    success "GP3 storage class is installed and configured:"
-    log "  ✓ Binding Mode: $BINDING_MODE"
-    log "  ✓ Provisioner: $PROVISIONER"
-    log "  ✓ Default Storage Class: $IS_DEFAULT"
-    
-    if [ "$BINDING_MODE" = "Immediate" ]; then
-      success "  ✓ Using recommended Immediate binding mode for optimal compatibility"
-    else
-      warn "  ⚠ Using $BINDING_MODE binding mode - consider Immediate for better compatibility"
-    fi
-  else
-    warn "GP3 storage class not found."
-  fi
-  
-  log "Verifying Karpenter node pools..."
-  kubectl get nodepools
-}
-
-# Main execution
-main() {
-  log "Starting validation and installation process..."
-  log "Detected EKS cluster name: $CLUSTER_NAME"
-  
-  check_prerequisites
-  validate_eks_cluster
-  install_kuberay_operator
-  install_nvidia_gpu_operator
-  install_nvidia_device_plugin  # Added NVIDIA device plugin installation
-  install_gp3_storage
-  install_karpenter_nodepools
-  verify_installations
-  
-  success "All components installed successfully!"
-  log "Your EKS cluster now has KubeRay, NVIDIA GPU operators, NVIDIA device plugin, GP3 storage class (with Immediate binding), and Karpenter node pools installed."
-  log ""
-  log "Storage Configuration:"
-  log "  ✓ GP3 storage class configured with Immediate binding mode"
-  log "  ✓ This prevents volume binding timeout issues with StatefulSets"
-  log "  ✓ Compatible with both simple deployments and complex workloads"
-}
-
-# Execute main function
-main
diff --git a/base_eks_setup/karpenter_nodepool/gpu-nodepool.yaml b/base_eks_setup/karpenter_nodepool/gpu-nodepool.yaml
deleted file mode 100644
index 5cf51aea..00000000
--- a/base_eks_setup/karpenter_nodepool/gpu-nodepool.yaml
+++ /dev/null
@@ -1,88 +0,0 @@
----
-# GPU Node Pool for ML inference workloads
-apiVersion: karpenter.sh/v1
-kind: NodePool
-metadata:
-  name: gpu-inference
-spec:
-  limits:
-    cpu: 1024
-    memory: 8192Gi
-  disruption:
-    consolidationPolicy: WhenEmptyOrUnderutilized
-    consolidateAfter: 30m
-  template:
-    metadata:
-      labels:
-        model-inferencing: "gpu-inference"
-        ray-control-plane: "false"
-        nvidia.com/gpu: "present"
-    spec:
-      nodeClassRef:
-        group: karpenter.k8s.aws
-        kind: EC2NodeClass
-        name: gpu-inference
-      expireAfter: 8h
-      requirements:
-        - key: karpenter.k8s.aws/instance-category
-          operator: In
-          values:
-          - g
-        - key: karpenter.k8s.aws/instance-family
-          operator: In
-          values: ["g5", "g6"]
-        - key: kubernetes.io/arch
-          operator: In
-          values: ["amd64"]
-        - key: kubernetes.io/os
-          operator: In
-          values: ["linux"]
-        - key: karpenter.sh/capacity-type
-          operator: In
-          values: ["on-demand"]
-        - key: karpenter.k8s.aws/instance-gpu-manufacturer
-          operator: In
-          values: ["nvidia"]
-        - key: karpenter.k8s.aws/instance-gpu-count
-          operator: In
-          values: ["4"]
----
-apiVersion: karpenter.k8s.aws/v1
-kind: EC2NodeClass
-metadata:
-  name: gpu-inference
-spec:
-  kubelet:
-    podsPerCore: 2
-    maxPods: 20
-    systemReserved:
-      cpu: 500m
-      memory: 900Mi
-  subnetSelectorTerms:
-    - tags:
-        Environment: dev
-        Name: ${CLUSTER_NAME}-private-*
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  securityGroupSelectorTerms:
-    - tags:
-        Environment: dev
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  amiFamily: "AL2023"
-  amiSelectorTerms:
-    - name: "amazon-eks-node-al2023-x86_64-nvidia-1.33-v*"
-  role: KarpenterNode-${CLUSTER_NAME}
-  tags:
-    Environment: dev
-    karpenter.sh/discovery: ${CLUSTER_NAME}
-    model-inferencing: "gpu-inference"
-    ray-control-plane: "false"
-    Provisioned-By: aws-solutions-library-samples/guidance-for-automated-provisioning-of-application-ready-amazon-eks-clusters
-  blockDeviceMappings:
-  - deviceName: /dev/xvda
-    ebs:
-      volumeSize: 500Gi
-      volumeType: gp3
-      iops: 10000
-      encrypted: false
-      deleteOnTermination: true
-      throughput: 512
diff --git a/base_eks_setup/karpenter_nodepool/graviton-nodepool.yaml b/base_eks_setup/karpenter_nodepool/graviton-nodepool.yaml
deleted file mode 100644
index 72ca20dd..00000000
--- a/base_eks_setup/karpenter_nodepool/graviton-nodepool.yaml
+++ /dev/null
@@ -1,83 +0,0 @@
----
-# Graviton Node Pool for ARM-based workloads
-apiVersion: karpenter.sh/v1
-kind: NodePool
-metadata:
-  name: graviton-inference
-spec:
-  limits:
-    cpu: 512
-    memory: 4096Gi
-  disruption:
-    consolidationPolicy: WhenEmptyOrUnderutilized
-    consolidateAfter: 30m
-  template:
-    metadata:
-      labels:
-        model-inferencing: "graviton-inference"
-        ray-control-plane: "false"
-    spec:
-      nodeClassRef:
-        group: karpenter.k8s.aws
-        kind: EC2NodeClass
-        name: graviton-inference
-      expireAfter: 8h
-      requirements:
-        - key: karpenter.k8s.aws/instance-category
-          operator: In
-          values:
-          - c
-          - m
-          - r
-        - key: karpenter.k8s.aws/instance-generation
-          operator: Gt
-          values: ["6"]
-        - key: kubernetes.io/arch
-          operator: In
-          values: ["arm64"]
-        - key: kubernetes.io/os
-          operator: In
-          values: ["linux"]
-        - key: karpenter.sh/capacity-type
-          operator: In
-          values: ["on-demand"]
----
-apiVersion: karpenter.k8s.aws/v1
-kind: EC2NodeClass
-metadata:
-  name: graviton-inference
-spec:
-  kubelet:
-    podsPerCore: 2
-    maxPods: 20
-    systemReserved:
-      cpu: 100m
-      memory: 100Mi
-  subnetSelectorTerms:
-    - tags:
-        Environment: dev
-        Name: ${CLUSTER_NAME}-private-*
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  securityGroupSelectorTerms:
-    - tags:
-        Environment: dev
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  amiFamily: "AL2023"
-  amiSelectorTerms:
-    - name: "amazon-eks-node-al2023-arm64-standard-1.33-*"
-  role: KarpenterNode-${CLUSTER_NAME}
-  tags:
-    Environment: dev
-    karpenter.sh/discovery: ${CLUSTER_NAME}
-    model-inferencing: "graviton-inference"
-    ray-control-plane: "false"
-    Provisioned-By: aws-solutions-library-samples/guidance-for-automated-provisioning-of-application-ready-amazon-eks-clusters
-  blockDeviceMappings:
-    - deviceName: /dev/xvda
-      ebs:
-        volumeSize: 100Gi
-        volumeType: gp3
-        iops: 10000
-        encrypted: false
-        deleteOnTermination: true
-        throughput: 256
diff --git a/base_eks_setup/karpenter_nodepool/inf2-nodepool.yaml b/base_eks_setup/karpenter_nodepool/inf2-nodepool.yaml
deleted file mode 100644
index 4bda8c39..00000000
--- a/base_eks_setup/karpenter_nodepool/inf2-nodepool.yaml
+++ /dev/null
@@ -1,84 +0,0 @@
----
-# Inf2 Node Pool for ML inference workloads
-apiVersion: karpenter.sh/v1
-kind: NodePool
-metadata:
-  name: inf2-inference
-spec:
-  limits:
-    cpu: 512
-    memory: 4096Gi
-  disruption:
-    consolidationPolicy: WhenEmptyOrUnderutilized
-    consolidateAfter: 30m
-  template:
-    metadata:
-      labels:
-        model-inferencing: "inf2-inference"
-        ray-control-plane: "false"
-    spec:
-      nodeClassRef:
-        group: karpenter.k8s.aws
-        kind: EC2NodeClass
-        name: inf2-inference
-      taints:
-        - key: "model-inferencing"
-          value: "inf2-inference"
-          effect: NoSchedule
-      expireAfter: 8h
-      requirements:
-        - key: karpenter.k8s.aws/instance-family
-          operator: In
-          values: ["inf2"]
-        - key: kubernetes.io/arch
-          operator: In
-          values: ["amd64"]
-        - key: kubernetes.io/os
-          operator: In
-          values: ["linux"]
-        - key: karpenter.sh/capacity-type
-          operator: In
-          values: ["on-demand"]
-        - key: karpenter.k8s.aws/instance-accelerator-manufacturer
-          operator: In
-          values: ["aws"]
----
-apiVersion: karpenter.k8s.aws/v1
-kind: EC2NodeClass
-metadata:
-  name: inf2-inference
-spec:
-  kubelet:
-    podsPerCore: 2
-    maxPods: 20
-    systemReserved:
-      cpu: 500m
-      memory: 900Mi
-  subnetSelectorTerms:
-    - tags:
-        Environment: dev
-        Name: ${CLUSTER_NAME}-private-*
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  securityGroupSelectorTerms:
-    - tags:
-        Environment: dev
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  amiFamily: "AL2023"
-  amiSelectorTerms:
-    - name: "amazon-eks-node-al2023-x86_64-neuron-1.33-v*"
-  role: KarpenterNode-${CLUSTER_NAME}
-  tags:
-    Environment: dev
-    karpenter.sh/discovery: ${CLUSTER_NAME}
-    model-inferencing: "inf2-inference"
-    ray-control-plane: "false"
-    Provisioned-By: aws-solutions-library-samples/guidance-for-automated-provisioning-of-application-ready-amazon-eks-clusters
-  blockDeviceMappings:
-  - deviceName: /dev/xvda
-    ebs:
-      volumeSize: 300Gi
-      volumeType: gp3
-      iops: 8000
-      encrypted: false
-      deleteOnTermination: true
-      throughput: 256
diff --git a/base_eks_setup/karpenter_nodepool/x86-nodepool.yaml b/base_eks_setup/karpenter_nodepool/x86-nodepool.yaml
deleted file mode 100644
index 28e514ce..00000000
--- a/base_eks_setup/karpenter_nodepool/x86-nodepool.yaml
+++ /dev/null
@@ -1,85 +0,0 @@
----
-# x86 Node Pool for x86-based workloads
-apiVersion: karpenter.sh/v1
-kind: NodePool
-metadata:
-  name: x86-inference
-spec:
-  limits:
-    cpu: 512
-    memory: 4096Gi
-  disruption:
-    consolidationPolicy: WhenEmptyOrUnderutilized
-    consolidateAfter: 30s
-  template:
-    metadata:
-      labels:
-        model-inferencing: "x86-inference"
-        ray-control-plane: "false"
-    spec:
-      nodeClassRef:
-        group: karpenter.k8s.aws
-        kind: EC2NodeClass
-        name: x86-inference
-      taints:
-        - key: "model-inferencing"
-          value: "x86-inference"
-          effect: NoSchedule
-      expireAfter: 8h
-      requirements:
-        - key: karpenter.k8s.aws/instance-category
-          operator: In
-          values:
-          - c
-          - m
-          - r
-        - key: karpenter.k8s.aws/instance-generation
-          operator: Gt
-          values: ["6"]
-        - key: kubernetes.io/arch
-          operator: In
-          values: ["amd64"]
-        - key: kubernetes.io/os
-          operator: In
-          values: ["linux"]
-        - key: karpenter.sh/capacity-type
-          operator: In
-          values: ["on-demand"]
----
-apiVersion: karpenter.k8s.aws/v1
-kind: EC2NodeClass
-metadata:
-  name: x86-inference
-spec:
-  kubelet:
-    podsPerCore: 2
-    maxPods: 20
-    systemReserved:
-      cpu: 100m
-      memory: 100Mi
-  subnetSelectorTerms:
-    - tags:
-        Environment: dev
-        Name: ${CLUSTER_NAME}-private-*
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  securityGroupSelectorTerms:
-    - tags:
-        Environment: dev
-        karpenter.sh/discovery: ${CLUSTER_NAME}
-  amiFamily: "AL2023"
-  amiSelectorTerms:
-    - name: "amazon-eks-node-al2023-x86_64-standard-1.29-*"
-  role: KarpenterNode-${CLUSTER_NAME}
-  tags:
-    Environment: dev
-    karpenter.sh/discovery: ${CLUSTER_NAME}
-    model-inferencing: "x86-inference"
-    ray-control-plane: "false"
-    Provisioned-By: aws-solutions-library-samples/guidance-for-automated-provisioning-of-application-ready-amazon-eks-clusters
-  blockDeviceMappings:
-    - deviceName: /dev/xvda
-      ebs:
-        volumeSize: 100Gi
-        volumeType: gp3
-        encrypted: false
-        deleteOnTermination: true
diff --git a/base_eks_setup/prometheus-monitoring.yaml b/base_eks_setup/prometheus-monitoring.yaml
deleted file mode 100644
index 10ef68fc..00000000
--- a/base_eks_setup/prometheus-monitoring.yaml
+++ /dev/null
@@ -1,59 +0,0 @@
----
-apiVersion: monitoring.coreos.com/v1
-kind: ServiceMonitor
-metadata:
-  name: vllm
-  namespace: monitoring
-  labels:
-    release: kube-prometheus-stack
-spec:
-  endpoints:
-  - path: '/metrics/'
-    port: metrics
-  selector:
-    matchLabels:
-      app.kubernetes.io/name: kuberay
----
-apiVersion: monitoring.coreos.com/v1
-kind: PodMonitor
-metadata:
-  labels:
-    release: prometheus
-  name: kuberay-cluster
-  namespace: monitoring  # ns where prometheus is deployed
-spec:
-  podMetricsEndpoints:
-    - port: metrics
-      path: '/metrics/'
-  namespaceSelector:
-    matchNames:
-      - kuberay-system               # ns where Ray cluster is deployed
-  selector:
-    matchLabels:
-      app.kubernetes.io/name: kuberay
----
-apiVersion: monitoring.coreos.com/v1
-kind: PodMonitor
-metadata:
-  name: ray-workers-monitor
-  namespace: monitoring
-  labels:
-    # `release: $HELM_RELEASE`: Prometheus can only detect PodMonitor with this label.
-    release: prometheus
-spec:
-  jobLabel: ray-workers
-  # Only select Kubernetes Pods in the "default" namespace.
-  namespaceSelector:
-    matchNames:
-      - kuberay-system
-  # Only select Kubernetes Pods with "matchLabels".
-  selector:
-    matchLabels:
-      ray.io/node-type: worker
-  # A list of endpoints allowed as part of this PodMonitor.
-  podMetricsEndpoints:
-  - port: metrics
-    path: '/metrics/'
-    relabelings:
-    - sourceLabels: [__meta_kubernetes_pod_label_ray_io_cluster]
-      targetLabel: ray_io_cluster
diff --git a/benchmark/Dockerfile b/benchmark/Dockerfile
deleted file mode 100644
index 1fc85c56..00000000
--- a/benchmark/Dockerfile
+++ /dev/null
@@ -1,19 +0,0 @@
-# Build stage
-FROM golang:1.21-alpine AS builder
-
-WORKDIR /app
-COPY . .
-RUN CGO_ENABLED=0 GOOS=linux go build -o benchmark perf_benchmark.go
-
-# Run stage
-FROM alpine:latest
-
-WORKDIR /app
-COPY --from=builder /app/benchmark .
-COPY prompts.txt /app
-
-ENV URL="http://localhost:8000/v1/chat/completions"
-ENV REQUESTS_PER_PROMPT=10
-ENV NUM_WARMUP_REQUESTS=3
-
-CMD ["./benchmark"]
diff --git a/benchmark/perf_benchmark.go b/benchmark/perf_benchmark.go
deleted file mode 100644
index 087a602a..00000000
--- a/benchmark/perf_benchmark.go
+++ /dev/null
@@ -1,327 +0,0 @@
-package main
-
-import (
-    "bytes"
-    "encoding/json"
-    "fmt"
-    "io/ioutil"
-    "net/http"
-    "strings"
-    "os"
-    "strconv"
-    "time"
-)
-
-type Result struct {
-    duration    time.Duration
-    totalTokens int
-    err         error
-}
-
-type Message struct {
-    Role    string `json:"role"`
-    Content string `json:"content"`
-}
-
-type RequestBody struct {
-    Messages  []Message `json:"messages"`
-    Model     string    `json:"model"`
-    MaxTokens int       `json:"max_tokens"`
-    TopP      float64   `json:"top_p"`
-    N         int       `json:"n"`
-    Stream    bool      `json:"stream"`
-}
-
-type RequestConfig struct {
-    URL       string
-    Prompt    string
-    MaxTokens int
-}
-
-type ResponseBody struct {
-    ID      string `json:"id"`
-    Object  string `json:"object"`
-    Created int64  `json:"created"`
-    Model   string `json:"model"`
-    Choices []struct {
-        Index   int `json:"index"`
-        Message struct {
-            Role    string `json:"role"`
-            Content string `json:"content"`
-        } `json:"message"`
-    } `json:"choices"`
-    Usage struct {
-        TotalTokens int `json:"total_tokens"`
-    } `json:"usage"`
-}
-
-func readPromptsFromFile(filename string) ([]string, error) {
-    content, err := ioutil.ReadFile(filename)
-    if err != nil {
-        return nil, fmt.Errorf("error reading file: %v", err)
-    }
-    
-    var prompts []string
-    for _, line := range strings.Split(string(content), "\n") {
-        if trimmed := strings.TrimSpace(line); trimmed != "" {
-            prompts = append(prompts, trimmed)
-        }
-    }
-    
-    if len(prompts) == 0 {
-        return nil, fmt.Errorf("no prompts found in file")
-    }
-    
-    return prompts, nil
-}
-
-func makeRequest(config RequestConfig, results chan<- Result) {
-    reqBody := RequestBody{
-        Messages: []Message{
-            {
-                Role:    "user",
-                Content: config.Prompt,
-            },
-        },
-        Model:     "meta/llama2-13b-chat-v1",
-        MaxTokens: config.MaxTokens,
-        TopP:      1,
-        N:         1,
-        Stream:    false,
-    }
-    
-    jsonData, err := json.Marshal(reqBody)
-    if err != nil {
-        results <- Result{duration: 0, totalTokens: 0, err: fmt.Errorf("error marshaling JSON: %v", err)}
-        return
-    }
-
-    client := &http.Client{
-        Timeout: 60 * time.Second, // Increased timeout to 60 seconds
-    }
-    
-    req, err := http.NewRequest("POST", config.URL, bytes.NewBuffer(jsonData))
-    if err != nil {
-        results <- Result{duration: 0, totalTokens: 0, err: fmt.Errorf("error creating request: %v", err)}
-        return
-    }
-
-    req.Header.Set("Content-Type", "application/json")
-    req.Header.Set("Accept", "application/json")
-    
-    start := time.Now()
-    
-    resp, err := client.Do(req)
-    if err != nil {
-        results <- Result{duration: 0, totalTokens: 0, err: fmt.Errorf("error making request: %v", err)}
-        return
-    }
-    defer resp.Body.Close()
-    
-    body, err := ioutil.ReadAll(resp.Body)
-    duration := time.Since(start)
-    
-    if err != nil {
-        results <- Result{duration: 0, totalTokens: 0, err: fmt.Errorf("error reading response: %v", err)}
-        return
-    }
-
-    if resp.StatusCode != http.StatusOK {
-        results <- Result{duration: 0, totalTokens: 0, err: fmt.Errorf("unexpected status code: %d, body: %s", resp.StatusCode, string(body))}
-        return
-    }
-
-    var responseBody ResponseBody
-    if err := json.Unmarshal(body, &responseBody); err != nil {
-        results <- Result{duration: 0, totalTokens: 0, err: fmt.Errorf("error parsing response JSON: %v", err)}
-        return
-    }
-
-    fmt.Printf("Request completed - Duration: %v, Tokens: %d\n", 
-        duration, responseBody.Usage.TotalTokens)
-    
-    results <- Result{
-        duration:    duration,
-        totalTokens: responseBody.Usage.TotalTokens,
-        err:        nil,
-    }
-}
-
-func calculateAverageResponseTime(config RequestConfig, numRequests int) (time.Duration, float64, int, error) {
-    results := make(chan Result, numRequests)
-    
-    for i := 0; i < numRequests; i++ {
-        go makeRequest(config, results)
-        time.Sleep(500 * time.Millisecond)
-    }
-    
-    var totalDuration time.Duration
-    var totalTokens int
-    var successfulRequests int
-    var errors []error
-    
-    for i := 0; i < numRequests; i++ {
-        result := <-results
-        if result.err != nil {
-            fmt.Printf("Request error: %v\n", result.err)
-            errors = append(errors, result.err)
-            continue
-        }
-        totalDuration += result.duration
-        totalTokens += result.totalTokens
-        successfulRequests++
-        
-        fmt.Printf("Request %d/%d - Duration: %v, Tokens: %d\n", 
-            i+1, numRequests, result.duration, result.totalTokens)
-    }
-    
-    if successfulRequests == 0 {
-        return 0, 0, 0, fmt.Errorf("no successful requests (HTTP 200). Errors: %v", errors)
-    }
-    
-    avgDuration := totalDuration / time.Duration(successfulRequests)
-    tokensPerSecond := float64(totalTokens) / totalDuration.Seconds()
-    
-    return avgDuration, tokensPerSecond, successfulRequests, nil
-}
-
-func warmup(config RequestConfig, numWarmupRequests int) error {
-    fmt.Printf("\n=== Warming up with %d requests ===\n", numWarmupRequests)
-    results := make(chan Result, numWarmupRequests)
-    
-    for i := 0; i < numWarmupRequests; i++ {
-        go makeRequest(config, results)
-        time.Sleep(500 * time.Millisecond)
-        
-        fmt.Printf("Warmup request %d/%d completed\n", i+1, numWarmupRequests)
-    }
-    
-    var successfulWarmups int
-    for i := 0; i < numWarmupRequests; i++ {
-        result := <-results
-        if result.err != nil {
-            fmt.Printf("Warmup request error: %v\n", result.err)
-            continue
-        }
-        successfulWarmups++
-    }
-    
-    if successfulWarmups == 0 {
-        return fmt.Errorf("all warmup requests failed")
-    }
-    
-    fmt.Printf("Warmup completed successfully with %d/%d requests\n", 
-        successfulWarmups, numWarmupRequests)
-    return nil
-}
-
-func main() {
-    benchmarkStart := time.Now()
-
-    prompts, err := readPromptsFromFile("prompts.txt")
-    if err != nil {
-        fmt.Printf("Error reading prompts: %v\n", err)
-        return
-    }
-
-    url := os.Getenv("URL")
-    if url == "" {
-        url = "http://localhost:8000/v1/chat/completions"
-    }
-
-    requestsPerPrompt := 10
-    if envVal := os.Getenv("REQUESTS_PER_PROMPT"); envVal != "" {
-        if val, err := strconv.Atoi(envVal); err == nil {
-            requestsPerPrompt = val
-        }
-    }
-
-    numWarmupRequests := 3
-    if envVal := os.Getenv("NUM_WARMUP_REQUESTS"); envVal != "" {
-        if val, err := strconv.Atoi(envVal); err == nil {
-            numWarmupRequests = val
-        }
-    }
-
-    warmupConfig := RequestConfig{
-        URL:       url,
-        Prompt:    prompts[0],
-        MaxTokens: 200,
-    }
-    
-    fmt.Printf("\n=== Benchmark Configuration ===\n")
-    fmt.Printf("URL: %s\n", url)
-    fmt.Printf("Number of prompts: %d\n", len(prompts))
-    fmt.Printf("Requests per prompt: %d\n", requestsPerPrompt)
-    fmt.Printf("Warmup requests: %d\n", numWarmupRequests)
-    fmt.Printf("Total requests planned: %d\n", len(prompts)*requestsPerPrompt+numWarmupRequests)
-    
-    if err := warmup(warmupConfig, numWarmupRequests); err != nil {
-        fmt.Printf("Warmup failed: %v\n", err)
-        return
-    }
-    
-    fmt.Println("\nWaiting 2 seconds before starting benchmark...")
-    time.Sleep(2 * time.Second)
-
-    var totalSuccessfulRequests int
-    var overallTotalDuration time.Duration
-    var overallTotalTokens int
-    totalPlannedRequests := len(prompts) * requestsPerPrompt
-
-    fmt.Printf("\n=== Starting Benchmark Test ===\n")
-    fmt.Printf("Start time: %v\n\n", time.Now().Format("2006-01-02 15:04:05"))
-
-    for i, prompt := range prompts {
-        config := RequestConfig{
-            URL:       url,
-            Prompt:    prompt,
-            MaxTokens: 200,
-        }
-        
-        fmt.Printf("\n--- Prompt %d/%d ---\n", i+1, len(prompts))
-        fmt.Printf("Prompt: %s\n", prompt)
-            
-        avgTime, tokensPerSec, successfulRequestsForPrompt, err := calculateAverageResponseTime(config, requestsPerPrompt)
-        if err != nil {
-            fmt.Printf("Error calculating average: %v\n", err)
-            continue
-        }
-
-        promptTotalDuration := avgTime * time.Duration(successfulRequestsForPrompt)
-        promptTotalTokens := int(tokensPerSec * avgTime.Seconds()) * successfulRequestsForPrompt
-        
-        overallTotalDuration += promptTotalDuration
-        overallTotalTokens += promptTotalTokens
-        totalSuccessfulRequests += successfulRequestsForPrompt
-        
-        fmt.Printf("Prompt Average Response Time: %v\n", avgTime)
-        fmt.Printf("Prompt Tokens per Second: %.2f\n", tokensPerSec)
-        fmt.Printf("Successful Requests for this prompt: %d/%d\n\n", successfulRequestsForPrompt, requestsPerPrompt)
-    }
-
-    totalBenchmarkDuration := time.Since(benchmarkStart)
-
-    if totalSuccessfulRequests > 0 {
-        overallAvgLatency := overallTotalDuration / time.Duration(totalSuccessfulRequests)
-        overallTokensPerSec := float64(overallTotalTokens) / overallTotalDuration.Seconds()
-
-        fmt.Printf("\n=== Overall Benchmark Results ===\n")
-        fmt.Printf("End time: %v\n", time.Now().Format("2006-01-02 15:04:05"))
-        fmt.Printf("Total Benchmark Duration: %v\n", totalBenchmarkDuration)
-        fmt.Printf("Total Successful Requests (HTTP 200): %d\n", totalSuccessfulRequests)
-        fmt.Printf("Failed Requests: %d\n", totalPlannedRequests-totalSuccessfulRequests)
-        fmt.Printf("Success Rate: %.2f%%\n", float64(totalSuccessfulRequests)/float64(totalPlannedRequests)*100)
-        fmt.Printf("Overall Average Latency: %v\n", overallAvgLatency)
-        fmt.Printf("Overall Average Tokens/Second: %.2f\n", overallTokensPerSec)
-        
-        fmt.Printf("\n=== Timing Breakdown ===\n")
-        fmt.Printf("Total wall clock time: %v\n", totalBenchmarkDuration)
-        fmt.Printf("Total processing time: %v\n", overallTotalDuration)
-        fmt.Printf("Overhead time (includes delays): %v\n", 
-            totalBenchmarkDuration-overallTotalDuration)
-    } else {
-        fmt.Printf("\n=== Benchmark Failed ===\n")
-        fmt.Printf("No successful requests completed (HTTP 200)\n")
-    }
-}
diff --git a/benchmark/prompts.txt b/benchmark/prompts.txt
deleted file mode 100644
index 0ca61c64..00000000
--- a/benchmark/prompts.txt
+++ /dev/null
@@ -1,20 +0,0 @@
-In about 150 tokens, explain how generative AI models create new content from training data.
-Using approximately 150 tokens, describe the key differences between GPT-3 and GPT-4 architectures.
-In around 150 tokens, explain how temperature affects AI model output diversity.
-Describe, in about 150 tokens, the role attention mechanisms play in transformer models.
-In approximately 150 tokens, outline the process of fine-tuning a language model.
-Using about 150 tokens, explain how RAG improves AI model accuracy and knowledge.
-In roughly 150 tokens, discuss the main challenges in prompt engineering.
-Explain the concept of zero-shot learning in AI models, using about 150 tokens.
-In approximately 150 tokens, describe how embeddings represent text in vector space.
-Discuss the significance of context length in LLMs, using about 150 tokens.
-In around 150 tokens, describe the token limitation problem in language models.
-Explain how few-shot learning works in generative AI, using approximately 150 tokens.
-In about 150 tokens, outline the benefits of model quantization.
-Using roughly 150 tokens, explain the concept of knowledge distillation in AI.
-In approximately 150 tokens, describe how RLHF improves AI model outputs.
-Discuss the key metrics for evaluating GenAI models, using about 150 tokens.
-In around 150 tokens, describe the challenges of AI model hallucination.
-Explain how prompt injection affects model security, using approximately 150 tokens.
-In about 150 tokens, discuss the role of tokenization in language models.
-Using approximately 150 tokens, explain the concept of model alignment in AI.
\ No newline at end of file
diff --git a/cleanup-langfuse.sh b/cleanup-langfuse.sh
new file mode 100644
index 00000000..6a9bc6a0
--- /dev/null
+++ b/cleanup-langfuse.sh
@@ -0,0 +1,37 @@
+#!/bin/bash
+
+# Script to clean up Langfuse deployment
+
+set -e
+
+# Color codes for better readability
+GREEN='\033[0;32m'
+BLUE='\033[0;34m'
+RED='\033[0;31m'
+YELLOW='\033[0;33m'
+NC='\033[0m' # No Color
+
+# Function to display messages with timestamp
+log() {
+  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
+}
+
+warn() {
+  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
+}
+
+success() {
+  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
+}
+
+log "Uninstalling Langfuse Helm release..."
+helm uninstall langfuse || warn "Failed to uninstall Langfuse Helm release, it may not exist"
+
+log "Deleting Langfuse PVCs..."
+kubectl delete pvc data-langfuse-clickhouse-shard0-0 data-langfuse-clickhouse-shard0-1 data-langfuse-clickhouse-shard0-2 data-langfuse-postgresql-0 data-langfuse-zookeeper-0 data-langfuse-zookeeper-1 data-langfuse-zookeeper-2 langfuse-s3 valkey-data-langfuse-redis-primary-0 || warn "Failed to delete some PVCs, they may not exist"
+
+log "Waiting for resources to be cleaned up (30 seconds)..."
+sleep 30
+
+success "Langfuse cleanup completed!"
+log "You can now run setup.sh to reinstall Langfuse with the auto-ebs-sc storage class"
diff --git a/custom-nodepool.yaml b/custom-nodepool.yaml
new file mode 100644
index 00000000..16f84b10
--- /dev/null
+++ b/custom-nodepool.yaml
@@ -0,0 +1,33 @@
+apiVersion: karpenter.sh/v1
+kind: NodePool
+metadata:
+  name: custom
+spec:
+  template:
+    spec:
+      expireAfter: 168h
+      nodeClassRef:
+        group: eks.amazonaws.com
+        kind: NodeClass
+        name: default
+      requirements:
+        - key: karpenter.sh/capacity-type
+          operator: In
+          values: ["spot", "on-demand"]
+        - key: "eks.amazonaws.com/instance-category"
+          operator: In
+          values: ["c", "m", "r"]
+        - key: "eks.amazonaws.com/instance-generation"
+          operator: Gt
+          values: ["5"]
+        - key: kubernetes.io/arch
+          operator: In
+          values: ["amd64", "arm64"]
+  limits:
+    cpu: 1000
+    memory: 1000Gi
+  disruption:
+    consolidationPolicy: WhenEmptyOrUnderutilized
+    consolidateAfter: 1m
+  
+    
\ No newline at end of file
diff --git a/health_agent_async.py b/health_agent_async.py
new file mode 100644
index 00000000..1cafe088
--- /dev/null
+++ b/health_agent_async.py
@@ -0,0 +1,179 @@
+import logging
+import asyncio
+import os
+import base64
+from dotenv import load_dotenv
+from strands import Agent
+from strands.models.openai import OpenAIModel
+from strands.tools.mcp import MCPClient
+from strands.telemetry import StrandsTelemetry
+from mcp.client.streamable_http import streamablehttp_client
+
+# Load environment variables from .env file
+load_dotenv()
+
+# Configure logging for debug information
+logging.getLogger("strands").setLevel(logging.INFO)
+logging.basicConfig(
+    format="%(levelname)s | %(name)s | %(message)s",
+    handlers=[logging.StreamHandler()]
+)
+
+
+def setup_langfuse_tracing():
+    """Configure Langfuse tracing with OpenTelemetry"""
+    # Set default values if environment variables are not set
+    langfuse_public_key = os.environ.get("LANGFUSE_PUBLIC_KEY", "")
+    langfuse_secret_key = os.environ.get("LANGFUSE_SECRET_KEY", "")
+    langfuse_host = os.environ.get("LANGFUSE_HOST", "")
+
+
+    if not langfuse_public_key or not langfuse_secret_key:
+        print("⚠️  Langfuse credentials not found. Tracing will be disabled.")
+        print("   Set LANGFUSE_PUBLIC_KEY and LANGFUSE_SECRET_KEY environment variables to enable tracing.")
+        return None
+    
+    try:
+        # Build Basic Auth header
+        langfuse_auth = base64.b64encode(
+            f"{langfuse_public_key}:{langfuse_secret_key}".encode()
+        ).decode()
+        
+        # Configure OpenTelemetry endpoint & headers
+        os.environ["OTEL_EXPORTER_OTLP_ENDPOINT"] = langfuse_host + "/api/public/otel"
+        os.environ["OTEL_EXPORTER_OTLP_HEADERS"] = f"Authorization=Basic {langfuse_auth}"
+        
+        # Configure the telemetry (creates new tracer provider and sets it as global)
+        strands_telemetry = StrandsTelemetry().setup_otlp_exporter()
+        print("✅ Langfuse tracing enabled successfully!")
+        return strands_telemetry
+        
+    except Exception as e:
+        print(f"⚠️  Failed to setup Langfuse tracing: {e}")
+        print("   Continuing without tracing...")
+        return None
+
+openai_model = OpenAIModel(
+    client_args={
+        #"base_url": "http://localhost:4000/v1",
+        "base_url": os.environ.get("LITELLM_HOST", ""), 
+        "api_key": "your-secret-key"  # Required but can be dummy for local servers
+    },
+    model_id="my-model",  # Model identifier
+    temperature=0.3,  # Lower temperature for more consistent medical advice
+    max_tokens=2048
+)
+
+def create_health_agent(session_id=None, provider_id=None):
+    """Create the health agent with MCP healthcare data server connection and Langfuse tracing"""
+    
+    mcp_host = os.environ.get("MCP_HOST", "")
+    
+    # Setup Langfuse tracing
+    strands_telemetry = setup_langfuse_tracing()
+    
+    # Connect to the MCP healthcare server using streamable HTTP client
+    mcp_client = MCPClient(lambda: streamablehttp_client(mcp_host))
+    
+    # Get tools from the MCP server
+    with mcp_client:
+        tools = mcp_client.list_tools_sync()
+        
+        # Configure tracing attributes for clinical context
+        trace_attributes = {
+            "session.id": session_id or f"clinical-session-{os.getpid()}",
+            "user.id": provider_id or "healthcare-provider@clinical-assistant.local",
+            "langfuse.tags": [
+                "Clinical-Assistant",
+                "Healthcare-AI", 
+                "Patient-Analysis",
+                "Medical-Records",
+                "MCP-Healthcare-Server"
+            ]
+        }
+        
+        # Create the health agent with MCP tools and tracing
+        health_agent = Agent(
+            model=openai_model,
+            tools=tools,  # Use the MCP server tools
+            trace_attributes=trace_attributes,  # Add Langfuse tracing attributes
+            system_prompt="""You are a Clinical Decision Support AI Assistant with access to patient data through an MCP healthcare data server. You help healthcare professionals with diagnostic reasoning and clinical decision-making.
+
+Your role is to:
+- Provide evidence-based clinical insights and differential diagnoses
+- Assist with symptom analysis and pattern recognition using patient data
+- Offer treatment recommendations based on current medical guidelines and patient history
+- Help interpret clinical findings and laboratory results
+- Support clinical reasoning with relevant medical knowledge and patient-specific data
+- Retrieve and analyze patient histories, lab results, and demographic information
+
+Available Healthcare Data Tools (via MCP server at http://localhost:8000):
+- get_patient_info: Retrieve patient demographics (use patient IDs: PAT001, PAT002, PAT003)
+- get_patient_history: Get complete medical history including conditions and diagnoses
+- get_lab_results: Retrieve lab results within specified timeframes
+- search_patients: Find patients by name or ID
+- get_patient_summary: Get comprehensive patient overview with risk assessment
+
+Important Guidelines:
+- Always emphasize that your recommendations are for clinical decision support only
+- Remind users that final diagnostic and treatment decisions must be made by qualified healthcare professionals
+- Base recommendations on established medical guidelines and evidence-based practices
+- Consider patient safety as the highest priority
+- Use the MCP healthcare data tools to provide personalized clinical insights
+- Acknowledge limitations and recommend specialist consultation when appropriate
+- Maintain patient confidentiality and HIPAA compliance principles
+
+You should provide structured, clear responses that include:
+1. Clinical assessment of presented information
+2. Patient-specific data analysis when relevant (using MCP tools)
+3. Differential diagnosis considerations
+4. Recommended diagnostic workup or tests
+5. Treatment considerations based on patient history
+6. Recommmended medication
+7. Red flags or urgent concerns to monitor
+
+Remember: You are a support tool for healthcare professionals, not a replacement for clinical judgment. Use the MCP healthcare data server tools to access patient information when needed."""
+        )
+        
+        return health_agent, mcp_client
+
+
+def run_health_agent(question, st):
+    message_placeholder = st.empty()
+    full_response = ""
+
+    async def process_streaming_response():
+        nonlocal full_response
+        
+        # Get optional session and provider information for tracing
+        session_id = os.environ.get("CLINICAL_SESSION_ID")
+        provider_id = os.environ.get("HEALTHCARE_PROVIDER_ID")
+        
+        try:
+            # Create the health agent with MCP connection and tracing
+            health_agent, mcp_client = create_health_agent(session_id=session_id, provider_id=provider_id)
+
+            
+            # Keep the MCP client connection alive during the session
+            with mcp_client:
+                try:
+                    # Stream the response
+                    agent_stream = health_agent.stream_async(question)
+                    async for event in agent_stream:
+                        if "data" in event:
+                            full_response += event["data"]
+                            message_placeholder.markdown(full_response)
+                except Exception as e:
+                    print(f"Error processing request: {e}")
+        except Exception as e:
+            print(f"Error processing request: {e}")
+            message_placeholder.markdown(
+                "Sorry, an error occurred while generating the response."
+            )
+            print(f"Error processing request: {e}")  # Detailed error logging
+
+    asyncio.run(process_streaming_response())
+
+    return full_response
+
+
diff --git a/healthcare-assistant-deployment.yaml b/healthcare-assistant-deployment.yaml
new file mode 100644
index 00000000..08adfb9e
--- /dev/null
+++ b/healthcare-assistant-deployment.yaml
@@ -0,0 +1,79 @@
+apiVersion: apps/v1
+kind: Deployment
+metadata:
+  name: healthcare-assistant
+  labels:
+    app: healthcare-assistant
+spec:
+  replicas: 1
+  selector:
+    matchLabels:
+      app: healthcare-assistant
+  template:
+    metadata:
+      labels:
+        app: healthcare-assistant
+    spec:
+      nodeSelector:
+        kubernetes.io/arch: arm64
+      containers:
+      - name: healthcare-assistant
+        image: public.ecr.aws/j4m3t0a6/agents/healthcare-assistant:latest
+        ports:
+        - containerPort: 8501
+        env:
+        - name: LANGFUSE_PUBLIC_KEY
+          value: "your_langfuse_public_key_here"
+        - name: LANGFUSE_SECRET_KEY
+          value: "your_langfuse_secret_key_here"
+        - name: LANGFUSE_HOST
+          value: "http://langfuse-web:3000"
+        - name: LITELLM_HOST
+          value: "http://litellm-graviton:4000/v1"
+        - name: MCP_HOST
+          value: "http://healthcare-mcp-server:8000/mcp"
+        - name: MODEL_ID
+          value: "claude-4-sonnet"
+        - name: CLINICAL_SESSION_ID
+          value: "clinical-session-k8s"
+        - name: HEALTHCARE_PROVIDER_ID
+          value: "healthcare-provider@clinical-assistant.k8s"
+        resources:
+          requests:
+            memory: "512Mi"
+            cpu: "250m"
+          limits:
+            memory: "1Gi"
+            cpu: "500m"
+---
+apiVersion: v1
+kind: Service
+metadata:
+  name: healthcare-assistant-service
+spec:
+  selector:
+    app: healthcare-assistant
+  ports:
+    - port: 8501
+      targetPort: 8501
+  type: ClusterIP
+---
+apiVersion: networking.k8s.io/v1
+kind: Ingress
+metadata:
+  name: healthcare-assistant-ingress
+  annotations:
+    alb.ingress.kubernetes.io/scheme: internet-facing
+    alb.ingress.kubernetes.io/target-type: ip
+spec:
+  ingressClassName: alb
+  rules:
+    - http:
+        paths:
+        - path: /
+          pathType: Prefix
+          backend:
+            service:
+              name: healthcare-assistant-service
+              port:
+                number: 8501
diff --git a/healthcare-mcp-deployment.yaml b/healthcare-mcp-deployment.yaml
new file mode 100644
index 00000000..14e67e77
--- /dev/null
+++ b/healthcare-mcp-deployment.yaml
@@ -0,0 +1,42 @@
+apiVersion: apps/v1
+kind: Deployment
+metadata:
+  name: healthcare-mcp-server
+  labels:
+    app: healthcare-mcp-server
+spec:
+  replicas: 1
+  selector:
+    matchLabels:
+      app: healthcare-mcp-server
+  template:
+    metadata:
+      labels:
+        app: healthcare-mcp-server
+    spec:
+      nodeSelector:
+        kubernetes.io/arch: arm64
+      containers:
+      - name: healthcare-mcp-server
+        image: public.ecr.aws/j4m3t0a6/agents/healthcare-mcp-server:latest
+        ports:
+        - containerPort: 8000
+        resources:
+          requests:
+            cpu: "100m"
+            memory: "128Mi"
+          limits:
+            cpu: "500m"
+            memory: "256Mi"
+---
+apiVersion: v1
+kind: Service
+metadata:
+  name: healthcare-mcp-server
+spec:
+  selector:
+    app: healthcare-mcp-server
+  ports:
+  - port: 8000
+    targetPort: 8000
+  type: ClusterIP
diff --git a/image/arch.png b/image/arch.png
deleted file mode 100644
index 3c67f176..00000000
Binary files a/image/arch.png and /dev/null differ
diff --git a/ingressclass.yaml b/ingressclass.yaml
new file mode 100644
index 00000000..ba67ccbe
--- /dev/null
+++ b/ingressclass.yaml
@@ -0,0 +1,16 @@
+apiVersion: networking.k8s.io/v1
+kind: IngressClass
+metadata:
+  name: alb
+  annotations:
+    # Use this annotation to set an IngressClass as Default
+    # If an Ingress doesn't specify a class, it will use the Default
+    ingressclass.kubernetes.io/is-default-class: "true"
+spec:
+  # Configures the IngressClass to use EKS Auto Mode
+  controller: eks.amazonaws.com/alb
+  parameters:
+    apiGroup: eks.amazonaws.com
+    kind: IngressClassParams
+    # Use the name of the IngressClassParams set in the previous step
+    name: alb
\ No newline at end of file
diff --git a/ingressclassparams.yaml b/ingressclassparams.yaml
new file mode 100644
index 00000000..2c98d3fd
--- /dev/null
+++ b/ingressclassparams.yaml
@@ -0,0 +1,6 @@
+apiVersion: eks.amazonaws.com/v1
+kind: IngressClassParams
+metadata:
+  name: alb
+spec:
+  scheme: internet-facing
\ No newline at end of file
diff --git a/model-observability/langfuse-secret.yaml b/langfuse-secret.yaml
similarity index 100%
rename from model-observability/langfuse-secret.yaml
rename to langfuse-secret.yaml
diff --git a/model-observability/langfuse-value.yaml b/langfuse-value.yaml
similarity index 96%
rename from model-observability/langfuse-value.yaml
rename to langfuse-value.yaml
index ae34a54d..0652ccd1 100644
--- a/model-observability/langfuse-value.yaml
+++ b/langfuse-value.yaml
@@ -1,5 +1,8 @@
 # This values.yaml file demonstrates how to use the basic chart with a single, pre-created secret.
 # Secrets must be set manually or via External Secrets Operator like https://external-secrets.io/latest or any other secret management tool.
+global:
+  storageClass: auto-ebs-sc
+
 langfuse:
   encryptionKey:
     secretKeyRef:
diff --git a/langfuse-web-ingress.yaml b/langfuse-web-ingress.yaml
new file mode 100644
index 00000000..7437935d
--- /dev/null
+++ b/langfuse-web-ingress.yaml
@@ -0,0 +1,18 @@
+---
+apiVersion: networking.k8s.io/v1
+kind: Ingress
+metadata:
+  name: langfuse-web-ingress
+  namespace: default
+spec:
+  ingressClassName: alb
+  rules:
+  - http:
+      paths:
+      - path: /
+        pathType: Prefix
+        backend:
+          service:
+            name: langfuse-web
+            port:
+              number: 3000
diff --git a/litellm-graviton.yaml b/litellm-graviton.yaml
new file mode 100644
index 00000000..8102f575
--- /dev/null
+++ b/litellm-graviton.yaml
@@ -0,0 +1,340 @@
+apiVersion: apps/v1
+kind: Deployment
+metadata:
+  name: litellm-graviton
+spec:
+  replicas: 1
+  selector:
+    matchLabels:
+      app: litellm-graviton
+  template:
+    metadata:
+      labels:
+        app: litellm-graviton
+    spec:
+      nodeSelector:
+        kubernetes.io/arch: arm64
+      containers:
+      - name: litellm
+        image: ghcr.io/berriai/litellm:main-latest
+        args:
+          - "--config"
+          - "/app/config.yaml"
+          - "--port"
+          - "4000"
+          - "--num_workers"
+          - "1"
+        ports:
+        - containerPort: 4000
+        env:
+        - name: LITELLM_MASTER_KEY
+          valueFrom:
+            secretKeyRef:
+              name: litellm-secret
+              key: master-key
+        - name: AWS_ACCESS_KEY_ID
+          valueFrom:
+            secretKeyRef:
+              name: aws-credentials
+              key: access-key-id
+        - name: AWS_SECRET_ACCESS_KEY
+          valueFrom:
+            secretKeyRef:
+              name: aws-credentials
+              key: secret-access-key
+        - name: AWS_DEFAULT_REGION
+          value: MY_REGION
+        resources:
+          requests:
+            cpu: "500m"
+            memory: "1Gi"
+          limits:
+            cpu: "2"
+            memory: "4Gi"
+        volumeMounts:
+        - name: config
+          mountPath: /app/config.yaml
+          subPath: config.yaml
+      volumes:
+      - name: config
+        configMap:
+          name: litellm-config
+---
+apiVersion: v1
+kind: ConfigMap
+metadata:
+  name: litellm-config
+data:
+  config.yaml: |
+    model_list:
+      # vLLM Models     
+      - model_name: llama3-8b
+        litellm_params:
+          model: openai/NousResearch/Meta-Llama-3.1-8B-Instruct
+          api_base: http://llama-vllm-neuron:8000/v1
+          api_key: "dummy-key"  # vLLM doesn't require a real API key
+          supports_function_calling: true 
+
+      # Amazon Bedrock Models
+      - model_name: claude-4-sonnet
+        litellm_params:
+          model: bedrock/us.anthropic.claude-sonnet-4-20250514-v1:0
+          aws_access_key_id: os.environ/AWS_ACCESS_KEY_ID
+          aws_secret_access_key: os.environ/AWS_SECRET_ACCESS_KEY
+          aws_region_name: os.environ/AWS_REGION_NAME
+      
+      # vLLM Models     
+      - model_name: my-model
+        litellm_params:
+          model: openai/NousResearch/Meta-Llama-3.1-8B-Instruct
+          api_base: http://llama-vllm-neuron:8000/v1
+          api_key: "dummy-key"  # vLLM doesn't require a real API key
+          supports_function_calling: true 
+
+      # Amazon Bedrock Models
+      - model_name: my-model
+        litellm_params:
+          model: bedrock/us.anthropic.claude-sonnet-4-20250514-v1:0
+          aws_access_key_id: os.environ/AWS_ACCESS_KEY_ID
+          aws_secret_access_key: os.environ/AWS_SECRET_ACCESS_KEY
+          aws_region_name: os.environ/AWS_REGION_NAME
+      
+    router_settings:
+      routing_strategy: simple-shuffle # Literal["simple-shuffle", "least-busy", "usage-based-routing","latency-based-routing"], default="simple-shuffle"
+    
+    general_settings:
+      master_key: os.environ/LITELLM_MASTER_KEY
+      database_url: "postgresql://litellm:postgrespassword@postgresql:5432/litellm"
+      store_model_in_db: true
+      
+    # Redis configuration for caching
+    cache:
+      type: "redis"
+      host: "redis"
+      port: 6379
+      password: "redispassword"
+      
+    # Optional: Add logging and monitoring
+    litellm_settings:
+      success_callback: ["langfuse"]
+      failure_callback: ["langfuse"]
+      set_verbose: true
+---
+apiVersion: v1
+kind: Secret
+metadata:
+  name: litellm-secret
+type: Opaque
+data:
+  master-key: eW91ci1zZWNyZXQta2V5  # base64 encoded "your-secret-key"
+---
+apiVersion: v1
+kind: Secret
+metadata:
+  name: aws-credentials
+type: Opaque
+data:
+  # Base64-encoded AWS credentials
+  access-key-id: MY_ACCESS_KEY  # PLACEHOLDER - UPDATE THIS!
+  # IMPORTANT: Replace this with your actual base64-encoded secret access key
+  # echo -n "your-actual-secret-access-key" | base64  
+  secret-access-key: MY_SECRET_KEY # PLACEHOLDER - UPDATE THIS!
+---
+apiVersion: v1
+kind: Service
+metadata:
+  name: litellm-graviton
+spec:
+  selector:
+    app: litellm-graviton
+  ports:
+  - port: 4000
+    targetPort: 4000
+  type: ClusterIP
+---
+apiVersion: networking.k8s.io/v1
+kind: Ingress
+metadata:
+  name: litellm-ingress
+  annotations:
+    alb.ingress.kubernetes.io/scheme: internet-facing
+    alb.ingress.kubernetes.io/target-type: ip
+spec:
+  ingressClassName: alb
+  rules:
+    - http:
+        paths:
+        - path: /
+          pathType: Prefix
+          backend:
+            service:
+              name: litellm-graviton
+              port:
+                number: 4000
+---
+# Redis Deployment
+apiVersion: apps/v1
+kind: Deployment
+metadata:
+  name: redis
+spec:
+  replicas: 1
+  selector:
+    matchLabels:
+      app: redis
+  template:
+    metadata:
+      labels:
+        app: redis
+    spec:
+      nodeSelector:
+        kubernetes.io/arch: arm64
+      containers:
+      - name: redis
+        image: redis:7-alpine
+        ports:
+        - containerPort: 6379
+        env:
+        - name: REDIS_PASSWORD
+          valueFrom:
+            secretKeyRef:
+              name: redis-secret
+              key: password
+        command:
+        - redis-server
+        - --requirepass
+        - $(REDIS_PASSWORD)
+        resources:
+          requests:
+            cpu: "100m"
+            memory: "128Mi"
+          limits:
+            cpu: "500m"
+            memory: "512Mi"
+        volumeMounts:
+        - name: redis-data
+          mountPath: /data
+      volumes:
+      - name: redis-data
+        persistentVolumeClaim:
+          claimName: redis-pvc
+---
+apiVersion: v1
+kind: Service
+metadata:
+  name: redis
+spec:
+  selector:
+    app: redis
+  ports:
+  - port: 6379
+    targetPort: 6379
+  type: ClusterIP
+---
+apiVersion: v1
+kind: Secret
+metadata:
+  name: redis-secret
+type: Opaque
+data:
+  password: cmVkaXNwYXNzd29yZA==  # base64 encoded "redispassword"
+---
+# Redis PersistentVolumeClaim
+apiVersion: v1
+kind: PersistentVolumeClaim
+metadata:
+  name: redis-pvc
+spec:
+  accessModes:
+    - ReadWriteOnce
+  storageClassName: auto-ebs-sc
+  resources:
+    requests:
+      storage: 5Gi
+---
+# PostgreSQL Deployment
+apiVersion: apps/v1
+kind: Deployment
+metadata:
+  name: postgresql
+spec:
+  replicas: 1
+  selector:
+    matchLabels:
+      app: postgresql
+  template:
+    metadata:
+      labels:
+        app: postgresql
+    spec:
+      nodeSelector:
+        kubernetes.io/arch: arm64
+      containers:
+      - name: postgresql
+        image: postgres:15-alpine
+        ports:
+        - containerPort: 5432
+        env:
+        - name: POSTGRES_DB
+          value: "litellm"
+        - name: POSTGRES_USER
+          valueFrom:
+            secretKeyRef:
+              name: postgresql-secret
+              key: username
+        - name: POSTGRES_PASSWORD
+          valueFrom:
+            secretKeyRef:
+              name: postgresql-secret
+              key: password
+        - name: PGDATA
+          value: /var/lib/postgresql/data/pgdata
+        resources:
+          requests:
+            cpu: "200m"
+            memory: "256Mi"
+          limits:
+            cpu: "1"
+            memory: "1Gi"
+        volumeMounts:
+        - name: postgresql-data
+          mountPath: /var/lib/postgresql/data
+      volumes:
+      - name: postgresql-data
+        persistentVolumeClaim:
+          claimName: postgresql-pvc
+---
+apiVersion: v1
+kind: Service
+metadata:
+  name: postgresql
+spec:
+  selector:
+    app: postgresql
+  ports:
+  - port: 5432
+    targetPort: 5432
+  type: ClusterIP
+---
+apiVersion: v1
+kind: Secret
+metadata:
+  name: postgresql-secret
+type: Opaque
+data:
+  username: bGl0ZWxsbQ==  # base64 encoded "litellm"
+  password: cG9zdGdyZXNwYXNzd29yZA==  # base64 encoded "postgrespassword"
+---
+# PostgreSQL PersistentVolumeClaim
+apiVersion: v1
+kind: PersistentVolumeClaim
+metadata:
+  name: postgresql-pvc
+spec:
+  accessModes:
+    - ReadWriteOnce
+  storageClassName: auto-ebs-sc
+  resources:
+    requests:
+      storage: 10Gi
+
diff --git a/llama3-8b-vllm-neuron.yaml b/llama3-8b-vllm-neuron.yaml
new file mode 100644
index 00000000..bb2d9e03
--- /dev/null
+++ b/llama3-8b-vllm-neuron.yaml
@@ -0,0 +1,66 @@
+---
+apiVersion: apps/v1
+kind: Deployment
+metadata:
+  name: llama-vllm-neuron
+spec:
+  replicas: 1
+  selector:
+    matchLabels:
+      app: llama-vllm-neuron
+  template:
+    metadata:
+      labels:
+        app: llama-vllm-neuron
+    spec:
+      tolerations:
+      - key: "aws.amazon.com/neuron"
+        operator: "Equal"
+        value: "true"
+        effect: "NoSchedule"
+      nodeSelector:
+        node.kubernetes.io/instance-type: inf2.xlarge
+        karpenter.sh/capacity-type: on-demand
+      containers:
+      - name: neuron-llm
+        image: public.ecr.aws/j4m3t0a6/vllm-neuron:latest
+        args:
+          - "--host=0.0.0.0"
+          - "--port=8000"
+          - "--model"
+          - "NousResearch/Meta-Llama-3.1-8B-Instruct"
+          - "--tensor-parallel-size"
+          - "2" 
+          - "--max-num-seqs"
+          - "2"
+          - "--max-model-len"
+          - "8192"
+          - --enable-auto-tool-choice
+          - --tool-call-parser=llama3_json
+          - --chat-template=/workspace/vllm/examples/tool_chat_template_llama3.1_json.jinja
+        resources:
+          limits:
+            cpu: "3"
+            memory: "12Gi"
+            aws.amazon.com/neuron: "1"
+          requests:
+            cpu: "3"
+            memory: "12Gi"
+            aws.amazon.com/neuron: "1"
+        ports:
+        - containerPort: 8000
+        env:
+        - name: FI_EFA_FORK_SAFE
+          value: "1"
+---
+apiVersion: v1
+kind: Service
+metadata:
+  name: llama-vllm-neuron
+spec:
+  selector:
+    app: llama-vllm-neuron
+  ports:
+  - port: 8000
+    targetPort: 8000
+  type: ClusterIP
diff --git a/mcpserver.py b/mcpserver.py
new file mode 100644
index 00000000..634c526b
--- /dev/null
+++ b/mcpserver.py
@@ -0,0 +1,274 @@
+from mcp.server import FastMCP
+import json
+from datetime import datetime, timedelta
+from typing import List, Dict, Optional
+
+# Initialize MCP server for healthcare data
+mcp = FastMCP("Healthcare Data Server", host="0.0.0.0")
+
+# Sample healthcare data (in production, this would connect to a real database/API)
+SAMPLE_PATIENTS = {
+    "PAT001": {
+        "patient_id": "PAT001",
+        "name": "John Doe",
+        "date_of_birth": "1975-03-15",
+        "gender": "Male",
+        "age": 49
+    },
+    "PAT002": {
+        "patient_id": "PAT002", 
+        "name": "Jane Smith",
+        "date_of_birth": "1982-07-22",
+        "gender": "Female",
+        "age": 42
+    },
+    "PAT003": {
+        "patient_id": "PAT003",
+        "name": "Robert Johnson", 
+        "date_of_birth": "1965-11-08",
+        "gender": "Male",
+        "age": 59
+    }
+}
+
+SAMPLE_MEDICAL_HISTORY = {
+    "PAT001": [
+        {
+            "condition": "Type 2 Diabetes Mellitus",
+            "diagnosis_date": "2020-01-15",
+            "status": "active",
+            "severity": "moderate",
+            "notes": "Well controlled with medication",
+            "provider": "Dr. Smith"
+        },
+        {
+            "condition": "Hypertension",
+            "diagnosis_date": "2018-06-01", 
+            "status": "active",
+            "severity": "mild",
+            "notes": "Controlled with ACE inhibitor",
+            "provider": "Dr. Smith"
+        }
+    ],
+    "PAT002": [
+        {
+            "condition": "Hypothyroidism",
+            "diagnosis_date": "2019-03-10",
+            "status": "active", 
+            "severity": "mild",
+            "notes": "On levothyroxine replacement",
+            "provider": "Dr. Jones"
+        }
+    ],
+    "PAT003": [
+        {
+            "condition": "Coronary Artery Disease",
+            "diagnosis_date": "2021-09-15",
+            "status": "active",
+            "severity": "high", 
+            "notes": "Post-MI, on dual antiplatelet therapy",
+            "provider": "Dr. Brown"
+        }
+    ]
+}
+
+SAMPLE_LAB_RESULTS = {
+    "PAT001": [
+        {
+            "test_name": "Glucose, Fasting",
+            "value": "145",
+            "unit": "mg/dL",
+            "reference_range": "70-100",
+            "status": "final",
+            "abnormal_flag": "H",
+            "collection_date": "2025-01-15",
+            "result_date": "2025-01-15",
+            "ordering_provider": "Dr. Smith",
+            "notes": "Elevated - diabetes monitoring"
+        },
+        {
+            "test_name": "Hemoglobin A1c",
+            "value": "7.2",
+            "unit": "%", 
+            "reference_range": "<5.7",
+            "status": "final",
+            "abnormal_flag": "H",
+            "collection_date": "2025-01-15",
+            "result_date": "2025-01-15",
+            "ordering_provider": "Dr. Smith",
+            "notes": "Above target for diabetes"
+        },
+        {
+            "test_name": "Total Cholesterol",
+            "value": "185",
+            "unit": "mg/dL",
+            "reference_range": "<200",
+            "status": "final",
+            "abnormal_flag": "",
+            "collection_date": "2025-01-15", 
+            "result_date": "2025-01-15",
+            "ordering_provider": "Dr. Smith",
+            "notes": "Within normal limits"
+        }
+    ],
+    "PAT002": [
+        {
+            "test_name": "TSH",
+            "value": "2.5",
+            "unit": "mIU/L",
+            "reference_range": "0.4-4.0",
+            "status": "final",
+            "abnormal_flag": "",
+            "collection_date": "2025-01-10",
+            "result_date": "2025-01-10", 
+            "ordering_provider": "Dr. Jones",
+            "notes": "Normal thyroid function"
+        }
+    ],
+    "PAT003": [
+        {
+            "test_name": "Troponin I",
+            "value": "0.02",
+            "unit": "ng/mL",
+            "reference_range": "<0.04",
+            "status": "final",
+            "abnormal_flag": "",
+            "collection_date": "2025-01-20",
+            "result_date": "2025-01-20",
+            "ordering_provider": "Dr. Brown", 
+            "notes": "Normal cardiac enzymes"
+        }
+    ]
+}
+
+@mcp.tool(description="Get patient demographic information by patient ID")
+def get_patient_info(patient_id: str) -> Dict:
+    """Retrieve patient demographic information."""
+    if patient_id not in SAMPLE_PATIENTS:
+        return {"error": f"Patient {patient_id} not found"}
+    
+    return SAMPLE_PATIENTS[patient_id]
+
+@mcp.tool(description="Get complete medical history for a patient")
+def get_patient_history(patient_id: str) -> Dict:
+    """Retrieve complete medical history for a patient."""
+    if patient_id not in SAMPLE_PATIENTS:
+        return {"error": f"Patient {patient_id} not found"}
+    
+    history = SAMPLE_MEDICAL_HISTORY.get(patient_id, [])
+    return {
+        "patient_id": patient_id,
+        "medical_history": history,
+        "total_conditions": len(history)
+    }
+
+@mcp.tool(description="Get lab results for a patient within specified timeframe")
+def get_lab_results(patient_id: str, days_back: int = 365) -> Dict:
+    """Retrieve lab results for a patient within specified timeframe."""
+    if patient_id not in SAMPLE_PATIENTS:
+        return {"error": f"Patient {patient_id} not found"}
+    
+    lab_results = SAMPLE_LAB_RESULTS.get(patient_id, [])
+    
+    # Filter by date range (simplified for sample data)
+    cutoff_date = datetime.now() - timedelta(days=days_back)
+    filtered_results = []
+    
+    for result in lab_results:
+        result_date = datetime.strptime(result["collection_date"], "%Y-%m-%d")
+        if result_date >= cutoff_date:
+            filtered_results.append(result)
+    
+    return {
+        "patient_id": patient_id,
+        "lab_results": filtered_results,
+        "total_results": len(filtered_results),
+        "date_range": f"Last {days_back} days"
+    }
+
+@mcp.tool(description="Search for patients by name or ID")
+def search_patients(query: str) -> Dict:
+    """Search for patients by name or patient ID."""
+    results = []
+    query_lower = query.lower()
+    
+    for patient_id, patient_data in SAMPLE_PATIENTS.items():
+        if (query_lower in patient_id.lower() or 
+            query_lower in patient_data["name"].lower()):
+            results.append({
+                "patient_id": patient_id,
+                "name": patient_data["name"],
+                "date_of_birth": patient_data["date_of_birth"],
+                "gender": patient_data["gender"]
+            })
+    
+    return {
+        "query": query,
+        "results": results,
+        "total_found": len(results)
+    }
+
+@mcp.tool(description="Get comprehensive patient summary including demographics, history, and recent labs")
+def get_patient_summary(patient_id: str, include_labs_days: int = 365) -> Dict:
+    """Get comprehensive patient summary."""
+    if patient_id not in SAMPLE_PATIENTS:
+        return {"error": f"Patient {patient_id} not found"}
+    
+    # Get all patient data
+    patient_info = SAMPLE_PATIENTS[patient_id]
+    medical_history = SAMPLE_MEDICAL_HISTORY.get(patient_id, [])
+    lab_results = SAMPLE_LAB_RESULTS.get(patient_id, [])
+    
+    # Filter recent lab results
+    cutoff_date = datetime.now() - timedelta(days=include_labs_days)
+    recent_labs = []
+    for result in lab_results:
+        result_date = datetime.strptime(result["collection_date"], "%Y-%m-%d")
+        if result_date >= cutoff_date:
+            recent_labs.append(result)
+    
+    # Get active conditions
+    active_conditions = [h for h in medical_history if h["status"].lower() == "active"]
+    
+    # Generate summary
+    summary = {
+        "patient_info": patient_info,
+        "active_conditions": active_conditions,
+        "recent_lab_results": recent_labs,
+        "summary_stats": {
+            "total_conditions": len(medical_history),
+            "active_conditions": len(active_conditions),
+            "recent_lab_count": len(recent_labs)
+        },
+        "risk_factors": _generate_risk_factors(active_conditions, recent_labs),
+        "summary_generated": datetime.now().isoformat()
+    }
+    
+    return summary
+
+def _generate_risk_factors(conditions: List[Dict], lab_results: List[Dict]) -> List[str]:
+    """Generate risk factors based on conditions and lab results."""
+    risk_factors = []
+    
+    # Check conditions
+    condition_names = [c["condition"].lower() for c in conditions]
+    if any("diabetes" in name for name in condition_names):
+        risk_factors.append("Diabetes - requires ongoing monitoring")
+    if any("hypertension" in name for name in condition_names):
+        risk_factors.append("Hypertension - cardiovascular risk factor")
+    if any("coronary" in name or "heart" in name for name in condition_names):
+        risk_factors.append("Cardiovascular disease - high risk")
+    
+    # Check lab results
+    for lab in lab_results:
+        if lab["abnormal_flag"] == "H":
+            if "glucose" in lab["test_name"].lower():
+                risk_factors.append("Elevated glucose levels")
+            elif "cholesterol" in lab["test_name"].lower():
+                risk_factors.append("High cholesterol levels")
+            elif "hba1c" in lab["test_name"].lower():
+                risk_factors.append("Poor diabetes control")
+    
+    return list(set(risk_factors))  # Remove duplicates
+
+mcp.run(transport="streamable-http")
\ No newline at end of file
diff --git a/milvus/README.md b/milvus/README.md
deleted file mode 100644
index 342afa33..00000000
--- a/milvus/README.md
+++ /dev/null
@@ -1,93 +0,0 @@
-# Milvus Vector Database on AWS EKS with Graviton
-
-This directory contains configuration files for deploying Milvus, a vector database, on Amazon EKS with AWS Graviton processors. This setup is part of the larger project for cost-effective and scalable Small Language Models inference on AWS Graviton4 with EKS.
-
-## Overview
-
-Milvus is an open-source vector database built to power embedding similarity search and AI applications. In this setup, we deploy Milvus in standalone mode on AWS Graviton-based EKS nodes to leverage the cost-effectiveness and performance of ARM64 architecture.
-
-## Prerequisites
-
-- An existing EKS cluster with Graviton (ARM64) nodes
-- Cert-manager installed on the cluster
-- Milvus Operator installed on the cluster
-- AWS EBS CSI driver configured for persistent storage
-
-## Configuration Files
-
-This directory includes the following configuration files:
-
-1. **ebs-storage-class.yaml**: Defines an AWS EBS storage class for Milvus persistent storage
-   - Uses gp3 volume type
-   - Enables encryption
-   - Configures WaitForFirstConsumer binding mode
-
-2. **milvus-standalone.yaml**: Deploys Milvus in standalone mode
-   - Configures Milvus to run on ARM64 (Graviton) nodes
-   - Sets up resource requests
-   - Configures in-cluster dependencies (etcd, pulsar, storage)
-   - All components are configured to run on ARM64 architecture
-
-3. **milvus-nlb-service.yaml**: Creates a Network Load Balancer service for external access
-   - Exposes Milvus service port (19530)
-   - Exposes metrics port (9091)
-   - Configures internet-facing NLB
-
-## Deployment Steps
-
-1. **Install cert-manager** (if not already installed):
-   ```bash
-   kubectl apply -f https://github.com/jetstack/cert-manager/releases/download/v1.5.3/cert-manager.yaml
-   kubectl get pods -n cert-manager
-   ```
-
-2. **Install Milvus Operator** (if not already installed):
-   ```bash
-   kubectl apply -f https://raw.githubusercontent.com/zilliztech/milvus-operator/main/deploy/manifests/deployment.yaml
-   kubectl get pods -n milvus-operator
-   ```
-
-3. **Create EBS Storage Class**:
-   ```bash
-   kubectl apply -f ebs-storage-class.yaml
-   ```
-
-4. **Deploy Milvus in standalone mode**:
-   ```bash
-   kubectl apply -f milvus-standalone.yaml
-   ```
-
-5. **Create NLB Service** (optional, if you need external access):
-   ```bash
-   kubectl apply -f milvus-nlb-service.yaml
-   ```
-
-## Accessing Milvus
-
-You can access Milvus using port-forwarding:
-```bash
-kubectl port-forward service/my-release-milvus 19530:19530
-```
-
-Or through the Network Load Balancer if you deployed the NLB service.
-
-## Integration with LLM Services
-
-This Milvus deployment can be integrated with the LLM services in the parent project for vector search capabilities, enabling:
-- Semantic search
-- Retrieval-augmented generation (RAG)
-- Document similarity matching
-- And other vector-based operations
-
-## Uninstalling
-
-To uninstall Milvus:
-```bash
-kubectl delete milvus my-release
-```
-
-## Additional Resources
-
-- [Milvus Documentation](https://milvus.io/docs)
-- [Milvus Operator GitHub](https://github.com/zilliztech/milvus-operator)
-- [Main Project README](../README.md)
diff --git a/milvus/ebs-storage-class.yaml b/milvus/ebs-storage-class.yaml
deleted file mode 100644
index ad4e40a2..00000000
--- a/milvus/ebs-storage-class.yaml
+++ /dev/null
@@ -1,10 +0,0 @@
-# ebs-storage-class.yaml
-apiVersion: storage.k8s.io/v1
-kind: StorageClass
-metadata:
-  name: ebs-sc
-provisioner: ebs.csi.aws.com
-volumeBindingMode: WaitForFirstConsumer
-parameters:
-  type: gp3
-  encrypted: "true"
diff --git a/milvus/milvus-nlb-service.yaml b/milvus/milvus-nlb-service.yaml
deleted file mode 100644
index e581e9dc..00000000
--- a/milvus/milvus-nlb-service.yaml
+++ /dev/null
@@ -1,24 +0,0 @@
-apiVersion: v1
-kind: Service
-metadata:
-  name: milvus-nlb
-  namespace: default
-  annotations:
-    service.beta.kubernetes.io/aws-load-balancer-type: nlb
-    service.beta.kubernetes.io/aws-load-balancer-scheme: internet-facing
-spec:
-  type: LoadBalancer
-  ports:
-  - name: milvus
-    port: 19530
-    targetPort: 19530
-    protocol: TCP
-  - name: metrics
-    port: 9091
-    targetPort: 9091
-    protocol: TCP
-  selector:
-    app.kubernetes.io/instance: my-release
-    app.kubernetes.io/managed-by: milvus-operator
-    app.kubernetes.io/name: milvus
-    "milvus.io/service": "true"
diff --git a/milvus/milvus-standalone.yaml b/milvus/milvus-standalone.yaml
deleted file mode 100644
index c921af9c..00000000
--- a/milvus/milvus-standalone.yaml
+++ /dev/null
@@ -1,55 +0,0 @@
-# kubectl apply -f https://github.com/jetstack/cert-manager/releases/download/v1.5.3/cert-manager.yaml
-# kubectl get pods -n cert-manager
-# kubectl apply -f https://raw.githubusercontent.com/zilliztech/milvus-operator/main/deploy/manifests/deployment.yaml
-# kubectl get pods -n milvus-operator
-# deploy Milvus in standalone mode
-# kubectl apply -f milvus-standalone.yaml
-# Uninstall milvus
-# kubectl delete milvus my-release
-# This is a sample to deploy a standalone milvus in milvus-operator's default configurations.
-# kubectl port-forward service/my-release-milvus 19530:19530
-# kubectl port-forward service/llama-cpp 8080:8080
-# curl --request POST --url http://localhost:8080/completion --header "Content-Type: application/json" --data '{"prompt": "What is llama3.2?","n_predict": 128}'
-apiVersion: milvus.io/v1beta1
-kind: Milvus
-metadata:
-  name: my-release
-spec:
-  mode: standalone
-  components:
-    nodeSelector:
-      kubernetes.io/arch: arm64
-    resources:
-      requests:
-        cpu: "1"
-  dependencies:
-    etcd:
-      inCluster:
-        deletionPolicy: Delete
-        pvcDeletion: true
-        values:
-          nodeSelector:
-            kubernetes.io/arch: arm64
-          resources:
-            requests: 
-              cpu: '1'
-    pulsar:
-      inCluster:
-        deletionPolicy: Delete
-        pvcDeletion: true
-        values:
-          nodeSelector:
-            kubernetes.io/arch: arm64
-          resources:
-            requests: 
-              cpu: '1'
-    storage:
-      inCluster:
-        deletionPolicy: Delete
-        pvcDeletion: true
-        values:
-          nodeSelector:
-            kubernetes.io/arch: arm64
-          resources:
-            requests: 
-              cpu: '1'
\ No newline at end of file
diff --git a/milvus/milvus-update.yaml b/milvus/milvus-update.yaml
deleted file mode 100644
index 7a32ae3a..00000000
--- a/milvus/milvus-update.yaml
+++ /dev/null
@@ -1,8 +0,0 @@
-apiVersion: milvus.io/v1beta1
-kind: Milvus
-metadata:
-  name: my-release
-  namespace: default
-spec:
-  components:
-    image: milvusdb/milvus:v2.5.12
diff --git a/model-gateway/litellm-deployment.yaml b/model-gateway/litellm-deployment.yaml
deleted file mode 100644
index d783a979..00000000
--- a/model-gateway/litellm-deployment.yaml
+++ /dev/null
@@ -1,326 +0,0 @@
----
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: custom-guardrail-config
-data:
-  custom_guardrail.py: |
-    from typing import Any, Dict, List, Literal, Optional, Union
-
-    import litellm
-    from litellm._logging import verbose_proxy_logger
-    from litellm.caching.caching import DualCache
-    from litellm.integrations.custom_guardrail import CustomGuardrail
-    from litellm.proxy._types import UserAPIKeyAuth
-    from litellm.proxy.guardrails.guardrail_helpers import should_proceed_based_on_metadata
-    from litellm.types.guardrails import GuardrailEventHooks
-    import json
-
-    import re,logging
-
-    # logging.basicConfig(level=logging.DEBUG, format='%(asctime)s - %(levelname)s - %(message)s')
-    logger = logging.getLogger(__name__)
-
-    class myCustomGuardrail(CustomGuardrail):
-        def __init__(
-            self,
-            **kwargs,
-        ):
-            # store kwargs as optional_params
-            self.optional_params = kwargs
-
-            super().__init__(**kwargs)
-
-        async def async_post_call_success_hook(
-                self,
-                data: dict,
-                user_api_key_dict: UserAPIKeyAuth,
-                response,
-            ):
-                """
-                Runs on response from LLM API call
-
-                It can be used to reject a response
-
-                If a response contains invalid JSON -> we will raise an exception
-                """
-                if isinstance(response, litellm.ModelResponse):
-                    for choice in response.choices:
-                        if isinstance(choice, litellm.Choices):
-                            if isinstance(choice.message.content, str):
-                                detected_pii = self.detect_pii(choice.message.content)
-                                logger.log(logging.CRITICAL, msg=f"detect_pii: {detected_pii}")
-                                if detected_pii:
-                                    raise ValueError(f"Guardrail failed PII Detected: {detected_pii}")
-                                                          
-                                # try:
-                                #     json_content = json.loads(choice.message.content)
-                                # except json.JSONDecodeError as e:
-                                #     raise ValueError(f"Invalid JSON in response content: {e}")
-                                
-        def detect_pii(self, content: str) -> List[str]:
-            """
-            Detects PII data in the given content.
-            
-            Args:
-                content (str): The content to check for PII data.
-            
-            Returns:
-                List[str]: A list of detected PII data.
-            """
-            pii_patterns = {
-                "email": r"[a-zA-Z0-9._%+-]+@[a-zA-Z0-9.-]+\.[a-zA-Z]{2,}",
-                "phone": r"\b\d{3}[-.]?\d{3}[-.]?\d{4}\b",
-                "ssn": r"\b\d{3}-\d{2}-\d{4}\b"
-            }
-            
-            detected_pii = []
-            
-            for pii_type, pattern in pii_patterns.items():
-                matches = re.findall(pattern, content)
-                if matches:
-                    return True
-                    # detected_pii.extend(matches)
-            
-            return False     
-
-
-
----
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: litellm-config
-data:
-  config.yaml: |
-    model_list:
-    - model_name: vllm-server-qwen3
-      litellm_params:
-        model: hosted_vllm/Qwen/Qwen3-14B
-        api_base: http://vllm-qwen-server:8000/v1
-    - model_name: llamacpp-embedding
-      litellm_params:
-        model: hosted_vllm/ChristianAzinn/snowflake-arctic-embed-s-gguf
-        api_base: http://ray-service-llamacpp-serve-svc:8000/v1
-        api_key: sk-1234
-    - model_name: vllm-server-qwen-vision
-      litellm_params:
-        model: hosted_vllm/Qwen/Qwen2.5-VL-7B-Instruct
-        api_base: http://vllm-qwen-server-vision:8000/v1
-        stream: false
-      model_info:
-        supports_function_calling: true
-
-    # guardrails:
-    #   - guardrail_name: "custom-post-guard"
-    #     litellm_params:
-    #       guardrail: custom_guardrail.myCustomGuardrail
-    #       mode: "post_call" 
-    #       default_on: true
-
-    litellm_settings:
-      cache: true
-      cache_params:
-        type: redis
-        # redis_startup_nodes: [{"host": "redis", "port": "6379"}] 
-        ttl: 10
-      drop_parmas: false
-      forward_to_langfuse: true
-      success_callback: ["langfuse"]
-      failure_callback: ["langfuse"]
-      langfuse_public_key: os.environ/LANGFUSE_PUBLIC_KEY
-      langfuse_secret: os.environ/LANGFUSE_SECRET_KEY
-      langfuse_host: os.environ/LANGFUSE_HOST
-
-      default_team_settings: 
-        - team_id: team-1
-          success_callback: ["langfuse"]
-          failure_callback: ["langfuse"]
-          langfuse_public_key: os.environ/LANGFUSE_PUBLIC_KEY
-          langfuse_secret: os.environ/LANGFUSE_SECRET_KEY
-          langfuse_host: os.environ/LANGFUSE_HOST
-
-    # https://docs.litellm.ai/docs/proxy/configs  
-
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: litellm
-  labels:
-    app: litellm
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: litellm
-  template:
-    metadata:
-      labels:
-        app: litellm
-    spec:
-      nodeSelector:
-        kubernetes.io/arch: arm64
-      containers:
-      - name: litellm
-        # image: ghcr.io/berriai/litellm:main-latest
-        image:  public.ecr.aws/p7b6k2h9/fmamazon/genai-eks:litellm-main-latest
-        ports:
-        - containerPort: 4000
-        livenessProbe:
-          httpGet:
-            path: /health/liveliness
-            port: 4000
-          initialDelaySeconds: 10
-          periodSeconds: 15
-          successThreshold: 1
-          failureThreshold: 3
-          timeoutSeconds: 10
-        readinessProbe:
-          httpGet:
-            path: /health/readiness
-            port: 4000
-          initialDelaySeconds: 30
-          periodSeconds: 15
-          successThreshold: 1
-          failureThreshold: 3
-          timeoutSeconds: 10        
-        args: [ "--config", "/app/config.yaml"]  
-        # args: [ "--config", "/app/config.yaml", "--detailed_debug"]  
-        env:
-        - name: DATABASE_URL
-          value: postgres://myuser:mypassword@postgres:5432/mydatabase      
-
-        - name: LANGFUSE_SECRET_KEY
-          value: ""
-        - name: LANGFUSE_PUBLIC_KEY
-          value: ""
-        - name: LANGFUSE_HOST
-          value: ""
-        - name: REDIS_HOST
-          value: redis
-        - name: REDIS_PORT
-          value: "6379"  
-        - name: LITELLM_MASTER_KEY
-          value: sk-123456
-        - name: LITELLM_SALT_KEY
-          value: abcd1234
-        - name: STORE_MODEL_IN_DB
-          value: "true"      
-        volumeMounts:
-        - name: config-volume
-          readOnly: true
-          mountPath: /app/config.yaml
-          subPath: config.yaml
-        - name: guardrail-volume
-          mountPath: /app/custom_guardrail.py
-          subPath: custom_guardrail.py          
-      volumes:
-      - name: config-volume
-        configMap:
-          name: litellm-config
-      - name: guardrail-volume
-        configMap:
-          name: custom-guardrail-config          
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: litellm
-spec:
-  selector:
-    app: litellm
-  ports:
-    - protocol: TCP
-      port: 4000
-      targetPort: 4000
-  type: ClusterIP
----
-apiVersion: apps/v1
-kind: StatefulSet
-metadata:
-  name: postgres
-spec:
-  serviceName: "postgres"
-  replicas: 1
-  selector:
-    matchLabels:
-      app: postgres
-  template:
-    metadata:
-      labels:
-        app: postgres
-    spec:
-      containers:
-      - name: postgres
-        image: postgres:15.12-bookworm
-        ports:
-        - containerPort: 5432
-          name: postgres
-        env:
-        - name: POSTGRES_DB
-          value: "mydatabase"
-        - name: POSTGRES_USER
-          value: "myuser"
-        - name: POSTGRES_PASSWORD
-          value: "mypassword"
-        volumeMounts:
-        - name: postgres-storage
-          mountPath: /var/lib/postgresql/data
-          subPath: postgres
-  volumeClaimTemplates:
-  - metadata:
-      name: postgres-storage
-    spec:
-      accessModes: ["ReadWriteOnce"]
-      resources:
-        requests:
-          storage: 1Gi
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: postgres
-spec:
-  ports:
-  - port: 5432
-    name: postgres
-  clusterIP: None
-  selector:
-    app: postgres  
-
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: redis
-  labels:
-    app: redis
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: redis
-  template:
-    metadata:
-      labels:
-        app: redis
-    spec:
-      containers:
-      - name: redis
-        image: redis:6.2.6
-        ports:
-        - containerPort: 6379
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: redis
-spec:
-  selector:
-    app: redis
-  ports:
-    - protocol: TCP
-      port: 6379
-      targetPort: 6379
-  type: ClusterIP
diff --git a/model-gateway/litellm-ingress.yaml b/model-gateway/litellm-ingress.yaml
deleted file mode 100644
index 57c4a741..00000000
--- a/model-gateway/litellm-ingress.yaml
+++ /dev/null
@@ -1,22 +0,0 @@
-apiVersion: networking.k8s.io/v1
-kind: Ingress
-metadata:
-  name: litellm-ingress-alb
-  annotations:
-    kubernetes.io/ingress.class: alb
-    alb.ingress.kubernetes.io/scheme: internet-facing
-    alb.ingress.kubernetes.io/target-type: ip
-    alb.ingress.kubernetes.io/healthcheck-path: /
-    alb.ingress.kubernetes.io/healthcheck-port: "4000"
-    alb.ingress.kubernetes.io/listen-ports: '[{"HTTP": 80}]'
-spec:
-  rules:
-    - http:
-        paths:
-          - path: /
-            pathType: Prefix
-            backend:
-              service:
-                name: litellm
-                port:
-                  number: 4000
diff --git a/model-gateway/setup.sh b/model-gateway/setup.sh
deleted file mode 100755
index 455fc9ff..00000000
--- a/model-gateway/setup.sh
+++ /dev/null
@@ -1,329 +0,0 @@
-#!/bin/bash
-
-# Script to deploy model gateway services
-
-set -e
-
-# Color codes for better readability
-GREEN='\033[0;32m'
-BLUE='\033[0;34m'
-RED='\033[0;31m'
-YELLOW='\033[0;33m'
-NC='\033[0m' # No Color
-
-# Function to display messages with timestamp
-log() {
-  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
-}
-
-warn() {
-  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
-}
-
-error() {
-  echo -e "${RED}[$(date '+%Y-%m-%d %H:%M:%S')] ERROR:${NC} $1"
-  exit 1
-}
-
-success() {
-  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
-}
-
-# Collect Langfuse configuration
-collect_langfuse_config() {
-  log "Configuring Langfuse integration..."
-  
-  echo ""
-  echo "=============================================================================="
-  echo "                        LANGFUSE CONFIGURATION REQUIRED"
-  echo "=============================================================================="
-  echo ""
-  
-  # Auto-detect Langfuse deployment in cluster
-  log "Checking for Langfuse deployment in your cluster..."
-  
-  LANGFUSE_SERVICE=$(kubectl get svc -l app.kubernetes.io/name=langfuse --no-headers 2>/dev/null | grep langfuse-web | head -1)
-  DETECTED_LANGFUSE_HOST=""
-  
-  if [ -n "$LANGFUSE_SERVICE" ]; then
-    success "Found Langfuse web service in your cluster!"
-    kubectl get svc langfuse-web
-    echo ""
-    
-    # Check for ingress first (more likely to be externally accessible)
-    LANGFUSE_INGRESS_HOST=$(kubectl get ingress langfuse-web-ingress-alb -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-    if [ -n "$LANGFUSE_INGRESS_HOST" ]; then
-      DETECTED_LANGFUSE_HOST="http://$LANGFUSE_INGRESS_HOST"
-      success "Detected Langfuse Host URL (via ingress): $DETECTED_LANGFUSE_HOST"
-    fi
-    
-    # Check for LoadBalancer service as alternative (handle errors gracefully)
-    LANGFUSE_LB=$(kubectl get svc -l app.kubernetes.io/name=langfuse,type=LoadBalancer -o jsonpath='{.items[0].status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-    if [ -n "$LANGFUSE_LB" ]; then
-      if [ -z "$DETECTED_LANGFUSE_HOST" ]; then
-        DETECTED_LANGFUSE_HOST="http://$LANGFUSE_LB"
-      fi
-      log "Alternative Langfuse URL (via LoadBalancer): http://$LANGFUSE_LB"
-    fi
-    
-    if [ -z "$DETECTED_LANGFUSE_HOST" ]; then
-      warn "Langfuse service found but no external access configured."
-      log "You may need to set up port-forwarding: kubectl port-forward svc/langfuse-web 3000:3000"
-    fi
-  else
-    warn "No Langfuse service found in your cluster."
-    log "Please deploy Langfuse first using: make setup-observability"
-  fi
-  
-  echo ""
-  echo "SETUP INSTRUCTIONS:"
-  echo "1. 🌐 ACCESS LANGFUSE:"
-  if [ -n "$DETECTED_LANGFUSE_HOST" ]; then
-    echo "   Open your browser and go to: $DETECTED_LANGFUSE_HOST"
-  else
-    echo "   Use your Langfuse URL (e.g., https://cloud.langfuse.com)"
-    echo "   Or set up port-forwarding: kubectl port-forward svc/langfuse-web 3000:3000"
-    echo "   Then access: http://localhost:3000"
-  fi
-  echo ""
-  echo "2. 🏢 CREATE ORGANIZATION: Name it 'test'"
-  echo "3. 📁 CREATE PROJECT: Name it 'demo' inside the organization"
-  echo "4. 🔑 GET API KEYS: Go to Settings → API Keys → Create new API key"
-  echo "   - Copy the Public Key (starts with 'pk-')"
-  echo "   - Copy the Secret Key (starts with 'sk-')"
-  echo ""
-  echo "=============================================================================="
-  echo ""
-  
-  # Prompt for Langfuse Host with auto-detected default
-  while [ -z "$LANGFUSE_HOST" ]; do
-    if [ -n "$DETECTED_LANGFUSE_HOST" ]; then
-      echo "Enter your Langfuse Host URL (press Enter to use detected URL):"
-      echo "Detected: $DETECTED_LANGFUSE_HOST"
-      echo ""
-      read -p "Langfuse Host URL [$DETECTED_LANGFUSE_HOST]: " LANGFUSE_HOST
-      
-      # Use detected URL if nothing entered
-      if [ -z "$LANGFUSE_HOST" ]; then
-        LANGFUSE_HOST="$DETECTED_LANGFUSE_HOST"
-      fi
-    else
-      echo "Enter your Langfuse Host URL:"
-      echo "Examples:"
-      echo "  - For Langfuse Cloud: https://cloud.langfuse.com"
-      echo "  - For self-hosted: http://your-langfuse-loadbalancer.region.elb.amazonaws.com"
-      echo "  - For port-forwarding: http://localhost:3000"
-      echo ""
-      read -p "Langfuse Host URL: " LANGFUSE_HOST
-    fi
-    
-    if [ -z "$LANGFUSE_HOST" ]; then
-      warn "Langfuse Host URL cannot be empty. Please try again."
-    elif [[ ! "$LANGFUSE_HOST" =~ ^https?:// ]]; then
-      warn "Please include http:// or https:// in the URL."
-      LANGFUSE_HOST=""
-    fi
-  done
-  
-  # Prompt for Langfuse Public Key with validation
-  while [ -z "$LANGFUSE_PUBLIC_KEY" ]; do
-    echo ""
-    echo "Enter your Langfuse Public Key:"
-    echo "  - Should start with 'pk-'"
-    echo "  - Found in Langfuse Settings → API Keys"
-    echo ""
-    read -p "Langfuse Public Key: " LANGFUSE_PUBLIC_KEY
-    
-    if [ -z "$LANGFUSE_PUBLIC_KEY" ]; then
-      warn "Langfuse Public Key cannot be empty. Please try again."
-    elif [[ ! "$LANGFUSE_PUBLIC_KEY" =~ ^pk- ]]; then
-      warn "Public Key should start with 'pk-'. Please check and try again."
-      LANGFUSE_PUBLIC_KEY=""
-    fi
-  done
-  
-  # Prompt for Langfuse Secret Key with validation
-  while [ -z "$LANGFUSE_SECRET_KEY" ]; do
-    echo ""
-    echo "Enter your Langfuse Secret Key:"
-    echo "  - Should start with 'sk-'"
-    echo "  - Found in Langfuse Settings → API Keys"
-    echo "  - Input will be hidden for security"
-    echo ""
-    read -s -p "Langfuse Secret Key: " LANGFUSE_SECRET_KEY
-    echo ""
-    
-    if [ -z "$LANGFUSE_SECRET_KEY" ]; then
-      warn "Langfuse Secret Key cannot be empty. Please try again."
-    elif [[ ! "$LANGFUSE_SECRET_KEY" =~ ^sk- ]]; then
-      warn "Secret Key should start with 'sk-'. Please check and try again."
-      LANGFUSE_SECRET_KEY=""
-    fi
-  done
-  
-  echo ""
-  echo "=============================================================================="
-  echo "CONFIGURATION SUMMARY:"
-  echo "  Host: $LANGFUSE_HOST"
-  echo "  Public Key: ${LANGFUSE_PUBLIC_KEY:0:10}..."
-  echo "  Secret Key: ${LANGFUSE_SECRET_KEY:0:10}..."
-  echo "=============================================================================="
-  echo ""
-  
-  # Auto-proceed without confirmation
-  log "Proceeding with configuration..."
-  
-  success "Langfuse configuration collected successfully!"
-}
-
-# Update deployment YAML with Langfuse configuration
-update_deployment_config() {
-  log "Updating deployment configuration with Langfuse settings..."
-  
-  # Create a backup of the original file
-  cp litellm-deployment.yaml litellm-deployment.yaml.backup
-  
-  # Use awk for more reliable replacement (works on both macOS and Linux)
-  awk -v secret_key="$LANGFUSE_SECRET_KEY" -v public_key="$LANGFUSE_PUBLIC_KEY" -v host="$LANGFUSE_HOST" '
-  /- name: LANGFUSE_SECRET_KEY/ { 
-    print $0; 
-    getline; 
-    print "          value: \"" secret_key "\""; 
-    next 
-  }
-  /- name: LANGFUSE_PUBLIC_KEY/ { 
-    print $0; 
-    getline; 
-    print "          value: \"" public_key "\""; 
-    next 
-  }
-  /- name: LANGFUSE_HOST/ { 
-    print $0; 
-    getline; 
-    print "          value: \"" host "\""; 
-    next 
-  }
-  { print }
-  ' litellm-deployment.yaml.backup > litellm-deployment.yaml.tmp && mv litellm-deployment.yaml.tmp litellm-deployment.yaml
-  
-  success "Deployment configuration updated with Langfuse settings!"
-}
-
-# Check prerequisites
-check_prerequisites() {
-  log "Checking prerequisites..."
-  
-  # Check kubectl
-  if ! command -v kubectl &> /dev/null; then
-    error "kubectl is not installed. Please install it first."
-  fi
-  
-  # Check if kubectl is configured to access a cluster
-  if ! kubectl cluster-info &> /dev/null; then
-    error "Cannot access Kubernetes cluster. Please check your kubeconfig."
-  fi
-  
-  success "All prerequisites satisfied."
-}
-
-# Install LiteLLM deployment
-install_litellm_deployment() {
-  log "Installing LiteLLM deployment..."
-  
-  if [ -f "litellm-deployment.yaml" ]; then
-    kubectl apply -f litellm-deployment.yaml
-    success "LiteLLM deployment applied successfully!"
-  else
-    error "litellm-deployment.yaml not found"
-  fi
-}
-
-# Wait for LiteLLM service to be running
-wait_for_litellm_service() {
-  log "Waiting for LiteLLM service to be ready..."
-  
-  # Wait for deployment to be available
-  kubectl wait --for=condition=available --timeout=600s deployment/litellm 2>/dev/null || {
-    warn "LiteLLM deployment might still be initializing. Checking pod status..."
-    kubectl get pods -l app=litellm
-  }
-  
-  # Check if pods are running
-  local max_attempts=30
-  local attempt=1
-  
-  while [ $attempt -le $max_attempts ]; do
-    local running_pods=$(kubectl get pods -l app=litellm --field-selector=status.phase=Running --no-headers | wc -l)
-    
-    if [ "$running_pods" -gt 0 ]; then
-      success "LiteLLM service is running!"
-      kubectl get pods -l app=litellm
-      return 0
-    fi
-    
-    log "Attempt $attempt/$max_attempts: Waiting for LiteLLM pods to be running..."
-    sleep 10
-    ((attempt++))
-  done
-  
-  error "LiteLLM service failed to start within the expected time. Please check the logs."
-}
-
-# Install LiteLLM ingress
-install_litellm_ingress() {
-  log "Installing LiteLLM ingress..."
-  
-  if [ -f "litellm-ingress.yaml" ]; then
-    kubectl apply -f litellm-ingress.yaml
-    success "LiteLLM ingress applied successfully!"
-  else
-    error "litellm-ingress.yaml not found"
-  fi
-}
-
-# Verify installations
-verify_installations() {
-  log "Verifying installations..."
-  
-  log "Checking LiteLLM deployment..."
-  kubectl get deployment litellm
-  
-  log "Checking LiteLLM service..."
-  kubectl get service litellm
-  
-  log "Checking LiteLLM ingress..."
-  kubectl get ingress litellm-ingress 2>/dev/null || log "No ingress found (this is normal if ingress is not configured)"
-  
-  log "Checking LiteLLM pods..."
-  kubectl get pods -l app=litellm
-  
-  # Get ingress URL if available
-  local ingress_url=$(kubectl get ingress litellm-ingress -o jsonpath='{.status.loadBalancer.ingress[0].hostname}' 2>/dev/null || echo "")
-  if [ -n "$ingress_url" ]; then
-    log "LiteLLM is accessible at: https://$ingress_url"
-  else
-    log "Ingress URL not yet available. It may take a few minutes for the load balancer to be provisioned."
-  fi
-  
-  success "Installation verification completed!"
-}
-
-# Main execution
-main() {
-  log "Starting model gateway deployment..."
-  
-  check_prerequisites
-  collect_langfuse_config
-  update_deployment_config
-  install_litellm_deployment
-  wait_for_litellm_service
-  install_litellm_ingress
-  verify_installations
-  
-  success "Model gateway deployed successfully!"
-  log "LiteLLM proxy is now available and can route requests to your model backends."
-  log "Langfuse integration has been configured for observability and monitoring."
-}
-
-# Execute main function
-main
diff --git a/model-hosting/ray-server/llamacpp.py b/model-hosting/ray-server/llamacpp.py
deleted file mode 100644
index 2ff80819..00000000
--- a/model-hosting/ray-server/llamacpp.py
+++ /dev/null
@@ -1,102 +0,0 @@
-
-
-
-import multiprocessing
-import os
-import logging
-import time
-from fastapi import FastAPI
-from starlette.requests import Request
-from starlette.responses import StreamingResponse, JSONResponse
-
-from ray import serve
-
-from starlette.requests import Request
-from starlette.responses import StreamingResponse, JSONResponse
-import logging
-
-from llama_cpp import Llama
-
-
-
-logger = logging.getLogger("ray.serve")
-
-app = FastAPI()
-
-# Define the deployment
-# ray_actor_options={"num_cpus": 14},
-@serve.deployment(name="LLamaCPPDeployment",  autoscaling_config={"min_replicas" : 10, "max_replicas": 10, "initial_replicas": 10, "upscale_delay_s": 5}, max_ongoing_requests=100, graceful_shutdown_timeout_s=600)
-@serve.ingress(app)
-class LLamaCPPDeployment:
-    def __init__(self, parallelism: str):
-        os.environ["OMP_NUM_THREADS"] = parallelism
-        # Initialize the LLamaCPP model
-        self.model_id = os.getenv("MODEL_ID", default="SanctumAI/Llama-3.2-1B-Instruct-GGUF")
-        # Get filename from environment variable with default fallback to "*Q4_0.gguf"
-        self.filename = os.getenv("MODEL_FILENAME", default="*Q4_0.gguf")
-        self.n_ctx = int(os.getenv("N_CTX"))
-        self.n_threads = int(os.getenv("N_THREADS"))
-        # self.n_batch = int(os.getenv("N_BATCH"))
-        # self.llama_cpp = Llama(model_path=MODEL_ID, n_ctx=self.n_ctx, n_batch=self.n_batch)
-        self.llm = Llama.from_pretrained(repo_id=self.model_id,filename=self.filename,n_ctx=self.n_ctx,n_threads=self.n_threads)
-        #"hugging-quants/Llama-3.2-3B-Instruct-Q8_0-GGUF",
-        print("__init__ Complete")
-
-    @app.post("/v1/chat/completions")
-    async def call_llama(self, request: Request):
-        try:
-            body = await request.json()
-
-            # Get the messages array from the body
-            messages = body.get("messages", [])
-
-            # Get the content from the last user message
-            prompt = ""
-            if messages:
-                for message in messages:
-                    if message.get("role") == "user":
-                        prompt = message.get("content", "")
-                        break
-        
-            
-            if not prompt:
-                return JSONResponse(
-                    status_code=400,
-                    content={"error": "prompt is required"}
-                )
-
-            output = self.llm(
-                "Q: " + prompt + " A: ",
-                max_tokens=body.get("max_tokens", 32)
-            )        
-            
-            return JSONResponse(content={
-                "id": "cmpl-" + os.urandom(12).hex(),
-                "object": "text_completion",
-                "created": int(time.time()),
-                "model": self.model_id,
-                "choices": [{
-                    "text": output["choices"][0]["text"],
-                    "index": 0,
-                    "finish_reason": "stop"
-                }],
-                "usage": {
-                    "prompt_tokens": len(prompt.split()),
-                    "completion_tokens": len(output["choices"][0]["text"].split()),
-                    "total_tokens": len(prompt.split()) + len(output["choices"][0]["text"].split())
-                }
-            })
-
-            
-        except Exception as e:
-            logger.error(f"Error: {str(e)}")
-            return JSONResponse(
-                status_code=500,
-                content={"error": str(e)}
-            )
-
-
-# Get host CPU count
-host_cpu_count = multiprocessing.cpu_count()
-
-model = LLamaCPPDeployment.bind("host_cpu_count")
\ No newline at end of file
diff --git a/model-hosting/ray-server/local-requirements.txt b/model-hosting/ray-server/local-requirements.txt
deleted file mode 100644
index 8cae3d83..00000000
--- a/model-hosting/ray-server/local-requirements.txt
+++ /dev/null
@@ -1,5 +0,0 @@
-llama_cpp_python==0.3.2
-transformers==4.46.0
-fastapi[all]
-ray==2.39.0
-starlette==0.41.3
\ No newline at end of file
diff --git a/model-hosting/ray-server/vllm.py b/model-hosting/ray-server/vllm.py
deleted file mode 100644
index 676cd670..00000000
--- a/model-hosting/ray-server/vllm.py
+++ /dev/null
@@ -1,131 +0,0 @@
-import json
-from typing import AsyncGenerator
-from fastapi import BackgroundTasks
-from starlette.requests import Request
-from starlette.responses import StreamingResponse, Response, JSONResponse
-from vllm.engine.arg_utils import AsyncEngineArgs
-from vllm.engine.async_llm_engine import AsyncLLMEngine
-from vllm.sampling_params import SamplingParams
-from vllm.utils import random_uuid
-from ray import serve
-import os
-import logging
-
-from huggingface_hub import login
-
-# Environment and configuration setup
-logger = logging.getLogger("ray.serve")
-
-@serve.deployment(name="mistral-deployment", route_prefix="/vllm",
-    ray_actor_options={"num_gpus": 1},
-    autoscaling_config={"min_replicas": 1, "max_replicas": 2},
-)
-class VLLMDeployment:
-    def __init__(self, **kwargs):
-        hf_token = os.getenv("HUGGING_FACE_HUB_TOKEN")
-        logger.info(f"token: {hf_token=}")
-        if not hf_token:
-            raise ValueError("HUGGING_FACE_HUB_TOKEN environment variable is not set")
-        login(token=hf_token)
-        logger.info("Successfully logged in to Hugging Face Hub")
-
-        args = AsyncEngineArgs(
-            model=os.getenv("MODEL_ID", "mistralai/Mistral-7B-Instruct-v0.2"),  # Model identifier from Hugging Face Hub or local path.
-            dtype="auto",  # Automatically determine the data type (e.g., float16 or float32) for model weights and computations.
-            gpu_memory_utilization=float(os.getenv("GPU_MEMORY_UTILIZATION", "0.8")),  # Percentage of GPU memory to utilize, reserving some for overhead.
-            max_model_len=int(os.getenv("MAX_MODEL_LEN", "4096")),  # Maximum sequence length (in tokens) the model can handle, including both input and output tokens.
-            max_num_seqs=int(os.getenv("MAX_NUM_SEQ", "512")),  # Maximum number of sequences (requests) to process in parallel.
-            max_num_batched_tokens=int(os.getenv("MAX_NUM_BATCHED_TOKENS", "32768")),  # Maximum number of tokens processed in a single batch across all sequences (max_model_len * max_num_seqs).
-            trust_remote_code=True,  # Allow execution of untrusted code from the model repository (use with caution).
-            enable_chunked_prefill=False,  # Disable chunked prefill to avoid compatibility issues with prefix caching.
-            tokenizer_pool_size=4,  # Number of tokenizer instances to handle concurrent requests efficiently.
-            tokenizer_pool_type="ray",  # Pool type for tokenizers; 'ray' uses Ray for distributed processing.
-            max_parallel_loading_workers=2,  # Number of parallel workers to load the model concurrently.
-            pipeline_parallel_size=1,  # Number of pipeline parallelism stages; typically set to 1 unless using model parallelism.
-            tensor_parallel_size=1,  # Number of tensor parallelism stages; typically set to 1 unless using model parallelism.
-            enable_prefix_caching=True,  # Enable prefix caching to improve performance for similar prompt prefixes.
-            enforce_eager=True,
-            disable_log_requests=True,
-        )
-
-        self.engine = AsyncLLMEngine.from_engine_args(args)
-        self.max_model_len = args.max_model_len
-        logger.info(f"VLLM Engine initialized with max_model_len: {self.max_model_len}")
-
-    async def stream_results(self, results_generator) -> AsyncGenerator[bytes, None]:
-        num_returned = 0
-        async for request_output in results_generator:
-            text_outputs = [output.text for output in request_output.outputs]
-            assert len(text_outputs) == 1
-            text_output = text_outputs[0][num_returned:]
-            ret = {"text": text_output}
-            yield (json.dumps(ret) + "\n").encode("utf-8")
-            num_returned += len(text_output)
-
-    async def may_abort_request(self, request_id) -> None:
-        await self.engine.abort(request_id)
-
-    async def __call__(self, request: Request) -> Response:
-        try:
-            request_dict = await request.json()
-        except json.JSONDecodeError:
-            return JSONResponse(status_code=400, content={"error": "Invalid JSON in request body"})
-
-        context_length = request_dict.pop("context_length", 8192)  # Default to 8k
-
-        # Ensure context length is either 8k or 32k
-        if context_length not in [8192, 32768]:
-            context_length = 8192  # Default to 8k if invalid
-        prompt = request_dict.pop("prompt")
-        stream = request_dict.pop("stream", False)
-
-        # Get model config and tokenizer
-        model_config = await self.engine.get_model_config()
-        tokenizer = await self.engine.get_tokenizer()
-
-        input_token_ids = tokenizer.encode(prompt)
-        input_tokens = len(input_token_ids)
-        max_possible_new_tokens = min(context_length, model_config.max_model_len) - input_tokens
-        max_new_tokens = min(request_dict.get("max_tokens", 8192), max_possible_new_tokens)
-
-        sampling_params = SamplingParams(
-            max_tokens=max_new_tokens,
-            temperature=request_dict.get("temperature", 0.7),
-            top_p=request_dict.get("top_p", 0.9),
-            top_k=request_dict.get("top_k", 50),
-            stop=request_dict.get("stop", None),
-        )
-
-        request_id = random_uuid()
-        logger.info(f"Processing request {request_id} with {input_tokens} input tokens")
-
-        results_generator = self.engine.generate(prompt, sampling_params, request_id)
-
-        if stream:
-            background_tasks = BackgroundTasks()
-            # Using background_tasks to abort the request
-            # if the client disconnects.
-            background_tasks.add_task(self.may_abort_request, request_id)
-            return StreamingResponse(
-                self.stream_results(results_generator), background=background_tasks
-            )
-
-        # Non-streaming case
-        final_output = None
-        async for request_output in results_generator:
-            if await request.is_disconnected():
-                # Abort the request if the client disconnects.
-                await self.engine.abort(request_id)
-                logger.warning(f"Client disconnected for request {request_id}")
-                return Response(status_code=499)
-            final_output = request_output
-
-        assert final_output is not None
-        prompt = final_output.prompt
-        text_outputs = [prompt + output.text for output in final_output.outputs]
-        ret = {"text": text_outputs}
-        logger.info(f"Completed request {request_id}")
-        return Response(content=json.dumps(ret))
-
-
-deployment = VLLMDeployment.bind()
\ No newline at end of file
diff --git a/model-hosting/ray-services/ingress/add-sg-lb-eks.sh b/model-hosting/ray-services/ingress/add-sg-lb-eks.sh
deleted file mode 100644
index 5c89c88e..00000000
--- a/model-hosting/ray-services/ingress/add-sg-lb-eks.sh
+++ /dev/null
@@ -1,23 +0,0 @@
-#!/bin/bash
-
-
-REGION=ap-southeast-2
-CLUSTER_NAME=llm-eks-cluster
-ALB_NAME=llama-cpp-cpu-lb
-export AWS_DEFAULT_REGION=$REGION
-
-CLUSTER_SG=$(aws eks describe-cluster \
-    --name $CLUSTER_NAME \
-    --query 'cluster.resourcesVpcConfig.clusterSecurityGroupId' \
-    --output text)
-
-ALB_SG=$(aws elbv2 describe-load-balancers \
-    --names $ALB_NAME \
-    --query 'LoadBalancers[0].SecurityGroups[0]' \
-    --output text)    
-
-aws ec2 authorize-security-group-ingress \
-    --group-id $CLUSTER_SG \
-    --source-group $ALB_SG \
-    --protocol tcp \
-    --port-range 0-65535
\ No newline at end of file
diff --git a/model-hosting/ray-services/ingress/ingress-cpu.yaml b/model-hosting/ray-services/ingress/ingress-cpu.yaml
deleted file mode 100644
index e9045e57..00000000
--- a/model-hosting/ray-services/ingress/ingress-cpu.yaml
+++ /dev/null
@@ -1,28 +0,0 @@
-apiVersion: networking.k8s.io/v1
-kind: Ingress
-metadata:
-  name: llama-3-8b-cpu-llama-serve-ingress
-  annotations:
-    alb.ingress.kubernetes.io/scheme: internet-facing
-    alb.ingress.kubernetes.io/target-type: ip
-    alb.ingress.kubernetes.io/load-balancer-name: "llama-cpp-cpu-lb"
-    alb.ingress.kubernetes.io/healthcheck-protocol: HTTP
-    alb.ingress.kubernetes.io/healthcheck-port: "8265"
-    alb.ingress.kubernetes.io/healthcheck-path: "/"
-    alb.ingress.kubernetes.io/success-codes: "200"
-spec:
-  ingressClassName: alb
-  rules:
-  - http:
-      paths:
-      - path: /
-        pathType: Prefix
-        backend:
-          service:
-            name: ray-service-llamacpp-serve-svc
-            port:
-              number: 8000
-
-
-
-
diff --git a/model-hosting/ray-services/ingress/ingress-embedding.yaml b/model-hosting/ray-services/ingress/ingress-embedding.yaml
deleted file mode 100644
index 6cd3151f..00000000
--- a/model-hosting/ray-services/ingress/ingress-embedding.yaml
+++ /dev/null
@@ -1,24 +0,0 @@
-apiVersion: networking.k8s.io/v1
-kind: Ingress
-metadata:
-  name: embedding-ray-service-ingress
-  annotations:
-    alb.ingress.kubernetes.io/scheme: internet-facing
-    alb.ingress.kubernetes.io/target-type: ip
-    alb.ingress.kubernetes.io/load-balancer-name: "embedding-ray-lb"
-    alb.ingress.kubernetes.io/healthcheck-protocol: HTTP
-    alb.ingress.kubernetes.io/healthcheck-port: "8265"
-    alb.ingress.kubernetes.io/healthcheck-path: "/"
-    alb.ingress.kubernetes.io/success-codes: "200"
-spec:
-  ingressClassName: alb
-  rules:
-  - http:
-      paths:
-      - path: /
-        pathType: Prefix
-        backend:
-          service:
-            name: ray-service-llamacpp-serve-svc
-            port:
-              number: 8000
diff --git a/model-hosting/ray-services/ray-service-llamacpp-with-embedding.yaml b/model-hosting/ray-services/ray-service-llamacpp-with-embedding.yaml
deleted file mode 100644
index ccc14396..00000000
--- a/model-hosting/ray-services/ray-service-llamacpp-with-embedding.yaml
+++ /dev/null
@@ -1,304 +0,0 @@
-apiVersion: v1
-kind: Secret
-metadata:
-  name: hf-token
-stringData:
-  token: HUGGING_FACE_TOKEN_HERE
-  llm_api_key: sk-1234
----
-apiVersion: v1
-kind: ConfigMap
-metadata:
-  name: llama-app-code-embedding
-data:
-  app.py: |
-    import multiprocessing
-    import os
-    import logging
-    import time
-    from fastapi import FastAPI, HTTPException
-    from starlette.requests import Request
-    from starlette.responses import JSONResponse
-    from ray import serve
-    from llama_cpp import Llama
-
-    logger = logging.getLogger("ray.serve")
-    logging.basicConfig(
-        level=logging.INFO,
-        format='%(asctime)s - %(name)s - %(levelname)s - %(message)s'
-    )
-    app = FastAPI()
-
-    @serve.deployment(
-        name="LLamaCPPDeployment", 
-        ray_actor_options={"num_cpus": 29}, 
-        autoscaling_config={
-            "min_replicas": 1, 
-            "max_replicas": 10, 
-            "initial_replicas": 1, 
-            "upscale_delay_s": 5
-        }, 
-        max_ongoing_requests=100, 
-        graceful_shutdown_timeout_s=600
-    )
-    @serve.ingress(app)
-    class LLamaCPPDeployment:
-        def __init__(self, parallelism: str):
-            os.environ["OMP_NUM_THREADS"] = parallelism
-            self.model_id = os.getenv("MODEL_ID", default="ChristianAzinn/snowflake-arctic-embed-s-gguf")
-            self.filename = os.getenv("MODEL_FILENAME", default="snowflake-arctic-embed-s-f16.GGUF")
-            self.n_ctx = int(os.getenv("N_CTX"))
-            self.n_threads = int(os.getenv("N_THREADS"))
-            self.api_key = os.getenv("LLM_API_KEY", default="sk-1234")
-            self.llm = Llama.from_pretrained(
-                repo_id=self.model_id,
-                filename=self.filename,
-                n_ctx=self.n_ctx,
-                n_threads=self.n_threads,
-                embedding=True
-            )
-            logger.info(f"Embedding model {self.model_id} loaded successfully with {self.n_threads} threads")
-            print("__init__ Complete")
-
-        @app.post("/v1/embeddings")
-        async def create_embeddings(self, request: Request):
-            try:
-                start_time = time.time()
-                body = await request.json()
-                
-                # Check for API key in request headers
-                auth_header = request.headers.get("Authorization", "")
-                if auth_header.startswith("Bearer "):
-                    api_key = auth_header.replace("Bearer ", "")
-                    if api_key != self.api_key:
-                        return JSONResponse(
-                            status_code=401,
-                            content={"error": "Invalid API key"}
-                        )
-                
-                # Extract parameters from request
-                input_text = body.get("input", "")
-                model = body.get("model", self.model_id)
-                encoding_format = body.get("encoding_format", "float")
-                
-                # Handle different input formats
-                if isinstance(input_text, list):
-                    texts = input_text
-                elif isinstance(input_text, str):
-                    texts = [input_text]
-                else:
-                    return JSONResponse(
-                        status_code=400,
-                        content={"error": "Input must be a string or array of strings"}
-                    )
-                
-                logger.info(f"Creating embeddings for {len(texts)} text(s)")
-                
-                # Generate embeddings
-                embeddings_data = []
-                total_tokens = 0
-                
-                for i, text in enumerate(texts):
-                    # Create embedding using llama-cpp-python
-                    embedding = self.llm.create_embedding(text)
-                    
-                    # Extract the embedding vector
-                    embedding_vector = embedding["data"][0]["embedding"]
-                    
-                    embeddings_data.append({
-                        "object": "embedding",
-                        "index": i,
-                        "embedding": embedding_vector
-                    })
-                    
-                    # Estimate token count (rough approximation)
-                    total_tokens += len(text.split())
-                
-                # Prepare the response in OpenAI format
-                response = {
-                    "object": "list",
-                    "data": embeddings_data,
-                    "model": model,
-                    "usage": {
-                        "prompt_tokens": total_tokens,
-                        "total_tokens": total_tokens
-                    }
-                }
-                
-                duration = time.time() - start_time
-                logger.info(f"Generated {len(embeddings_data)} embeddings in {duration:.2f} seconds")
-                
-                return JSONResponse(content=response)
-                
-            except Exception as e:
-                logger.error(f"Error creating embeddings: {str(e)}")
-                return JSONResponse(
-                    status_code=500,
-                    content={"error": str(e)}
-                )
-
-        @app.get("/health")
-        async def health_check(self):
-            return {"status": "healthy", "model": self.model_id, "type": "embedding"}
-
-    host_cpu_count = multiprocessing.cpu_count()
-
-    model = LLamaCPPDeployment.bind("host_cpu_count")
----
-apiVersion: ray.io/v1
-kind: RayService
-metadata:
-  name: ray-service-llamacpp
-spec:
-  serveConfigV2: |
-    applications:
-    - name: llmcpp-arm
-      route_prefix: /
-      import_path: app:model
-      deployments:
-      - name: LLamaCPPDeployment
-        ray_actor_options:
-          num_cpus: 29
-      runtime_env:
-        pip: ["llama_cpp_python", "transformers"]
-        env_vars:
-          LD_LIBRARY_PATH: "/home/ray/anaconda3/lib:$LD_LIBRARY_PATH"
-          MODEL_ID: "ChristianAzinn/snowflake-arctic-embed-s-gguf" 
-          MODEL_FILENAME: "snowflake-arctic-embed-s-f16.GGUF"
-          N_CTX: "0"
-          N_THREADS : "28"
-          FORCE_CMAKE: "1"
-          CMAKE_ARGS: "-DCMAKE_CXX_FLAGS='-mcpu=native -fopenmp' -DCMAKE_C_FLAGS='-mcpu=native -fopenmp'"
-          CMAKE_CXX_COMPILER: "/usr/bin/g++"  
-          CMAKE_C_COMPILER: "/usr/bin/gcc"  
-          CXX: "/usr/bin/g++"  
-          CC: "/usr/bin/gcc" 
-          PYTHONPATH: "/home/ray/anaconda3/lib/python3.11/site-packages:$PYTHONPATH" 
-  rayClusterConfig:
-    rayVersion: '2.33.0'
-    enableInTreeAutoscaling: true
-    headGroupSpec:
-      rayStartParams:
-        dashboard-host: '0.0.0.0'
-        num-cpus: '0'
-      template:
-        metadata:
-          labels:
-            ray-control-plane: "true"
-        spec:
-          nodeSelector:
-            kubernetes.io/arch: arm64
-          affinity:
-            nodeAffinity:
-              requiredDuringSchedulingIgnoredDuringExecution:
-                nodeSelectorTerms:
-                - matchExpressions:
-                  - key: kubernetes.io/arch
-                    operator: In
-                    values:
-                    - arm64           
-          restartPolicy: Always
-          containers:
-          - name: ray-head
-            image: rayproject/ray:2.39.0-py312-cpu-aarch64
-            volumeMounts:
-              - name: app-code
-                mountPath: /home/ray/app.py
-                subPath: app.py
-            resources:
-              limits:
-                cpu: "10"
-                memory: "20Gi"
-              requests:
-                cpu: "10"
-                memory: "20Gi"
-            ports:
-            - containerPort: 6379
-              name: gcs-server
-            - containerPort: 8265
-              name: dashboard
-            - containerPort: 10001
-              name: client
-            - containerPort: 8000
-              name: serve
-            env:
-            - name: HUGGING_FACE_HUB_TOKEN
-              valueFrom:
-                secretKeyRef:
-                  name: hf-token
-                  key: token
-            - name: LLM_API_KEY
-              valueFrom:
-                secretKeyRef:
-                  name: hf-token
-                  key: llm_api_key
-            - name: RAY_enable_autoscaler_v2
-              value: "1"
-            - name: RAY_num_heartbeats_timeout
-              value: "300" 
-          volumes:
-              - name: app-code
-                configMap:
-                  name: llama-app-code-embedding
-    workerGroupSpecs:
-    - replicas: 1
-      minReplicas: 1
-      maxReplicas: 10
-      groupName: cpu-group
-      rayStartParams: 
-        num-cpus: "29"
-      template:
-        spec:
-          nodeSelector:
-            kubernetes.io/arch: arm64
-          affinity:
-            nodeAffinity:
-              requiredDuringSchedulingIgnoredDuringExecution:
-                nodeSelectorTerms:
-                - matchExpressions:
-                  - key: kubernetes.io/arch
-                    operator: In
-                    values:
-                    - arm64           
-          restartPolicy: Always
-          containers:
-          - name: llm
-            image: rayproject/ray:2.39.0-py312-cpu-aarch64
-            volumeMounts:
-              - name: app-code
-                mountPath: /home/ray/app.py
-                subPath: app.py           
-            env:
-            - name: HUGGING_FACE_HUB_TOKEN
-              valueFrom:
-                secretKeyRef:
-                  name: hf-token
-                  key: token
-            - name: LLM_API_KEY
-              valueFrom:
-                secretKeyRef:
-                  name: hf-token
-                  key: llm_api_key
-            - name: CMAKE_ARGS
-              value: "-DCMAKE_CXX_FLAGS=-fopenmp"  
-            - name: "CC"
-              value: "/usr/bin/gcc"   
-            - name: "CXX"
-              value: "/usr/bin/g++"   
-            - name: CMAKE_CXX_COMPILER
-              value: "/usr/bin/g++"  
-            - name: CMAKE_C_COMPILER
-              value: "/usr/bin/gcc" 
-            - name: PYTHONPATH
-              value: "/home/ray/anaconda3/lib/python3.11/site-packages:$PYTHONPATH" 
-            resources:
-              limits:
-                cpu: "30"
-                memory: "55Gi"        
-              requests:
-                cpu: "30"
-                memory: "55Gi"
-          volumes:
-              - name: app-code
-                configMap:
-                  name: llama-app-code-embedding
diff --git a/model-hosting/setup.sh b/model-hosting/setup.sh
deleted file mode 100755
index 946cb872..00000000
--- a/model-hosting/setup.sh
+++ /dev/null
@@ -1,212 +0,0 @@
-#!/bin/bash
-
-# Script to deploy model hosting services
-
-set -e
-
-# Color codes for better readability
-GREEN='\033[0;32m'
-BLUE='\033[0;34m'
-RED='\033[0;31m'
-YELLOW='\033[0;33m'
-NC='\033[0m' # No Color
-
-# Function to display messages with timestamp
-log() {
-  echo -e "${BLUE}[$(date '+%Y-%m-%d %H:%M:%S')]${NC} $1"
-}
-
-warn() {
-  echo -e "${YELLOW}[$(date '+%Y-%m-%d %H:%M:%S')] WARNING:${NC} $1"
-}
-
-error() {
-  echo -e "${RED}[$(date '+%Y-%m-%d %H:%M:%S')] ERROR:${NC} $1"
-  cleanup_on_exit
-  exit 1
-}
-
-success() {
-  echo -e "${GREEN}[$(date '+%Y-%m-%d %H:%M:%S')] SUCCESS:${NC} $1"
-}
-
-# Cleanup function to restore original files
-cleanup_on_exit() {
-  log "Performing cleanup..."
-  if [ -f "ray-services/ray-service-llamacpp-with-embedding.yaml.backup" ]; then
-    log "Restoring original YAML file..."
-    mv "ray-services/ray-service-llamacpp-with-embedding.yaml.backup" "ray-services/ray-service-llamacpp-with-embedding.yaml"
-    success "Original YAML file restored!"
-  fi
-}
-
-# Set up trap to cleanup on script exit
-trap cleanup_on_exit EXIT
-
-# Function to prompt for Hugging Face token
-get_hugging_face_token() {
-  log "Hugging Face token is required for model access..."
-  
-  # Check if token is already set as environment variable
-  if [ -n "$HUGGING_FACE_TOKEN" ]; then
-    log "Using Hugging Face token from environment variable HUGGING_FACE_TOKEN"
-    HF_TOKEN="$HUGGING_FACE_TOKEN"
-  else
-    # Provide instructions for getting a token
-    echo
-    echo "To get a Hugging Face token:"
-    echo "1. Go to https://huggingface.co/settings/tokens"
-    echo "2. Create a new token with 'Read' permissions"
-    echo "3. Copy the token and paste it below"
-    echo
-    echo "Alternatively, you can set the HUGGING_FACE_TOKEN environment variable:"
-    echo "export HUGGING_FACE_TOKEN=your_token_here"
-    echo
-    
-    # Prompt user for token
-    echo -n "Please enter your Hugging Face token: "
-    read -s HF_TOKEN
-    echo
-    
-    if [ -z "$HF_TOKEN" ]; then
-      error "Hugging Face token is required. Please provide a valid token."
-    fi
-    
-    # Basic validation - HF tokens typically start with 'hf_'
-    if [[ ! "$HF_TOKEN" =~ ^hf_.* ]]; then
-      warn "Warning: Hugging Face tokens typically start with 'hf_'. Please verify your token is correct."
-      echo -n "Continue anyway? (y/N): "
-      read -r confirm
-      if [[ ! "$confirm" =~ ^[Yy]$ ]]; then
-        error "Token validation failed. Please provide a valid Hugging Face token."
-      fi
-    fi
-  fi
-  
-  success "Hugging Face token configured successfully!"
-}
-
-# Function to update YAML files with Hugging Face token
-update_yaml_with_token() {
-  log "Updating YAML files with Hugging Face token..."
-  
-  # Update ray-service YAML file
-  if [ -f "ray-services/ray-service-llamacpp-with-embedding.yaml" ]; then
-    # Create a backup of the original file
-    cp "ray-services/ray-service-llamacpp-with-embedding.yaml" "ray-services/ray-service-llamacpp-with-embedding.yaml.backup"
-    
-    # Replace the token placeholder with actual token
-    sed -i.tmp "s/HUGGING_FACE_TOKEN_HERE/$HF_TOKEN/g" "ray-services/ray-service-llamacpp-with-embedding.yaml"
-    rm "ray-services/ray-service-llamacpp-with-embedding.yaml.tmp" 2>/dev/null || true
-    
-    success "Ray service YAML updated with Hugging Face token!"
-  else
-    error "ray-service-llamacpp-with-embedding.yaml not found in ray-services directory"
-  fi
-}
-
-# Check prerequisites
-check_prerequisites() {
-  log "Checking prerequisites..."
-  
-  # Check kubectl
-  if ! command -v kubectl &> /dev/null; then
-    error "kubectl is not installed. Please install it first."
-  fi
-  
-  # Check if kubectl is configured to access a cluster
-  if ! kubectl cluster-info &> /dev/null; then
-    error "Cannot access Kubernetes cluster. Please check your kubeconfig."
-  fi
-  
-  success "All prerequisites satisfied."
-}
-
-# Install Ray service with llamacpp and embedding
-install_ray_llamacpp_embedding() {
-  log "Installing Ray service with llamacpp and embedding..."
-  
-  if [ -f "ray-services/ray-service-llamacpp-with-embedding.yaml" ]; then
-    kubectl apply -f ray-services/ray-service-llamacpp-with-embedding.yaml
-    success "Ray service with llamacpp and embedding deployed successfully!"
-  else
-    error "ray-service-llamacpp-with-embedding.yaml not found in ray-services directory"
-  fi
-}
-
-# Install standalone vLLM reasoning service
-install_standalone_vllm_reasoning() {
-  log "Installing standalone vLLM reasoning service..."
-  
-  if [ -f "standalone-vllm-reasoning.yaml" ]; then
-    kubectl apply -f standalone-vllm-reasoning.yaml
-    success "Standalone vLLM reasoning service deployed successfully!"
-  else
-    error "standalone-vllm-reasoning.yaml not found"
-  fi
-}
-
-# Install standalone vLLM vision service
-install_standalone_vllm_vision() {
-  log "Installing standalone vLLM vision service..."
-  
-  if [ -f "standalone-vllm-vision.yaml" ]; then
-    kubectl apply -f standalone-vllm-vision.yaml
-    success "Standalone vLLM vision service deployed successfully!"
-  else
-    error "standalone-vllm-vision.yaml not found"
-  fi
-}
-
-# Wait for services to be ready
-wait_for_services() {
-  log "Waiting for services to be ready..."
-  
-  # Wait for Ray service
-  log "Waiting for Ray service to be ready..."
-  kubectl wait --for=condition=ready --timeout=600s rayservice --all 2>/dev/null || warn "Ray service might still be initializing"
-  
-  # Wait for standalone services
-  log "Waiting for standalone services to be ready..."
-  kubectl wait --for=condition=available --timeout=600s deployment --all 2>/dev/null || warn "Some deployments might still be initializing"
-  
-  success "Services are ready!"
-}
-
-# Verify installations
-verify_installations() {
-  log "Verifying installations..."
-  
-  log "Checking Ray services..."
-  kubectl get rayservice
-  
-  log "Checking deployments..."
-  kubectl get deployments
-  
-  log "Checking services..."
-  kubectl get services
-  
-  log "Checking pods..."
-  kubectl get pods
-  
-  success "Installation verification completed!"
-}
-
-# Main execution
-main() {
-  log "Starting model hosting deployment..."
-  
-  check_prerequisites
-  get_hugging_face_token
-  update_yaml_with_token
-  install_ray_llamacpp_embedding
-  install_standalone_vllm_reasoning
-  wait_for_services
-  verify_installations
-  
-  success "All model hosting services deployed successfully!"
-  log "You can now access your model hosting services."
-}
-
-# Execute main function
-main
diff --git a/model-hosting/standalone-llamacpp-embedding.yaml b/model-hosting/standalone-llamacpp-embedding.yaml
deleted file mode 100644
index 03f63f3c..00000000
--- a/model-hosting/standalone-llamacpp-embedding.yaml
+++ /dev/null
@@ -1,97 +0,0 @@
----
-apiVersion: v1
-kind: PersistentVolumeClaim
-metadata:
-  name: llamacpp-embedding-server
-  annotations:
-    kubernetes.io/pvc-protection: "false"  
-spec:
-  accessModes:
-  - ReadWriteOnce
-  resources:
-    requests:
-      storage: 100Gi
-  storageClassName: gp3
-  volumeMode: Filesystem
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: llamacpp-embedding-server
-  labels:
-    app: llamacpp-embedding-server
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: llamacpp-embedding-server
-  template:
-    metadata:
-      labels:
-        app: llamacpp-embedding-server
-    spec:
-      nodeSelector:
-            kubernetes.io/arch: arm64
-      affinity:
-            nodeAffinity:
-              requiredDuringSchedulingIgnoredDuringExecution:
-                nodeSelectorTerms:
-                - matchExpressions:
-                  - key: kubernetes.io/arch
-                    operator: In
-                    values:
-                    - arm64 
-      volumes:
-      - name: cache-volume
-        persistentVolumeClaim:
-          claimName: llamacpp-embedding-server
-      containers:
-      - name: llamacpp-embedding-server
-        image: ghcr.io/ggml-org/llama.cpp:server
-        args: [
-          "--model-url https://huggingface.co/ChristianAzinn/snowflake-arctic-embed-s-gguf/blob/main/snowflake-arctic-embed-s-f16.GGUF --port 8000 --host 0.0.0.0 --embedding --threads 16"
-        ]
-        env:
-        - name: OMP_NUM_THREADS
-          value: "16"
-        ports:
-        - containerPort: 8000
-        resources:
-          limits:
-            memory: 32Gi
-          requests:
-            cpu: "16"
-            memory: 32Gi
-        volumeMounts:
-        - mountPath: /models
-          name: cache-volume
-        livenessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 120
-          periodSeconds: 10
-          failureThreshold: 15
-          successThreshold: 1
-        readinessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 120
-          periodSeconds: 10
-
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: llamacpp-embedding-server
-spec:
-  ports:
-  - name: http-llamacpp-embedding-server
-    port: 8000
-    protocol: TCP
-    targetPort: 8000
-  selector:
-    app: llamacpp-embedding-server
-  sessionAffinity: None
-  type: ClusterIP
diff --git a/model-hosting/standalone-vllm-reasoning.yaml b/model-hosting/standalone-vllm-reasoning.yaml
deleted file mode 100644
index 05646c50..00000000
--- a/model-hosting/standalone-vllm-reasoning.yaml
+++ /dev/null
@@ -1,128 +0,0 @@
----
-apiVersion: v1
-kind: PersistentVolumeClaim
-metadata:
-  name: vllm-qwen-server
-  annotations:
-    kubernetes.io/pvc-protection: "false"  
-spec:
-  accessModes:
-  - ReadWriteOnce
-  resources:
-    requests:
-      storage: 900Gi
-  storageClassName: gp3
-  volumeMode: Filesystem
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: vllm-qwen-server
-  labels:
-    app: vllm-qwen-server
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: vllm-qwen-server
-  template:
-    metadata:
-      labels:
-        app: vllm-qwen-server
-    spec:
-      # Updated nodeSelector to target GPU instances specifically
-      nodeSelector:
-            kubernetes.io/arch: amd64
-            nvidia.com/gpu: present
-            karpenter.sh/nodepool: gpu-inference
-          # Updated tolerations to match the taint on the GPU nodepool
-      tolerations:
-          - key: "model-inferencing"
-            operator: "Equal"
-            value: "gpu-inference"
-            effect: "NoSchedule"
-      volumes:
-      - name: cache-volume
-        persistentVolumeClaim:
-          claimName: vllm-qwen-server
-      # vLLM needs to access the host's shared memory for tensor parallel inference.
-      - name: shm
-        emptyDir:
-          medium: Memory
-          sizeLimit: "32Gi"
-      containers:
-      - name: vllm-qwen-server
-        image: vllm/vllm-openai:latest
-        # image: vllm/vllm-openai:v0.7.3
-        command: ["/bin/sh", "-c"]
-        args: [
-          "vllm serve Qwen/Qwen3-14B  --enable-auto-tool-choice --tool-call-parser hermes  --trust-remote-code --max-num-batched-tokens 32768  --max-num-seqs 8 --max-model-len 32768 --dtype bfloat16 --tensor-parallel-size 4 --gpu-memory-utilization 0.90"
-          
-        ]
-        env:
-        - name: HUGGING_FACE_HUB_TOKEN
-          valueFrom:
-            secretKeyRef:
-              name: hf-token
-              key: token
-        - name: OMP_NUM_THREADS
-          value: "8"  
-        - name: VLLM_LOGGING_LEVEL
-          value: "DEBUG"  
-        - name: VLLM_DISABLE_COMPILE_CACHE
-          value: "0"  
-        # - name: PYTORCH_CUDA_ALLOC_CONF
-        #   value: "max_split_size_mb:512,expandable_segments:True"
-        - name: CUDA_VISIBLE_DEVICES
-          value: "0,1,2,3"
-        ports:
-        - containerPort: 8000
-        resources:
-          limits:
-            memory: 64Gi
-            nvidia.com/gpu: "4"
-          requests:
-            cpu: "22"
-            memory: 64Gi
-            nvidia.com/gpu: "4"
-        volumeMounts:
-        - mountPath: /root/.cache/huggingface
-          name: cache-volume
-        - name: shm
-          mountPath: /dev/shm
-        livenessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 240
-          periodSeconds: 10
-          failureThreshold: 30
-          successThreshold: 1
-
-          
-        readinessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 240
-          periodSeconds: 10
-
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: vllm-qwen-server
-spec:
-  ports:
-  - name: http-vllm-qwen-server
-    port: 8000
-    protocol: TCP
-    targetPort: 8000
-  # The label selector should match the deployment labels & it is useful for prefix caching feature
-  selector:
-    app: vllm-qwen-server
-  sessionAffinity: None
-  type: ClusterIP          
-
-
-
diff --git a/model-hosting/standalone-vllm-vision.yaml b/model-hosting/standalone-vllm-vision.yaml
deleted file mode 100644
index 566a9e70..00000000
--- a/model-hosting/standalone-vllm-vision.yaml
+++ /dev/null
@@ -1,128 +0,0 @@
----
-apiVersion: v1
-kind: PersistentVolumeClaim
-metadata:
-  name: vllm-qwen-server-vision
-  annotations:
-    kubernetes.io/pvc-protection: "false"  
-spec:
-  accessModes:
-  - ReadWriteOnce
-  resources:
-    requests:
-      storage: 900Gi
-  storageClassName: gp3
-  volumeMode: Filesystem
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: vllm-qwen-server-vision
-  labels:
-    app: vllm-qwen-server-vision
-spec:
-  replicas: 1
-  selector:
-    matchLabels:
-      app: vllm-qwen-server-vision
-  template:
-    metadata:
-      labels:
-        app: vllm-qwen-server-vision
-    spec:
-      # Updated nodeSelector to target GPU instances specifically
-      nodeSelector:
-            kubernetes.io/arch: amd64
-            nvidia.com/gpu: present
-            karpenter.sh/nodepool: gpu-inference
-          # Updated tolerations to match the taint on the GPU nodepool
-      tolerations:
-          - key: "model-inferencing"
-            operator: "Equal"
-            value: "gpu-inference"
-            effect: "NoSchedule"
-      volumes:
-      - name: cache-volume
-        persistentVolumeClaim:
-          claimName: vllm-qwen-server-vision
-      # vLLM needs to access the host's shared memory for tensor parallel inference.
-      - name: shm
-        emptyDir:
-          medium: Memory
-          sizeLimit: "32Gi"
-      containers:
-      - name: vllm-qwen-server-vision
-        image: vllm/vllm-openai:latest
-        # image: vllm/vllm-openai:v0.7.3
-        command: ["/bin/sh", "-c"]
-        args: [
-          "vllm serve Qwen/Qwen2.5-VL-7B-Instruct  --enable-auto-tool-choice --tool-call-parser hermes  --trust-remote-code --max-num-batched-tokens 8192  --max-num-seqs 8 --max-model-len 8192 --dtype bfloat16 --tensor-parallel-size 4 --gpu-memory-utilization 0.90"
-          
-        ]
-        env:
-        - name: HUGGING_FACE_HUB_TOKEN
-          valueFrom:
-            secretKeyRef:
-              name: hf-token
-              key: token
-        - name: OMP_NUM_THREADS
-          value: "8"  
-        - name: VLLM_LOGGING_LEVEL
-          value: "DEBUG"  
-        - name: VLLM_DISABLE_COMPILE_CACHE
-          value: "0"  
-        # - name: PYTORCH_CUDA_ALLOC_CONF
-        #   value: "max_split_size_mb:512,expandable_segments:True"
-        - name: CUDA_VISIBLE_DEVICES
-          value: "0,1,2,3"
-        ports:
-        - containerPort: 8000
-        resources:
-          limits:
-            memory: 64Gi
-            nvidia.com/gpu: "4"
-          requests:
-            cpu: "22"
-            memory: 64Gi
-            nvidia.com/gpu: "4"
-        volumeMounts:
-        - mountPath: /root/.cache/huggingface
-          name: cache-volume
-        - name: shm
-          mountPath: /dev/shm
-        livenessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 240
-          periodSeconds: 10
-          failureThreshold: 30
-          successThreshold: 1
-
-          
-        readinessProbe:
-          httpGet:
-            path: /health
-            port: 8000
-          initialDelaySeconds: 240
-          periodSeconds: 10
-
----
-apiVersion: v1
-kind: Service
-metadata:
-  name: vllm-qwen-server-vision
-spec:
-  ports:
-  - name: http-vllm-qwen-server-vision
-    port: 8000
-    protocol: TCP
-    targetPort: 8000
-  # The label selector should match the deployment labels & it is useful for prefix caching feature
-  selector:
-    app: vllm-qwen-server-vision
-  sessionAffinity: None
-  type: ClusterIP          
-
-
-
diff --git a/model-observability/langfuse-redis-port-patch.yaml b/model-observability/langfuse-redis-port-patch.yaml
deleted file mode 100644
index 3577b956..00000000
--- a/model-observability/langfuse-redis-port-patch.yaml
+++ /dev/null
@@ -1,27 +0,0 @@
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: langfuse-web
-  namespace: default
-spec:
-  template:
-    spec:
-      containers:
-      - name: langfuse-web
-        env:
-        - name: REDIS_PORT
-          value: "6379"
----
-apiVersion: apps/v1
-kind: Deployment
-metadata:
-  name: langfuse-worker
-  namespace: default
-spec:
-  template:
-    spec:
-      containers:
-      - name: langfuse-worker
-        env:
-        - name: REDIS_PORT
-          value: "6379"
diff --git a/model-observability/langfuse-web-ingress.yaml b/model-observability/langfuse-web-ingress.yaml
deleted file mode 100644
index 5d585582..00000000
--- a/model-observability/langfuse-web-ingress.yaml
+++ /dev/null
@@ -1,22 +0,0 @@
-apiVersion: networking.k8s.io/v1
-kind: Ingress
-metadata:
-  name: langfuse-web-ingress-alb
-  annotations:
-    kubernetes.io/ingress.class: alb
-    alb.ingress.kubernetes.io/scheme: internet-facing
-    alb.ingress.kubernetes.io/target-type: ip
-    alb.ingress.kubernetes.io/healthcheck-path: /
-    alb.ingress.kubernetes.io/healthcheck-port: '3000'
-    alb.ingress.kubernetes.io/listen-ports: '[{"HTTP": 80}]'
-spec:
-  rules:
-    - http:
-        paths:
-          - path: /
-            pathType: Prefix
-            backend:
-              service:
-                name: langfuse-web
-                port:
-                  number: 3000
diff --git a/model-observability/values.yaml.DEPRECATED b/model-observability/values.yaml.DEPRECATED
deleted file mode 100644
index 81ab0ff4..00000000
--- a/model-observability/values.yaml.DEPRECATED
+++ /dev/null
@@ -1,68 +0,0 @@
-# FOR DEMO USE ONY
-langfuse: 
-  additionalEnv:
-    - name : REDIS_PORT
-      value: "6379"
-    # - name: LANGFUSE_S3_EVENT_UPLOAD_SECRET_ACCESS_KEY
-    #   value: "changeme"
-      # valueFrom:
-      #   secretKeyRef:
-      #     name: langfuse-s3
-      #     key: root-password
-    # - name: LANGFUSE_S3_BATCH_EXPORT_SECRET_ACCESS_KEY
-    #   value: "changeme"
-      # valueFrom:
-      #   secretKeyRef:
-      #     name: langfuse-s3
-      #     key: root-password
-  salt:
-    value: TOO_SALTY
-  nextauth:
-    secret:
-      value: "changeme"
-
-postgresql:
-  auth:
-    password: "changeme"
-
-clickhouse:
-  auth:
-    password: "changeme"
-
-redis:
-  auth:
-    password: "changeme"
-
-s3:
-  secretAccessKey:
-    value: "changeme"
-
-# FOR NON DEMO USE YOU SHYLD DEFINE THE SENSITIVE DATA IN SECRETS and/or use cloud storage services such as S3
-# langfuse: 
-#   salt:
-#     secretKeyRef:
-#       name: langfuse-general
-#       key: salt
-#   nextauth:
-#     secret:
-#       secretKeyRef:
-#         name: langfuse-nextauth-secret
-#         key: nextauth-secret
-
-# postgresql:
-#   auth:
-#     existingSecret: langfuse-postgresql-auth
-#     secretKeys:
-#       userPasswordKey: password
-
-# clickhouse:
-#   auth:
-#     existingSecret: langfuse-clickhouse-auth
-#     secretKeys:
-#       userPasswordKey: password
-
-# redis:
-#   auth:
-#     existingSecret: langfuse-redis-auth
-#     secretKeys:
-#       userPasswordKey: password    
\ No newline at end of file
diff --git a/neuron-nodepool.yaml b/neuron-nodepool.yaml
new file mode 100644
index 00000000..8a68043f
--- /dev/null
+++ b/neuron-nodepool.yaml
@@ -0,0 +1,28 @@
+apiVersion: karpenter.sh/v1
+kind: NodePool
+metadata:
+  name: neuron-pool
+spec:
+  template:
+    spec:
+      nodeClassRef:
+        group: eks.amazonaws.com
+        kind: NodeClass
+        name: default
+      requirements:
+        - key: "eks.amazonaws.com/instance-category"
+          operator: In
+          values: ["inf"]  # Inferentia instance families
+        - key: karpenter.sh/capacity-type
+          operator: In
+          values: ["on-demand"]  # Recommended for ML inference workloads
+      taints:
+        - key: aws.amazon.com/neuron
+          value: "true"
+          effect: NoSchedule
+  limits:
+    cpu: 1000
+    memory: 1000Gi
+  disruption:
+    consolidationPolicy: WhenEmptyOrUnderutilized
+    consolidateAfter: 30s
diff --git a/requirements.txt b/requirements.txt
new file mode 100644
index 00000000..c22e27d2
--- /dev/null
+++ b/requirements.txt
@@ -0,0 +1,21 @@
+# Core Strands SDK dependencies for AI agent orchestration
+strands-agents[otel]>=0.1.0
+strands-agents-tools
+strands-agents[openai]
+
+# Langfuse tracing dependencies for clinical assistant monitoring
+langfuse>=2.0.0
+
+# MCP (Model Context Protocol) dependencies for healthcare data server
+mcp>=1.0.0
+
+# Environment and configuration management
+python-dotenv>=1.0.0
+
+# Standard library dependencies (usually included with Python but listed for completeness)
+# logging - built-in
+# os - built-in  
+# base64 - built-in
+# json - built-in
+# datetime - built-in
+# typing - built-in (Python 3.5+)
diff --git a/model-observability/setup.sh b/setup.sh
old mode 100755
new mode 100644
similarity index 72%
rename from model-observability/setup.sh
rename to setup.sh
index 698749b6..512d8428
--- a/model-observability/setup.sh
+++ b/setup.sh
@@ -59,8 +59,9 @@ else
   log "Installing Langfuse using Helm..."
   if [ -f "langfuse-value.yaml" ]; then
     helm install langfuse langfuse/langfuse -f langfuse-value.yaml \
-      --set nodeSelector."kubernetes\.io/arch"=arm64
-    success "Langfuse Helm installation initiated with arm64 node selector!"
+      --set nodeSelector."kubernetes\.io/arch"=arm64 \
+      --set global.storageClass=auto-ebs-sc
+    success "Langfuse Helm installation initiated with arm64 node selector and auto-ebs-sc storage class!"
   else
     error "langfuse-value.yaml not found"
   fi
@@ -101,32 +102,34 @@ EOF
   kubectl apply -f langfuse-redis-port-patch.yaml
   success "Redis port configuration patch applied!"
 
-  log "Waiting for Langfuse pods to be running (timeout: 15 minutes)..."
-  # Wait for pods to be in Running state instead of Ready condition
-  start_time=$(date +%s)
-  timeout=900  # 15 minutes in seconds
+  log "Waiting for Langfuse pods to be running (timeout: 10 minutes)..."
+  # Wait for a short time to allow pods to start
+  sleep 30
   
+  # Check if all pods are in Running state (regardless of readiness)
+  TIMEOUT=600
+  START_TIME=$(date +%s)
   while true; do
-    current_time=$(date +%s)
-    elapsed=$((current_time - start_time))
+    CURRENT_TIME=$(date +%s)
+    ELAPSED_TIME=$((CURRENT_TIME - START_TIME))
     
-    if [ $elapsed -gt $timeout ]; then
-      warn "Timeout reached after 15 minutes, but continuing with deployment"
+    if [ $ELAPSED_TIME -gt $TIMEOUT ]; then
+      error "Langfuse deployment failed - pods did not enter Running state within 10 minutes"
       break
     fi
     
-    # Count running pods vs total pods
-    total_pods=$(kubectl get pods --selector=app.kubernetes.io/instance=langfuse --no-headers | wc -l)
-    running_pods=$(kubectl get pods --selector=app.kubernetes.io/instance=langfuse --no-headers | grep -c "Running" || echo "0")
+    # Count total pods and running pods
+    TOTAL_PODS=$(kubectl get pods --selector=app.kubernetes.io/instance=langfuse --no-headers | wc -l)
+    RUNNING_PODS=$(kubectl get pods --selector=app.kubernetes.io/instance=langfuse --no-headers | grep -c "Running" || true)
     
-    if [ "$total_pods" -gt 0 ] && [ "$running_pods" -gt 0 ]; then
-      log "$running_pods out of $total_pods Langfuse pods are running"
-      success "Langfuse has running pods - continuing with deployment"
+    if [ "$TOTAL_PODS" -eq "$RUNNING_PODS" ] && [ "$TOTAL_PODS" -gt 0 ]; then
+      success "Langfuse deployment completed successfully! All $TOTAL_PODS pods are running."
+      kubectl get pods --selector=app.kubernetes.io/instance=langfuse
       break
+    else
+      log "Waiting for pods to be running ($RUNNING_PODS/$TOTAL_PODS are running)... Elapsed time: ${ELAPSED_TIME}s"
+      sleep 10
     fi
-    
-    log "Waiting for Langfuse pods to start running ($elapsed seconds elapsed)..."
-    sleep 10
   done
 fi
 
@@ -144,7 +147,7 @@ fi
 log "Verifying Langfuse installation..."
 kubectl get pods -l app.kubernetes.io/instance=langfuse
 kubectl get service -l app.kubernetes.io/instance=langfuse
-kubectl get ingress langfuse-web-ingress-alb 2>/dev/null || warn "Langfuse ingress not found"
+kubectl get ingress langfuse-web-ingress 2>/dev/null || warn "Langfuse ingress not found"
 
 success "Model observability setup completed!"
 log "Refer to README.md to access Langfuse and define Public/Private Keys"
diff --git a/base_eks_setup/gp3.yaml b/storageclass.yaml
similarity index 56%
rename from base_eks_setup/gp3.yaml
rename to storageclass.yaml
index 298078ad..afdee363 100644
--- a/base_eks_setup/gp3.yaml
+++ b/storageclass.yaml
@@ -1,12 +1,11 @@
 apiVersion: storage.k8s.io/v1
 kind: StorageClass
 metadata:
-  name: gp3
+  name: auto-ebs-sc
   annotations:
     storageclass.kubernetes.io/is-default-class: "true"
-provisioner: ebs.csi.aws.com
+provisioner: ebs.csi.eks.amazonaws.com
+volumeBindingMode: WaitForFirstConsumer
 parameters:
   type: gp3
-  fsType: ext4
-reclaimPolicy: Delete
-volumeBindingMode: Immediate
\ No newline at end of file
+  encrypted: "true"
\ No newline at end of file